text
stringlengths
1.9k
1.3M
url
stringlengths
24
511
HOTEL GAILLAC-D'AVEYRON : Hotels near Gaillac-d'Aveyron 12310 France HOTEL GAILLAC-D'AVEYRON : Find the best hotel among all the hotels near Gaillac-d'Aveyron and BOOK NOW for your trip in France ! 12310 Aveyron Here is the list of the hotels near Gaillac-d'Aveyron. Book your hotel near Gaillac-d'Aveyron today, Saturday 03 June for the best price, reservation and cancellation free of charge thanks to our partner Booking.com, leader in on-line hotels reservation. To help you find available hotels, you can follow these links to check the list of hotels in nearby towns of Gaillac-d'Aveyron : - Recoules-Prévinquières hotels (12150) : town located at 3.53 km - Buzeins hotels (12150) : town located at 3.95 km - Vimenet hotels (12310) : town located at 4.99 km - Sévérac-l'Église hotels (12310) : town located at 6.62 km - Lavernhe hotels (12150) : town located at 7.47 km - Coussergues hotels (12310) : town located at 7.62 km - Palmas hotels (12310) : town located at 8.19 km - Lapanouse hotels (12150) : town located at 8.45 km - Vézins-de-Lévézou hotels (12780) : town located at 8.60 km - Laissac hotels (12310) : town located at 8.95 km - Saint-Martin-de-Lenne hotels (12130) : town located at 9.02 km To help you choose your destination as well as the place of the hotel here is: - pictures of Gaillac-d'Aveyron : photo Gaillac-d'Aveyron - the map of Gaillac-d'Aveyron : map Gaillac-d'Aveyron - the road map of Gaillac-d'Aveyron : road map Gaillac-d'Aveyron Below here is the list the 50 closest hotels of Gaillac-d'Aveyron, sortable according your criteria. You will find the position of these accommodations on the Gaillac-d'Aveyron hotels map . Share the hotels list of Gaillac-d'Aveyron ! Search Hotels Book now, Best Price Guaranteed ! Where ? Gaillac-d'Aveyron Check-in date 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 May 2023 June 2023 July 2023 August 2023 September 2023 October 2023 November 2023 December 2023 January 2024 February 2024 March 2024 April 2024 _link_ Check-out date 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 May 2023 June 2023 July 2023 August 2023 September 2023 October 2023 November 2023 December 2023 January 2024 February 2024 March 2024 April 2024 _link_ on I have no specific dates Search Hotels near Gaillac-d'Aveyron Book your hotel online now. Save up to 75% on your reservation whith FREE cancellation ! Sort hotels by : Most popular Distance between hotel and town hall Price (increasing) Price (decreasing) Number of stars (increasing) Number of stars (decreasing) -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- La cazette Bed and Breakfast Recoules-Prévinquières Featuring a private hot tub and a terrace, La cazette offers accommodation in Recoules-Prévinquières. Free private parking is available on site. Built in a stone arch, the 60m² suite offers a 220cm round bed and a flat-screen TV. You can relax in the seating area after a busy day. You will find a fully equipped kitchen with a coffee machine, toaster, microwave and dining area. The suite features a walk-in shower with free toiletries and a hairdryer. La cazette features free WiFi throughout the property. Breakfast is included. Millau is 27 km from La cazette, while Mende is 49 km away. Rodez - Aveyron Airport is 38 km from the property. Price : from 160.00 € Bed and Breakfast of Gaillac-d'Aveyron or nearby towns : Address : Recoules Prévinquières Prévinquières 12150 Recoules-Prévinquières Distance on map, Hotel - Gaillac-d'Aveyron : 3.26 kilometers Chambres d'hôtes Entre Dolmens et Fontaines Bed and Breakfast Buzeins Preferred hotel ! Entre Dolmens et Fontaines is located in Buzeins. Free WiFi access is available. Featuring a shower, private bathroom also comes with free toiletries. Extras include a desk and bed linen. Upon prior reservation, guests can enjoy evening meals at the owner's table. An array of activities can be enjoyed on site or in the surroundings, including cycling and hiking. The property offers free parking. Prices : from 55.00 € to 105.00 € Bed and Breakfast of Gaillac-d'Aveyron or nearby municipalities : Location : Rue du Puech / Buzeins 12150 Buzeins Route on map, Hotel - Gaillac-d'Aveyron : 4.01 kilometer Le Clos du Barry Bed and Breakfast Sévérac-lʼÉglise Preferred hotel ! Set in a stone farmhouse, Le Clos du Barry is an Aveyron Bed and Breakfast located just 3km from the village of Laissac. There guests will find a garden and a terrace, as well as a living room with games, books and free Wi-Fi access. At Le Clos du Barry, all rooms feature a small seating area, a private bathroom, while the family room offers 2 separate rooms, a common area with a kitchen, a mezzanine, a larger shower room and separate toilets. Each morning, a continental breakfast, including hot beverage, juice and homemade produce is served. Guests can share a meal, featuring the garden’s vegetable and regional specialties, at the owners’ table. An array of activities can be enjoyed on site or less than 20 km away, such as horse riding, cycling, tree climbing and hiking. Bicycles can be borrowed for free onsite and the hosts can provide more information about the trails on request. Rodez Train Station is a 25-minute drive from the property which offers free parking. Rate : from 65.77 € to 156.00 € Bed and Breakfast Gaillac-d'Aveyron : Address : 5 rue du Barry 12310 Sévérac-lʼÉglise Distance on map between hotel and center of Gaillac-d'Aveyron : 6.40 km Room in hotel : 5 Les Inseparables Guest accommodation Sévérac-lʼÉglise Situated in Sévérac-lʼÉglise, Les Inseparables offers air-conditioned accommodation with a terrace and free WiFi. Guests staying at this holiday home have access to a fully equipped kitchen. This 1-bedroom holiday home includes 1 bathroom equipped with a shower and a hair dryer. A flat-screen TV is offered. If you would like to discover the area, hiking is possible in the surroundings. Rodez is 28 km from the holiday home. Rodez - Aveyron Airport is 38 km away. Guest accommodation Gaillac-d'Aveyron : Location : 5 Place du Griffoul 12310 Sévérac-lʼÉglise Distance between hotel and center of Gaillac-d'Aveyron : 6.52 kms Rooms in hotel : 1 Domaine d'Angel-Berg Guest accommodation Vézins-de-Lévézou Domaine d'Angel-Berg is 25 km north of Millau. It is set in the former farm of Vézins castle, which is situated 200 metres away and is owned by the same family for 1000 years. This guest house is located in Vézins-de-Lévézou and offers a large estate and free WiFi access in some areas. Each room has a private bathroom with shower and toilet. Pension and infrastructure for horses are available. You can order a breakfast basket, including continental items such as bread and pastries. Packed lunches are available if requested 24 hours in advance. The gîte and apartment have a private kitchen or kitchenette. Domaine d'Angel-Berg is located in the regional park of Grand Causses and an array of activities can be enjoyed in the surroundings, including cycling, horse riding and hiking. Set 14 km from the A75 Motorway, the property offers free parking. Guest accommodation of Gaillac-d'Aveyron or nearby towns : Address : Domaine d'Angel-Berg 12780 Vézins-de-Lévézou Distance on map, Hotel - Gaillac-d'Aveyron : 8.15 kilometers Number of room : 4 L'ANCIENNE FORGE Guest accommodation Gaillac-dʼAveyron Situated in Gaillac-dʼAveyron in the Midi-Pyrénées region, L'ANCIENNE FORGE features a terrace. This holiday home features barbecue facilities as well as a garden. This holiday home comes with 3 bedrooms, a flat-screen TV, and a kitchen. Fishing and hiking can be enjoyed nearby. Rodez is 27 km from the holiday home, while Laguiole is 45 km from the property. The nearest airport is Rodez - Aveyron Airport, 37 km from the property. Guest accommodation Gaillac-d'Aveyron : Location : Le Bourg 12310 Gaillac-dʼAveyron Route on map, Hotel - Gaillac-d'Aveyron : 8.40 kilometer Number of rooms : 1 Logis de France Cazes Arazat Hotel Laissac Located 23 km from Rodez Train Station, this 2-star hotel has a restaurant that serves regional dishes. Free internet access is provided in the guest rooms. Each of the soundproofed rooms is elegantly decorated and includes a LCD TV with Canal + channels. The en suite bathrooms include a hairdryer. Breakfast is prepared every morning at the Logis de France Cazes Arazat. You can enjoy a drink in the bar, and evening meals can be taken on the terrace. You can go canoeing in the Gorges du Tarn, located 30 km from this hotel and the centre of Rodez, with its Soulage Museum, is 20 km away. Secure parking is free on site. Price : from 69.00 € to 86.00 € Hotel Gaillac-d'Aveyron : Address : 15 avenue de la Roque 12310 Laissac Distance on map between hotel and center of Gaillac-d'Aveyron : 8.92 km Room in hotel : 13 Hôtel Armony Hotel Laissac With free Wi-Fi internet access, this hotel features an outdoors swimming pool, a terrace and free private parking. Located in Laissac, it is 25 km from Rodez Train Station and a 35-minute drive from Marcillac Airport. Provided with LCD TVs including Canal+, the soundproofed rooms at Hôtel Armony are provided with a telephone and private bathroom. The studios/apartments also feature an equipped kitchenette with microwave. A continental breakfast is served daily. On Tuesday you can go shopping at the local market and a traditional restaurant can be found 100 metres away. Viaduc de Millau is a 45-minute drive away and the Tarn Gorges are 55 km from Hôtel Armony. Prices : from 70.00 € to 86.00 € Hotel Gaillac-d'Aveyron : Location : Place Abbé Bessou 12310 Laissac Distance between hotel and center of Gaillac-d'Aveyron : 9.08 kms Rooms in hotel : 16 Hotel de la Gare Hotel Sévérac-le-Château Preferred hotel ! Hotel de la Gare is located in the heart of the village of Severac, right opposite the train station and a 15-minute walk away from the castle. It features free Wi-Fi access and a restaurant with a shaded terrace. Each bright room is equipped with a TV and an en suite bathroom with a shower. You can enjoy pastries in the café for breakfast and the restaurant serves regional cuisine. There is free public parking on site and Hotel de la Gare also has an interior courtyard for two-wheel vehicles. Rate : from 48.00 € to 65.00 € Hotel of Gaillac-d'Aveyron or nearby towns : Address : 1 Avenue Pierre Semard 12150 Sévérac-le-Château Distance on map, Hotel - Gaillac-d'Aveyron : 10.70 kilometers Number of room : 9 Maison d'Hôtes La Singulière Bed and Breakfast Sévérac-le-Château Surrounded by a garden, La Singulière is located in Séverac-Le-Château and boasts exposed wooden beams, stone walls and a fireplace. You can borrow the bicycles to discover the area, relax in the living room and enjoy the cinema room. Decorated with antique furniture, all of the rooms at La Singulière feature a TV and an electric kettle. The private bathroom is fitted with a hairdryer and a bath or a shower. Some of the rooms offer castle and garden views. A continental breakfast with organic produce is included and served every morning in the dining room. Dinners with traditional dishes from the region are also available upon prior reservation. Free Wi-Fi is provided throughout the property. You can decide to visit the on-site photo exhibitions or the Millau Viaduct, which is a 35-minute drive from the B&B. Price : from 105.00 € to 185.00 € Bed and Breakfast of Gaillac-d'Aveyron or nearby municipalities : Location : 7 rue Emile Zola 12150 Sévérac-le-Château Route on map, Hotel - Gaillac-d'Aveyron : 11.46 kilometer Number of rooms : 3 Sev'hotel Hotel Sévérac-le-Château In a frame of greenery, built on the side of the castle, near the Viaduct of Millau, gorges of the Tarn, in the National park of the Big Causses plateau. The hotel has 30 comfortable, quiet rooms with shower, wc and tv. Prices : from 40.00 € to 61.00 € Hotel of Gaillac-d'Aveyron or nearby towns : Address : Avenue de Paris 12150 Sévérac-le-Château Distance on map between hotel and center of Gaillac-d'Aveyron : 11.49 km Room in hotel : 30 Book now Village de Gite - La Cascade Guest accommodation Sainte-Eulalie-dʼOlt Offering an outdoor swimming pool, La Cascade is a 3-star holiday park located in the Lot near the medieval village of Sainte-Eulalie-d’Olt, one of France most beautiful villages. Free WiFi is available in all areas. At La Cascade, each accommodation offers a terrace and views over the mountain. It features a sofa, a TV and a dining area, as well as a bathroom with a shower. A fully equipped kitchenette with kitchenware, a microwave and a refrigerator can also be found. A restaurant is located 3 km from this holiday park and there is a bar on site. At La Cascade, guests will also enjoy a children's playground, as well as canoeing, horse riding and fishing in the surroundings. Campagnac Train Station is 15 km away. The property offers free parking. Guest accommodation of Gaillac-d'Aveyron or nearby municipalities : Location : La Montberte 12130 Sainte-Eulalie-dʼOlt Distance between hotel and center of Gaillac-d'Aveyron : 12.21 kms Rooms in hotel : 15 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Marmotel Village Guest accommodation Saint-Geniez-dʼOlt Marmotel Village is situated in a 5-hectare park in Saint-Geniez d'Olt, by the banks of the River Lot and 20 km from the A75 motorway. It offers a swimming pool with water slides, a tennis court and evening entertainment in summer. The chalets and mobile homes at Marmotel feature a furnished terrace and a living area with a TV. At an extra cost, BBQ facilities can be rented on site. Guests can use the stove in the kitchenette to prepare meals. A continental breakfast is available every morning and there is also a restaurant in July and August. Other on-site facilities include a laundrette, a volleyball pitch and a basketball court. Free Wi-Fi access is available in public areas and free private parking is possible on site. Guests can chose to explore the valley or drive 30 minutes to the Tarn Gorges. Guest accommodation of Gaillac-d'Aveyron or nearby towns : Address : La Salle 12130 Saint-Geniez-dʼOlt Distance on map, Hotel - Gaillac-d'Aveyron : 12.29 kilometers Number of room : 80 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Le Clos Des Lavandes Bed and Breakfast Sévérac-le-Château Featuring free WiFi and a hot tub, Le Clos Des Lavandes guest house offers pet-friendly accommodation in Sévérac-le-Château. Free private parking is available on site. Le Clos Des lavandes has a free private relaxation area with spa, hammam and sauna, as well as a seasonal heated swimming pool. You will find a shared lounge at the property. Guest can enjoy a meal with the owners upon prior booking. You can play table tennis and darts at the bed and breakfast. Millau is 25 km from Le Clos Des Lavandes, while Mende is 39 km from the property. Prices : from 121.44 € to 160.00 € Bed and Breakfast of Gaillac-d'Aveyron or nearby municipalities : Location : Villeplaine 12150 Sévérac-le-Château Route on map, Hotel - Gaillac-d'Aveyron : 12.53 kilometer Number of rooms : 4 Résidence Le Village Goélia Guest accommodation Saint-Geniez-dʼOlt Le Village Goelia features 2 swimming pools, a mini golf, a mini football field and a volleyball court. There are also a bar, a fitness room and a mini club with a children’s playground. Facing south, most rooms have a balcony or a terrace with garden furniture. They all feature a TV, dining area, and kitchenette with microwave. The private bathrooms include free toiletries. A continental breakfast can be served daily at an additional cost. During summer, outdoors activities including kayaking, horse riding and biking. These are available at an additional cost. Set in the Lot Valley, 500 metres from the Lot River, Le Village Goelia offers free private parking, and Wi-Fi is free of charge in public areas. Guest accommodation of Gaillac-d'Aveyron or nearby towns : Address : La Falque - Route des monts d'Aubrac 12130 Saint-Geniez-dʼOlt Distance on map between hotel and center of Gaillac-d'Aveyron : 12.67 km Room in hotel : 25 Hotel de France Hotel Saint-Geniez-dʼOlt Situated in the Lot Valley, the Hotel De France is in the village of Saint-Geniez d’Olt, just 300 metres from the Lot River. It offers a restaurant and a bar. The guest rooms at the Hotel De France are equipped with TVs and each has a private bathroom with bath or shower. Guests can enjoy cuisine from the Aveyron region in the hotel’s restaurant, and a continental breakfast is served every morning. There is also an outdoor terrace where guests can relax. Additional facilities at the Hotel De France include a lift and a free garage is also provided. Hotel De France is well located for exploring France’s Midi-Pyrénées region. Hotel of Gaillac-d'Aveyron or nearby municipalities : Location : 18 Place du General de Gaulle 12130 Saint-Geniez-dʼOlt Distance between hotel and center of Gaillac-d'Aveyron : 12.73 kms Rooms in hotel : 45 Au Pied De L'Aubrac Apartment Saint-Geniez-dʼOlt Featuring a private beach area and barbecue facilities, Au Pied De L'Aubrac provides accommodation in Saint-Geniez-dʼOlt with free WiFi and city views. The accommodation is 44 km from Rodez. This apartment has 1 bedroom, a living room and a fully equipped kitchen. A flat-screen TV is provided. A continental breakfast is served each morning at the property. The apartment offers a terrace. Guests at Au Pied De L'Aubrac can enjoy darts on site, or go skiing or cycling in the surroundings. Laguiole is 49 km from the accommodation. The nearest airport is Rodez - Aveyron Airport, 54 km from the property. Prices : from 70.00 € Apartment of Gaillac-d'Aveyron or nearby towns : Address : 5,rue du commerce 12130 Saint-Geniez-dʼOlt Distance on map, Hotel - Gaillac-d'Aveyron : 12.86 kilometers Number of room : 1 St Geniez D Olt Guest accommodation Saint-Geniez-dʼOlt St Geniez D Olt is located in Saint-Geniez-dʼOlt and offers barbecue facilities, a garden and a terrace. Complimentary WiFi is offered. The holiday home features a TV. The accommodation is equipped with a kitchen. Rodez is 44 km from the holiday home, while Laguiole is 49 km away. The nearest airport is Rodez - Aveyron Airport, 54 km from St Geniez D Olt. Guest accommodation of Gaillac-d'Aveyron or nearby municipalities : Location : 12130 Saint-Geniez-dʼOlt Route on map, Hotel - Gaillac-d'Aveyron : 12.88 kilometer Number of rooms : 1 Book now -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Hotel Le Lion d'Or Hotel Saint-Geniez-dʼOlt This 2-star hotel has a unique location next to the Augustinian Convent’s former monastery. Set in the very centre of St-Geniez-d'Olt, it offers a large garden with a terrace. Decorated in neutral tones, the rooms at Hotel Le Lion d'Or feature views of the garden and free Wi-Fi access. They also have an LCD TV with satellite channels and a private bathroom with free toiletries. Continental breakfast is served every morning in the dining room or in the comfort of guest rooms. You can also relax in the bar and read the free newspapers before sampling French cuisine in the restaurant. The hotel is ideally located 15 km from the A75, which leads directly to Millau in 1 hour. You may also choose to drive the 15 km to Aubrac Plateau or explore Grands Causses Regional Park, 3 km away. Price : from 54.00 € to 79.00 € Hotel of Gaillac-d'Aveyron or nearby towns : Address : Place de l'Hôtel de Ville 12130 Saint-Geniez-dʼOlt Distance on map between hotel and center of Gaillac-d'Aveyron : 12.90 km Room in hotel : 7 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Chez Christiane et Claude Bed and Breakfast Saint-Geniez-dʼOlt Situated in Saint-Geniez-d'Olt, Chez Christiane et Claude is a B&B with garden, terrace and views of the countryside and the mountains. Free Wi-Fi and free private parking are available on site. Located on the 1st floor, the rooms feature a wardrobe, parquet floor and access to a shared bathroom. The common living room offers a TV, board games and regional guides and maps. A continental breakfast with homemade jams is served in the dining room offering a microwave and electric kettle. Meals based on home-grown and organic produce can be prepared, upon request. Restaurants and supermarkets are 500 metres away. One bike is available on site for free. Grandes Causses Natural Regional Park is just 5 km away. Guests can go canoeing and hiking 1 km away. Sévérac-le-Château train Station is located just 25 km away. Prices : from 46.00 € Bed and Breakfast of Gaillac-d'Aveyron or nearby municipalities : Location : 58 chemin du Séminaire 12130 Saint-Geniez-dʼOlt Distance between hotel and center of Gaillac-d'Aveyron : 13.01 kms Rooms in hotel : 2 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Hôtel Rodier Hotel Campagnac Preferred hotel ! Set in a flowery garden with a terrace, this hotel is located a 30-minute drive from the Gorges du Tarn canyon. Free Wi-Fi internet access is provided in the rooms. A flat-screen TV features in the guest rooms, which offer a view of the garden. Each room has a traditional décor with wooden furnishings, and the private bathrooms include free toiletries. Regional dishes are served in the restaurant, which features an original open fire. You can enjoy a drink in the bar at Hôtel Rodier, and packed lunches are possible upon request. A laptop and board games are available for guests’ use, and there are newspapers and magazines at reception. Campagnac Train Station is 400 metres from this hotel and the Millau Viaduct is 30 minutes away. Free private parking is possible on site and exit 41 of the A75 is just a 10-minute drive away. Rate : from 45.00 € to 89.00 € Hotel of Gaillac-d'Aveyron or nearby towns : Address : Campagnac-Gare 12560 Campagnac Distance on map, Hotel - Gaillac-d'Aveyron : 13.31 kilometers Number of room : 9 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Relais du Bois du Four Hotel Saint-Léons Le Relais du Bois du Four welcomes you in the heart of the mountains and lakes of Lévézou in Aveyron in the Parc Naturel Régional des Grands Causses. Facing a small lake and a mill, it is in a quiet area and offers modern and spacious guestrooms. They are all equipped with modern en suite facilities, free Wi-Fi internet access and a view of the countryside. Enjoy traditional and regional cuisine in the charming restaurant and also, relax in the hotel bar with a drink by the fireplace. The family-run Le Relais du Bois du Four is situated 3 km of Saint Leons and 8 km from the A75 Motorway. It is also a 10-minute drive from Millau Viaduct. Hotel of Gaillac-d'Aveyron or nearby municipalities : Location : Lieu-dit Bois Du Four 12780 Saint-Léons Route on map, Hotel - Gaillac-d'Aveyron : 13.48 kilometer Number of rooms : 26 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Mas de La Boheme - L'Hermet Bed and Breakfast Saint-Léons Mas de La Boheme - L'Hermet is set in Saint-Léons in the Midi-Pyrénées Region, on Lévézou Mountain in Grands Causses Regional Park. Free private parking is available on site. You will find a coffee machine in the room. Rooms have a private bathroom. A flat-screen TV is provided. Guests can enjoy the garden. Animals run freely on the property. Evening meals can be cooked and served on site upon prior request. You will find free shuttle service at the property. You can engage in various activities, such as fishing and canoeing. The property is 17 km from Millau and 40 km from Rodez. Gorges du Tarn is a 15-minute drive away. Rodez - Aveyron Airport is 44 km from the property. Prices : from 85.56 € to 92.00 € Bed and Breakfast of Gaillac-d'Aveyron or nearby towns : Address : MAS DE LA BOHEME L'HERMET 12780 Saint-Léons Distance on map between hotel and center of Gaillac-d'Aveyron : 13.88 km Room in hotel : 5 Book now Studio à Campagnac Apartment Campagnac Featuring barbecue facilities, a garden, and a terrace, Studio à Campagnac features accommodation in Campagnac with free WiFi and garden views. The accommodation is 46 km from Millau. This apartment comes with 1 bedroom, a flat-screen TV, a dining area, a kitchenette and a living room. An Italian breakfast is available each morning at the apartment. Speaking English, Spanish, French and Italian at the 24-hour front desk, staff are ready to help around the clock. Skiing and cycling can be enjoyed nearby. Marvejols is 34 km from Studio à Campagnac. Rodez - Aveyron Airport is 61 km away. Rate : from 50.40 € to 80.00 € Apartment of Gaillac-d'Aveyron or nearby municipalities : Location : route de st.laurent lot.la sagne 12560 Campagnac Distance between hotel and center of Gaillac-d'Aveyron : 14.59 kms Rooms in hotel : 1 Gîte de Montrozier Guest accommodation Montrozier Located in Montrozier in the Midi-Pyrénées region, Gîte de Montrozier has a terrace. The holiday home features mountain views and is 18 km from Rodez. This holiday home comes with a seating area, a kitchen with a dishwasher, and a TV. The holiday home also includes 1 bathroom with a shower and a washing machine. Laguiole is 41 km from the holiday home. The nearest airport is Rodez - Aveyron Airport, 27 km from the property. Guest accommodation of Gaillac-d'Aveyron or nearby towns : Address : Montrozier 12000 Montrozier Distance on map, Hotel - Gaillac-d'Aveyron : 15.60 kilometers Number of room : 1 Maison d'Hôtes "La Pierre Pointue" Bed and Breakfast Saint-Léons Situated in Saint-Léons in the Midi-Pyrénées Region, 100 metres from Micropolis Insect Museum, Maison d'Hôtes "La Pierre Pointue" features a sun terrace and views of the gardens and valley. Some rooms include a seating area to relax in after a busy day. You will find a courtesy tray in the room. Each room is fitted with a private bathroom. Extras include free toiletries and a hairdryer. Maison d'Hôtes "La Pierre Pointue" features free WiFi throughout the property. There is a shared kitchen at the property for guests who wish to prepare their meals. Upon prior request, a basket with local produce can be prepared for you. The property is conveniently located a 5-minute drive from Motorway A75 and a 15-minute drive from Millau Viaduct. Rodez - Aveyron Airport is 45 km away. Bed and Breakfast of Gaillac-d'Aveyron or nearby municipalities : Location : Le Bourg Rue Jean Henri Fabre 12780 Saint-Léons Route on map, Hotel - Gaillac-d'Aveyron : 16.04 kilometer Number of rooms : 3 Les Cahutes d'Olt Guest accommodation Saint-Laurent-dʼOlt Preferred hotel ! Set in Saint-Laurent-dʼOlt in the Midi-Pyrénées region, Les Cahutes d'Olt has a terrace. Guests may enjoy free WiFi. The lodge features a flat-screen TV. A fridge and a stovetop can be found in the kitchenette. The lodge offers a barbecue. Mende is 49 km from Les Cahutes d'Olt, while Marvejols is 30 km away. The nearest airport is Rodez - Aveyron Airport, 62 km from the accommodation. Guest accommodation of Gaillac-d'Aveyron or nearby towns : Address : Camping de Galinieres 12560 Saint-Laurent-dʼOlt Distance on map between hotel and center of Gaillac-d'Aveyron : 16.53 km Room in hotel : 1 Gîte La Grange Guest accommodation Saint-Laurent-dʼOlt Offering free WiFi and a garden, Gîte La Grange is located in Saint-Laurent-d’Olt. Millau is 36 km from the property. Free private parking is available on site. All units feature a seating area. Some units include a dining area and/or terrace. There is also a kitchen, equipped with a dishwasher. An oven and microwave are also provided, as well as a coffee machine. There are 2 bathrooms, 1 upstairs and 1 downstairs. Towels and bed linen are available. Gîte La Grange also includes a barbecue. The area is popular for cycling and fishing. Mende is 32 km from Gîte La Grange, while Rodez is 44 km away. Guest accommodation of Gaillac-d'Aveyron or nearby municipalities : Location : Ajas 12560 Saint-Laurent-dʼOlt Distance between hotel and center of Gaillac-d'Aveyron : 16.69 kms Rooms in hotel : 1 La Meliere Bed and Breakfast Saint-Laurent-de-Lévézou La Meliere features rooms in Saint-Laurent-de-Lévézou, 68 km from Marvejols. This bed and breakfast offers a garden. Both free WiFi and private parking are accessible on site. At the bed and breakfast, each room is fitted with a wardrobe. Featuring a private bathroom with a shower, rooms at La Meliere also boast a garden view. The accommodation offers a continental or vegetarian breakfast. Homemade vegetarian evening meals are available upon request and for an extra charge. La Meliere offers a terrace. Guests can take part in various activities in the surroundings, including cycling and hiking. Millau is 18 km from the bed and breakfast, while Rodez is 48 km from the property. The nearest airport is Rodez - Aveyron Airport, 57 km from the property. Bed and Breakfast of Gaillac-d'Aveyron or nearby towns : Address : lieu dit La Melière 12620 Saint-Laurent-de-Lévézou Distance on map, Hotel - Gaillac-d'Aveyron : 17.46 kilometers Number of room : 2 Les Hôtes du Lac, Chambres et tables d'hôtes Bed and Breakfast Mandailles Located in Mandailles, this 16th-century B&B features a veranda opening onto the Lot Valley and a living room with a fireplace. A pétanque field, free Wi-Fi and a secure parking are available on site. Each room at Les Hôtes du Lac includes a bathroom with a walk-in shower and hairdryer, an LCD TV and an electric kettle with tea and coffee making facilities. Fresh fruits and orange juice, hot drinks, bread, homemade jams and cereal are proposed for breakfast, which is served under the veranda. Evening meals can be enjoyed at an extra cost if you reserve at least 48 hours in advance. Guests are invited to read a book on the deckchairs in the shade of the trees. Guests can have a swim or fish in the Castelnau-Lassouts Lake or go hiking and biking in the surrounding area. Espalion is 13 km away and Lassouts is a 15-minute drive from Les Hôtes du Lac. Bed and Breakfast of Gaillac-d'Aveyron or nearby municipalities : Location : Mandailles 12500 Mandailles Route on map, Hotel - Gaillac-d'Aveyron : 17.50 kilometer Number of rooms : 2 Auberge du Lac Hotel Mandailles This inn is located in the heart of the Lot Valley, near Plateau de l’Aubrac. It offers rooms with flat-screen TVs and hydro-massage showers. The individually-decorated guestrooms are also equipped with air-conditioning. The Auberge Du Lac has its own restaurant, which serves regional cuisine. Guests can relax on the terrace, which has panoramic views of Lake Castelnau-Lassouts. The Auberge Du Lac is in the small village of Mandailles, 12 kilometres from Espalion. Hotel of Gaillac-d'Aveyron or nearby towns : Address : Mandailles 12500 Mandailles Distance on map between hotel and center of Gaillac-d'Aveyron : 17.55 km Room in hotel : 10 Preferred hotel ! Logis Des Voyageurs is located in Pont De Salars in Aveyron. It offers guestrooms with TV and free Wi-Fi internet access. This Logis hotel has a gourmet restaurant that serves local and regional specialties. It also offers an exceptional wine list. Logis Des Voyageurs’ location in the department of Aveyron puts guests close to Gorges du Tarn, Roquefort, Conques and Aubrac. Private parking is available for guests driving to the residence. Prices : Hotel of Gaillac-d'Aveyron or nearby municipalities : Guest accommodation of Gaillac-d'Aveyron or nearby towns : LIEU DIT RECOULES DE L'HOM 48500 Le Massegros Distance on map, Hotel - Gaillac-d'Aveyron : 18.70 kilometers Bed and Breakfast of Gaillac-d'Aveyron or nearby municipalities : Lieu dit de Vezouillac 12520 Verrières Set in Saint-Côme-dʼOlt, Au Pont d'Olt offers accommodation with free WiFi and flat-screen TV, as well as a garden. Some units feature a terrace and/or a balcony with mountain views. A continental breakfast is served every morning at the property. Guests can also relax in the shared lounge area. Rodez is 38 km from the bed and breakfast, while Laguiole is 27 km from the property. The nearest airport is Rodez - Aveyron Airport, 46 km from Au Pont d'Olt.
https://www.map-france.com/Gaillac-d%27Aveyron-12310/hotel-Gaillac-d%27Aveyron.html
Highly uniform SERS substrates formed by wrinkle-confined drying of gold colloids | Request PDF Request PDF | Highly uniform SERS substrates formed by wrinkle-confined drying of gold colloids | SERS substrates were fabricated through self-assembly of gold nanoparticles upon solution-drying in a periodic confining structure. The technique... | Find, read and cite all the research you need on ResearchGate Article Highly uniform SERS substrates formed by wrinkle-confined drying of gold colloids Chemical Science1:174-178 DOI: 10.1039/c0sc00132e Authors: <here is a image 81098b62e08a423a-e5cea4c8d60c389a> Nicolas Pazos-Perez Universitat Rovira i Virgili <here is a image d8a5582e527fc743-4c517747d3c4f9b9> Weihai Ni Soochow University (PRC) <here is a image 9ab12c66aa77ff1f-3d02187f674dbb34> Alexandra Schweikart University of Innsbruck <here is a image e41958dfa33ffd50-622e8a5db888cb31> Ramón A Alvarez-Puebla Universitat Rovira i Virgili Abstract SERS substrates were fabricated through self-assembly of gold nanoparticles upon solution-drying in a periodic confining structure. The technique leads to uniform, parallel linear nanoparticle arrays with the precise arrangement defined through the dimensions of the particles and the grooves, which provide high and uniform SERS enhancement over extended areas. © The Royal Society of Chemistry 2011. ... 30 The narrow gap distances are also a great advantage of the nanochains, in contrast to nanoconstructs such as elongated nanorods, because intense photoinduced electric field hotspots are generated in the gaps of the chains, which have been shown to exhibit great intensity (higher than the corresponding elongated nanorod systems). 33,34 The welldocumented electric field hotspots of nanochain systems 32,35, 36 are highly advantageous; they have applications for surface enhanced Raman (SERS), super resolution, and single molecule microscopies, in addition to therapeutic utility (enhancement of photothermal therapy). 37−41 To fabricate narrow-gap nanochain systems, several methods have been developed, including template-based methods and templatefree methods (interparticle force assembly). ... ... Lastly, using UV−vis spectroscopy to "monitor" the chain assembly, the growth of the nanochains can be controllably quenched, at a given time, by adding thiol terminated methoxy poly(ethylene glycol) (mPEG-SH), as shown in Figure 1 As demonstrated within the manuscript, the synthesized Au nanobead chains have short interparticle gap distances, indicating that they have a high D/r ratio (center-to-center distance between the NP monomers in the chain/radius of the NP monomer), 31 of great importance for optical and electric field hotspot enhancement. 30,35, 36 The nanochains are assembled in an aqueous solution, with no solvent transfer required, and have high linearity (high morphological control) with easy-to-conjugate surfaces. Furthermore, the nanobead chains exhibit red-shifted tunable plasmon resonance, as well as an intense optical scattering. ... ... 56 Furthermore, alongside the red-shifted plasmonic extinction, the electric field hot spots have been demonstrated to red-shift with the linear chain length, with the induced electric field magnitudes being the highest for linear chains (as opposed to when stacking occurs). 36 As shown in Figure 3G, the 590 nm longitudinal SPR sample has few branches, with greater than 90% of the samples still being unbranched (linear). By 630 nm longitudinal SPR, unbranched chains constitute approximately 50% of the total sample, and 50% of the chains do have branches. ... Au Nanobead Chains with Tunable Plasmon Resonance and Intense Optical Scattering: Scalable Green Synthesis, Monte Carlo Assembly Kinetics, Discrete Dipole Approximation Modeling, and Nano-Biophotonic Application The development of optically tunable and intensely scattering materials is of wide interest in biophotonics and medicine, provided they are biocompatible. Highly linear, tunable, narrow-gap, and intensely scattering gold nanobead chains were prepared by a green synthesis scheme, starting from ultrapure gold nanosphere monomers having a virgin surface. These Au nanochains exhibit a tunable longitudinal surface plasmon resonance (SPR) over the range from 590 to 710 nm. To determine the ensemble statistics of the synthesized nanobead chain lengths and their branching, transmission electron microscopy (TEM) images were acquired, in batch, correlated with the nanochain longitudinal SPR maxima (590 to 640 nm). Monte Carlo simulations quantify the selectivity of the chemical reaction: chain-end gold nanosphere units are about 4 times more reactive than chain-center units and assemble under a high-inverse-order-dependent diffusion. Discrete dipole approximation (DDA) computations predict the experimental extinction spectra and the narrow gap distance of the chains, as well as the elongated chain’s optical scattering enhancement, relative to Au nanosphere monomers (approximately 3× enhancement at equivalent mass). In vitro dark-field microscopy, cell studies, and biocompatibility tests demonstrate the nanochains’ (1) intense optical scattering cross sections, related to the plasmon coupling between the constituent nanospheres, (2) highly accessible gold surfaces, enabling facile conjugation with cell targeting ligands, and (3) absence of cell toxicity. The herein reported scalable, green synthesized, readily conjugatable gold nanobead chains are thus of great potential utility for serving as a wide range of biophotonic platforms, such as for enhanced in vitro and in vivo contrast imaging, diagnostics, and targeted nanotheranostics. ... The thickness, intensity, uniformity and sharpness of the peaks at~1085 cm −1 increase in the order as A2 > A3 > A4 > A1. The enhancement of the SERS intensity directly depends upon interface area, volume, isotropy, homogenous nature of hot spots etc. [71] . In the case of the sample A2, the isotropic nature of the spherical shaped AuNPs leads to higher interface area and hence, in relatively larger isotopic volume distribution. ... ... Such homogeneous distribution of the electromagnetic field results in the formation of relatively higher numbers of homogeneous hot spots, throughout the aragonitic structures. This can and does happen regardless of how much volume of the particles precisely interact in each particular site of the aragonitic structures [71, 72]. ... ... On the other hand, in the samples A3 and A4 the presence of anisotropic shapes such as triangles, nanoflower agglomerates etc. causes field focalization (i.e., the nano-antenna effect) [71, 72]. Thus, due to the inhomogeneous agglomerated distribution of AuNPs over aragonitic structures much lower enhancement is observed in the case of A4 samples ( Fig. 3b and Inset). ... Au nanoparticle-decorated aragonite microdumbbells for enhanced antibacterial and anticancer activities <here is a image e3bbcbed53c2467c-d662e239dc4afc59> Aniruddha Samanta <here is a image 4cb8f92ef6b15d0c-aa55b53546ed02af> Soumik Podder <here is a image d517c708899e819b-88b077491c7a6148> Kumarasamy Murali <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Anoop Kumar Mukhopadhyay The present work reports the very first hydrothermal synthesis of 100% triclinic phase pure aragonite (A1) with microdumbbell microstructural architecture and Au Nanoparticle-decorated (AuNP-decorated) aragonites (A2, A3 and A4) with spherical, pentagonal/hexagonal and agglomerated AuNP-decorated microdumbbells having triclinic aragonite phase as the major and cubic AuNPs as the minor phase. Even in dark the AuNP-decorated aragonites (especially A2) show efficacies as high 90% against gram-negative e.g., Pseudomonas putida (P. putida) bacteria. Further the AuNP-decorated aragonites (A3) show anti-biofilm capability of as high as about 20% against P. putida. Most importantly the AuNP-decorated aragonites (A3) offer anti-cancer efficacy of as high as 53% while those of A1, A2, and A4 are e.g., 26%, 46% and 37%, respectively. For the very first time, based on detailed investigations, the mechanisms behind such advance antibiofilm and anticancer activities are linked to the generation of excess labile toxic reactive oxygen species (ROS). Thus, these materials show enormous potential as futuristic, multi-functional biomaterials for anti-bacterial, anti-biofilm and anti-cancer applications. ... Для получения эффекта ГКР используются материалы, в которых наблюдается поверхностный плазмонный резонанс, так как при возбуждении образца с поверхностью, покрытой серебром [9], золотом [10] или медью, лазером с соответствующей длиной волны излучения интенсивность сигнала значительно возрастает [11,12]. Немаловажным фактором для эффекта ГКР является форма используемых металлических структур и морфология микрочастиц в наноразмерном масштабе. ... ... Так, с помощью ЛБ-технологии были получены функционализированные наночастицы металлов в высокоупорядоченных наноструктурах [24][25][26]. Эффект ГКР был также получен на монослоях из серебряных нанонитей [27], серебряных наносфер [28] и несферических наночастиц серебра [29], серебряных наностержнях [30], золотых упорядоченных частицах [10] . ... Different Types of Surface Enhancement Raman Scattering Platforms and their Applications <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Inna Stetciura <here is a image bf7a7aa546115c4d-4d41995c35ddb880> Dmitry A. Gorin ... To achieve a strong Raman enhancement effect, various metal nanostructures with high "hot spot" densities have been produced for use as SERS substrates including island films, porous films, nanoparticles, nanowires, nanorods and dendrites [18,32]. Few reports have focused on wrinkly Ag-and Au-based SERS substrates [33][34][35] [36] [37][38][39][40][41]. SERS substrates with wrinkle patterns can be formed by laser irradiation of Si surfaces coated with a thin Au film or Si surfaces immersed in an AgNO 3 solution [33,34]. ... ... SERS substrates with wrinkle patterns can be formed by laser irradiation of Si surfaces coated with a thin Au film or Si surfaces immersed in an AgNO 3 solution [33,34]. Wrinkly SERS substrates can also be generated by depositing Ag or Au on wrinkly templates [35, 36] . SERS substrates with wrinkly Ag and Au nanostructures can also be produced by buckling flat Ag and Au films on pre-strained polymer substrates after releasing the strain [37][38][39][40][41]. On the other hand, wrinkly films have been formed on liquid surfaces through the relief of residual stress [42]. ... Surface-enhanced Raman scattering substrates of flat and wrinkly titanium nitride thin films by sputter deposition Titanium nitride (TiN) thin films were prepared by RF magnetron sputtering on a bare Si surface and a silicone-oil-covered Si surface as surface-enhanced Raman scattering (SERS) substrates. The TiN film deposited on the bare Si surface had a flat surface with densely packed grains measuring 18 nm in diameter, whereas the TiN film deposited on the oil surface had a wrinkly pattern made of grains measuring 19 nm in diameter. To analyze the SERS effect, Rhodamine 6G (R6G) was used as a Raman probe molecule at various concentrations ranging from 10 −4 to 10 −8 M. The analytical enhancement factor (AEF) values at 10 −6 M R6G were respectively 6.2 × 10 3 and 1.3 × 10 4 for the flat TiN film and wrinkly TiN film. The SERS effect could be attributed to the enhancement of the local electromagnetic field at the top of the nano-sized grains. The wrinkly TiN film had a higher AEF than the flat TiN film, possibly due to the increased area of the Raman active spots. The wrinkly TiN film exhibited high level of SERS activity and achieved an R6G detection limit of 10 −8 M. ... The assembly of metal NPs into lines, as well as the optical properties of the resulting colloidal wires have been the subject of a plethora of investigations. Lines of plasmonic nanoparticles show optical effects, such as the coupling of plasmonic modes [16][17][18][19], and higher enhancement factors for surfaceenhanced Raman spectroscopy (SERS) than single plasmonic NPs [20, 21] . Whereas topdown methods can fabricate metal nanowires of arbitrary shape, large-scale fabrication is challenging, and lithographic methods are energy consuming and environmentally critical. ... Heading toward Miniature Sensors: Electrical Conductance of Linearly Assembled Gold Nanorods Metal nanoparticles are increasingly used as key elements in the fabrication and processing of advanced electronic systems and devices. For future device integration, their charge transport properties are essential. This has been exploited, e.g., in the development of gold-nanoparticle-based conductive inks and chemiresistive sensors. Colloidal wires and metal nanoparticle lines can also be used as interconnection structures to build directional electrical circuits, e.g., for signal transduction. Our scalable bottom-up, template-assisted self-assembly creates gold-nanorod (AuNR) lines that feature comparably small widths, as well as good conductivity. However, the bottom-up approach poses the question about the consistency of charge transport properties between individual lines, as this approach leads to heterogeneities among those lines with regard to AuNR orientation, as well as line defects. Therefore, we test the conductance of the AuNR lines and identify requirements for a reliable performance. We reveal that multiple parallel AuNR lines (>11) are necessary to achieve predictable conductivity properties, defining the level of miniaturization possible in such a setup. With this system, even an active area of only 16 µm2 shows a higher conductance (~10−5 S) than a monolayer of gold nanospheres with dithiolated-conjugated ligands and additionally features the advantage of anisotropic conductance. ... For this reason the functionalization of the carrier with plasmonic nanoparticles on the shell could provide the detection function for such carrier [40]. For example, among these reported lectures, silver and gold nanoparticles were common involved as enhancers [41] [42] [43]. ... Surface enhanced Raman scattering (SERS)-active bacterial detection by Layer-by-Layer (LbL) assembly all-nanoparticle microcapsules Polymeric microcapsules composed by the layer-by-layer (LbL) approach have been used for various applications including drug delivery into cells and in vivo, conducting enzyme catalyzed reactions, performing sensoric functions. Typically, LbL-assembled microcapsules have been formulated via alternating deposition of positively and negatively charged polyelectrolytes onto sacrificial templates or so-called cores. In this work, we extend the LbL assembly to produce microcapsules solely based on nanoparticles instead of polymers. Both gold and silver nanoparticles have been deposited as oppositely charged layers in the LbL assembly. We have identified that 5 layers of nanoparticles is the minimum number of layers for a stable assembly of capsules on calcium carbonate templates. Subsequently, the composite capsules comprised of nanoparticles were applied as Surface Enhanced Raman Scattering (SERS) platform, where the nanoparticle-based shell of capsules is shown to enable SERS of both solutes and macromolecular structures such as bacterial cells. ... Higher uniformity and spectral reproducibility of dried nanoparticles can be obtained by control of drying properties in order to avoid the "coffee-ring" effect. This was done in the case of nanoparticles dropped and dried on aluminium oxide surface [13] or wrinkle-confined surface [14] . On the other hand, the enhancement factor was low (10 4 ), hence the same as for measurement directly from colloidal suspensions [13]. ... “Coffee Ring” Effect of Ag Colloidal Nanoparticles Dried on Glass: Impact to Surface-Enhanced Raman Scattering (SERS) It is well known that spontaneous drying of some fluid droplets on certain solid surfaces forms a “coffee ring” pattern. In this paper, we studied “coffee ring” formation for two kinds of Ag colloidal nanoparticles (borohydride-reduced (b.-r.) and hydroxylamine-reduced (h.-r.)) and its impact on surface-enhanced Raman scattering (SERS). Optical and scanning electron microscopies were used to observe the morphology of the dried rings as well. We used 5,10,15,20-tetrakis(1-methyl-4-pyridyl)porphyrin (TMPyP) as a testing SERS molecular probe. The results showed that the structure of the edge rings of dried drops of Ag colloid/TMPyP systems was different for b.-r. and h.-r. nanoparticles. The inherent limitation of our approach is inhomogeneity in particle and “hot spots” distribution, SERS signal fluctuation, and consequently low spectral reproducibility. However, in the case of h.-r. nanoparticles, it formed a structure with highly enhancing sites (“hot spots”) providing enormous SERS signal of TMPyP. Higher sensitivity and the possibility of spectral mapping over the dried pattern are advantages in comparison with the measurements from colloidal suspension. Although our approach is not reliable for quantitative analytical SERS applications, it can serve as a simple, cheap, and fast prescan method, which can be easily implemented for preliminary SERS analysis. ... Spectral acquisition delivers average spectra of the diffraction-limited areas. The uniformity of the signal enhancement on a SERS substrate is most often checked by pointwise [22][23] [24] or linewise 25 Raman mapping or by randomly selecting different measurement spots on the substrate 15,26,27 . However, the long spectral acquisition times hinder the imaging of large areas in high resolution in short time, for example to study the distribution of hot spots. ... SERS background imaging – A versatile tool towards more reliable SERS analytics Surface-enhanced Raman scattering (SERS) is a highly selective and sensitive straightforward analytical method, which is however not yet established in routine analysis due to a lack of reliability and reproducibility. To address this limitation, we show the distinct correlation of the ever-present but often neglected broad SERS background continuum with the SERS signal intensity of the analyte and how to exploit this correlation for an easy-to-handle, automatable and more reliable SERS measurement. First, fast and high-contrast imaging of the SERS substrate is performed for hot spot localisation utilizing the SERS background. Subsequently, highly enhanced SERS spectra are recorded at the centre of these spots. Furthermore, we correlate our SERS background imaging with other optical imaging modalities and electron microscopy to assess structure-property relationships. Monte Carlo simulations based on actual measurements illustrate the sampling error of a conventional SERS experiment and the advantages our method provides. ... Parallel lines of single and double 66 nm Au nanospheres were tested as uniform and efficient SERS substrates. 25 Figure 7A shows the schematic representation of the stamping process and the corresponding SEM images of the assembled NPs. Figure 7B shows the white light, dark field, and SERS images (normalized at 1072 cm −1 ) obtained for single and double line arrays after testing benzenethiol as the molecular probe. The average SERS intensity shown in Figure 7B shows a slightly higher intensity for double lines; however, when calculating the SERS intensity per particle, it shows that the ordering into single NP lines is more efficient than for double lines, with 155 counts for the single line and 99 counts for the double line. ... Fabrication of Plasmonic Supercrystals and Their SERS Enhancing Properties María Blanco-Formoso <here is a image 81098b62e08a423a-e5cea4c8d60c389a> Nicolas Pazos-Perez <here is a image e41958dfa33ffd50-622e8a5db888cb31> Ramón A Alvarez-Puebla Supercrystals, made of ordered plasmonic nanoparticles (NPs) in close contact, turn out as efficient SERS substrates. However, the production of highly homogeneous structures implies precise control over a multitude of parameters including quality of the building blocks, solvent evaporation rate, and surface chemistry interactions. To pursue this goal, different approaches using templates to self-assembly NPs have been developed in recent years. Here, we review the most common procedures employing two different substrates, planar and patterned templates. Several approaches and strategies are described showing the optical properties of the resulted supercrystals and their behavior as SERS substrates. ... Spectral acquisition delivers average spectra of the diffraction-limited areas. The uniformity of the signal enhancement on a SERS substrate is most often checked by pointwise [22][23] [24] or linewise 25 Raman mapping or by randomly selecting different measurement spots on the substrate 15,26,27 . However, the long spectral acquisition times hinder the imaging of large areas in high resolution in short time, for example to study the distribution of hot spots. ... SERS background imaging – A versatile tool towards more reliable SERS analytics Paul Ebersbach <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ute Münchberg <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Erik Freier Surface-enhanced Raman scattering (SERS) is a highly selective and sensitive straightforward analytical method, which is however not yet established in routine analysis due to a lack of reliability and reproducibility. To address this limitation, we show the distinct correlation of the ever-present but often neglected broad SERS background continuum with the SERS signal intensity of the analyte and how to exploit this correlation for an easy-to-handle, automatable and more reliable SERS measurement. First, fast and high-contrast imaging of the SERS substrate is performed for hot spot localisation utilizing the SERS background. Subsequently, highly enhanced SERS spectra are recorded at the centre of these spots. Furthermore, we correlate our SERS background imaging with other optical imaging modalities and electron microscopy to assess structure-property relationships. Monte Carlo simulations based on actual measurements illustrate the sampling error of a conventional SERS experiment and the advantages our method provides. ... Conventional platforms for SERS consists of a wide variety of metallic nanostructures and their controlled assemblies obtained through either lithographic processes or chemically-induced interactions. 27, 28 In spite of these developments, major limitation of employing SERS for analytical detection continues to be the fundamental trade-off between ultrasensitivity and reliability of detection. [29][30][31] The unreliability of detection mainly originates from the non-uniformity and irregularity in spatial distribution of 5 electromagnetic hot-spots. ... Xenobiotic Contamination of Water by Plastics and Pesticides Revealed Through Real-time, Ultrasensitive and Reliable Surface Enhanced Raman Scattering Article May 2020 <here is a image 363b1930cb66fdc2-0dec4f2568679113> Sudeshna Mondal <here is a image dbe52af9b4dd1e67-9f011d9671f08d7b> Chandramouli Subramaniam Uncontrolled utilization and consequent ubiquitous percolation of carcinogenic and xenobiotic contaminants such as plasticizers and pesticides into ecosystem, have created an immediate demand for robust analytical detection techniques for identifying their presence in water. Addressing this demand, we uncover the presence of xenobiotic contaminants such as Bisphenol A (BPA), Triclosan (TC), and Dimethoate (DM) through a robust, ultrasensitive and reliable Surface Enhanced Raman Scattering (SERS) platform. Thereby, conclusive real-time evidence of degradation of polyethylene terephthalate (PET) leading to release of BPA into water is presented. Worryingly, the release of BPA occurs at ambient temperature (40 ⁰C) and realistic timescales (12 hours) that are regularly encountered during the handling, transport and storage of PET-based water containers. Complementary mass-spectrometric, surface-specific atomic force microscopy and surface selective X-ray Photoelectron spectroscopy confirms the nanoscale surface degradation of PET through loss of C=O and C-O surface functionalities and concurrent increase in the surface roughness. Such ultra-sensitive (ppm-level), spectroscopic detection is enabled by the bottom-up assemblies of metal nanoparticles (Soret Colloids) acting as SERS platform to provide high analytical enhancement factor (10⁸) with high reliability (RSD <5%). Effective and rapid detection (30 s) of several other potential xenobiotic contaminants such as Triclosan and Dimethoate over a wide range of concentrations (10⁻¹ to 10⁻⁵ M) has also been achieved. Finally, non-destructive real-time spectroscopic “sniffing” of organophosphorous pesticides from the surface of fruits is achieved, illustrating the multi-phasic versatility of this label-free, non-lithography-based SERS platform. ... On a related report, uniform and parallel linear gold nanoparticle arrays SERS substrates were prepared by a stamping technique using wrinkled PDMS. Stretched PDMS was treated by oxygen plasma to create wrinkles and stamped on concentrated gold nanoparticle droplets on a glass surface [151] . ... Recent Approaches toward Creation of Hot Spots for SERS Detection* Chapter Apr 2020 <here is a image d3de08e91a0c9ea0-9969fed0bf8e11b7> Amane Shiohara Yusong Wang <here is a image 862245e6cfab6911-b1fcf6e4af8cc46a> Luis M Liz-Marzán ... For sensing and imaging of organic compounds, SERS is often used. In many applications, specific ordering (arraying) of NPs for local field enhancement is required [34, 190, 191]. Recently, a combination of electron beam lithography (EBL) with cluster deposition has been suggested as a route to form plasmonic structures of desired configuration [144]. ... Applications of polymer films with gas-phase aggregated nanoparticles Chapter Jan 2020 <here is a image 847ec4a57787dea3-e53a7d732c16bb4f> Ondřej Kylián <here is a image ff5432c46881aded-2a0c52c884f778f5> Vladimir Popok Nanoparticles (NPs) of different types, especially those of metals and metal oxides, are widely used in research and industry for a variety of applications utilizing their unique physical and chemical properties. Polymers as plastic, flexible, easily processed and formed materials are attractive supporting and hosting media for NPs. In this chapter, recent research results on formation of polymer composites with NPs produced by means of gas-aggregation (cluster beam technique) are presented focusing on advantages of this method compared to other synthesis routes and showing a number of examples on different approaches providing deposition and implantation of clusters into polymer films, namely: soft-landing of NPs followed by thermal annealing to embed the NPs in a controllable manner; use of supersonic beams with sufficient kinetic energy for the implantation of clusters into thin layers and sequential or codeposition of the clusters and plasma polymers. These ways allow producing of composites with well-controlled and required characteristics. Second part of the chapter overviews applications of polymer composites with metal and metal-oxide NPs as functional materials and devices emphasizing the research on elastomeric electrodes, paper electronic components, memristors for neuromorphic architectures, plasmonic media with tunable parameters, transducers for gas and biosensors, coatings for precise control of wettability or surface interaction with biomolecules or cells, antibacterial media, etc. The review is finalized by outlook on future perspectives of the cluster beam technique in application to polymer materials and conclusions. ... 8 Because wrinkles provide an extra area that can accommodate bending and stretching, wrinkled surfaces can serve as substrates for flexible electronic devices. 9−11 Surface wrinkles have been used as templates for colloidal self-assembly for applications in optical metasurfaces, 12 surface-enhanced spectroscopy, 13 and strain sensing. 14,15 Reversible wrinkle formation under cyclical stretching and release has been used to dynamically manipulate light transmission, 16 liquid wetting, 17 and surface adhesion. ... Scalable Manufacturing of Bending-Induced Surface Wrinkles Article Jan 2020 <here is a image f555d119d2d321e4-1040e63b67994601> Xu Zhang <here is a image 57d748a27585c6de-0fd35fb0b454136c> Yijie Jiang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Bharath Venkatesh <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Lee D.H. The wide range of textures that can be generated via wrinkling can imbue surfaces with functionalities useful for a variety of applications including tunable optics, stretchable electronics, and coatings with controlled wettability and adhesion. Conventional methods of wrinkle fabrication rely on batch processes in piece-by-piece fashion, not amenable for scale-up to enable commercialization of surface wrinkle-related technologies. In this work, a scalable manufacturing method for surface wrinkles is demonstrated on a cylindrical support using bending-induced strains. A bending strain is introduced to a thin layer of ultraviolet-curable poly(dimethylsiloxane) (UV-PDMS) coated on top of a soft PDMS substrate by wrapping the bilayer around a cylindrical roller. After curing the UV-PDMS and subsequently releasing the bending strain, one-dimensional or checkerboard surface wrinkles are produced. Based on experimental and computational analyses, we show that these patterns form as a result of the interplay between swelling and bending strains. The feasibility of continuous manufacturing of surface wrinkles is demonstrated by using a two-roller roll-to-roll prototype, which paves the way for scalable roll-to-roll processing. To demonstrate the utility of these textures, we show that surface wrinkles produced in this manner enhance the light harvesting and thus efficiency of a solar cell at oblique angles of illumination due to their strong light scattering properties. ... To enable reliable quantification, several approaches have been proposed, which provide uniform, homogeneous substrates and consequently reproducible sensors. 9,30−32 Sensitivity can be improved by means of specific surface functionalization facilitating the localization of analytes in close proximity of the electromagnetic (EM) hotspots, 30, 33, 34 where the EM-field enhancement is highest. 35 Additionally, when combining electrochemistry with SERS and utilizing the SERS substrate as working electrode, precise control of surface charges can be achieved. ... Quantitative SERS Assay on a Single Chip Enabled by Electrochemically Assisted Regeneration: A Method for Detection of Melamine in Milk Jan 2020 Marlitt Viehrig <here is a image 54bc177f8ba88120-36ffc4a2fdc38dca> Sriram Thoppe Rajendran <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Kuldeep Sanger <here is a image a69430fd1417edad-cbed1ccb2c2b01e9> Anja Boisen Reusability of sensors is relevant when aiming to decrease variation between measurements, cost and time of analysis. We present an electrochemically assisted surface-enhanced Raman spectroscopy (SERS) platform with the capability to reverse the analyte-surface interaction, without damaging the SERS substrate, allowing for efficient sensor reuse. The platform was used in combination with a sample pre-treatment step, when detecting melamine from milk. We found that the electrochemically enhanced analyte-surface interaction results in significant improvement in detection sensitivity, with detection limits (0.01 ppm in PBS and 0.3 ppm in milk) below the maximum limit allowed in food samples. The reversibility of interaction enabled continuous measurement in aqueous solution and a complete quantitative assay on a single SERS substrate. ... In this case, typically polymer or enzyme characteristics lines and peaks intensities are used to control the quality of the hybrid co-deposits depending on the preparation conditions. RAMAN spectroscopy can be extremely helpful for the identification and quantification of chemical species as well as for chain orientation analysis in hybrid nanomaterials, characterization of multilayered systems, crystal size determination, crystallization degree estimation, stress, defects and contaminants verifications [65, 66] . ... The Role of Nanoanalytics in the Development of Organic-Inorganic Nanohybrids—Seeing Nanomaterials as They Are Article Full-text available Nov 2019 <here is a image 7e69a89a01b9a77f-6bd1ba43abbb3ac4> Daria Semenova <here is a image de130923c5c85654-b018b7c792d349e3> Yuliya Silina The functional properties of organic-inorganic (O-I) hybrids can be easily tuned by combining system components and parameters, making this class of novel nanomaterials a crucial element in various application fields. Unfortunately, the manufacturing of organic-inorganic nanohybrids still suffers from mechanical instability and insufficient synthesis reproducibility. The control of the composition and structure of nanosurfaces themselves is a specific analytical challenge and plays an important role in the future reproducibility of hybrid nanomaterials surface properties and response. Therefore, appropriate and sufficient analytical methodologies and technical guidance for control of their synthesis, characterization and standardization of the final product quality at the nanoscale level should be established. In this review, we summarize and compare the analytical merit of the modern analytical methods, viz. Fourier transform infrared spectroscopy (FTIR), RAMAN spectroscopy, surface plasmon resonance (SPR) and several mass spectrometry (MS)-based techniques, that is, inductively coupled plasma mass spectrometry (ICP-MS), single particle ICP-MS (sp-ICP-MS), laser ablation coupled ICP-MS (LA-ICP-MS), time-of-flight secondary ion mass spectrometry (TOF-SIMS), liquid chromatography mass spectrometry (LC-MS) utilized for characterization of O-I nanohybrids. Special attention is given to laser desorption ionization mass spectrometry (LDI-MS) as a reliable nanoanalytical platform for characterization of O-I hybrid nanomaterials, their quality, design verification and validation. ... In their approach, a suspension of nanoparticles was restrained between a highly ordered periodic wrinkled surface and a glass substrate as shown in Fig. 14a(i), or between two crossed wrinkled templates (Fig. 14a(ii)). Moreover, this technique has applications in surfaceenhanced Raman spectroscopy (SERS) 123, 281, 282 -an easy-to-use approach that provides ultrasensitive detection of molecules. ... Advanced Functional Surfaces through Controlled Damage and Instabilities Article Oct 2019 <here is a image f0bdb9e66c5298bd-75f0faab394fe229> Navid Namdari <here is a image f61b8a37d8360970-f7fe9f87cfc76faf> Behrouz Mohammadian <here is a image 56ae9a4c89277681-430073d648577128> Parham Jafari <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Reza Rizvi Functional surfaces are of paramount engineering importance with applications in non-wettable components, adhesion, anti-biofouling, static or dynamic optical properties, and energy scavenging. Traditionally, such functional surfaces have been produced through... ... For example, we demonstrated the fabrication of SERS substrates through a confinement self-assembly of gold nanoparticles using wrinkled PDMS stamps as templates. 152 Depending on the dimensions of the wrinkled PDMS, the nanoparticles can be arranged into single-or double-line arrays, and the difference in arrangement then leads to disparate SERS enhancement behavior. Although hot spots are similarly created at the nanometer gaps (with an average interparticle distance of 8 nm) between the gold nanoparticles, the electromagnetic field generated by the single-line array is up to 1 order of magnitude greater than that from the double-line array. ... [80] [128, [140] ... A simple, yet very efective method to make nano-paterns of Au NPs was invented by Whitesides and perfected by Fery [60, 69] Nano- and Micro-Patterning of Gold Nanoparticles on PEG- Based Hydrogels for Controlling Cell Adhesion [48, 49] techniques were also successfully employed to fabricate SERS substrates. ... Flexible surface-enhanced Raman scattering-active substrates based on nanofibrous membranes [17] [18][19] are recently being in use to fabricate state-of-art SERS active substrates. However, surprisingly, most of those substrates exhibit moderate enhancement factors (EFs) of SERS signals ranging between 10 6 to 10 7 orders of magnitude which are considered to be far less than single molecule sensitivity regime [20][21][22][23]. ... Effects of Surface Topography on SERS response: Correlating Nanoscopy with Spectroscopy This paper reports for the first time the hidden correlation between the topographical features of the bilayer Langmuir-Blodgett (LB) film substrates of stearic acid (SA) incubated in [email protected] nanocolloids over various dipping times (DTs) with their corresponding SERS responses. The topographies of the as prepared substrates are investigated from the statistical considerations in terms of lateral correlation length, interface width, Hurst and Lyapnov exponents. The real space of the substrates are mapped directly from the FESEM and AFM images of the bilayer LB film of SA immersed in [email protected] nanocolloids over various DTs ranging between 6 and 72 h. The SERS spectra of the Rhodamine 6G molecules adsorbed on the as prepared substrates have been reported. The statistical parameters of the substrates that exhibit maximum SERS efficacy have been suggested. The far field distributions in presence and in absence of Raman dipole together with spatial distribution of the near field from the hottest spot of the as prepared substrate have also been reported. To our knowledge, this is the first report that links nanoscopy with SERS spectroscopy from statistical considerations and is expected to open a new window towards the fabrication of more efficient and reproducible SERS active substrates in future endeavours. 28] Nano-Contact Transfer with Gold Nanoparticles on PEG Hydrogels and Using Wrinkled PDMS-Stamps
https://www.researchgate.net/publication/224001002_Highly_uniform_SERS_substrates_formed_by_wrinkle-confined_drying_of_gold_colloids
Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection Gay CL, Mayo AJ, Mfalila CK, Chu H, Barry AC, Kuruc JD, McGee KS, Kerkau M, Sebastian J, Fiscus SA, Margolis DM, Hicks CB, Ferrari G, Eron JJ; Duke-UNC Acute HIV Infection Consortium. Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection. AIDS. 2011 Apr 24;25(7):941-9. doi: 10.1097/QAD.0b013e3283463c07. Cynthia L Gay, Ashley J Mayo, Chelu K Mfalila, Haitao Chu, Anna C Barry, JoAnn D Kuruc, Kara S McGee, Melissa Kerkau, Joe Sebastian, Susan A Fiscus, David M Margolis, Charles B Hicks, Guido Ferrari, Joseph J Eron, Duke-UNC Acute HIV Infection Consortium, Cynthia L Gay, Ashley J Mayo, Chelu K Mfalila, Haitao Chu, Anna C Barry, JoAnn D Kuruc, Kara S McGee, Melissa Kerkau, Joe Sebastian, Susan A Fiscus, David M Margolis, Charles B Hicks, Guido Ferrari, Joseph J Eron, Duke-UNC Acute HIV Infection Consortium Abstract Objective:Characterize responses to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral treatment (ART) initiated during acute HIV infection (AHI). Design:This was a prospective, single-arm evaluation of once-daily, co-formulated emtricitabine/tenofovir/efavirenz initiated during AHI. Methods:The primary endpoint is the proportion of responders with HIV RNA less than 200 copies/ml by week 24. We examined time to viral suppression and CD8 cell activation in relation to baseline participant characteristics. We compared time to viral suppression and viral dynamics using linear mixed-effects models between acutely infected participants and chronically infected controls. Results:Between January 2005 and May 2009, 61 AHI participants were enrolled. Of participants whose enrollment date allowed 24 and 48 weeks of follow-up, 47 of 51 (92%) achieved viral suppression to less than 200 copies/ml by week 24, and 35 of 41 (85.4%) to less than 50 copies/ml by week 48. The median time from ART initiation to suppression below 50 copies/ml was 93 days (range 14-337). Higher HIV RNA levels at ART initiation (P = 0.02), but not time from estimated date of infection to ART initiation (P = 0.86), were associated with longer time to viral suppression. The median baseline frequency of activated CD8+CD38+HLA-DR+ T cells was 67% (range 40-95), and was not significantly associated with longer time to viral load suppression (P = 0.15). Viremia declined to less than 50 copies/ml more rapidly in AHI than chronically infected participants. Mixed-model analysis demonstrated similar phase I HIV RNA decay rates between acute and chronically infected participants, and more rapid viral decline in acutely infected participants in phase II. Conclusion:Once-daily emtricitabine/tenofovir/efavirenz initiated during AHI achieves rapid and sustained HIV suppression during this highly infectious period. Conflict of interest statement Potential Financial Conflicts of Interest: C.G. has received research support from Bristol Myers Squibb, Gilead Sciences, Abbott and Tibotec Therapeutics. C.H. has received grant support and/or consulting/honoraria from BMS, GSK, Merck, Tibotec, Gilead, Myriad Pharmaceuticals, Pfizer. D.M. has received research support from Bristol Myers Squibb, Gilead Sciences, Merck, Abbott, and Roche, and is a honoraria for professional services to Bristol Myers Squibb, Merck, Chimerix, and Tibotec Therapeutics. J.E. receives research support from Merck and GlaxoSmithKline and is a consultant to Bristol Myers Squibb, Merck, and Tibotec Therapeutics. A.M., A.B., J.K., K.M., M.K., S.F., G.F. - No conflicts. Figures Figure 1 Time to viral load suppression among acutitely-infected participants who initiated antiretroviral therapy during acute HIV infection compared with chronically infected patients starting an efavirenz-based regimen. The black line in Figure 1A shows the time-to-viral-suppression to <50 copies/mL among all acutely infected participants started on antiretroviral therapy during the acute period. The blue and red lines show the time-to-viral-suppression <50 copies/mL stratified by baseline HIV RNA levels among acutely-infected subjects who started antiretroviral therapy. Figure 1B shows the comparison of time-to-viral-suppression with a NNRTI-based regimen between participants starting antiretroviral therapy during acute HIV infection and chronically-infected participants starting treatment during established HIV infection. Figure 1 Time to viral load suppression among acutitely-infected participants who initiated antiretroviral therapy during acute HIV infection compared with chronically infected patients starting an efavirenz-based regimen. The black line in Figure 1A shows the time-to-viral-suppression to <50 copies/mL among all acutely infected participants started on antiretroviral therapy during the acute period. The blue and red lines show the time-to-viral-suppression <50 copies/mL stratified by baseline HIV RNA levels among acutely-infected subjects who started antiretroviral therapy. Figure 1B shows the comparison of time-to-viral-suppression with a NNRTI-based regimen between participants starting antiretroviral therapy during acute HIV infection and chronically-infected participants starting treatment during established HIV infection. Figure 2 Estimates of log10HIV RNA from a nonlinear mixed model from 0 to 11 months following ART initiation among acutely- and chronically-infected participants with one inflection point at 10 days. Figure 3 Figure 3 Figure 3A shows immune activation dynamics among acutely-infected participants from the time of antiretroviral initiation. Figure 3B compares levels of immune activation among acutely-infected individuals by time since antiretroviral initiation with a seronegative cohort. Source:PubMed
https://ichgcp.net/clinical-trials-registry/publications/54563-efficacy-of-nnrti-based-antiretroviral-therapy-initiated-during-acute-hiv-infection
r sequence stratigraphy of continental rift successions\u003C\/span\u003E, \u003Cem\u003Ein\u003C\/em\u003E \u003Cspan class=\u0022cit-ed\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMontenari\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM\u003C\/span\u003E\u003C\/span\u003E, editor, \u003Cspan class=\u0022cit-source\u0022\u003EAdvances in Sequence Stratigraphy\u003C\/span\u003E: \u003Cspan class=\u0022cit-publ-name\u0022\u003EAcademic Press, Stratigraphy \u0026amp; Timescales\u003C\/span\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E2\u003C\/span\u003E, p.\u003Cspan class=\u0022cit-fpage\u0022\u003E119\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E186\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/bs.sats.2017.07.002\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DAdvances%2Bin%2BSequence%2BStratigraphy%26rft.volume%253D2%26rft.spage%253D119%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1016%252Fbs.sats.2017.07.002%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1016\/bs.sats.2017.07.002\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-18-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-18\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.18\u0022 data-doi=\u0022https:\/\/doi.org\/10.1016\/j.earscirev.2018.02.004\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHuang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EB.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYan\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EPiper\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ. D. A.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ED.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EZ.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhou\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2018\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EPaleomagnetic constraints on the paleogeography of the East Asian blocks during Late Paleozoic and Early Mesozoic times\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EEarth-Science Reviews\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E186\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E8\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E36\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.earscirev.2018.02.004\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DEarth-Science%2BReviews%26rft.volume%253D186%26rft.spage%253D8%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1016%252Fj.earscirev.2018.02.004%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1016\/j.earscirev.2018.02.004\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-19-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-19\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.19\u0022 data-doi=\u0022https:\/\/doi.org\/10.1016\/j.precamres.2015.10.001\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHuang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EQ.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKamenetsky\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EV. S.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMcPhie\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EEhrig\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMeffre\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMaas\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ER.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EThompson\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKamenetsky\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EChambefort\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EI.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EApukhtina\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EO.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2015\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003ENeoproterozoic (ca. 820\u2013830 Ma) mafic dikes at Olympic Dam, South Australia: Links with the Gairdner Large Igneous Province\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EPrecambrian Research\u003C\/abbr\u003E, v.\u003Cspan class=\u0022cit-vol\u0022\u003E271\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E160\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E172\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.precamres.2015.10.001\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DPrecambrian%2BResearch%26rft.stitle%253DPrecambrian%2BResearch%26rft.aulast%253DHuang%26rft.auinit1%253DQ.%26rft.volume%253D271%26rft.spage%253D160%26rft.epage%253D172%26rft.atitle%253DNeoproterozoic%2B%2528ca.%2B820-830%2BMa%2529%2Bmafic%2Bdykes%2Bat%2BOlympic%2BDam%252C%2BSouth%2BAustralia%253B%2Blinks%2Bwith%2Bthe%2BGairdner%2Blarge%2Bigneous%2Bprovince%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1016%252Fj.precamres.2015.10.001%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1016\/j.precamres.2015.10.001\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=2016016313\u0026amp;link_type=GEOREF\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-georef\u0022\u003E\u003Cspan\u003EGeoRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-20-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-20\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.20\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EJensen\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EL. S.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E1976\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EA new cation plot for classifying subalkalic volcanic rocks\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EOntario Ministry of Natural Resources Miscellaneous Paper\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E66\u003C\/span\u003E, \u003Cspan class=\u0022cit-fpage\u0022\u003E22\u003C\/span\u003E p.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DOntario%2BMinistry%2Bof%2BNatural%2BResources%2BMiscellaneous%2BPaper%26rft.volume%253D66%26rft.spage%253D22%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-21-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-21\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.21\u0022 data-doi=\u002210.1073\/pnas.1804350116\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKeller\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EC. B.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHusson\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ. M.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMitchell\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ER. N.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EBottke\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW. F.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EGernon\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET. M.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EBoehnke\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EP.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EBell\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EE. A.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESwanson-Hysell\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EN. L.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EPeters\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES. E.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2019\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003ENeoproterozoic glacial origin of the Great Unconformity\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EProceedings of the National Academy of Sciences of the United States of America\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E116\u003C\/span\u003E, n. \u003Cspan class=\u0022cit-issue\u0022\u003E4\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E1136\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E1145\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1073\/pnas.1804350116\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DProceedings%2Bof%2Bthe%2BNational%2BAcademy%2Bof%2BSciences%2Bof%2Bthe%2BUnited%2BStates%2Bof%2BAmerica%26rft_id%253Dinfo%253Adoi%252F10.1073%252Fpnas.1804350116%26rft_id%253Dinfo%253Apmid%252F30598437%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czoxMDoiMTE2LzQvMTEzNiI7czo0OiJhdG9tIjtzOjE5OiIvYWpzLzMyMi81LzcwNS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-22-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-22\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.22\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELai\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EC. G.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EG. Z.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EXiang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EL. W.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E1984\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003ENew data from the Cambrian and Ordovian in the Shihuigou area, Ulan county, Qinghai Province\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EGeological Review\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E30\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E311\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E318\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DDizhi%2BLunping%2B%253D%2BGeological%2BReview%26rft.stitle%253DDizhi%2BLunping%2B%253D%2BGeological%2BReview%26rft.volume%253D30%26rft.issue%253D4%26rft.spage%253D311%26rft.epage%253D317%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=1998018381\u0026amp;link_type=GEOREF\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-georef\u0022\u003E\u003Cspan\u003EGeoRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-23-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-23\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.23\u0022 data-doi=\u0022https:\/\/doi.org\/10.1002\/dep2.46\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELe Heron\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ED. P.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EVandyk\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET. M.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EG.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMeng\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ELi.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2018\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003ENew perspectives on the Luoquan glaciation (Ediacaran\u2010Cambrian) of North China\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EThe Depositional Record\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E4\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E274\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E292\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1002\/dep2.46\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DThe%2BDepositional%2BRecord%26rft.volume%253D4%26rft.spage%253D274%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1002%252Fdep2.46%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1002\/dep2.46\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-24-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-24\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.24\u0022 data-doi=\u0022https:\/\/doi.org\/10.1016\/j.gr.2019.06.010\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EC.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ER. S.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMeert\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ. G.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EPeng\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ. H.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2019\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EIdentifying late Neoproterozoic\u2013early Paleozoic sediments in the South Qilian Belt, China: A peri-Gondwana connection in the northern Tibetan Plateau\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EGondwana Research\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E76\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E173\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E184\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.gr.2019.06.010\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DGondwana%2BResearch%26rft.volume%253D76%26rft.spage%253D173%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1016%252Fj.gr.2019.06.010%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1016\/j.gr.2019.06.010\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-25-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-25\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.25\u0022 data-doi=\u0022https:\/\/doi.org\/10.1016\/j.jseaes.2020.104327\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EVandyk\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET. M.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EG.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELiu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELe Heron\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ED. P.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EXiao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2020\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EA window into the Great Unconformity: Insights from geochemistry and geochronology of Ediacaran glaciogenic rocks in the North China Craton\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJournal of Asian Earth Sciences\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E194\u003C\/span\u003E, \u003Cspan class=\u0022cit-fpage\u0022\u003E104327\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.jseaes.2020.104327\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJournal%2Bof%2BAsian%2BEarth%2BSciences%26rft.volume%253D194%26rft.spage%253D104327%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1016%252Fj.jseaes.2020.104327%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1016\/j.jseaes.2020.104327\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-26-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-26\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-book\u0022 id=\u0022cit-322.5.705.26\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EQ. Z.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E1980\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003ESinian subearthem in the minor Qinling range in Shaanxi Province\u003C\/span\u003E, \u003Cem\u003Ein\u003C\/em\u003E: \u003Cspan class=\u0022cit-auth cit-collab\u0022\u003ETianjin Institute of Geology and Mineral Resources\u003C\/span\u003E, editors, \u003Cspan class=\u0022cit-source\u0022\u003EResearch on Precambrian Geology Sinian Suberathem in China\u003C\/span\u003E: \u003Cspan class=\u0022cit-publ-loc\u0022\u003ETianjin, China\u003C\/span\u003E, \u003Cspan class=\u0022cit-publ-name\u0022\u003ETianjin Science and Technology Press\u003C\/span\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E1\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E314\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E331\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DResearch%2Bon%2BPrecambrian%2BGeology%2BSinian%2BSuberathem%2Bin%2BChina%26rft.volume%253D1%26rft.spage%253D314%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-27-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-27\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.27\u0022 data-doi=\u0022https:\/\/doi.org\/10.1016\/j.earscirev.2017.01.011\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELiu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EX.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ECao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003 ass=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-78-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-78\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.78\u0022 data-doi=\u002210.1016\/j.precamres.2012.11.014\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ. X.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES. Y.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EGong\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ. H.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH. K.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHou\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK.J .\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2013a\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EThe latest Neoarchean\u2013Paleoproterozoic evolution of the Dunhuang block, eastern Tarim craton, northwestern China: evidence from zircon U\u2013Pb dating and Hf isotopic analyses\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EPrecambrian Research\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E226\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E21\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E42\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.precamres.2012.11.014\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DPrecambrian%2BResearch%26rft.stitle%253DPrecambrian%2BResearch%26rft.aulast%253DZhang%2BJianxin%26rft.volume%253D226%26rft.spage%253D21%26rft.epage%253D42%26rft.atitle%253DThe%2Blatest%2BNeoarchean-Paleoproterozoic%2Bevolution%2Bof%2Bthe%2BDunhuang%2BBlock%252C%2Beastern%2BTarim%2BCraton%252C%2Bnorthwestern%2BChina%253B%2Bevidence%2Bfrom%2Bzircon%2BU%252FPb%2Bdating%2Band%2BHf%2Bisotopic%2Banalyses%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.precamres.2012.11.014%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1016\/j.precamres.2012.11.014\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=2013051882\u0026amp;link_type=GEOREF\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-georef\u0022\u003E\u003Cspan\u003EGeoRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-79-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-79\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.79\u0022 data-doi=\u0022http:\/\/dx.doi.org\/10.1016\/j.jsg.2013.10.002\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EXiao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EQi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2013b\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EKinematics and geochronology of multistage ductile deformation along the eastern Alxa block, NW China: New constraints on the relationship between the North China Plate and the Alxa block\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJournal of Structural Geology\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E57\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E38\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E57\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.jsg.2013.10.002\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJournal%2Bof%2BStructural%2BGeology%26rft.stitle%253DJournal%2Bof%2BStructural%2BGeology%26rft.aulast%253DZhang%26rft.auinit1%253DJ.%26rft.volume%253D57%26rft.spage%253D38%26rft.epage%253D57%26rft.atitle%253DKinematics%2Band%2Bgeochronology%2Bof%2Bmultistage%2Bductile%2Bdeformation%2Balong%2Bthe%2Beastern%2BAlxa%2BBlock%252C%2BNW%2BChina%253B%2Bnew%2Bconstraints%2Bon%2Bthe%2Brelationship%2Bbetween%2Bthe%2BNorth%2BChina%2BPlate%2Band%2Bthe%2BAlxa%2BBlock%26rft_id%253Dinfo%253Adoi%252Fhttp%253A%252F%252Fdx.doi.org%252F10.1016%252Fj.jsg.2013.10.002%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=http:\/\/dx.doi.org\/10.1016\/j.jsg.2013.10.002\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=2014016524\u0026amp;link_type=GEOREF\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-georef\u0022\u003E\u003Cspan\u003EGeoRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000328872500003\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-80-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-80\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.80\u0022 data-doi=\u002210.1016\/j.gr.2014.09.012\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY. P.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EXiao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW. X.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY. N.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EB. H.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2015\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003ELinking the Alxa Terrane to the eastern Gondwana during the Early Paleozoic: Constraints from detrital zircon U-Pb ages and Cambrian sedimentary records\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EGondwana Research\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E28\u003C\/span\u003E, n. \u003Cspan class=\u0022cit-issue\u0022\u003E3\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E1168\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E1182\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.gr.2014.09.012\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DGondwana%2BResearch%26rft.volume%253D28%26rft.spage%253D1168%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.gr.2014.09.012%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1016\/j.gr.2014.09.012\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-81-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-81\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.81\u0022 data-doi=\u0022https:\/\/doi.org\/10.1016\/j.gr.2015.11.009\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ. X.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES. Y.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMattinson\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EC. G.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2017\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EEarly Paleozoic polyphase metamorphism in northern Tibet, China\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EGondwana Research\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E41\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E267\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E289\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.gr.2015.11.009\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DGondwana%2BResearch%26rft.volume%253D41%26rft.spage%253D267%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1016%252Fj.gr.2015.11.009%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1016\/j.gr.2015.11.009\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-82-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-82\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.82\u0022 data-doi=\u0022https:\/\/doi.org\/10.1016\/j.earscirev.2018.10.003\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EG. C.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY. J.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHuang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EB. C.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EDong\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY. P.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES. Z.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EG. W.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2018\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EGeological reconstructions of the East Asian blocks: from the breakup of Rodinia to the assembly of Pangea\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EEarth-Science review\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E186\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E262\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E286\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.earscirev.2018.10.003\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DEarth-Science%2Breview%26rft.volume%253D186%26rft.spage%253D262%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1016%252Fj.earscirev.2018.10.003%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1016\/j.earscirev.2018.10.003\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-83-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-83\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.83\u0022 data-doi=\u0022https:\/\/doi.org\/10.1002\/gj.2975\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES. J.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES. Z.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EX. Y.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESomerville\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EI. D.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ECao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH. H.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELiu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EX.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EP. C.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2017\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EStructural analysis of ductile shear zones in the North Qinling Orogen and its implications for the evolution of the Proto\u2010Tethys Ocean\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EGeological Journal\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E52\u003C\/span\u003E, n. \u003Cspan class=\u0022cit-issue\u0022\u003ES1\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E202\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E214\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1002\/gj.2975\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DGeological%2BJournal%26rft.volume%253D52%26rft.spage%253D202%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1002%252Fgj.2975%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1002\/gj.2975\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-84-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-84\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.84\u0022 data-doi=\u002210.1038\/327141a0\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EX.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ECoe\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ER. S.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E1987\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EPaleomagnetic constraints on the collision and rotation of North and South China\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003ENature\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E327\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E141\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E144\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1038\/327141a0\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DNature%26rft.stitle%253DNature%26rft.volume%253D327%26rft.issue%253D6118%26rft.spage%253D141%26rft.epage%253D144%26rft.atitle%253DPalaeomagnetic%2Bconstraints%2Bon%2Bthe%2Bcollision%2Band%2Brotation%2Bof%2BNorth%2Band%2BSouth%2BChina%26rft_id%253Dinfo%253Adoi%252F10.1038%252F327141a0%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1038\/327141a0\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=1987057235\u0026amp;link_type=GEOREF\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-georef\u0022\u003E\u003Cspan\u003EGeoRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=A1987H282700055\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-85-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-85\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.85\u0022 data-doi=\u0022https:\/\/doi.org\/10.1016\/j.gr.2015.08.012\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESun\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EDiwu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EC. R.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EGuo\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA. L.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EAo\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW. H.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2016\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EThe Dunhuang block is a Paleozoic Orogenic Belt and part of the Central Asian Orogenic Belt (CAOB), NW China\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EGondwana Research\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E30\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E207\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E223\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.gr.2015.08.012\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DGondwana%2BResearch%26rft.volume%253D30%26rft.spage%253D207%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1016%252Fj.gr.2015.08.012%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1016\/j.gr.2015.08.012\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-86-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-86\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.86\u0022 data-doi=\u0022https:\/\/doi.org\/10.1016\/j.gr.2010.12.009\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EX. Y.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EChen\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EF. K.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELiu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES. Q.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY. Z.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENie\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESiebel\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhai\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM. G.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2011\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003ECrustal evolution of the North Qinling terrain of the Qinling Orogen, China: evidence from detrital zircon U-Pb ages and Hf isotopic composition\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EGondwana Research\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E20\u003C\/span\u003E, n. \u003Cspan class=\u0022cit-issue\u0022\u003E1\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E194\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E204\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1016\/j.gr.2010.12.009\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DGondwana%2BResearch%26rft.stitle%253DGondwana%2BResearch%26rft.volume%253D20%26rft.issue%253D1%26rft.spage%253D194%26rft.epage%253D204%26rft.atitle%253DCrustal%2Bevolution%2Bof%2Bthe%2BNorth%2BQinling%2BTerrain%2Bof%2Bthe%2BQinling%2BOrogen%252C%2BChina%253B%2Bevidence%2Bfrom%2Bdetrital%2Bzircon%2BU%252FPb%2Bages%2Band%2BHf%2Bisotopic%2Bcomposition%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1016%252Fj.gr.2010.12.009%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1016\/j.gr.2010.12.009\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=2012085143\u0026amp;link_type=GEOREF\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-georef\u0022\u003E\u003Cspan\u003EGeoRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-87-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-87\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.87\u0022 data-doi=\u0022https:\/\/doi.org\/10.1007\/s11430-020-9657-0\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EX.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET. P.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EPang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EL.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhai\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2020\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003EZircon U-Pb geochronology of tuffite beds in the Baishugou Formation: Constraints on the revision of Ectasian System at the southern margin of the North China Craton\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EScience China Earth Sciences\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E63\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E1817\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E1830\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1007\/s11430-020-9657-0\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DScience%2BChina%2BEarth%2BSciences%26rft.volume%253D63%26rft.spage%253D1817%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1007%252Fs11430-020-9657-0%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1007\/s11430-020-9657-0\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-88-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-88\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-322.5.705.88\u0022 data-doi=\u0022https:\/\/doi.org\/10.1130\/B31721.1\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZuza\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA. V.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EC.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EReith\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ER. C.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYin\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ. H.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ. Y.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY. X.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EL.\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELiu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW. C.\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E, \u003Cspan class=\u0022cit-pub-date\u0022\u003E2018\u003C\/span\u003E, \u003Cspan class=\u0022cit-article-title\u0022\u003ETectonic evolution of the Qilian Shan: an early Paleozoic orogen reactivated in the Cenozoic\u003C\/span\u003E: \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EGeological Society of America Bulletin\u003C\/abbr\u003E, v. \u003Cspan class=\u0022cit-vol\u0022\u003E130\u003C\/span\u003E, n. \u003Cspan class=\u0022cit-issue\u0022\u003E5\u20136\u003C\/span\u003E, p. \u003Cspan class=\u0022cit-fpage\u0022\u003E881\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E925\u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id-sep cit-pub-id-doi-sep\u0022\u003E, \u003C\/span\u003E\u003Cspan class=\u0022cit-pub-id cit-pub-id-doi\u0022\u003E\u003Cspan class=\u0022cit-pub-id-scheme-doi\u0022\u003Edoi:\u003C\/span\u003Ehttps:\/\/doi.org\/10.1130\/B31721.1\u003C\/span\u003E\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DGeological%2BSociety%2Bof%2BAmerica%2BBulletin%26rft.volume%253D130%26rft.spage%253D881%26rft_id%253Dinfo%253Adoi%252Fhttps%253A%252F%252Fdoi.org%252F10.1130%252FB31721.1%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=https:\/\/doi.org\/10.1130\/B31721.1\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003C\/div\u003E\u003C\/div\u003E \u003C\/div\u003E\n\n \n \u003C\/div\u003E\n\u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022https:\/\/www.ajsonline.org\/sites\/default\/files\/js\/js_am8GAfrhW3uXc7HVCmqF3MltMmNunvhyJ6MM_6EffRE.js\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}
https://www.ajsonline.org/panels_ajax_tab/jnl_ajs_tab_refs/node:53138/1
Possibilities Girl - SCP Foundation The SCP Foundation's 'top-secret' archives, declassified for your enjoyment. Possibilities Girl Possibilities Girl After some serious lurking, I'm attempting to make an SCP of my very own! Sandbox link here:http://scpsandbox2.wikidot.com/sora2455 Here's hoping I'm original enough to be liked. :) Re: Possibilities Girl Ehh. I can't say I'm overly interested. It could just be that I'm tired, but does the article ever actually state what an SCP-XXXX-1 instance is and looks like? What's so great about SCP-XXXX that makes the -1 instances want her to pick "their" future? In the company example, what if XXXX was a terrible worker? It seems way, way too convenient that XXXX was able to call a Foundation front organization. I feel like XXXX is effectively irrelevant. It's the XXXX-1s that are the anomaly. If anything, the XXXX and XXXX-1 should be switched, or have the manifestations be the actual SCP and the girl be the current victim or current location of manifestation or something. I don't think the -008 reference is necessary. If it's famous and you didn't write it, then some people might read a reference to it as an attempt by the author to use something elses fame to make their own work seem more important than it actually is. Crosslinks should benefit both pieces for the betterment of expanding the Foundation'verse, not just a namedrop when some other thing (for example, any other anomalous disease in this case) could be used interchangeably That last bit on the GOI seems contrived. It's almost like the article is pushing excessively to attempt to prove this thing's usefulness. Also the entire premise reminds me of the Judgmental Turtle… Maybe read overthis guideto get an idea of what elements to avoid putting in an SCP article. Besides, humanoids are actually pretty difficult to write successfully; if you're reallyset on writing one, then take a look atthis handy guide. Fold Re: Possibilities Girl The majority of SCP-XXXX-1 instances are identical to SCP-XXXX with one aspect changed - most commonly they will be wearing the uniform of a corporation with which SCP-XXXX is not affiliated. The reason XXXX is the anomaly is because she generates XXXX-1. Evidently I need to show that better. Well, calling the Foundation directly would be even worse. Any suggestions? 008 reference redacted. GOI reference at the end removed. Dang it! Was hoping to be different… Re: Possibilities Girl If you're continuing a conversation, you can click the "reply" link at the lower right of the comment you're responding to. Helps so people are sure of who you're talking to. Yeah, I wasn't really getting the sense that this girl is generating anything. Keep in mind that as the author, you know the entire story, but the Foundation needs to have discovered what it knows about the SCP through observation and experimentation. How would someone with no prior knowledge whatsoever of the object, using only experimentation and observation, figure out all the things the article states? The Foundation usually has some level of surveillance of things, whether agents planted in the field or people who are called to investigate once local rumors get too noticeable, so probably something like that. Someone who contacts the Foundation and isn't Foundation-affiliated would be considered incrediblysuspicious, and such a narrative approach is usually tough to believe on top of that. Re: Possibilities Girl Okay, I guess I'll cut the origin story and instead put in an interview with SCP-XXXX-1. Make it clear that XXXX is generating them, or at least that they are not an outside force. Reply Options Re: Possibilities Girl It seems nice and clear with the updates. I like it. It's original and well written. I just have one small suggestion. In Test 36- Further questioning revealed that SCP-XXXX-1 was in possession what knowledge would be expected of a Foundation employee with level 2 clearance. It possessed no knowledge from the future. Probably want something more like "possession of knowledge which would". Also, the thing about it not being able to see the future seemed a bit unnecessary. I didn't think we had any reason to believe it could? Other than that, I'd upvote. :) Cuil Theory A Mathematical unit of Surrealism.
https://scp-wiki.wikidot.com/forum/t-1320473/possibilities-girl
All inspections: Dolphin Lane - Care Quality Commission Dolphin Lane 1 Dolphin Lane, Thorpe, Wakefield, West Yorkshire, WF3 3DN (01924) 872080 Provided and run by:J C Care Limited All Inspections During a monthly review of our data We carried out a review of the data available to us about Dolphin Lane on 8 June 2023. We have not found evidence that we need to carry out an inspection or reassess our rating at this stage.This could change at any time if we receive new information. We will continue to monitor data about this service.If you have concerns about Dolphin Lane, you cangive feedback on this service. During an inspection looking at part of the service Dolphin Lane is a residential care home in Leeds. The home provides accommodation and personal care for people living with learning disabilities. At the time of our inspection there were 15 people using the service. We found the following examples of good practice. • Visitors had to sign a COVID-19 risk assessment and declaration before entering the building and had their temperature checked on entry. • The home completed PPE competency checks on all staff to ensure they were competent in donning and doffing PPE. • There was easy read information prominently displayed which had been written to help explain the most recent lockdown and what it meant for people living at the service. • Staff used easy read materials and meetings to discuss COVID-19 and reduce anxieties around COVID-19, with people who used the service. During a routine inspection This was an unannounced inspection which took place on 17 and 20 August 2018. At the last inspection in December 2015 the service was rated good. At this inspection we found the provider had improved the service to achieve an outstanding rating. Dolphin Lane is a ‘care home’ registered to provide care for people with learning disabilities. People in care homes receive accommodation and nursing or personal care as single package under one contractual agreement. The Care Quality Commission regulates both the premises and the care provided, and both were looked at during this inspection. Dolphin Lane accommodates up to 15 people in one adapted building. The care service was developed and designed many years ago, and in the main the provider ensured the service operated in line with the values that underpin the Registering the Right Support and other best practice guidance. These values include choice, promotion of independence and inclusion. People with a learning disability and autism using the service can live as ordinary a life as any citizen. Although the service did not meet these principles in terms of the number of people it accommodated, this was mitigated by the fact that there was a vision for the long term development of the service. There was a registered manager in post. A registered manager is a person who has registered with the Care Quality Commission to manage the service. Like registered providers, they are ‘registered persons’. Registered persons have legal responsibility for meeting the requirements in the Health and Social Care Act 2008 and associated Regulations about how the service is run. People were supported by staff to lead fulfilling lives, ranging from gaining education and employment to achieving their ‘hopes and dreams’. The service went the ‘extra mile’ to ensure that people were able to engage with their hobbies and interests as much as possible. The service had made extensive efforts to integrate the service with the local community, this included charity events designed and chosen by people to give back to the community, engaging with local councillors and ministers and giving people encouragement to speak up about how local services could improve the lives of people with learning disabilities. We saw how staff went ‘above and beyond’ in caring for people at the end of their lives. People received highly person- centred care. Care plans were designed and reviewed in partnership with people, with outcome-focused goals. The service was able to evidence how it had helped people learn new skills and form and maintain meaningful relationships. There were enough staff who had been recruited safely to deliver care. There was a consistent care team, and each person had a named keyworker. This ensured good continuity of care. People were supported to maintain good health. This included access to healthcare professionals, eating and drinking enough, and support with their medicines. People were supported to take their medicines safely. Staff were skilled enough to meet people’s needs. Staff were supported through regular supervisions and appraisals. Staff spoke very positively about the leadership and the open and positive culture of the service, and felt well supported by the registered manager Everyone we spoke with told us staff were kind, caring and compassionate. Staff supported people to maintain independent lives, and people told us their privacy and dignity was protected. There were appropriate governance systems in place to ensure quality of care was monitored and improved. The service was a high performer within the provider’s network of services both in terms of training levels and staff survey feedback. There was a clear vision for the future development of the service. The service engaged positively with people using the service and took their ideas into account. People felt they were listened to and their contributions were valued. People were proud of the service and helped maintain it by cleaning and tidying communal areas. During a routine inspection This was an unannounced inspection carried out on the 3 December 2015. At the last inspection in October 2013 we found the provider met the regulations we looked at. Dolphin Lane is registered to provide accommodation and personal care for up to 15 people who have a learning disability. The home has a kitchen, dining area and lounge. The home has en suite facilities in all rooms and two self-contained flats. The home has a small garden area and is within easy walking distance of the local amenities. There was a registered manager in post. A registered manager is a person who has registered with the Care Quality Commission to manage the service. Like registered providers they are ‘registered persons’. Registered persons have legal responsibility for meeting the requirements in the Health and Social Care Act and associated Regulations about how the service is run. The registered manager was on planned absence from the service at the time of the inspection and the provider had appointed an acting manager. There was a very person centred approach and culture in the service. It was clear the service was tailored to meet individual needs and support people to achieve their dreams, aspirations, hopes and ambitions. People participated in a range of activities both in the home and community, this included paid employment and voluntary work. People were very happy living at the home and felt well cared for. People’s support plans contained sufficient and relevant information to provide consistent, care and support. People who used the service had positive relationships with staff. It was clear staff knew people and their needs well. People told us they felt safe at the service. Staff showed a good understanding of safeguarding vulnerable adults and knew what to do to keep people safe from harm while also encouraging and supporting people’s independence. Staff and the acting manager demonstrated a good understanding of risk management and how this was used to maximise people’s potential and independence skills. Overall, people were protected against the risks associated with medicines because the provider had appropriate arrangements in place to manage medicines safely. There were enough staff to support people and keep people safe. Staff training and support provided staff with the knowledge and skills to support people well. Robust recruitment and selection procedures were in place to make sure suitable staff worked with people who used the service. There were policies and procedures in place in relation to the Mental Capacity Act (MCA) 2005. Staff were trained in the principles of the MCA and could describe how people were supported to make decisions; and where people did not have the capacity; decisions were made in their best interests. Health, care and support needs were assessed and met by regular contact with health professionals. People were supported by staff who treated them with kindness and were respectful of their privacy and dignity. Staff were aware of how to support people to raise concerns and complaints and there were effective systems in place to assess and monitor the quality of the service; which included seeking and acting on feedback received from people who used the service. During a routine inspection The environment in which people lived promoted their privacy and dignity and supported their rights to choose and retain a level of independence. Each person had their own room which was decorated in the way people wanted. We spoke to six people who used the service and one visitor. People who used the service said they were given choices about how they spent their days. One person said " You can do what you want here, I have my own key to my room'. Another person said ' I go out to the shops when I want. It's a nice place to live I've been here two years'. All of the people we spoke to, and the visitor, spoke highly of the staff. People said they were happy with the care they received and that the staff were very nice. One person said ' I like it here I'm with my mates', another said ' Yes its very nice here. I go out to see my friend'. We spoke to one visitor who said that he had no complaints. He said' I think he is well protected here and he seems happy'. All of the staff we spoke to during our visit were familiar with safeguarding procedures. All staff members said they would report any abuse to the manager or the deputy manager. They said they found them both to be very supportive. Care records had documentation on Being Safe a document which helped assess peoples risk in relation to travelling on public transport, road safety, working in the kitchen and gardening. Staff received appropriate professional development. This was identified through their supervision and appraisal. There was evidence of regular supervision where training needs were identified. The home carried out monthly 'Your Voice' meetings with people who lived in the home and the minutes from September 2013 identified that people were asked about college courses they would like to attend, who would like to join the health and safety committee and other information on social activities. People were asked if they were happy with the menu and one person said 'It's good that we can pick what we have for tea and have our favourite meals'. During a routine inspection We spoke with four people who used the service. People said the staff treated them with dignity and respect. One person told us; 'I can stay up as long as I want.' Another person said; 'I like it here.' People said they had a say in what happened in the running of the home. Two people told us they did this through, 'Your Voice meetings.' Another said they did this through 'one to ones with my key worker.' Two people we spoke with told us they had jobs which helped them to remain independent. People said they liked the staff. People told us they had a regular one to one with their key worker and could input into their care record. People we spoke with told us they had a choice of food. One person said; 'I like the food.' Another person told us; 'I can choose what I want to eat.' Two people we asked both with told us they felt 'safe' living at Dolphin Lane. We asked two people what they would do if they didn't like something that was happening at the home; both people knew to speak to the manager or deputy manager.
https://www.cqc.org.uk/location/1-130890642/reports
Implications of microRNA dysregulation in the development of prostate cancer in: Reproduction Volume 154 Issue 4 (2017) MicroRNAs (miRNAs) are non-coding small RNAs that target mRNA to reduce protein expression. They play fundamental roles in several diseases, including prostate cancer (PCa). A single miRNA can target hundreds of mRNAs and coordinately regulate them, which implicates them in nearly every biological pathway. Hence, miRNAs modulate proliferation, cell cycle, apoptosis, adhesion, migration, invasion and metastasis, most of them constituting crucial hallmarks of cancer. Due to these properties, miRNAs emerged as promising tools for diagnostic, prognosis and management of cancer patients. Moreover, they come out as potential targets for cancer treatment, and several efforts are being made to progress in the field of miRNA-based cancer therapy. In this review, we will summarize the recent information about miRNAs in PCa. We will recapitulate all the miRNAs involved in the androgen pathway and the biology of PCa, focusing in PCa initiation and progression. In particular, we will describe the miRNAs associated with cell proliferation, cell cycle and apoptosis in PCa, as well as invasion, adhesion and metastatic miRNAs. We will revise the recent progress made understanding the role of circulating miRNAs identified in PCa that might be useful for PCa patient stratification. Another key aspect to be discussed in this review is miRNAs’ role in PCa therapy, including the miRNAs delivery. Sign in Create account Home Browse Implications of microRNA dysregulation in the development of prostate cancer in Reproduction Authors: Cintia Massillo Cintia Massillo Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina Search for other papers by Cintia Massillo in Current site Google Scholar PubMed Close , Guillermo N Dalton Guillermo N Dalton Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina Search for other papers by Guillermo N Dalton in Current site Google Scholar PubMed Close , Paula L Farré Paula L Farré Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina Search for other papers by Paula L Farré in Current site Google Scholar PubMed Close , Paola De Luca Paola De Luca Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina Search for other papers by Paola De Luca in Current site Google Scholar PubMed Close , and Adriana De Siervi Adriana De Siervi Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina Search for other papers by Adriana De Siervi in Current site Google Scholar PubMed Close DOI: https://doi.org/10.1530/REP-17-0322 Volume/Issue: Volume 154: Issue 4 Page Range: R81–R97 Article Type: Review Article Online Publication Date: Oct 2017 Copyright: © 2017 Society for Reproduction and Fertility 2017 MicroRNAs (miRNAs) are non-coding small RNAs that target mRNA to reduce protein expression. They play fundamental roles in several diseases, including prostate cancer (PCa). A single miRNA can target hundreds of mRNAs and coordinately regulate them, which implicates them in nearly every biological pathway. Hence, miRNAs modulate proliferation, cell cycle, apoptosis, adhesion, migration, invasion and metastasis, most of them constituting crucial hallmarks of cancer. Due to these properties, miRNAs emerged as promising tools for diagnostic, prognosis and management of cancer patients. Moreover, they come out as potential targets for cancer treatment, and several efforts are being made to progress in the field of miRNA-based cancer therapy. In this review, we will summarize the recent information about miRNAs in PCa. We will recapitulate all the miRNAs involved in the androgen pathway and the biology of PCa, focusing in PCa initiation and progression. In particular, we will describe the miRNAs associated with cell proliferation, cell cycle and apoptosis in PCa, as well as invasion, adhesion and metastatic miRNAs. We will revise the recent progress made understanding the role of circulating miRNAs identified in PCa that might be useful for PCa patient stratification. Another key aspect to be discussed in this review is miRNAs’ role in PCa therapy, including the miRNAs delivery. Abstract MicroRNAs (miRNAs) are non-coding small RNAs that target mRNA to reduce protein expression. They play fundamental roles in several diseases, including prostate cancer (PCa). A single miRNA can target hundreds of mRNAs and coordinately regulate them, which implicates them in nearly every biological pathway. Hence, miRNAs modulate proliferation, cell cycle, apoptosis, adhesion, migration, invasion and metastasis, most of them constituting crucial hallmarks of cancer. Due to these properties, miRNAs emerged as promising tools for diagnostic, prognosis and management of cancer patients. Moreover, they come out as potential targets for cancer treatment, and several efforts are being made to progress in the field of miRNA-based cancer therapy. In this review, we will summarize the recent information about miRNAs in PCa. We will recapitulate all the miRNAs involved in the androgen pathway and the biology of PCa, focusing in PCa initiation and progression. In particular, we will describe the miRNAs associated with cell proliferation, cell cycle and apoptosis in PCa, as well as invasion, adhesion and metastatic miRNAs. We will revise the recent progress made understanding the role of circulating miRNAs identified in PCa that might be useful for PCa patient stratification. Another key aspect to be discussed in this review is miRNAs’ role in PCa therapy, including the miRNAs delivery. Introduction After the discovery of the first microRNA (miRNA) ( see Box 1 for definition), lin-4 in Caenorhabditis elegans, the regulation of multiple biological pathways by miRNAs was investigated. Nowadays, we know that miRNAs regulate post-transcriptional gene expression mostly by imperfect binding of miRNA to the partially complementary sequence in 3′UTR, which represses protein translation, but also by cleavage of mRNA with perfect base-pairing homology through the action of AGO in the RISC complex (Jackson & Standart 2007). Interestingly, it is estimated that miRNAs regulate up to 30% of all protein-coding genes (Jackson & Standart 2007). BOX1: miRNAs definition and biogenesis MicroRNAs (miRNAs) are an abundant class of non-coding small RNAs of 19–25 nucleotides length that target mRNA to reduce protein expression. They play fundamental roles in most biological processes, including several diseases. miRNA biogenesis is a multistep process that starts with transcription of miRNA genes by RNA polymerase II generating a long primary precursor (pri-miRNA). This precursor, which can be thousands of nucleotide long, has a local hairpin structure, which is cleaved by the enzymes Drosha and DGCR8, producing a hairpin ~80 bp long, called pre-miRNA. This pre-miRNA is exported to the cytoplasm by Exportin 5, where it is processed by the enzyme Dicer and bound to Argonaute (AGO) protein, resulting in the RISC complex. The mature miRNA assembled into the RISC complex typically binds to the 3′ untranslated region (UTR) of the target mRNA and usually inhibits protein translation. miRNAs modulate multiple biological processes such as genome stability, proliferation, cell cycle, apoptosis, adhesion, migration, invasion and inflammation, most of them constituting crucial hallmarks of cancer (Ruan et al.2009). Functional studies identified several miRNAs with key roles in carcinogenesis, cancer progression and metastasis. Cancer-related miRNAs could be grouped in two main categories: oncomiRs that repress tumor suppressor genes resulting in oncogenic properties and tumor suppressor miRs (tsmiRs), with a role in tumor suppression since they reduce oncogene protein expression (Ruan et al.2009). Even when individual miRNAs can be oncomiRs or tsmiRs, global levels of miRNAs seems to be suppressed in tumors compared with normal tissues suggesting that miRNA biogenesis could be dysregulated in cancer (Lin & Gregory 2015). Numerous studies show that miRNA expression profiles could differentiate between normal and tumor tissues to identify tumors of unknown origin and to classify subtypes of the same tumor (Metias et al.2009). Increasing evidence support that miRNAs can be detected in serum in a very stable form, making circulating miRNAs a useful field in active research for diagnosis and follow-up of cancer. miRNA expression could predict clinical outcome and prognosis in some types of tumors or they can be used as markers of disease relapse and metastases (Metias et al.2009). Therefore, miRNAs emerged as promising tools for diagnostic, prognosis and management of cancer patients. Since miRNAs target multiple gene pathways, they come out as potential targets for cancer treatment, and progress is being made in the field of miRNA-based cancer therapy (Metias et al.2009). In this review, we will summarize the recent information about miRNAs in PCa. We will recapitulate all the miRNAs involved in the androgen pathway and the biology of PCa, focusing in PCa initiation and progression. In particular, we will describe the miRNAs associated with cell proliferation, cell cycle and apoptosis in PCa, as well as invasion, adhesion and metastatic miRNAs. In addition, we will revise the recent progress made understanding the role of circulating miRNAs identified in PCa that might be useful as diagnostic and prognostic tools. Another key aspect to be discussed in this review is the role of miRNAs in PCa therapy, including the miRNAs delivery. miRNAs in the Androgen Receptor (AR) signaling pathway in PCa The controversial use of PCa biomarkers, such as PSA (Cary & Cooperberg 2013), established the need for novel clinically useful biomarkers, including miRNAs ( see Box 2 for PCa related terms). AR signaling axis is persistently activated and plays an important role in the growth and survival of hormone-refractory PCa cells. Both AR itself and its downstream signaling processes remain attractive targets for treating CRPC. BOX2: Prostate cancer (PCa)-related terminology Prostate gland development is initially androgen sensitive. Under constant stimulation of androgen, prostate gland can gradually develop into androgen-sensitive PCa, which is the most common cancer among men (after skin cancer) (https://www.cancer.org/cancer/prostate-cancer.html). For patients who show locally advanced or disseminated PCa, androgen deprivation therapy (ADT) is widely used as a treatment. Most patients initially respond to ADT; however, castration-resistant prostate cancer (CRPC), the terminal stage of PCa, arises when hormone-refractory growth occurs in a castrate androgen-level environment. Bone metastases occur in 80–90% of men with CRPC, which seriously jeopardizes the patient’s quality of life and morbidity. Despite several advances in PCa treatment, metastatic CRPC remains an incurable disease. The androgen receptor (AR) is one of the most important nuclear transcription factors from the steroid hormone receptor superfamily of genes. Normal prostate growth and development, PCa carcinogenesis and CRPC progression are dependent on AR expression and function. Currently prostate-specific antigen (PSA) is the most specific marker used to detect PCa and strongly correlates with the risk of harboring PCa. However, PSA has limitations for PCa detection given its low specificity and poor sensitivity. The lack of specificity of PSA for PCa has led to both unnecessary biopsies and overdiagnosis of indolent cancers (Cary & Cooperberg 2013). As AR regulates the expression of several miRNAs, and the ARmRNA has a long 3′UTR, which is a predicted target of many miRNAs, in this section, we will review the impact of miRNAs linked to reactivation of the AR signaling axis and the relevance of miRNAs in the development of CRPC (Fig. 1). Figure 1 miRNAs involved in AR signaling pathway. miRNAs that target 3′UTR of the ARmRNA, including the miRNAs target genes, are indicated ( left panel). In the right panel, scheme of AR protein structure including miRNAs repressed (red arrow) and induced (green arrow) by AR are indicated. DBD, DNA-binding domain; HR, Hinge region. Citation: Reproduction 154, 4;10.1530/REP-17-0322 Figure 1 miRNAs involved in AR signaling pathway. miRNAs that target 3′UTR of the ARmRNA, including the miRNAs target genes, are indicated ( left panel). In the right panel, scheme of AR protein structure including miRNAs repressed (red arrow) and induced (green arrow) by AR are indicated. DBD, DNA-binding domain; HR, Hinge region. Citation: Reproduction 154, 4;10.1530/REP-17-0322 Figure 1 miRNAs involved in AR signaling pathway. miRNAs that target 3′UTR of the ARmRNA, including the miRNAs target genes, are indicated ( left panel). In the right panel, scheme of AR protein structure including miRNAs repressed (red arrow) and induced (green arrow) by AR are indicated. DBD, DNA-binding domain; HR, Hinge region. Citation: Reproduction 154, 4;10.1530/REP-17-0322 Androgen-upregulated miRNAs We will describe miR-135a, miR-32, miR-125b, miR-27a, miR-141and miR-21as the most important miRNAs reported that are induced by AR (Fig. 1). miR-135a AR directly binds to AR-binding sites (ARBSs) in the miR-135agene activating its transcription. Overexpression of miR-135a decreased in vivoand in vitroinvasion and migration of PCa cells through ROCK1 and ROCK2 downregulation (Kroiss et al.2015). miR-32 miR-32 was also reported as a miRNA induced by androgens. The stimulation of LNCaP cells with dihydrotestosterone (DHT) leads to miR-32 overexpression. This miRNA showed putative ARBSs in close proximity to the miRNA genomic loci. miR-32 overexpression significantly induced LNCaP cells growth while reduced apoptosis, which correlates with BTG2-downregulated expression (Jalava et al.2012). miR-125b miR-125b is overexpressed in PCa and it is regulated by androgens, but also is an important regulator of AR. Shi et aldemonstrated that androgen stimulation of LNCaP cells increased miR-125b expression. Transfection of synthetic miR-125b mimic stimulated the androgen-independent growth and downregulated the expression of the proapoptotic regulator Bak1 (Shi et al.2007). The authors found that AR regulates miR-125b expression through an androgen-responsive element within the promoter region of the miR gene. They also showed that miR-125b is a downstream effector of AR pathway that promotes tumor growth by targeting proapoptotic-genes (Shi et al.2011). miR-27a miR-27a is an androgen-regulated oncomiR in PCa, targeting the tumor suppressor and AR corepressor Prohibitin. miR-27a reduced Prohibitin mRNA and protein levels and increased the expression of AR target genes inducing PCa cell growth (Fletcher et al.2012). In addition, Mo et alfound that miR-27a is directly upregulated by AR and promoted PCa-malignant phenotype by direct regulation of ABCA1 and PDS5B, which facilitates PCa cell proliferation (Mo et al.2013). However, more recently, Wan and coworkers reported to miR-27a as a tsmiR downregulated by PI3K signaling in CRPC cells. Overexpression of miR-27a decreased PCa cell proliferation and migration and induced PCa cell cycle arrest and apoptosis (Wan et al.2016). miR-141 Waltering et aldemonstrated that four miRNAs (miR-10a, miR-141, miR-150*, miR-1225-5p) showed similar androgen regulation in both, cell lines and xenografts. miR-141 overexpression enhanced LNCaP cells proliferation while its inhibition by anti-miR-141 suppressed cell growth (Waltering et al.2011). The small heterodimer partner (SHP) also known as NR0B2 is an AR corepressor that represses AR-regulated transcriptional activity. miR-141 targets 3′UTR of SHPmRNA resulting in its translational suppression and mRNA degradation causing an increase in AR-regulated transcriptional activity in LNCaP cells (Xiao et al.2012). miR-21 TGFβ is one of the most important pathways altered in PCa. Mishra and coworkers showed that the coordinated action of miR-21 and AR signaling played a critical role inhibiting TGFβ receptor II (TGFBR2) expression in PCa cells through a positive feedback loop that inhibits growth responses (Mishra et al.2014). AR binds to ARBSs in the miR-21promoter and increases its transcription (Ribas et al.2009). miR-21 overexpression enhanced androgen-dependent PCa growth and mediates castration resistance (Ribas et al.2009). miR-21 is overexpressed in different human cancers, and it was described as an oncomiR due to its ability to negatively modulate the expression of the tumor suppressor gene PTEN(Talotta et al.2009). However, miR-21 was not differently expressed in carcinomas with respect to normal tissues in 36 samples from PCa patients subjected to radical prostatectomy (Folini et al.2010). Androgen-downregulated miRNAs In this section, we will explain miR-221/222 cluster and miR-99a as the major miRNAs that are directly downregulated by AR (Fig. 1). miR-221/222 cluster The oncomiRs miR-221 and miR-222 are transcribed from a gene cluster on the X chromosome with identical seed sequences and target genes. Sun and coworkers showed that miR-221/222 cluster was downregulated by androgens and significantly upregulated in CRPC cells. Overexpression of miR-221/222 in LNCaP cells promoted the development of the CRPC phenotype through downregulation of its targets, HECTD2 and RAB1A (Sun et al.2009). In addition, miR-221/222 cluster was overexpressed in PC3 cells (a model of aggressive prostate carcinoma) compared with LNCaP and 22Rv1 cell lines (models of slowly growing carcinomas). This cluster targeted p27 KIP1, a tumor suppressor and cell cycle inhibitor, and confers high growth advantage to LNCaP cells and LNCaP-derived tumors in SCID mice (Galardi et al.2007,Mercatelli et al.2008). Consistently, the anti-miR-221/222 treatment of established subcutaneous tumors derived from PC3 cells reduced tumor growth by increasing intratumor p27 KIP1protein expression (Mercatelli et al.2008). These studies suggest that miR-221/222 cluster has an oncogenic role in PCa. Nevertheless, the differential expression pattern of miRNA-221/222 associated with PCa progression remains contradictory. Several groups have shown that miR-221/222 was highly expressed in patient-derived primary cell lines and bone metastatic CRPC tumor specimens. They showed a positive association of miR-221 expression with the pathological stage, lymph node metastasis, capsular invasion, organ-confined disease, Gleason score, biochemical recurrence and patient follow-up (Mercatelli et al.2008,Li et al.2012,Sun et al.2013). However, two independent cohort studies using microarrays revealed a progressive reduction of miR-221 in aggressive PCa tumors and their metastasis, which might be used for clinical recurrence prognosis (Spahn et al.2010,Gordanpour et al.2011). miR-99a Androgen directly binds to the miR-99a/let7c/125b-2 cluster gene and represses its expression in AR-positive PCa cells. Insulin-like growth factor 1 receptor (IGF1R), mammalian target of rapamycin (mTOR) and chromatin remodeling factors SMARCA5 and SMARCD1 are involved in androgen-induced growth and PCa progression by repression of miR-99a (Sun et al.2011,2014 a,Rane et al.2016). Several groups have shown that miR-99a was underexpressed in human prostate tumor tissue, metastatic PCa and CRPC samples compared to normal prostate tissues (Sun et al.2011,2014 b,Lin et al.2013,Rane et al.2016). The reduction in miR-99a expression could provide a growth advantage for AR-positive cells under androgen-depleted condition. Moreover, miR-99a overexpression inhibited the growth of PCa cells and decreased the expression of PSA indicating its potential role as tsmiR (Sun et al.2011,2014 a). As downregulation of miR-99a requires an active AR, it is expected that the hyperactivated AR frequently seen in CRPC could trigger increased expression of IGF1R and mTOR through transcriptional repression of miR-99a, which may contribute to CRPC progression (Shih et al.2015). Andro-miRs: miRNAs that regulate AR expression and their role in CRPC Another group of miRNAs highly relevant in PCa are andro-miRs that include all the miRNAs that regulate AR expression. We will give details about the most important reported andro-miRs: miR-185, miR-31, miR-205, Let-7c, miR-488* and miR-124 (Fig. 1). miR-185 miR-185 is a tsmiR reduced in clinical PCa samples that downregulates AR (Qu et al.2013,Liu et al.2015 a). Overexpression of miR-185 reduced AR expression and inhibited LNCaP cell proliferation arresting cells at G1 phase and inducing apoptosis. miR-185 suppressed the invasive and migration abilities of cells and inhibited the tumorigenicity in PCa xenografts models. Also, miR-185 tumor suppressor functions could be mediated by downregulation of its target gene CDC6. A recent study of Jiang and coworkers found that miR-185 attenuated AR function indirectly by binding to the 3′UTR of the AR co-activator BRD8ISO2 (bromodo­main containing 8 isoform 2). Additionally, BRD8ISO2mRNA expression was inversely correlated with miR-185 expression in clinical specimens (Jiang et al.2016). miR-31 A complex interaction between the tsmiR miR-31 and AR signaling was reported by Lin and coworkers (Lin et al.2013). miR-31 expression was reduced in primary and metastatic PCa as a result of promoter hypermethylation and its expression was inversely correlated with the aggressiveness of the disease. The expression of AR and miR-31 was inversely correlated in cell lines suggesting that miR-31 and AR could mutually repress each other. Upregulation of miR-31 suppressed AR expression and inhibited PCa growth. Additionally, miR-31 suppressed cell cycle regulators; including E2F1, E2F2, EXO1, FOXM1 and MCM2 (Lin et al.2013). Creighton and coworkers found that miR-31 has anti-proliferative effects inducing apoptosis in PC3 cells through a dysfunctional p53 pathway. Loss of miR-31 is associated with defects in the p53 pathway in PCa suggesting that patients with p53-deficient cancers might benefit from therapeutic delivery of miR-31 (Creighton et al.2010). Fuse et alfound 56 miRNAs significantly downregula­ted in PCa compared with non-PCa tissues, being the top four downregulated miRNAs: miR-187, miR-205, miR-222 and miR-31. They validated the expression levels of these four miRNAs in PCa specimens (15 PCa tissues and 17 non-PCa tissues) and demonstrated that miR-31 inhibited cell proliferation, invasion and migration in PCa cell lines (Fuse et al.2012). By methylation status analysis in PCa vs non-PCa tissues, Daniunaite et alfound that miR-31-5p promoter methylation was predictive of biochemical disease recurrence-free patient survival and increased the prognostic value of clinicopathologic factors (Daniunaite et al.2017). Bhatnagar et alcompared miRNA expression profiles of a low aggressive PCa cell line (WPE1-NA22) and a highly malignant cell line (WPE1-NB26). The authors found that miR-205 and miR-31 were significantly downregulated in WPE1-NB26 cells, as well as in other cell lines representing advanced-stage PCa. They identified the antiapoptotic gene E2F6as miR-31 target (Bhatnagar et al.2010). miR-205 miR-205 binds to the 3′UTR of AR and represses its expression. miR-205 levels were significantly lower in CRPC than in hormone- naivepatients. It was inversely correlated with AR levels in malignant epithelial cells, but there was no correlation in benign epithelium. Moreover, miR-205 expression is inversely correlated with the occurrence of metastases and shortened overall survival of the patients. miR-205 regulated genes involved in crucial pathways for the development of primary tumor, and the progression to incurable CRPC, such as MAPK/ERK, Toll-like receptor and IL-6 signaling pathways (Hagman et al.2013). Boll and coworkers recently demonstrated that miR-130a, miR-203 and miR-205 jointly interfere with important oncogenic pathways in PCa and are downregulated in cancer tissues. miR-205 overexpression in LNCaP cells resemble the effect of androgen deprivation including morphological changes and impeded growth by suppressing several AR coactivators (Boll et al.2013). Gandellini and coworkers found that the restoring expression of miR-205 in PCa cells resulted in cell rearrangements consistent with a mesenchymal-to-epithelial transition, such as up-regulation of E-cadherin and reduction of cell migration and invasion. miR-205 repressed a group of pro-metastatic genes, including N-chimerin, ErbB3, E2F1, E2F5, ZEB2and protein kinase CE, which are well known to drive EMT (Gandellini et al.2009). miR-205 overexpression in PCa cells induced apoptosis and cell cycle arrest and impaired cell growth, migration and invasion by targeting the tumor suppressor genes IL24 and IL32 (Majid et al.2010). Altogether these data suggest that miR-205 might possibly act as tsmiR in PCa and could interfere with progression to castration resistance. Let-7c Let-7 family is composed of 12 members located on eight different chromosomes. Typically, it correlates with poor prognosis in several cancer types. miR-let-7c represses AR expression in human PCa cells by targeting c-Myc, which in turn decreases cell proliferation, clonogenicity and anchorage-independent growth of human PCa cells. Downregulation of Let-7c in CRPC cells, PCa xenograft models as well as in PCa clinical specimens is inversely correlated with AR expression, whereas the expression of LIN28, a Let-7 repressor, is correlated positively with AR expression. Furthermore, Let- 7c overexpression significantly reduced tumor burden in human PCa xenografts (Nadiminty et al.2012 a, b). Schubert and coworkers demonstrated that the members of let-7 family were downregulated in the majority of a large, well-characterized high-risk PCa cohort and the expression of let-7a/b/and -c was correlated to clinical outcome parameters of this group. Let-7b and let-7c were associated with clinical failure in PCa patients and functioned partially as independent prognostic marker (Schubert et al.2013). Gao and coworkers showed that AR serves as a positive regulator of c-Myctranscription and both are increased in human CRPC tumor progression (Gao et al.2013). Also, it has been demonstrated that c-Mycis a let-7c target gene, but how let-7c negatively regulates c-Mycexpression in PCa remains unclear (Koscianska et al.2007). Sun and coworkers reported that AR directly binds to the host gene of the miR-99a/let7c/125b-2 cluster and represses its transcription. Of the twelve mRNA, potential targets of the miR-99a/let7c/125b-2 cluster induced by androgens, nine mRNAs are downregulated by the miRNA cluster, indicating that downregulation of the cluster by androgen protects many of their target mRNAs from degradation and indirectly assist in gene induction (Sun et al.2014 a). miR-488* miR-488* is another miRNA that directly targeted AR by binding to the AR 3′UTR. Although miR-488* expression was not detected in PCa cell lines and no evidence of changes in human PCa specimens was found, the ectopic expression of miR-488* effectively downregulated AR protein expression and inhibited the AR functional activity resulting in retardation of cellular growth and increased apoptosis of PCa cells. Hence, miR-488* might function as a tsmiR disrupting the AR signaling pathway (Sikand et al.2011). miR-124 miR-124 is a tsmiR involved in the control of multiple steps of cancer progression, including tumor cell proliferation, invasion, angiogenesis and metastasis in many cancer types (Shih et al.2015). miR-124 directly targets the AR by binding to its 3′UTR and decreased the AR protein levels and activity, which subsequently leads to an upregulation of p53 and the inhibition of growth and apoptosis of AR-positive PCa cells and xenograft tumors (Shi et al.2007,2013). miR-124 is significantly downregulated in PCa cells compared to normal cells, and it is negatively correlated with AR in human PCa tissues (Shi et al.2013). Loss of miR-124 expression in PCa is epigenetically regulated by promoter hypermethylation, and it is associated with elevated AR levels in both cell lines and clinical prostate samples. Also although miR-124 inhibited AR expression, miR-124 was positi­vely regulated by AR, suggesting a negative feedback loop between the AR and miR-124, controlling the progression of CRPC (Shi et al.2013,Chu et al.2015). miRNAs associated with cell cycle and apoptosis in PCa miRNAs play a critical role in PCa through modulation of protein expression involved in cell cycle regulation and apoptosis, such as p53, Bcl2/Bcl-xl, E2F, cyclins, CDKs, among others ( see box 3 for related terminology,Fig. 2). BOX3: Cell cycle-related terminology Cyclins are a family of proteins that control cell cycle progression by activating cyclin-dependent kinase (CDK) enzymes. Cyclin D1 (CCND1) is expressed in the early G1 phase and binds to CDK4 and CDK6. Activation of these kinases results in the phosphorylation of retinoblastoma (RB) protein, which leads to E2Fs activation and entering into S-phase. Thus, E2F family of transcription factor proteins are key regulators of the G1/S-phase transition acting as cell cycle checkpoint control. The Cdk inhibitors (CDKI) p21 cip/WAF1and p27 KIP1prevents the activation of CCNE-CDK2 or CCND1-CDK4/CDK6 complexes, and thus, controls the cell cycle progression at G1. The aberrant expression of CCND1, p21 cip/WAF1, p27 KIP1or E2Fs leads to abnormal cellular proliferation. Figure 2 miRNAs associated to cell cycle progression in PCa. miRNAs that target cell cycle proteins are indicated. Citation: Reproduction 154, 4;10.1530/REP-17-0322 Figure 2 miRNAs associated to cell cycle progression in PCa. miRNAs that target cell cycle proteins are indicated. Citation: Reproduction 154, 4;10.1530/REP-17-0322 Figure 2 miRNAs associated to cell cycle progression in PCa. miRNAs that target cell cycle proteins are indicated. Citation: Reproduction 154, 4;10.1530/REP-17-0322 miRNAs associated to p53 p53 is a tumor suppressor gene that stimulates apoptosis via Noxa and p53 upregulated modulator of apoptosis (PUMA) proapoptotic proteins. Loss of p53 function has a critical role in several cancer types, including PCa. Besides miR-125b is involved in AR signaling pathway and overexpressed in PCa cells and tissues, it was reported that it promoted the growth of PCa xenografts through p53-dependent apoptosis regulation. miR-125b downregulated p53, and its target proapoptotic genes PUMA, p21 cip/waf1and Bak1 (Shi et al.2011). miRNAs associated to Bcl-2/Bcl-xl Members of the B-cell lymphoma 2 (BCL-2) family regulate the apoptosis intrinsic pathway. BCL-2 is directly inhibited by miR-34a, miR-34c, miR-15a and miR-204-5p in PCa, which reduces proliferation, increases apoptosis and sensitivity of multidrug-resistant PCa cells to chemotherapeutic agents. Bcl-2 exerts antiapoptotic effects by inhibiting Noxa and Puma (Kojima et al.2016). Bcl-xl, an antiapoptotic member of the Bcl-2 family, is expressed in variety of cancer types, including PCa. miR-574-3p reduces Bcl-xl in PCa cells, and its expression could be upregulated by genistein, a soy isoflavone with antitumor activity (Chiyomaru et al.2013). miRNAs possess a major role in chemotherapeutic agent-induced apoptosis modulation in PCa cells. For instance, miR-205 and miR-31 were identified to target Bcl-w (a Bcl-2 family member) and E2F6 respectively (Bhatnagar et al.2010). Downregulation of both miRNAs resulted in apoptosis resistance in highly malignant WPE1-NB26 cells (Bhatnagar et al.2010). Several miRNAs regulate the extrinsic cell death pathway of apoptosis. miR-24 directly downregulated Fas-associated factor 1 (FAF1), a Fas-binding proapoptotic protein, resulting in a reduction in apoptosis of the hormone-resistant DU 145 PCa cells (Qin et al.2010). In contrast, the proapoptotic protein TRAIL was upregulated by miR-145 (Zaman et al.2010). miRNAs associated to cell cycle progression The miR-15a/16 cluster has been reported to be downregulated in 80% of advanced PCa (Aqeilan et al.2010). Downregulation of this cluster resulted in increased BCL-2 activity and upregulation of CCND1, which facilitates G1/S-phase transition and cell survival (Aqeilan et al.2010,Bonci et al.2015). miR-16 overexpression significantly inhibits the growth of prostate tumors through the downregulation of CDK1 and CDK2 (Takeshita et al.2010). miR-221/222 promotes tumor cell proliferation and represses apoptosis through p27 kip1and caspase-10 downregulation in PCa (Galardi et al.2007,Wang et al.2015 a). p27 kip1is also a direct target of miR-429 in PCa. miR-429 expression downregulation leads to p27 kip1overexpression, which inhibited cell proliferation through G1 cell cycle arrest (Ouyang et al.2015). It was published that E2F1-3 bound to miR-17-92cluster promoter and activated its transcription, which in turn, downregulated the expression of E2F1-3, thereby producing a negative feedback loop that maintains E2F1-3 expression levels at a relatively constant level (Sylvestre et al.2007). miR-17-92 expression is usually upregulated in PCa cells, resulting in E2F1-3 depletion and consequently apoptosis avoidance. miR-25 and miR-205 have also been shown to downregulate E2F1-3 expression (Ambs et al.2008,Gandellini et al.2009). miRNA let-7a is a tsmiR downregulated in PCa. Let-7a inhibited cell proliferation and promoted cell cycle arrest at the G1 phase in PCa cells by downregulating the expression of E2F2 and CCND2 (Dong et al.2010). miRNA-330 induced apoptosis in PCa cells through E2F1-mediated suppression of AKT phosphorylation and suppresses tumor growth (Lee et al.2009). miR-449a can cause cell cycle arrest, apoptosis and a senescent-like phenotype by hindering the HDAC1 expression (histone deacetylase 1), frequently overexpressed in cancer (Noonan et al.2009). Noonan and coworkers identified miR-449a-mediated growth arrest dependent on the Rb protein. miR-449a was found to suppress phosphorylation by knockdown of CCND1 and target HDAC1 (Noonan et al.2010). miRNAs associated with invasion/adhesion/EMT/metastasis During the last years, miRNAs have gained importance in many aspects of metastatic cancer research (see box 4 for related terminology).In this review, we have divided the miRNAs associated with metastasis in two large groups, pro- and antimetastatic (Fig. 3). Metastasis-related terminology (BOX 4) The spread of cancer cells from the place where they first formed to another part of the body followed by secondary tumor formation is called metastasis. Metastatic disease is responsible for the majority of cancer-related deaths and PCa is no exception. More than 80% of advanced-stage PCa manifests bone metastasis, and at this point, the disease is nearly incurable. Progression from localized to metastatic disease requires cells to detach from the primary tumor mass, invade the adjacent stroma, intravasate, survive in circulation, extravasate and colonize organs. All these steps are orchestrated by epithelial-to-mesenchymal (EMT) and mesenchymal -to-epithelial (MET) transitions. These are well-characterized events that play a highly relevant role in cancer metastasis. Cells that undergo EMT show shape changes, such as loss of apico-basal polarity and cell adhesion, the repression of E-cadherin (CDH1) expression and increased cell mobility. Accordingly, mesenchymal cell exhibits upregulation of tyrosine kinases, N-cadherin (CDH2), vimentin, fibronectin, zinc-finger domain proteins (SNAI1/SAIL, SNAI2/SLUG, ZEB2/SIP1) and matrix metalloproteinases, as well as basic helix-loop-helix domain protein Twist1 expression. There is a plethora of proteins involved in EMT-MET regulation, from transcription factors (ZEB1/2, SLUG or SNAIL) to cell adhesion molecules, like CDHs or integrins. Figure 3 miRNAs associated to PCa metastasis. Antimetastatic and pro-metastatic miRNAs are indicated. Also bone and other organs metastatic miRNAs are highlighted. Citation: Reproduction 154, 4;10.1530/REP-17-0322 Figure 3 miRNAs associated to PCa metastasis. Antimetastatic and pro-metastatic miRNAs are indicated. Also bone and other organs metastatic miRNAs are highlighted. Citation: Reproduction 154, 4;10.1530/REP-17-0322 Figure 3 miRNAs associated to PCa metastasis. Antimetastatic and pro-metastatic miRNAs are indicated. Also bone and other organs metastatic miRNAs are highlighted. Citation: Reproduction 154, 4;10.1530/REP-17-0322 Pro-metastatic miRNAs These miRNAs are essentially oncomiRs, since they target and downregulate tumor suppressor genes, cell adhesion molecules and pro-apoptosis/anoikis regulators (Fig. 3). Lin and coworkers demonstrated that the oncomiR miR-30d induced PCa cell proliferation, migration, invasion and capillary tube formation of endothelial cells. Moreover, it increased angiogenesis in LNCaP and DU 145-derived-xenografts downregulating MYPT1 expression. miR-30d was also overexpressed in PCa cells and PCa patient samples. miR-30d expression was associated with clinical features of PCa progression, such as high pre-operative PSA and Gleason score, advanced clinical and pathological stages, biochemical recurrence, reduced overall survival and metastasis. Also, they identified miR-30d/MYPT1 axis as an independent factor to predict biochemical recurrence of PCa patients (Lin et al.2017). In agreement, Kobayashi and coworkers found that miR-30d increased PC3 and LNCaP cell invasion. They also showed that miR-30d was increased in PCa tissue compared to adjacent normal tissue. Furthermore, high expression of miR-30d correlates with shorter time of biochemical recurrence and together with low SOCS1 expression is associated with increased risk of early biochemical recurrence (Kobayashi et al.2012). The repression of CDH1 observed in PCa EMT is, in part, consequence of miR-22 targeting. Dhar and coworkers reported that overexpression of miR-22 in PCa cells promotes cell invasiveness and migration through CDH1 downregulation (Dhar et al.2017). Raf kinase inhibitor protein (RKIP) is a tumor and metastasis suppressor gene in PCa (Escara-Wilke et al.2012), and it has been shown to negatively correlate in patient samples with miR-543 expression. RKIP downregulation by miR-543 in PCa cell lines increased invasion and migration in vitroand tumor proliferation and VIM/CDH1 ratio in vivo(Du et al.2017). miR-590-3p is overexpressed in PCa samples and its expression is associated to increased cell proliferation, invasion and accelerated growth of xenograft tumors possibly targeting the tumor suppressor inositol polyphosphate-4-phosphatase type II B (INPP4B) (Chen et al.2017). Ras suppressor protein 1 ( RSU1), suppressor genes like stromal antigen 2 ( STAG2) and nitrogen permease regulator-like 2 (NPRL2) are tumor suppressors whose functions range from inhibition of oncogenic ras/MAPK to inhibition of aneuploidy. They are involved in different stages of cancer progression; however, they are all downregulated by miR-409-3p/5p. Upregulation of miR-409-3p/5p increased the invasive and migratory capability of ARCaP cells, while downregulation of these miRNAs decreased PCa bone metastases in mice. Direct miRNA delivery into the murine prostate gland induced tumors with higher expression of EMT markers compared to the control (Josson et al.2014). STAG2 and Mothers Against Decantaplegic homolog 7 (SMAD7) are also targeted by miR-154-3p (Gururajan et al.2014). Inhibition of miR-154-3p increased survival and decreased bone metastasis. Furthermore, the same research group worked with miR-379 and demonstrated that its inhibition resulted in increased CDH1 expression and EMT reversion. These three miRNAs are part of the DLK1-DIO3 miRNA mega-cluster that share similar mRNAs targets and are deregulated in many cancer types (Gururajan et al.2014). miR-106b-25 cluster was overexpressed in PCa tumors and metastases compared to normal prostate tissue. Increased expression of this miRNA correlated with disease recurrence. Moreover, a combination of high miR-106b and low caspase 7 (CASP7, a direct target of miR-106b) expressions is an independent predictor of early recurrence. 22Rv1 cells overexpressing miR-106b-25 showed enhanced soft agar growth and high adhesion to bone matrix-related extracellular filaments (Hudson et al.2013). This may be interpreted as the acquisition of anoikis resistance and a phenotype that allows for survival and proliferation in the bone microenvironment. Also, it has been shown that hypoxia increases miR-106b-25 expression, accounting in part for the elevated expression seen on tumor and metastasis (Liang et al.2014). Antimetastatic miRNAs These miRNAs are metastasis suppressor genes. They target and downregulate many genes involved in tumor progression and metastatic spread (Fig. 3). miR-218 overexpression inhibited PC3 and DU 145 cell migration and invasion through downregulation of LIM and SH3 protein 1 (LASP1), a cytoskeletal scaffold protein that plays a crucial role in cytoskeleton organization and cell migration (Nishikawa et al.2014). A similar effect was reported for miR-802 ectopic expression in DU 145 cells through direct downregulation of Flotillin-2 (Flot2). Overexpression of Flot2 canceled the effect of miR-802 and restored DU 145 migratory and invasive capabilities (Wang et al.2017). Recently, several studies showed that miR-195 is a crucial metastasis suppressor miRNA. Thus, in vitrogain- or loss-of-function experiments revealed that miR-195 inhibited proliferation, invasion and migration of PC3, DU 145 and LNCaP cells (Cai et al.2015 a,Liu et al.2015 b,Wu et al.2015). Target genes proposed to be responsible of the metastasis suppressor function of miR-195 are the cell motility regulator Fra-1, MMP-1, MMP9, c-Met (Wu et al.2015), RPS6KB1 (Cai et al.2015 a), BCOX1 and FGF-2 (Liu et al.2015 b). Besides to its capability to reduce tumor growth, murine models demonstrated that miR-195 repressed angiogenesis and invasion related-genes in LNCaP- and DU 145-derived xenografts (Cai et al.2015 a) and reduced metastasis in PC3-derived xenografts (Guo et al.2015). More important, clinical studies determined that miR-195 downregulation positively correlates with metastasis in PCa patients (Cai et al.2015 a) and several features of malignancy, such as high Gleason score (Cai et al.2015 a), poor biochemical recurrence-free time (Cai et al.2015 a,Guo et al.2015) and overall survival (Guo et al.2015). Also miR-195 was significantly diminished in metastatic tissues compared to primary PCa tissues (Guo et al.2015,Liu et al.2015 b). Overexpression of miR-375 on PC3 cells induced epithelial markers, repressed mesenchymal markers and inhibit invasion in vitro(Selth et al.2016). More important, ZEB1 was identified as a transcriptional repressor of miR-375, and in turn, this miRNA target to Yes-associated protein 1 (YAP1), a known oncogene that drives EMT on many cancer models (Selth et al.2016). miR-573 inhibited migration, invasion and spontaneous PCa metastasis to the lung. miR-573 actions could be through direct downregulation of FGFR1. In addition, GATA3 was found to directly increase miR-573, which in turn, downregulates FGFR1 expression leading to the inhibition of invasion and migration (Wang et al.2015 b). Zhu and coworkers reported that TGFBI, a member of the TGFβ signaling pathway that is associated to metastatic spread in many types of cancer, is a direct target of miR-675. Ectopic expression of miR-675 reduced migration and invasion of PCa cells (Zhu et al.2014). Another study reported that miR-940 inhibited cell migration and invasion, anchored-independent growth and increased CDH1 expression. Migration and invasion enhancer 1 (MIEN1) was found to be a direct target of miR-940 and a candidate that explains miR-940 function over migration and invasion (Rajendiran et al.2014). We previously discussed the miRNA mega-cluster DLK1-DIO3 for the pro-metastatic function of some of its members. However, there have been reports that identified other members of this cluster as inhibitors of tumor progression and metastasis, such is the case of miR-377. It was shown that miR-377 inhibited migration and invasion of PC3 cells, in part by direct targeting of FZD4, accompanied by epithelial markers increase (Formosa et al.2014). Re-expression of miR-132, a miRNA hypermethylated in several PCa cell lines, inhibited migration and invasion increasing anoikis in PC3 cells. Formosa and coworkers explained these effects, probably due to the direct target of miR-132, Talin 2 (TLN2), a protein that connects integrins to the actin cytoskeleton (Formosa et al.2013). miR-23a inhibited migration and invasion in a panel of PCa cell lines, and in an orthoropic PCa model. miR-23a targeted serine/threonine-protein kinase (PAK6), downregulation of which resulted in the inhibition of LIM domain kinase 1 (LIMK1) phosphorylation leading to cytoskeleton remodeling and ultimately inhibition of invasion and migration (Cai et al.2015 b). The experimental metastasis in vivomodel can be used to analyze anoikis resistance, homing to a particular organ and colonization of that organ. One study shown that PC3 cells transfected with miR-130b were unable to form metastasis on nudemice after left ventricle injection. This was attributed to miR-130b direct downregulation of MMP2. Silencing of miR-130b led to increased invasion and migration and further MMP2 knockdown antagonized the effect of miR-130b silencing (Chen et al.2015 a). Ectopic expression of miR-29b on PC3 cells impaired metastasis formation in SCID mice, increased CDH1 expression and decrease CDH2, TWIST and SNAIL expressions (Ru et al.2012). The miR-200 family is regarded as a cornerstone of MET-induced miRNAs. Recently, more evidence has been added to support this claim. PC3 cells overexpressing miR-200b injected orthotopically in mice showed reduced angiogenesis and number of metastases due to EMT reversion, evidenced by CDH1 and specific markers of prostate epithelium induction while mesenchymal markers were downregulated (Williams et al.2013). Another member of the miR-200s family, miR-141, was revealed to be a strong epithelial phenotype inducer by upregulation of CDH1, cytokeratins and many other epithelial markers, but caused partial loss of EMT, evidenced by downregulation of merely ZEB1 and VIM (Liu et al.2017). Induction of an epithelial phenotype by ectopic expression of miR-200c and miR-205 in PCa cell lines resistant to chemotherapy resulted in EpCAM re-expression (Massoner et al.2014). However, the role of this adhesion molecule in PCa is controversial. EpCAM has been associated to proliferative oncogenic pathways and poor patient overall survival (van der Gun et al.2010). It was reviewed by several authors that together with the miR-200s family, miR-205 is a major EMT repressor that favor MET (Fenderico et al.2013,Sekhon et al.2016). A novel role of miR-205 in base membrane deposition and cell-ECM interaction was reported (Gandellini et al.2012). miR-205 expression inhibition in RWPE-1 cells was enough to reduce laminin-332 secretion and integrin β4 expression. Thus, loss of miR-205 as PCa progresses may favor metastatic spread by creating discontinuities in the basal membrane (Gandellini et al.2012). Finally, another study reported that miR-205 is directly repressed by HIF-1α upon cancer-associated fibroblast (CAF) stimulation of PCa cells (Gandellini et al.2014). miRNAs associated to PCa bone metastasis The bone is a common metastatic site for advanced PCa. Bone lesions following metastatic colonization can aberrantly modify osteoblast and osteoclast proliferation and differentiation causing bone density alterations, pain and, in some cases, render patients bedridden, which greatly lower their quality of life. Advanced PCa is incurable after bone colonization, been responsible for the majority of PCa morbidity and mortality (Weilbaecher et al.2011). miRNAs were also associated to bone metastasis (Fig. 3). Activation of the EGFR signaling pathways tends to lead to PCa bone metastases. miR-1 was shown to have metastasis suppressor functions in PCa. Chang and coworkers demonstrated a role for EGFR translocation in regulating transcription of miR-1, which directly targets expression of TWIST1. The authors observed decreased miR-1 levels that correlated with enhanced expression of activated EGFR and TWIST1 in a cohort of human PCa specimens. Moreover, EGFR activation caused miR-1 downregulation, TWIST1 induction and subsequent bone metastasis in a mice model (Chang et al.2015). Inhibition of the EGFR pathway seems to be the obvious therapeutic option. Sadly, therapies against EGFR with tyrosine kinase inhibitors (TKI) have had limited success and led to development of drug resistance. As a study demonstrated, miR-203 downregulation is associated to EGFR activation and TKI resistance. Ectopic expression of miR-203 on the highly metastatic cell line RasB1 (KRAS constitutive overexpression) produced a reduction of bone metastasis and TKI resistance. This is due to miR-203 targets EGFR ligands (AREG, EREG and TGFA) and antiapoptotic proteins (AIP5, BIRC2 and TRIAP1) (Siu et al.2014). RUNX2 is a transcription factor essential for osteogenesis that is associated to bone metastasis. It has been reported that miR-466 directly targeted RUNX2, which induced downregulation of RUNX-target genes involved in migration, invasion, EMT and metastasis. Overexpression of miR-466 in PC3 orthotopic xenografts greatly reduced the number of spontaneous bone metastases and improved mice overall survival (Colden et al.2017). A recent study showed that miR-21 upregulation and loss of miR-15/miR-16 cluster can cooperate to promote bone homing, colonization and damage via TGFβ signaling (Bonci et al.2015). Vascular cell adhesion protein 1 (VCAM-1) is a cell to vascular endothelium adhesion molecule that exhibits aberrant expression in different type of cancers, and it is involved in bone homing and protection from apoptosis. A study suggested that osteoblast-derived Wnt-1-induced secreted protein 1 (WISP-1) promotes migration and VCAM-1 expression by downregulation of miR-126 expression through α5β6 integrin, p38 and FAK signaling (Tai et al.2014). Circulating miRNAs in body fluids Circulating miRNAs represent the miRNA population in cell-free portion of body fluids, which attracted tremendous interest in the field of biomarker discovery. Features such as high stability, access by minimally invasive methods and possibility of repeated sampling make them ideal candidates for use as biomarkers (Kosaka et al.2010). Currently, the stratification of PCa patients is guided by the PSA kinetics, clinical stage and tumor grade (Gleason score). Although these parameters are still clinically useful, they have limitations in detecting cases, predicting disease outcomes and guiding clinical management decisions. The most important clinical challenge for the miRNA use is to distinguish men who have a potentially lethal form of PCa from those with an indolent disease. In addition, metastasis is another parameter that might be predicted by circulating miRNAs. Hundreds of reports showing the valuable use of circulating miRNAs are in the literature. Here, we present a table resuming the major studies that identified circulating miRNAs in body fluids from PCa patients (Table 1). Table 1 Circulating miRNAs from body fluids with potential prognostic value. Ref# miRNA up or down relative to control Sample Number of cases Extraction method Detection method Remarks ( Kachakova et al. 2015 ) let-7e Downlet-7c DownmiR-30c DownmiR-622 UpmiR-1284 Up Plasma 158:54 Healthy44 BPH80 PCa Trizol LS (Invitrogen) qPCRmiScript Reverse Transcription kit (Qiagen) Cancer diagnosisAUC = let-7c, 0.775; let-7e, 0.804; miR-30c, 0.818; miR-622, 0.791; miR-285, 0.644Discriminate between PCa and BPHAUC = let-7c, 0.784; let-7e, 0.805; miR-30c, 0.759; miR-622, 0.755; miR-1285, 0.644 ( Cheng et al. 2013 ) miR-141 UpmiR-200a UpmiR-200c UpmiR-210 UpmiR-375 Up Serum 50:25 Healthy25 PCa16:8 Healthy8 mCRPC mirVana PARIS kit (Ambion)miRNeasy RNA isolation kit (Qiagen) qPCRTaqMan miRNA Assay (Applied Biosystems)Three synthetic C. elegans miRNAs Discrimination between healthy and PCa:miR-141 AUC = 0.899; miR-200aAUC = 0.699; miR-375 AUC = 0.773; miR-200c AUC = 0.721 and miR-210 AUC = 0.678miR-210 correlated with treatment response as assessed by change in PSA in a cohort of mCRPC patients ( Alhasan et al. 2016 ) miR-200c UpmiR-605 UpmiR-135a* UpmiR-433 UpmiR-106a Up Commercial serum 28:10 Healthy9 VHR PCa9 LR PCa mirVana miRNA isolation kit (Ambion) qPCRTaqMan miRNA Assay (Applied Biosystems) Discrimination between VHR PCa and control group (healthy + LR PCa):miR-200c AUC = 1.0miR-433 AUC = 0.98miR-135a* AUC = 0.98miR-605 AUC = 0.92miR-106a AUC = 0.89 ( Westermann et al. 2014 ) miR-26a-1 NAmiR-141 Up Serum 133:79 BPH54 PCa Ambion mirVana Paris Kit, Life Technologies qPCRmiScript SYBR Green PCR Kit (Qiagen) Both microRNAs failed as diagnostic biomarker. AUC = 0.519 for miR-26a-1 and 0.49 for miR-141However miR-141 levels were significantly increased in patients with a higher Gleason score ( P = 0.049) ( Haldrup et al. 2014 ) Panel 1: miR-562, miR-210, miR-501-3p, miR-375, miR-551bPanel 2: let-7a*, miR-210/miR-562, miR-616Panel 3: miR-375, miR-708, miR-1203, miR-200a Serum 44:13 BPH11 LPC9 N1/M111 CRPC QIAzol / miRNeasy (Qiagen) qPCRmicroRNA Ready-to-Use PCR (Exiqon) Panel 1 was able to identify 84% of all PCa patients; Panel 2 was able to identify 80% of patients with disseminated PCa when compared to BPH patients; Panel 3 was able to identify 75% of disseminated PCa patients when compared to localized PCa patients. All 3 panels showed 100% specificity ( Mihelich et al. 2015 ) miR-24miR-106amiR-451miR-107miR-93miR-103let-7amiR-30cmiR-26bmiR-100miR-130bmiR-874miR-223miR-146a Serum 150:50 BPH100 PCa miRNeasy (Qiagen) qPCRExiqon SYBR green and custom Pick&MixmiRNA PCR plates miRNA Score able to identify serum miRNAs that could pre-surgically classify patients with low risk or harboring aggressive cancer or BCR(AUC = 0.668) ( Huang et al. 2015 ) miR-1290 UpmiR-375 Up Plasma 100:CRPC after ADT failure miRNeasy Micro Kit (Qiagen) qPCRTaqMan MicroRNA Assays (Life Technologies) Incorporation of miR 1290/-375 into putative clinical prognostic factors-based models in CRPC stage significantly improved predictive performance with a time dependent AUC increase from 0.66 to 0.73 ( P = 6.57 × 10 −6 ) ( Watahiki et al. 2013 ) miR-141miR-375miR-151-3p UpmiR-126 UpmiR-16 DownmiR-205 Down Plasma 50:25 LPC25 mCRPC Trizol LS (Invitrogen)/miRNeasy mini kit (Qiagen) qPCRmicroRNA qPCR panel (Exiqon) A combination of miR-141, miR-151-3p and miR-16 yielded an AUC of 0.944, slightly below that for PSA (0.964). PSA test and miR-141/151-3p/16 test increased PSA sensitivity by 8% ( Wang et al. 2016 ) miR-410-5p Serum 32757 Healthy81 BPH149 PCa40 other urinary diseases Trizol LS isolation kit (Thermo Fisher) qPCRmiScript SYBR Green PCR Kit (Qiagen) Discrimination between PCa and Healthy control or other urinary diseases.AUC = 0.8097 ( Chen et al. 2016 ) miR-21miR-152 Plasma 190:74 Healthy51 BPH65 PCa miRNeasy Mini kit(Qiagen) qPCRTaqman miRNAassay kits (Applied Biosystems) No significant differences in expression between PCa patients and healthy controls ( Li et al. 2016 ) miR-141 Up Serum (Exosomes) 9140 Healthy31 PCa20 metastatic PCa miRNeasy Serum/Plasma kit (Qiagen) qPCRPrimeScript RT Reagent kit and SYBR Premix Ex Taq kit, Takara Bio Inc Discriminating metastatic PCa from LPC (AUC = 0.8694). Better than PSA (AUC = 0.7758) ( Srivastava et al. 2013 ) miR-205 DownmiR-214 Down Urine 48:12 Healthy36 PCa mirVana miRNA isolation kit (Ambion) qPCRTaqMan miRNA Assays, AppliedBiosytems Discriminates PCa patients from normal control (AUC = 0.7083 for miR-205 and AUC = 0.7431 for miR-214). Additionally miR-205 and miR-214 can tougher discriminate PCa patients from healthy individuals with 89% sensitivity and 80% specificity ( Stuopelyte et al. 2016 ) miR-148a UpmiR-375 Up Urine 300:62 ASC23 BPH215 PCa (143 cohort 1, 72 cohort 2) miRNeasy Mini Kit (Qiagen) TaqMan Human MiRNA Assays (Applied Biosystems) Combined analysis of miR-148a and miR-375 was highly sensitive and specific for PCa in both cohorts (AUC = 0.79 and 0.84) and improved the diagnostic power of the PSA test (AUC = 0.85, cohort 1), including the 4-10 ng/ml zone (AUC = 0.90) ( Lewis et al. 2014 ) miR-888 Up EPS urine (after DRE) 56:24 Healthy32 PCa miRNeasy Mini Kit (Qiagen) qPCRTaqMan miRNA assays (Applied Biosystems) miR-888 levels were preferentially elevated in PCa patients with high-grade disease ( Casanova-Salas et al. 2014 ) miR-182miR-187 Urine (after DRE) 92:47 negative biopsy45 Positive biopsy mirVana miRNA Isolation Kit qPCRTaqMan miRNA assays (Applied Biosystems) Combination of miR-187, PCA3 and PSA for the prediction of positive biopsy or diagnosis (AUC = 0.711) better than PSA only (AUC = 0.615) ( Egidi et al. 2013) miR-9-3p DownmiR-19a-3p Up Urine (after DRE) 79:38 BPH41 LPC Total RNA Extraction Kit (Norgen Biotek Corp) qPCRmercury LNA Universal RT microRNA PCR SYBR Green master mix (Exiqon) Combination of KLK3 (gene that encodes PSA) mRNA and miR-19a-3p for the diagnosis of PCa or positive biopsy (AUC = 0.880) ADT, Androgen deprivation therapy; AUC, Area under receiver-operator characteristic curve; BCR, Biochemical recurrence; BPH, Benign prostate hyperplasia; DRE, Digital rectal examination; EPS, Expressed prostatic secretion; HR, High risk; IR, Intermediate risk; LPC, Localize prostate cancer; LR, Low risk; mCRPC, Metastatic castration-resistant prostate cancer; VHR, Very high risk; ASC, asymptomatic control. PCa therapy using miRNAs As prostate tumors develop and progress in an androgen-sensitive form, ADT is used as the first treatment either as monotherapy or in combination with other regimens. However, in most of the patients, the disease progresses to CRPC suffering metastases. The available therapeutic approach for the treatment of CRPC is conventional chemotherapy with a survival time lower than 19 months and unpleasant side effects. Here is when the development of new therapeutic approaches such as targeted therapies emerges as an urgent necessity. Therapeutic strategies based on miRNAs modulation come out as promising approach for treatment of heterogeneous disease such as cancer (Chen et al.2015 b). Given that miRNAs constitute natural oligonucleotides, usually show less immune response and toxicity than other gene therapy approaches (Chen et al.2015 b). miRNA therapeutic strategies could be divided into two main groups: (i) miRNA replacement therapy that involves restoration of miRNAs lost in cancer and (ii) OncomiRs inhibition (Chen et al.2015 b). However, one of the main challenges for the use of miRNA-based therapy is the optimization of a proper miRNA delivery system to avoid blood clearance and to optimize their bioavailability in the target tissue and the capability of trapping miRNA in intracellular space (Chen et al.2015 b). Several miRNA modifications and conjugates were developed to overcome this problem. For local delivery, cholesterol-conjugate, d2’-Omethyl-modified, lentiviral vectors and polyethyleneimine (PEI) were tested (Chen et al.2015 b). In the case of systemic delivery, some of the miRNA formulations tested were seed-targeting tiny LNAs, cationic liposomes, lentiviral vectors, adeno-associated viruses, silica nanoparticles, PEGylated-PLGA, PLGA-penetratin, PEI, LNP-DP1, cationic DOTMA lipoplexes, neutral lipid and LPH-PEG-GC4 (Chen et al.2015 b). For proper delivery of miRNA-based therapy as treatment for PCa, strategies for specific delivery to target tissue should be considered, in regards of primary tumor and metastatic sites. The design of a delivery system to target miRNAs to the bone is even more challenging compared to lung or liver (Chalanqui et al.2016). In the cases where bone metastases are accessible, local administration is a suitable method. However, this approach is faulty as is not a possibility for undetectable micrometastases (Chalanqui et al.2016). Mercatelli and coworkers showed that intratumor delivery of anti-miR-221/222 significantly reduced tumor growth for as long as 25 days (Mercatelli et al.2008). However, intratumor administration might not be possible for PCa treatment. Nadiminty and coworkers demonstrated that intratumor injection with let-7c-containing lentiviruses reduced tumor size in AR-positive androgen-insensitive PCa xenograft models (C4-2B and PC346C cells) (Nadiminty et al.2012 b). Another successful study investigated miR-328 effect in tumor growth after local injection of miR-328 mimics into PC3-derived xenografts. It demonstrated an inhibition of tumor growth after treatment (Liu et al.2015 c). Several efforts were carried out to introduce miR-34a in targeted therapy for PCa, given its broad tumor suppressor activity in cancer that made possible the development of a liposome-formulated miR-34a mimic (MRX34) and is currently the first phase I clinical trial using miRNA-based therapy for treatment of liver cancer and liver metastasis patients (Bouchie 2013). Liu and coworkers tested the efficacy of miR-34a assembled with the lipid-based delivery agent NLE for systemic treatment of PCa. They demonstrated that intravenous injection with miR-34a reduced tumor growth of PC3- and LAPC9-derived xenografts (Bader 2012). Moreover, miR-34a administration prolonged survival of LAPC9 xenograft mice likely due to diminished metastases to the lung and other tissues (Bader 2012). Zhang and coworkers overcome the concern about specific delivery of miRNAs to PCa cells by developing an efficient in vivodelivery using miR-145 complexed with the polyarginine peptide (R11)-labeled non-toxic SSPEI. This nanocarrier showed less toxicity in PCa and optimal transfection efficacy into PCa cells (Zhang et al.2015). Systemic administration of this compound reduced tumor growth and prolonged survival time in a peritoneal PC3-derived tumor model (Zhang et al.2015). Finally, Takeshita and coworkers showed that in a model of bone metastases by intracardiac inoculation of PC3 cells, systemic delivery of synthetic miR-16 using atelocollagen-based nonviral vector caused growth retardation of bone metastases (Takeshita et al.2010). Conclusions This review summarizes the information published about miRNAs in PCa. miRNAs are promising molecules that might be useful for patient diagnosis, management and therapy. Despite all the information about each miRNA, still we are in the biomarker discovery stage. We recapitulated all the miRNAs involved in AR signaling pathways (Fig. 1), proliferation and cell cycle (Fig. 2), apoptosis, metastasis (Fig. 3) and circulating miRNAs in body fluids (Table 1). As expected by their ability to modulate complete molecular pathways, most of the miRNAs are implicated in two or more processes, such as miR-205 (metastasis, apoptosis and AR signaling), miR-125b (p53 and AR), miR-21 (AR signaling, bone metastasis), miR-221/222 (AR signaling, cell cycle). Few studies present one particular miRNA unequivocally as biomarker. This is because most of the studies were carried out in a limited number of patients. In addition, the inconsistency of data has to be overcome before diagnostic, prognostic and predictive miRNAs are translated to the patients. Although miRNAs are inherently stable molecules, optimization and standardization of miRNA detection methods are required to obtain high-quality and reproducible results. Currently, the imperative challenge is the selection of the appropriate miRNA for clinical applications. Larger screening studies to select the proper miRNA are urgently needed. Finally, there are few studies that define the value of miRNAs in the management of PCa. In summary, hundreds of publications come up every year about miRNAs in PCa, future challenge will be to validate them for clinical use. Declaration of interests The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review. Funding This research was supported by the Argentinean Agency of Science and Technology (ANPCyT PICT 2014-324; ANPCyT PICT 2013-2151; ANPCyT PICT 2015-1345). The authors thank the Fundación Williams (Argentina) and Fundación Rene Barón (Argentina) for their support. References Alhasan AH , Scott AW , Wu JJ , Feng G , Meeks JJ , Thaxton CS & Mirkin CA 2016 Circulating microRNA signature for the diagnosis of very high-risk prostate cancer . PNAS 113 10655 – 10660 . (doi:10.1073/pnas.1611596113 ) Crossref Alhasan AH Scott AW Wu JJ Circulating microRNA signature for the diagnosis of very high-risk prostate cancer Aqeilan RI , Calin GA & Croce CM 2010 miR-15a and miR-16-1 in cancer: discovery, function and future perspectives . Cell Death and Differentiation 17 215 – 220 . (doi:10.1038/cdd.2009.69 ) Bader AG 2012 miR-34 - a microRNA replacement therapy is headed to the clinic . Frontiers in Genetics 3 120 . (doi:10.3389/fgene.2012.00120 ) Bhatnagar N , Li X , Padi SKR , Zhang Q , Tang M-S & Guo B 2010 Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells . Cell Death and Disease 1 e105 . (doi:10.1038/cddis.2010.85 ) Boll K , Reiche K , Kasack K , Mörbt N , Kretzschmara K , Tomm JM , Verhaegh G , Schalken J , von Bergen M & Horn F et al. 2013 MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma . Oncogene 32 277 – 285 . (doi:10.1038/onc.2012.55 ) Bonci D , Coppola V , Patrizii M , Addario A , Cannistraci A , Francescangeli F , Pecci R , Muto G , Collura D & Bedini R et al. 2015 A microRNA code for prostate cancer metastasis . Oncogene 35 1 – 13 . (doi:10.1038/onc.2015.176 ) Bouchie A 2013 First microRNA mimic enters clinic . Nature Biotechnology 31 577 – 577 . (doi:10.1038/nbbib713-577 ) Cai C , Chen QB , Han ZD , Zhang YQ , He HC , Chen JH , Chen YR , Yang SB , Wu YD & Zeng YR et al. 2015a miR-195 inhibits tumor progression by targeting RPS6KB1 in human prostate cancer . Clinical Cancer Research 21 4922 – 4934 . (doi:10.1158/1078-0432.CCR-15-0217 ) Cai S , Chen R , Li X , Cai Y , Ye Z , Li S , Li J , Huang H , Peng S & Wang J et al. 2015b Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway . Oncotarget 6 3904 – 3917 . (doi:10.18632/oncotarget.2880 ) Cary KC & Cooperberg MR 2013 Biomarkers in prostate cancer surveillance and screening: past, present, and future . Therapeutic Advances in Urology 5 318 – 329 . (doi:10.1177/1756287213495915 ) Casanova-Salas I , Rubio-Briones J , Calatrava A , Mancarella C , Masiá E , Casanova J , Fernández-Serra A , Rubio L , Ramírez-Backhaus M & Armiñán A et al. 2014 Identification of miR-187 and miR-182 as biomarkers of early diagnosis and prognosis in patients with prostate cancer treated with radical prostatectomy . Journal of Urology 192 252 – 259 . (doi:10.1016/j.juro.2014.01.107 ) Chalanqui MJ , O’Doherty M , Dunne NJ & McCarthy HO 2016 MiRNA 34a: a therapeutic target for castration-resistant prostate cancer . Expert Opinion on Therapeutic Targets 20 1075 – 1085 . (doi:10.1517/14728222.2016.1162294 ) Chang YS , Chen WY , Yin JJ , Sheppard-Tillman H , Huang J & Liu YN 2015 EGF receptor promotes prostate cancer bone metastasis by downregulating miR-1 and activating TWIST1 . Cancer Research 75 3077 – 3086 . (doi:10.1158/0008-5472.CAN-14-3380 ) Cheng HH , Mitchell PS , Kroh EM , Dowell AE , Chéry L , Siddiqui J , Nelson PS , Vessella RL , Knudsen BS & Chinnaiyan AM et al. 2013 Circulating microRNA profiling identifies a subset of metastatic prostate cancer patients with evidence of cancer-associated hypoxia. PLoS ONE 8 e69239 . (doi:10.1371/journal.pone.0069239 ) Chen Q , Zhao X , Zhang H , Yuan H , Zhu M , Sun Q , Lai X , Wang Y , Huang J & Yan J et al. 2015a MiR-130b suppresses prostate cancer metastasis through down-regulation of MMP2 . Molecular Carcinogenesis 54 1292 – 1300 . (doi:10.1002/mc.22204 ) Chen Y , Gao D-Y & Huang L 2015b In vivo delivery of miRNAs for cancer therapy: challenges and strategies . Advanced Drug Delivery Reviews 81 128 – 141 . (doi:10.1016/j.addr.2014.05.009 ) Chen H , Liu H , Zou H , Chen R , Dou Y , Sheng S , Dai S , Ai J , Melson J & Kittles RA et al. 2016 Evaluation of plasma miR-21 and miR-152 as diagnostic biomarkers for common types of human cancers . Journal of Cancer 7 490 – 499 . (doi:10.7150/jca.12351 ) Chen H , Luo Q & Li H 2017 MicroRNA-590-3p promotes cell proliferation and invasion by targeting inositol polyphosphate 4-phosphatase type II in human prostate cancer cells . Tumor Biology 39 (doi:101042831769594 )
https://rep.bioscientifica.com/view/journals/rep/154/4/REP-17-0322.xml
Vacuum-plasma multilayer protective coatings for turbine blades 9789916951651, 9789916951644 - EBIN.PUB ... Vacuum-plasma multilayer protective coatings for turbine blades 9789916951651, 9789916951644 253 103 12MB English Pages [104] Year 2021 Report DMCA / Copyright Table of contents : Title Page Copyright Page Authors Abstract Contents List of Tables List of Figures Preface Circle of readers and Scope of Application 1 Introduction 2 Experimental equipment. Avinit vacuum plasma cluster 2.1 Avinit C unit (vacuum-arc coating methods) 2.2 Avinit V unit (gas phase deposition methods (CVD and PECVD)) [16] 2.3 Avinit M unit for coating by magnetron sputtering 2.4 Avinit E unit (ionic treatment (cleaning) of the surface before coating) 2.5 Avinit N unit (ion-plasma surface modification) [17] 2.6 Power supplies of the Avinit installation 2.7 Measurement of plasma source parameters of the Avinit cluster 3 Experimental studies of Avinit coating processes 3.1 The study of the structure and tribological properties of Avinit coatings 3.1.1 Method of coating 3.1.2 Methods of studying the properties of experimental samples 3.1.3 Methods of research of friction and wear characteristics 3.2 Properties of functional multilayer Avinit coatings 3.2.1 Avinit С 100 coatings (based on titanium nitrides) 3.2.2 Avinit C 200 coating (based on molybdenum nitrides) 3.2.3 Avinit C 700 coating (based on chromium nitrides) 3.2.4 Avinit C 300 coating (based on Ti-Al-N) 3.3 Research of friction and wear characteristics of coatings 3.4 Plasma chemical heat treatment Avinit N 3.4.1. Plasma precision nitriding Avinit N 3.4.2 Contact fatigue strength 3.4.3 Development of duplex technologies Avinit 4 Development of industrial research technologies for Avinit coatings 4.1 The choice of coatings to improve the reliability of thermal equipment of turbines 4.2 Coatings to increase the service life of steam distribution and steam control mechanisms of turb 4.3 Avinit duplex technologies 4.4 Vacuum-plasma multilayer protective coatings for turbines blades 5 Implementation of Avinit technologies into serial production References Abbreviation Author / Uploaded Alex Sagalovych Vlad Sagalovych Viktor Popov Stas Dudnik Citation preview Alex Sagalovych, Vlad Sagalovych, Viktor Popov, Stas Dudnik Hi-tech technologies based on advanced fundamental researchVacuum-plasma multilayer protective coatings for turbine blades Monograph Edited by Doctor of Technical Sciences, Professor Vlad Sagalovych March, 2021Tallinn EstoniaPublished in 2021 by «Scientific Route» OÜ Narva mnt 7-634, Tallin, Harju maakond, Estonia, 10117 ©  A. Sagalovych, V. Sagalovych, V. Popov, S. Dudnik. 2021 All rights reserved. No part of this book may be reprinted or reproduced or utilised in any form or by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying and recording, or in  any information storage or retrieval system, without permission in writing from the authors. This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. National Library of Estonia Cataloging-in-Publication Data. A catalog record for this book is available from the National Library of Estonia. DOI: 10.21303/978-9916-9516-5-1 ISBN 978-9916-9516-4-4 (Hardback) ISBN 978-9916-9516-5-1 (eBook) ISBN 978-9916-9516-5-19 789916 951651Authors Alex Sagalovych Head of Special Technologies Board. Academician of AТS Ukraine. Leading specialist of Ukraine in the field of physics and chemistry of coatings, the latest technologies for applying functional coatings using the latest physical ion-plasma processes and technologies. The memder of ASM, TMS, SVC, HTS (USA).Vlad Sagalovych Chief Technical Officer. Doctor of Technical Sciences, Professor. Academician of AТS Ukraine. Well-known scientist in the field of coating physics and chemistry, nonequilibrium plasma chemistry. The memder of EFDS (Germany). Honored Worker of Science and Technology of Ukraine.Viktor Popov Chairman of the Management Board. PhD. Academician of AТS Ukraine. Laureate of the State Prize of Ukraine in the field of science and technology. Honored Mechanical Engineer of Ukraine.Stas Dudnik Head of Department. PhD. Well-known scientist in the field of physics and technology of modern vacuum-plasma coatings.Sumskaya str. 132, 61023 Kharkiv, Ukraine Tel.: +380 57 700 50 41. Fax: +380 57 715 64 76 Website: www.fed.com.ua E-mail:[email protected] The methods of creating the advanced nanomaterials and nanotechnologies of functional multicomponent coatings Avinit (mono- and multilayer, nanostructured, gradient) to improve the performance of materials, components and parts are considered. The vacuum-plasma nanotechnologies Avinit were developed based on the use of gas-phase and plasma-chemical processes of atomic-ionic surface modification and the formation of nanolayer coatings in the environment of non-steady low-temperature plasma. Considerable attention is paid to the equipment for application of functional multilayer composite coatings: an experimental-technological vacuum-plasma automated cluster Avinit, which allows to implement complex methods of coating, combined in one technological cycle. The information about the structure and service characteristics of Avinit coatings has a large place. The results of metallographic, metallophysical, tribological investigations of properties of the created coatings and linking of their characteristics with parameters of sedimentation process are described. The possibilities of parameters processes regulation for the purpose of reception of functional materials with the set physicochemical, mechanical complex and other properties are considered. The investigation of creating of multilayer protective surface coatings Аvinit based on Ti-TiN for turbine blades by vacuum-arc method was carried out. The influence of different methods and modes of vacuum-plasma treatment of coated surface of substrates to the adhesion value of nanolayer protective TiTiN coatings is studied. On the basis of carried out investigations the technology of coating the steam turbines blades for protection against flow-accelerated corrosions is developed. The issues of development and industrial implementation of the latest technologies for applying wear-resistant antifriction coatings Avinit with the use of nanotechnology to increase the life of various critical elements of steam and nuclear turbines are covered in detail. The book is aimed at specialists working in the field of ion-plasma surface modification of materials and functional coatings application.Keywords Vacuum plasma multilayer protective coatings Avinit, titanium, titanium nitride, turbine blades, development of nanotechnologies Avinit.Contents List of Tables..................................................................................................... vii List of Figures................................................................................................... viii Preface................................................................................................................. xi Circle of readers and Scope of Application................................................... xii 1 Introducion....................................................................................................... 1 2 Experimental equipment. Avinit vacuum plasma cluster.......................... 5 2.1 Avinit C unit (vacuum-arc coating methods)................................... 8 2.2 Avinit V unit (gas phase deposition methods (CVD and PECVD)) [16]..................................................................... 8 2.3 Avinit M unit for coating by magnetron sputtering......................... 9 2.4 Avinit E unit (ionic treatment (cleaning) of the surface before coating)............................................................................................... 10 2.5 Avinit N unit (ion-plasma surface modification) [17].................... 12 2.6 Power supplies of the Avinit installation......................................... 12 2.7 Measurement of plasma source parameters of the Avinit cluster................................................................................................. 14 3 Experimental studies of Avinit coating processes.................................... 16 3.1 The study of the structure and tribological properties of Avinit coatings.............................................................................................. 16 3.1.1 Method of coating.................................................................. 16 3.1.2 Methods of studying the properties of experimental samples.................................................................................... 17 3.1.3 Methods of research of friction and wear characteristics... 18 3.2 Properties of functional multilayer Avinit coatings....................... 18 3.2.1 Avinit С 100 coatings (based on titanium nitrides)............. 19 3.2.2 Avinit C 200 coating (based on molybdenum nitrides)...... 25 3.2.3 Avinit C 700 coating (based on chromium nitrides)............ 29 3.2.4 Avinit C 300 coating (based on Ti-Al-N).............................. 29 3.3 Research of friction and wear characteristics of coatings............. 38 3.4 Plasma chemical heat treatment Avinit N....................................... 41 3.4.1 Plasma precision nitriding Avinit N...................................... 44 3.4.2 Contact fatigue strength........................................................ 56 3.4.3 Development of duplex technologies Avinit....................... 58 vVacuum-plasma multilayer protective coatings for turbine blades4 Development of industrial research technologies for Avinit coatings... 65 4.1 The choice of coatings to improve the reliability of thermal equipment of turbines....................................................................... 65 4.2 Coatings to increase the service life of steam distribution and steam control mechanisms of turbines............................................ 65 4.3 Avinit duplex technologies............................................................... 69 4.4 Vacuum-plasma multilayer protective coatings for turbines blades...............................................................................................71 5 Implementation of Avinit technologies into serial production............... 80 References.......................................................................................................... 85 Abbreviation...................................................................................................... 91viList of Tables 2.1 Vacuum-plasma methods of coating and surface modification implemented in the vacuum-plasma cluster Avinit 2.2 The results of measuring the parameters of plasma sources 3.1 Growth rate of coatings with various composition 3.2 Characteristics of the samples 3.3 The growth rate of MoN coatings of different composition 3.4 Characteristics of the samples 3.5 The growth rate of different composition coatings 3.6 Characteristics of the samples 3.7 The parameters of Avinit coatings 3.8 The results of hardness measurements 3.9 The results of measurements of the hardness of the nitrided layer 3.10 Generalized parameters for the implementation of the of plasma precision nitriding Avinit N method 3.11 Comparative characteristics of traditional nitriding and Avinit N plasma precision nitriding processes 3.12 The average results of tribotechnical parameters in accelerated tests 3.13 The hardness of the nitrided layer 3.14 Characteristics of the nitrided layer and the thickness of the coating Avinit 4.1 Characteristics of the studied samples with multilayer coatings 4.2 Experiments for the choice of multilayer protective coating design 4.3 Experiments to study the effect of different stages of surface pre-treatment on adhesion and coating quality 4.4 Experiments to select parameters of stabilizing annealing 4.5 Characteristics of coatings on witness specimens located in different blade areas 5.1 Avinit multilayer antifriction wear-resistant coatingsvii8 15 22 23 26 27 31 32 38 49 49 54 54 56 61 63 66 72 76 77 78 81List of Figures 2.1 2.2 3.13.2 3.3 3.43.5 3.6 3.7 3.8 3.9 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17Avinit vacuum-plasma automated cluster Location of the Langmuir probe in the vacuum chamber of the Avinit installation: a – cross-sectional side view; b – a top view The fragment of the automated control system’s protocol of the Ti-TiN nanocoating deposition technological process with the recurrence interval of 10 nm and single nanolayers’ thickness of 2 and 8 nm TiN coating (×200): а – without separator; b – with a rectilinear separator Profilogram of the nanocomposite Ti-TiN coating Protocols of the automated control system are the process of obtaining Mo-MoN coatings with a repeatability period of 20 nm and equal thickness of individual nanolayers Profilogram of the nanocomposite Ti-TiN coating A fragment of the protocol of the automated control system of the technological process of nanocoating TiN-AlN: a– TiN-AlN (50/50) nanocoating with a recurrence period of 20 nm and the similar thickness of individual nanolayers; b– TiN-AlN nanocoating (30/70) with a recurrence period of 12 nm and a thickness of individual nanolayers of 4 and 8 nm Distribution of characteristic X-ray radiation of element atoms in Avinit C 320 coating: a – at. % Ti; b – at. % Al Appearance of a covering of Avinit C/P 310 (cross section) in the mode of mapping of a site of a coating Appearance of Avinit C/P 310-n1 coating in line analysis mode Load diagram for measuring nanohardness and Young's modulus of Avinit C 320 сoating Dependences of secondary Al+, Ti+ ions currents on sputtering time: a – Avinit C 320 coating; b – Avinit C 310 coating Friction factors Generalized tribological test results Volt-ampere characteristic of a double arc discharge probe Spectral parameters of plasma Depth of nitrided layer on 34NiCrMoV14-5 steel (×500) The microstructure of the nitrided layer on 34NiCrMoV14-5 steel (×500) viii6 1423 24 2527 2831 34 35 35 36 37 38 39 46 46 47 47List of Figures3.18 Appearance of the sample for plasma precision nitriding Avinit N steel DIN 1.8509 48 3.19 Impressions of microhardness measurements: a – not etched section; b – etched section 48 3.20 Nitriding of steel DIN 1.773 49 3.21 Depth of nitrided layer 50 3.22 Microstructure in the zone of the nitrided layer 50 3.23 The nitrided layer depth 51 3.24 Imprints of microhardness measurements (unetched polished section) 51 3.25 Imprints of microhardness measurements (etched polished) 51 3.26 Prototype of the titanium alloy DIN 3.7165 52 3.27 The microstructure of the sample. Side No. 1 (×200) 52 3.28 The microstructure of the sample. Side No. 2 (×500) 52 3.29 The magnitudes of change in the hardness of the nitrided layer 52 3.30 The magnitudes of change in the hardness of the nitrided layer 52 3.31 Appearance of micro-hardness measurements imprints. Side No.1 53 3.32 Appearance of micro-hardness measurements imprints. Side No.2 53 3.33 Housing from DIN 3.7165 titanium alloy. The structure of the nitrided layer on the inner cylindrical part of the housing surface 53 3.34 Slide valve. Structure of nitrided layers on slide valve surface 53 3.35 Coatings Avinit C 350 based on (Ti-Al-N) and Avinit D 100 based on Ti-C 59 3.36 Details of serial aviation hydraulic units with Avinit nanocoatings 59 3.37 Spools of hydraulic units with Avinit nanocoatings 60 3.38 Appearance of Avinit coating in line analysis mode. The coating thickness is 1.5 μm. The microhardness of the coating was 2500...3000 HV 61 3.39 Full-size high-precision gear, made using duplex technology Avinit. Depth of the nitrided layer 0.3 mm. Microhardness Нμ=730–930. Avinit coating layer thickness 1-2- μm, Нμ=3000 62 3.40 Freewheel clutch separator. Plasma nitriding of Avinit N+Avinit C coating 63 3.41 The structure of the nitrided layer. Depth of the nitrided layer 0.2 mm. Microhardness Нμ=730–830. Avinit coating layer thickness 1-2- μm, Нμ=3000 63 3.42 Appearance of Ti-Al-N coating (cross section) in mapping mode 64 4.1 Duplex technology of Avinit on turbine steam distribution elements 70 4.2 Turbine blades with developed protective coating using new complex plasma chemical nanotechnologies and equipment (1.300 mm long) 79 4.3 Turbine blades in the course of coating deposition 79 ixVacuum-plasma multilayer protective coatings for turbine blades4.4 5.1Turbine rail tooth gear with protective coating (length – 1.000 mm, weight – 70 kg) Elements of mechanisms of steam distribution and steam regulation of steam turbines working in hinged connections and sliding bearings with wear-resistant antifriction nanocoatings Avinit 5.2 Elements of mechanisms of steam distribution and steam regulation of steam turbines working in hinged connections and sliding bearings with wear-resistant antifriction nanocoatings Avinit 5.3 A fragment of the protocol of the automated control system of the technological process of nanocoatingx798283 84Preface The task of creating new modern materials with improved performance characteristics when working in extreme conditions is closely related to the research and development of nanostructured materials and nanotechnologies. The monograph presented to the attention of the reader presents the results of the authors' research on the development and practical implementation of the latest nanomaterials and Avinit nanotechnologies to improve the characteristics of materials. A distinctive feature of these works is the complex use of complex vacuum-plasma coating methods (plasma-chemical CVD, vacuum-plasma PVD (vacuum arc, magnetron), ion saturation and ionic surface treatment processes) under the influence of non-equilibrium low-temperature plasma, combined in one technological cycle. The experimental and technological equipment created for these purposes – the vacuum-plasma automated cluster Avinit – makes it possible to implement complex technologies for applying multicomponent coatings (single- and multilayer, nanostructured, gradient) for various functional purposes (antifriction, strengthening, etc.). The monograph presents the results of the authors' work in a wide area – from fundamental research to the development of pilot technologies based on these studies and their serial implementation in turbine construction.xiCircle of readers and Scope of Application The large factual material is undoubtedly interesting and useful for engineering and technical specialists involved in the development of new materials, and will contribute to the further development of this promising direction. Attention is paid to the prospects for the development of Avinit vacuum-plasma nanotechnologies and the expansion of applications of these methods in mechanical engineering, aviation, power engineering, astronautics and other branches of science and technology. The theoretical and experimental results presented in the monograph are of considerable interest for scientific and technical specialists engaged in solving the problem of increasing the durability of materials with improved functional, in particular, tribological characteristics. The book is intended for specialists working in the field of ion-plasma surface modification of materials and the application of functional coatings.xiiIntroduction The operation reliability and service life of various heat engineering equipment: turbines, steam generators, heat exchangers, valves and control valves, pumps, etc. largely depends on the degree of wear of the working surfaces of highly loaded machine elements, particularly working blades of steam turbines and compressors of gas turbine engines (GTE) and gas turbine units (GTU). The greatest number of damage cases, that significantly reduce the service life is due to erosion, corrosion and flow-accelerated corrosion of structural materials that are in the course of operation are subjected to the simultaneous damaging effect of corrosion-erosion factors in conditions of gas-abrasive and wet-steam environment at temperatures up to 500–540 °C, a significant dynamic and static loads [1–3]. To date, the possibility of significant increasing the equipment durability by improving the properties of structural materials, the introduction of more advanced design and technological solutions are almost exhausted. Usually, in production conditions strengthening of steam turbine working steel blades is carried out by soldering of stellite (WC) plates on the leading edge or by deposition of a very hard coating in air atmosphere (supersonic and detonation sputtering). As it was proven by operating experience, such methods are ineffective. Soldering of the plates does not solve the erosive wear issue. At the same time, this significantly deteriorates the aerodynamic properties and efficiency factor of the turbine. The coating sputtered in the air is characterized by a weak adhesion to the substrate and low endurance due to the occurrence of oxide films. The most effective way to improve the wear resistance of structural materials is the use of protective coatings [4, 5]. Vacuum ion-plasma coating technology has become widespread in various branches of engineering, mainly to enhance the products durability (including erosion, corrosion and fretting resistance). In the technological aspect has an exceptionally difficult issue of the application of the required coatings on the elements having complex configuration and a large length, and depositing of coating on the parts inner surface. Because in most cases temper of materials of the parts coated is not allowed, depositing of vacuum-plasma coatings should not be carried out 1Vacuum-plasma multilayer protective coatings for turbine bladesat temperatures which can reduce the base hardness, heat-treated to high hardness (~65 HRC 55). No deformations and distortions are tolerated on the coated parts. Tempering temperature of steels normally used for the manufacture of parts is 200–250 °С, therefore, the technology must provide an implementation of the low-temperature coating processes, with good adhesion to the base, at temperatures at least, not exceeding 200 °С. Preferably no additional machining should be applied to the surface after coating. In addition, the coating must provide a significant increase in the service life of the friction pair at a thickness which does not lead to going beyond the tolerances of dimensions of parts which may be only a few micrometers, and does not reduce the treatment cleanliness class of surfaces covered, which is determined by the requirements of the design documentation, as further additional machining of parts surface after manufacture is almost impossible in most cases. It is sufficient to only mention the enormous costs – financial and technological necessary to achieve the necessary size of parts of complex configuration and large relative length with stellite coatings. A large number of works is known on sputtering of vacuum-plasma coatings for the protection of turbine blades [6–13]. Many researches on studying of properties of vacuum-plasma coatings concerning work of constructional materials of the thermal engineering equipment in the conditions of action of erosion corrosion and corrosionfatigue factors are carried out. Wear-resistant and corrosion-resistant coatings can be layers of corrosion-resistant metal layers, which are repeatedly alternating, and are selected from the group consisting of molybdenum, niobium, tantalum, tungsten, chromium, titanium, zirconium, nickel or alloys based on them. In work [7], a three-layer coating was developed, the first layer of which consists of a layer of one metal or metals alloy of 1VA or V1A groups of the Periodic table of elements formed in a neutral gas environment, the second one – in a mixture of neutral and reaction gases, and the third one – a layer of nitrides, carbides, borides or alloys thereof. The coating contains a layer of scandium, yttrium or rare earth metal having thickness of 0.02–0.08  μm, the number of layers can vary from 10  to  500, the ratio thickness is (0.02–5.0) : (0.04–10) : (0.1–12.5), the thicknesses of the first two layers have ration 1.0 : 2.0 : 2.5. Tests of these coatings revealed improved corrosion and erosion resistance of titanium blades in comparison with the resistance to erosion and corrosion without coating, but low adhesive ability significantly reduces the operational reliability of the products. Coatings resistant to erosion are described in [8]. They contain solid nitrided layer created on the surface of the core material and at least one hard layer obtained by PVD method, created on nitrided solid layer, 21 Introductionin which layers of chromium nitrides, titanium nitrides, and nickel nitrides are created, which alternate with layers of nitrides of chromium/aluminum, titanium/aluminum, chromium and titanium. Such coatings improve anti-erosion properties of the surface, however, this does not always provide the necessary erosion and corrosion resistance of turbine blades during their operation under conditions of wet-steam erosion due to poor adhesion ability. In [9] a method of coating in vacuum is described, comprising preliminary cleaning the product surface, in which passivation-deformation treatment is performed by a flux of high-energy neutral particles before ignition. The of result passivation-deformation treatment is obtaining a high-strength coating with high density and passivity, which increases its durability significantly. But this method is more suitable for treatment of products that do not work in environments with a considerable load of erosive factors. A method of depositing a multilayer coating on metal products by means of cathode sputtering is also known; it comprises ion cleaning and/ or surface modification of products, application of at least three-layer wear-resistant coating by sputtering of the metal layer and solid solutions of gases and layers of nitride, carbide and/or borides [10] in an inert gas environment. The method of obtaining erosion-resistant nano-layer coating for the turbo-machines blades is described in [11]. The coating contains nano-layers that include a metal sublayer and nano-layers of titanium nitrides [11], as well as carbides and/or titanium carbonitride, zirconium carbonitride, aluminum carbonitride, and nano-layers of these metals compounds with nitrogen and carbon, as well as the implanted ions. Vacuum-plasma application of metal sublayer and layer based titanium nitrides, which are form during the rotation of the blades relative to their own axis [11], and relative to consecutively located cathodes of different materials, in which their ion-implantation treatment is carried out after depositing of each layer. The above-described technical solutions are used to protect turbine blades against salt and gas corrosion, gas-abrasive and drip-impact erosion. These coatings increase the blades resistance to salt corrosion and dripimpact erosion by 1.5–2 times. In [12] erosion and corrosion-resistant ion-plasma protective coatings based on titanium nitride for blades steel protection are described. Obtaining high quality firmly joint coatings of the multilayer structure requires the good condition of surface on which the coating is deposited, as well as layers interface surfaces. Therefore, the technological processes of the surface pre-treatment before depositing coating and in the course of coating deposition are particularly important. The possibility of pre-treatment of the surface with high-energy ions is the most distinguishing feature of all ion-plasma technologies. 3Vacuum-plasma multilayer protective coatings for turbine bladesDue to the surface treatment by the high-energy particles flow it is possible to achieve modification of the materials surface properties, which usually has a positive effect on the properties of the formed coatings. To improve the microstructure of the surface layer the new effective plasma methods of surface components preparation (plasma annealing, plasma hardening, plasma modification) is used successfully. Electrolytic-plasma polishing of parts is broadly used [13]. In combination with surface ultrasonic treatment such combined methods of vacuum ion-plasma treatment are capable of ensuring elimination of possible deficiencies in the previous process operations to improve the cleanliness class of the surface to roughness grade 12, 0.025–0.05 Ra, which contributes to improvement of adhesion characteristics at the next deposition of vacuum-plasma coatings. To improve operational properties of steam turbines working blades [14] multilayer nanostructured vacuum-plasma coating system of Ti-TiN system were developed using a combined vacuum ion-plasma treatment. Processing includes pre-electrolytic-plasma surface polishing, ionbeam cleaning of the surface from oxide films, ion implantation of the surface with subsequent depositing of multilayer vacuum-plasma coating of very hard nitride compounds: Ti-TiN Zr-ZrN. All operations are carried out in one vacuum chamber. Such coatings (with thickness of 40  µm) are distinguished for strong adhesion to the blades material and high corrosion and wear resistance. Thus, these data allow to conclude about the prospects for use in the energy of vacuum-plasma wear-resistant protective coatings that increase the life of power equipment at least to the design, and in some cases significantly increase it (3–4  times) by significantly reducing erosion, corrosion and corrosion-erosion wear of the surface of structural materials.4Experimental equipment. Avinit vacuum plasma cluster It is possible to satisfy the requirements, often contradictory, to the surface properties (high hardness and wear resistance, high antifriction characteristics) and bulk properties (high strength and toughness) by creating compositions with layered arrangement of materials that perform different functions. The most successful solution to these problems is provided by technologies for modifying the surface layers of contact materials and applying wear-resistant and antifriction coatings to improve the tribotechnical characteristics of friction pairs. Without coatings for various functional purposes, it is impossible to imagine modern technology and further progress in all areas of its application. Increasingly high requirements for the properties of materials and the complex nature of these requirements stimulate the constant search for new materials and technologies for their production. Coating of certain materials not only improves the properties, but leads to the creation of a new composite material with its own set of characteristics. Among the methods of coating, a special place is occupied by methods of forming coatings from ionized atomic and molecular fluxes. The ability to change the energy of ionized particles of condensed matter streams in a wide range (from units to hundreds and thousands of electron volts) can effectively influence most important in practical application characteristics of coatings (density, adhesion, structure, etc.) and thus achieve high values of the corresponding indicators in comparison with other methods. An important feature that distinguishes these methods is the ability to create multicomponent composite materials in nonequilibrium conditions of their formation. Vacuum coating technologies have taken a leading place in many areas of industrial production of various products of modern technology. This became possible due to the success in the development of technology for the formation of high-quality coatings for various functional purposes (protective, wear-resistant, optical and others), and the creation of appropriate industrial equipment for coating. Further progress in the application of vacuum coatings is associated with the development of technologies and equipment that would provide the ability to obtain multifunctional coatings 5Vacuum-plasma multilayer protective coatings for turbine bladesof complex composition, high homogeneity, reproduction in composition and other characteristics. We have created [15–17] vacuum-plasma complex (cluster) Avinit for application of multicomponent multilayer coatings by complex ion-plasma and plasma-chemical methods and testing of technological methods and industrial technologies for obtaining nanolayer composite functional coatings on parts with different geometry surfaces. The peculiarity of the developed coating processes lies in their complexity: different coating methods (plasma chemical CVD, vacuum-plasma PVD (vacuum arc, magnetron), ion saturation and ionic surface treatment processes) are combined in a single technological cycle. The use of gasphase and plasma-chemical methods in combination with other methods of coating and surface modification (ion doping, implantation, vacuum-plasma, diffusion, vacuum-thermal methods, etc.) significantly expands the possibilities of creating fundamentally new materials. A wide range of coatings (almost any element, refractory oxides, carbides, nitrides, cermet compositions based on refractory metals and oxides), as well as the unique structure and properties of ion-condensed materials (amorphous, nanocrystalline, microlayer structures, etc.) open new opportunities for the creation of components and parts for various purposes to work in extreme conditions of temperature, aggressive environments, mechanical loads. The main efforts are aimed at the formation of nano- and microlayer multicomponent coatings as the most promising to achieve the required functional characteristics. Nanolayer nanocomposite coatings have great potential in creating materials with unique properties, including exceptional hardness, strength, chemical stability, low friction coefficient and high wear resistance due to the possibility of combining in various combinations of different materials and varying the thickness of the layers. Technological vacuum-plasma automated cluster Avinit for multicomponent multilayer coatings is a high-vacuum unit with high energy saturation of power supplies of various types (gas-phase and vacuum-arc evaporators) (Fig. 2.1).  Fig. 2.1  Avinit vacuum-plasma automated cluster62 Experimental equipment. Avinit vacuum plasma clusterIt consists of such functional blocks:  Avinit C unit for application of hard and superhard multilayer and nanolayer functional coatings by the method of modernized vacuumarc spraying;  Avinit V unit for gas-phase (CVD) and plasma-chemical (PECVD) coating deposition on parts internal and external surfaces;  Avinit M unit for coating by magnetron sputtering;  Avinit N unit for ion-plasma treatment;  Avinit E unit for ionic etching and purification processes;  Avinit T unit for heat and thermochemical processes. The Avinit vacuum-plasma automated cluster is created for working off methods of receiving composite functional coverings on details with surfaces of various geometry with precision processing. The solution of these problems is provided by the use of complex methods – CVD (gas-phase and plasma-chemical deposition) and PVD (vacuum-arc and magnetron sputtering) in combination with ion-plasma surface modification to form multicomponent multilayer nanocoatings with high functional characteristics. It is important to use automated equipment with vacuum-arc sputtering sources with plasma filtration from the drip component, which is able to ensure the requirements for maintaining the cleanliness of surfaces with precision treatment and the appropriate degree of control over processing and coating due to the requirements for geometry and size of such surfaces. In the presence of such capabilities of the equipment control system, it is possible to form multicomponent nanolayer coatings with the most diverse ratio of elements that are part of the layers. The ability to control the energy of ions in vacuum-plasma processes allows to influence the processes of nucleation, growth of the coating, and hence its structure, the level of internal stresses and other characteristics. The expediency of using one or another method in the technological scheme of formation of functional coatings is primarily determined by its capabilities and features of application. The Avinit multi-purpose complex provides a mode of operation when using any evaporating devices, systems and control devices that are part of it, while allowing the simultaneous operation of all the same type of evaporators or alternating (in any sequence) different types of evaporators. The Avinit complex is not focused on any specific technological process, but provides for the possibility of implementing various technological processes, which can use different methods of coating and pre-treatment of the substrate. It is presented in Table 2.1. Use of effective methods of surface cleaning – in glow discharge Ar, in high-density plasma discharge and metal ions at voltage above zero point of growth, and also prevention of damage of a surface by mi7Vacuum-plasma multilayer protective coatings for turbine bladescroarcs by means of the effective three-level system of arc quenching provided in Avinit equipment, oxides and other contaminants without electrical breakdowns. When using spray systems, coatings can be applied by igniting a DC or RF discharge, which can be excited in an inert gas, reactive gas or in multicomponent gas mixtures, which include an inert gas and one or more reactive gases. Pure metals, alloys, various combinations can be used as targets that allows to receive a coating of practically any set structure in the mode of simultaneous or consecutive work of magnetron sources.   Table 2.1  Vacuum-plasma methods of coating and surface modification implemented in the vacuum-plasma cluster Avinit Vacuum-arc coating methodAvinit C unitGas phase deposition methods (CVD and PECVD)Avinit V unitMagnetron coating methodAvinit M unitMethods of plasma diffusion saturationAvinit N unitMethods of ion-plasma purificationAvinit E unit2.1 Avinit C unit (vacuum-arc coating methods) The installation provides the application of monolayer, multilayer, nanolayer and nanostructured coatings of metals, alloys and their compounds with nitrogen, carbon, oxygen.The presence of an effective system of protection against arc and microarc discharges, which can damage the surface of the coated parts, as well as plasma separation devices from the drip component of the arc evaporators ensure the preservation of surface finish at a level not worse than 11–12  class. This allows to apply coatings on precision surfaces of high purity, eliminating the need for any finishing coatings after application. Gas supply to the chamber of inert and reaction gases is carried out by 2  independent lines with regulators – flow meters of fine regulation from 0 to 200 cm3/min of the Bronkhorst company (Holland).2.2 Avinit V unit (gas phase deposition methods (CVD and PECVD)) [16] The Avinit V unit for vacuum-plasma and plasma-chemical surface treatment and application of functional coatings is designed for experimental development of new technologies for the application of metal and metalcarbide coatings based on molybdenum and tungsten by decomposition of their carbonyls. 82 Experimental equipment. Avinit vacuum plasma clusterThe Avinit V unit is designed for the implementation of coating processes by thermal decomposition of organometallic compounds, mainly hexacarbonyls of metals VI-B of the Mo, W, Cr groups and their compounds with nitrogen, carbon, and others. The use of gas-phase and plasma-chemical methods in combination with other methods of coating and surface modification (ion doping, implantation, vacuum-plasma, diffusion, vacuum-thermal methods, etc.) further expands the possibilities of creating fundamentally new materials and coatings.2.3 Avinit M unit for coating by magnetron sputtering The Avinit vacuum-plasma cluster provides for the possibility of using various sources of sputtering, in particular magnetron sputtering systems. The Avinit M unit is intended for magnetron coating and experimental testing of new technologies for coating of and non-conductive materials of HF and DC magnetron sputtering of targets. The magnetron is powered by a DC power supply with a strongly decreasing volt-ampere characteristic with a power of 2  kW and an idle voltage of 6  kV. The RF power is supplied to the inductor through a matching device from the serial generator UV-1 with an operating frequency of 13.56  MHz and a power of 1 kW. The Avinit M unit is equipped with a modern high-voltage power supply of the magnetron and devices of plasma and plasma chemical surface treatment of TruPlasma DC01 BP Kurt J. Lesker products with a capacity of 1 kW with output voltage up to 800 V. The source provides operation in stabilization modes for power, current or voltage with protection from overloads at interruptions of burning of plasma of a glowing discharge in a microarc or arc modes, and also provides a possibility of remote computer control. The Avinit M unit provides an opportunity to put coverings from metals and their various connections, including, not electrically conductive, and also nonmetals (carbon, fluoroplastic, optical, etc.) and different in composition and structure (monolayer, multilayer, including nanolayer and nanostructured). This variety of coatings makes the method of RF magnetron sputtering of targets and technologies based on its use, one of the most popular in a number of areas of modern production, as well as in the development of new types of coatings and technologies for their production. The Avinit M unit with magnetrons (DC and RF) is fully combined with the Avinit N unit and the Avinit C unit, which allows the development of hybrid technologies. 9Vacuum-plasma multilayer protective coatings for turbine blades2.4 Avinit E unit (ionic treatment (cleaning) of the surface before coating) The Avinit E unit, designed for ion-plasma treatment of materials, is equipped with devices for the implementation of plasma glow discharge of high density, excited in the hollow cathode. This allows the development of new and improvement of existing technologies of ion-plasma surface treatment of materials in the plasma of the glow discharge. The installation provides the ability to process the surface of materials in plasma glow discharge of high density in gaseous media of different composition (argon, nitrogen, gases containing carbon, and mixtures of these gases), including internal cavities and channels of certain sizes. The use of high-density glow discharge plasma in the processes of ionic nitriding, nitrocementation can reduce many times compared to gas furnace technologies the time of formation of reinforced layers up to 0.3–0.4  mm, while maintaining virtually unchanged dimensions of the processed products and preventing the formation of brittle phases on their surface. Therefore, the development of new technologies for surface treatment in high-density plasma is one of the current areas of improvement of modern technologies in a number of industries. Structurally, the Avinit E Unit can be combined with the Avinit C Unit and the Avinit N Unit for glow discharge cleaning, metal ion cleaning in a vacuum arc discharge, and high-density double-arc plasma cleaning in high-density plasma. Ion-plasma methods provide a high value of adhesion of coatings due to the high energy of condensing ions and pre-cleaning of the coated surface. Ionic treatment of products can be carried out using special ion sources or in plasma gas discharge, which is ignited in the volume of the vacuum chamber. The basis of ion-plasma methods of surface cleaning are the processes of interaction of vacuum-plasma flows with the surface of the substrate material. The nature of the interaction of particle fluxes falling on the surface with the substrate material is determined by the flux density of particles, their energy, degree of ionization, temperature in the interaction zone and may consist either exclusively in spraying, etching of surface layers (at high ion energies) or condensation (at low energies). The consequence of the purification process (ion bombardment) is:  purification from sorbed surface atoms of contaminants;  heating of the substrate material;  degassing;  selective etching, which changes the morphology (purity of processing of the surface; 102 Experimental equipment. Avinit vacuum plasma cluster activation of surface atoms, which ensures the flow of plasma-chemical processes of interaction with the atoms of condensed matter. All these factors contribute to the formation of high adhesive bonds of the coatings to the substrate material. In the Avinit installation, the surface can be treated with inert or reaction gas ions (Ar, N2, etc.) when the glow discharge is ignited. Due to the lower ion density in the glow discharge plasma, the intensity of heating and the associated gas evolution from the surface to be covered will be less and the intensive formation of microarc discharges can be avoided. Devices with electric arc evaporators, in addition to the known advantages, have a number of serious disadvantages. First of all, this applies to problems arising from ionic cleaning in electric arc spraying due to the appearance of erosion traces from the cathode spots of the arc discharge (microarcs), which leads to a significant deterioration in the purity of the treated surface, as well as a significant number of macroparticles ("drip component"), which are generated by the cathode spot of the vacuum arc. There are technological problems in which the presence of defects in the coating caused by metal microparticles is absolutely unacceptable (application of functional coatings on precision surfaces, anti-corrosion, decorative, optical, etc. coatings). In installations with electric arc evaporators, the working volume is filled with highly ionized metal-gas plasma. Effective ionic purification is possible if there is highly ionized gas plasma in the working volume. In the Avinit installation taking into account complexity of methods (plasma-chemical, vacuum-arc, magnetron) and also specifics of geometry and precision of a surface of the covered products, for replacement of metalgas plasma by gas plasma the gas plasma generator on the basis of two-stage vacuum gas plasma for the purposes of highly efficient ionic treatment by cathodic spraying of the surface with ions of the working gas, which provides a strong adhesion of the coating to the substrate and the application of high quality functional coatings. When ion-plasma purification using DVDR in the presence of gas plasma there is no problem of deposition on the surface of metal particles, and therefore the potentials for the product can be changed smoothly, starting from zero. It is possible to achieve the complete absence of electrical breakdowns on contaminated areas of the surface in comparison with the case when the complete cleaning of the surface is carried out by metal ions, and thus achieve the preservation of the original purity of the treated surface. In addition, purification by gas rather than metal ions may have the advantage that often the gas ion sputtering ratio is higher than the metal ion sputtering ratio, and therefore the ionic purification process at the same ionic current and ion energy is more intense. 11Vacuum-plasma multilayer protective coatings for turbine bladesAnd although the power consumption in a DVDR installation is twice the power consumption in a magnetron installation, which makes the use of magnetrons for cleaning purposes more common, the possibility of efficient surface cleaning of complex products with high surface finish (eg hemispheres) using DVDR when spray targets can be of almost any shape, and the use of magnetrons is inefficient, the use of two-stage arc discharge (DVDR) is very appropriate.2.5 Avinit N unit (ion-plasma surface modification) [17] The Avinit N unit is intended for carrying out processes of ion-plasma modification of surfaces, in particular, for ion-plasma surface treatment, plasma diffusion saturation (nitriding, nitrocementation, etc.) of steel and alloy parts in high-density low-temperature nonequilibrium plasma, in precision, without processes of diffusion saturation in plasma with a poly cathode. The Avinit N unit is designed in such a way that it is possible to connect devices for simultaneous magnetron sputtering processes. The Avinit N unit is equipped with a gas plasma generator for carrying out processes of vacuum-plasma high-precision nitriding of steels and alloys in high-density low-temperature nonequilibrium plasma. Plasma burns evenly in large volumes, providing uniform heating of details to necessary temperature and nitriding of difficult-profile products of various forms and the sizes, including through and deaf openings. Its density is several orders of magnitude higher than that of ionic nitriding in a conventional glow discharge, as a result of which the process of formation of the nitrided layer intensifies 2–5 times in comparison with the traditional method of ionic nitriding in a glow discharge and 5–10 times in comparison with gas nitriding. This ensures the absence of deformation (curvature) of the parts while maintaining the original geometric dimensions after nitriding with an accuracy of 1–2  μm, there is no brittle surface layer, typical of traditional methods of nitriding. This avoids finishing grinding of parts and to carry out the operation of precision nitriding "in size".2.6 Power supplies of the Avinit installation The ionization degree of the vapors of the evaporating substance depends on the parameters of the evaporator, the composition of the evaporating substance, and the conditions of excitation of the discharge, the design features of the nodes, the ionization system of vapors. Methods of vapor ionization using an arc discharge require high-current (tens and hundreds of amperes) power supplies with a voltage of up to 122 Experimental equipment. Avinit vacuum plasma cluster100  V, which are equipped with all serial installations of vacuum-plasma spraying. The Avinit installation also includes the use of plasma sources, which are equipped with magnetron sources of DC and RF current. When using glow discharge technology schemes, the most effective methods are those that use a non-self-contained glow discharge. The presence of power supplies of magnetron evaporators on direct current as a part of Avinit installation allows to provide realization of schemes of not independent glow discharge with use of direct-burning cathodes without essential additional expenses. When the glow discharge is excited, the RF discharge has certain advantages over the DC discharge. It can be excited at a lower electric field strength and lower pressure, provides a higher density of ions in the discharge, can be implemented in the "non-contact" version. Power supplies of the RF-magnetron evaporators, which are part of the Avinit unit, are used to power the RF discharge system, providing in them the possibility of coordination with the inductive load. The existing in-cluster system of inert and reaction gases in the Avinit cluster is able to fully provide the necessary conditions for the pressure of the medium to excite the discharge in the vapor ionization circuit of the evaporator at almost any mode of evaporator operation, including operation at minimum power. CVD processes using non-equilibrium low-temperature plasma are implemented in the Avinit installation. Low-temperature nonequilibrium plasma of low pressure in the environment of the used precursors is ignited by means of standard RF generators and metal concentrators specially designed according to the geometry of the vacuum chamber. The plasmaization possibility of the gaseous medium in the implementation of CVD-processes significantly expands the possibilities of implementing the latest methods and technologies of coating in the Avinit installation. One of the most interesting directions in development of PECVD methods is the method developing now connected with use of plasma of high density (HDP-CVD). The generated ion density for this method is from 1011 to 1013  ions/cm3, while for conventional PECVD methods it is in the range of 108...1010  ions/cm3. Unlike conventional PECVD processes, electromagnetic energy in HDP-CVD processes is transmitted in a relatively small spatial region of the reaction volume, and the plasma flow from the excitation zone is directed to the substrate, which is outside the electromagnetic field that excites the plasma. Due to the selected design of the chamber, the configuration of the magnetic field, the elements forming the gas flow, a uniform flow of plasma to the substrate is created. And although the plasma density is reduced by about 10  times compared to the excitation site, it is possible to change the plasma density in a wide range without affecting the deposition zone of the coating by the exciting electromagnetic field, which makes the process more controlled and controlled. 13Vacuum-plasma multilayer protective coatings for turbine blades2.7 Measurement of plasma source parameters of the Avinit cluster The solution to the problem of obtaining multifunctional coatings with the required characteristics is largely related to the possibility of more complete control of technological parameters and their support and management in automatic mode. First of all, it concerns plasma parameters. In the Avinit installation realization of the following plasma sources used for the purposes of drawing functional coverings and surface modification is possible:  glow discharge plasma (surface cleaning and ion saturation);  plasma vacuum-arc discharge (reactive coating);  magnetron discharge plasma (reactive coating);  plasma double arc discharge (surface cleaning and ion saturation);  HF plasma for the implementation of deposition processes from the gas phase PECVD, activated by low-temperature nonequilibrium plasma (reactive coating). In [18, 24] a comparative analysis is done for different plasma sources used in reactive coating and diffusion saturation of metals in the Avinit installation. To measure the plasma parameters, the Langmuir probe method was used, implemented using the PlasmaMeter device. A tungsten probe with a diameter of 0.1 mm and a length of 5 mm with an L-type support assembled from metal and ceramic tubes was introduced into the vacuum chamber through a movable seal, which allowed 2-coordinate movement of the probe inside the chamber without violating vacuum conditions (Fig. 2.2).  Fig. 2.2  Location of the Langmuir probe in the vacuum chamber of the Avinit installation: a – cross-sectional side view; b – a top view142 Experimental equipment. Avinit vacuum plasma clusterProbe measurements of process plasma parameters in the Avinit installation were performed [18] using fundamentally different sources that cover a very wide range of plasma parameters. In [18], the results of measurements of the parameters of two plasma sources intended for coating (magnetron and arc) and two gas discharges for diffusion saturation of metals (incandescent and double arc) are presented. Experimental study of different plasma sources of the Avinit installation showed that the achievable plasma parameters cover a wide range, which provides an opportunity to implement a wide range of technological processes. Table 2.2 summarizes the results of measuring the plasma parameters of all four sources used in Avinit installations.   Table 2.2  The results of measuring the parameters of plasma sources Type of discharge Plasma density, cm-3Electron temperature, eVThe degree of ionization53·10−4Magnetron1010Arc4·1090.40.5Smoldering1080.1510−7Double arc6·109510−4The results of the glow discharge study show low values of plasma density and ionic current density on the treated surface. Such plasma can be successfully used for surface cleaning or ionic assistance in coating, however, the technology of diffusion saturation of metals (eg, nitriding) requires the use of denser plasma. The Avinit installation uses a double arc discharge for this purpose, which allows you to create a high-density plasma in the chamber. Estimation of the ratio of ion fluxes and neutral atoms for plasma of a double arc discharge gives a value of the order of 104  atoms per ion, ie approximately 300–1000  times more intense ion flux compared to the case of the glow discharge. Such plasma is successfully used in the Avinit installation both for cleaning of a surface or ionic assistance at drawing functional coverings, and in technologies of diffusion saturation of metals (for example, nitriding) with use of much denser plasma. An important role in plasma technology is played by the homogeneity of the plasma in the volume of the chamber, because in group processing to comply with the optimal technological regime, all machined parts must be in the same conditions. To study the homogeneity of the plasma of the double arc discharge, the plasma parameters were measured at seven angular positions of the probe at three levels along the height of the chamber, at a distance of 170, 300 and 470  mm from the bottom wall of the chamber. The measurement results showed high homogeneity (±10  %) of plasma throughout the chamber. This result is extremely important for increasing the stability of technological operations to obtain high quality products for coating and modification of metal surfaces. 15Experimental studies of Avinit coating processes 3.1 The study of the structure and tribological properties of Avinit coatings 3.1.1 Method of coating The development of processes for the application of new functional multilayer composite coatings was carried out on a vacuum cluster Avinit, created for the implementation of complex coating methods (plasma chemical CVD, vacuum-plasma PVD (vacuum arc, magnetron), ion saturation and ionic surface treatment). The coating was applied according to a given program using one-component cathodes in the reaction gas medium and without it. Control of all basic parameters of the coating process was carried out automatically. Avinit coatings were deposited on precision surfaces of high purity class up to class 12–13 without reducing the surface purity class. This was achieved by using in the developed technologies effective methods of surface cleaning – cleaning in a glow discharge Ar, cleaning in a two-stage vacuum-arc discharge and cleaning with metal ions at voltages above zero point of growth, as well as preventing surface damage by microarcs, arc extinguishing system that provides high quality surface cleaning from oxides and other contaminants without electrical breakdowns. The deposition was carried out at low temperatures not exceeding the tempering temperatures of the base, ensuring the preservation of mechanical characteristics and the absence of curvature of the coated products. The magnitude of the current of the vacuum arc discharge with a molybdenum cathode was 140–150  A, respectively, with a titanium or aluminum cathode 100–110 A. When coating in a nitrogen environment, its pressure was in the range (1.3–3)·10−1 Pa. An RF inductor with an operating frequency of 3 MHz and an effective power of ~0.2 kW was used to heat the sample. The temperature of the sample is monitored by an IR pyrometer through a special window in the camera door. 163 Experimental studies of Avinit coating processes3.1.2 Methods of studying the properties of experimental samples The main attention was focused on the study of the reproduction of the composition of ceramic compositions in their formation by vacuum-plasma methods, adhesion of film materials, structural state and some other properties. The degree of reproduction of the film composition was evaluated according to X-ray (X-ray diffractometer DRON-3, filtered Cu-Kα radiation) and spectral (ISP-30 spectrograph) studies, comparing the spectra of starting materials (targets) and condensed films. The study of surface morphology, fractographic studies were performed using the methods of electron, scanning and optical microscopy. Metallographic studies (structure and properties of working surfaces (micro section, hardness of the coating, determination of surface geometry after coating) and determination of material parameters (layer thickness, uniformity, defect and structure of the material) were performed using metallographic methods (Tesa Visio 300  gL microscope), chemical, X-ray diffraction and micro-X-ray spectral analyzes, measurement of microhardness, roughness of friction surfaces. automatic mode on the device model "EKOMET 3+AUTOMET 2" company "BUEHLER". The microhardness of the layers was measured using a microhardness tester AMN-43 company "LECO", in automatic mode at a load of 50 G. Measurements of microhardness and Young's modulus in multilayer and nanolayer coatings of Avinit type with a thickness of 1…3 μm were performed using a nanohardness measuring device from CSM (Switzerland) (loading speed 20.00 mH/min, max depth 100.00 nm at a load of 0.6 G, processing the results in the model Oliver-Farah). Metal-physical measurements of the obtained coatings on mock-ups were performed on a JSM T-300 scanning electron microscope. Measurement of the characteristics of the geometric dimensions of the control samples was performed with an accuracy of 0.5 μm before and after nitriding. Measurement of involute surfaces was performed on a control and measuring machine Wenzel LH65 using surface points applied to the 3-D model of the part. The surface roughness of the samples before and after coating was measured on a profilier-profilograph Jenoptik. Removal of profiles of change of chemical individuality and nanolayers of functional coverings was carried out by means of a method of mass spectrometry of secondary ions (MSVI) on the secondary emission mass spectrometer MS 7201M. The maximum depth of profiling is 5 microns. A beam of Ar+ ions with an energy of 5–7 keV was used for sputtering. Examination of the functional areas of the surface of the samples was performed using scanning electron microscopy (SEM). Removal of the volume distribution of chemical elements was performed using electron-probe X-ray microanalysis (EZRMA). 17Vacuum-plasma multilayer protective coatings for turbine bladesPlasma parameters (ion current, ion density, volt-ampere characteristics, spectral characteristics) were continuously monitored and archived using a plasmameter "PlasmaMeter" and a spectrometer "PlasmaSpectr".3.1.3 Methods of research of friction and wear characteristics Tribological tests of coated samples were performed on friction machines to determine critical values of load parameters that lead to burr, i.e. finding the limits of application of the studied friction pairs, determining the coefficients of friction and wear and their change during friction to predict material compatibility. Tribological tests of antifriction, wear properties and setting of samples with coatings were performed on a friction machine 2070 SMT-1 according to the schemes – "cube (basic sample) – roller (counterbody)" and "ring– ring" (for wear tests) at step load in load intervals 1–20 MPa. To determine the setting of the surface layers of the materials of the friction pairs, the load was carried out from Pmin to the critical mark Pcr, at which setting takes place. In the process of tribological tests recorded the values of friction force Ffr, normal load N, contact pressure P, the value of which was judged on the mechanical losses in the tribosystems. The coefficients of friction were defined as f = Ffr/N. The roughness and geometry of the friction surfaces of the samples after coating met the requirements for parts of fuel pumps. Additionally, the wear rate was measured by the method of acoustic emission. As an informative parameter of acoustic emission used the acoustic emission power, which was estimated in relative units. The application of the acoustic emission method is an effective tool for accelerated testing, as it is extremely sensitive when registering the transition of tribosystems from normal (mechanochemical) wear to the initial destruction of the fatigue surface.3.2 Properties of functional multilayer Avinit coatings Properties of coatings produced by vacuum-arc deposition method depend on many parameters, and determining the optimal one in each specific case requires a significant study. We have studied the impact of the main parameters on the properties changing of the coatings based on molybdenum, aluminium, zirconium, and their compounds in the form of nitrides, carbides, oxides. Temperature of the coating forming is an essential parameter. In many cases, coating deposition process is required to preserve mechanical properties of the basis material that can be obtained by relevant heat treatment 183 Experimental studies of Avinit coating processesmodes, wherein tempering temperatures do not exceed 180–240  °C. This imposes certain restrictions on both coating deposition temperature, and given materials. Achievement of sufficient level of coating adhesion under given temperatures is not an easy task even for vacuum-plasma methods that compare favorably with the other types in this relation. This task requires thorough preparation and selection of the surface vacuum-plasma treatment modes, and subsequent coating deposition modes. This moment was chosen as one of the initial factors when developing coating deposition modes. As shown by previous studies, when depositing coatings produced by vacuum-arc method in various modes, uniformity degree of the coating allocation is very sensitive to the parameters of coating deposition process. These modes vary in previous ion-plasma cleaning time, and in the value of negative offset voltage that applies to the sample in the process of coating deposition. By selecting optimal parameters of the process, it becomes possible to form coatings on the sharp edges and spherical surfaces. Besides, sensitivity of coating deposition uniformity to the process conditions makes it useful to optimize the coating process on the samples coating stage. Previous studies are underlying factors of the time-temperature parameters selection when producing hardening coatings, applied for enhancing wear-resistance of precision friction pairs working surfaces.3.2.1 Avinit С 100 coatings (based on titanium nitrides) For deposition of monolayer coatings of one compound and multilayer coatings, comprising the sequence of soft and hard layers, the following technological schemes were used [19]: а) monocathodic scheme with continuously working coating source and impulse (intermittent) reaction gas supply was performed in two versions. The first version had a substrate rotating on its axis thus covering the whole sample surface. In the second version, the substrate was not rotating having only one side of the sample coated. These schemes were applied to produce coatings in TiN, MoN, CrN systems, and in (TiN-Ti), (MoN-Мо) systems. b) bicathodic scheme (hі>θі) with two turned towards each other coating sources, working in impulse mode, and impulse supply of nitrogen reaction gas synchronized by timing with coating source work. Thus, rotating the sample on its axis allows for a hard layer forming. These scheme was applied to produce coatings in (MoN-Сu) system. For deposition of multilayer coatings of hard compounds, the following two technological schemes were used: a) dicathodic scheme (hі>θі) with two turned towards each other coating supplies working simultaneously in nitrogen reaction gas environment, while rotating the sample on its axis; 19Vacuum-plasma multilayer protective coatings for turbine bladesb) dicathodic scheme (hі>θі) with two turned towards each other coating supplies working in impulse mode in nitrogen reaction gas environment, while rotating the sample on its axis. These schemes were applied to produce nanostructure coatings in (TiN-AlN) system. Studying of nitride-titanium vacuum-arc coatings deposition process has been conducted to determine optimal parameters of high-quality coatings production process using specific technological equipment Avinit. This data is essential for further producing new types of functional composite multilayer coatings in order to enhance wear-resistance of precision friction pairs working surfaces. One of the essential coating characteristics is its composition. Studying the phase composition of coatings obtained through the methods of ion-plasma deposition of titanium in nitrogen environment, shows existence of three phases depending on nitrogen pressure. These are α-Τі, ε-Τі2Ν with tetragonal crystal lattice and δ-ΤіΝ with cubic crystal lattice [20–22]. These phases have rather wide concentration areas of solid solutions and TiN compounds homogeneity. Having several phases in the Ti-N system state figure, rather wide concentration areas of solid solutions, TiN compound homogeneity, lead to differences in coatings’ mechanical characteristics depending on the nitrogen concentration in them. Nitrogen partial pressure value under which one of these phases or their set is obtained depends on both the equipment and its characteristics, and conditions of forming the coating on the substrate. Among these conditions, temperature and offset voltage are the factors of greatest impact. But despite all the differences in coatings’ reaction deposition in nitrogen environment, partial pressure value under which titanium nitride phases can already be detected is at the rate close to 1·10-3 Pa. Increasing nitrogen partial pressure is accompanied by transition from the heterophasic coating composition (α-Τі, ε-Τі2Ν, δ-ΤіΝ) with sequentially disappearing phases α-Τі, ε-Τі2Ν to the single-phase state δ-ΤіΝ, wherein transition to the single-phase TiN coating can occur while nitrogen total concentration in it has already reached ~38–40 % [20, 21], that is close to the δ-ΤіΝ homogeneity limit. Crystal lattice parameter а for the massive titanium nitride has a value of 0,424 nm while films generally have а of slightly higher value (0.425–0.428) nm. The value of crystal lattice parameter а increases with the nitrogen level increasing, coating thickness declining, internal tensions increasing [20–22]. In the work [22] there has been studied possibility of forecasting the phase composition of coatings based on titanium and chrome nitrides by thermodynamic calculations of TiN system equilibrium. Calculations were conducted using entropy maximum principle [23] depending on nitrogen pressure, coatings forming temperature, coating growth rate, and the ratio of nitrogen ion flow to metal ion flow. The result of phase composition com203 Experimental studies of Avinit coating processesparison based on adopted model with experimental results and data of other authors’ studies, showed satisfactory results. Depending on the nitrogen pressure while condensation, coatings can be conditionally subdivided into two groups: I – coatings of heterophasic composition; II – coatings of almost single-phase composition of δ-ΤіΝ compound (disregarding titanium-phase drops available in condensates, obtained under any nitrogen pressure value). In condensates deposited under the nitrogen pressure lying within the range of 2·10−3–2·10−2 mm Hg, nitrogen level increases from 42 at. % to 52 at. %. This is consistent with changing the ratio of nitrogen level to titanium level from 0.7 to 1.04. These values characterize TiNх homogeneity area wherein microhardness changes monotonously with the growth of (x), reaching its maximum Н=2·104 MPa, which is common for stoichiometric TiN. In this case, changing of the ratio of microhardness to nitrogen level occurs not monotonously, reaching the maximum value Н=35·103 MPa under С=45 at. %. With the approach of the nitrogen level in the coating to 50 % at. (Р=(2...5)·10−3 mm Hg) microhardness nears to 24·103 MPa. With the further increasing of nitrogen pressure (Р=5·10−3 mm Hg) its level in the coating reaches (50...52) at. % and microhardness increases again. In condensates obtained under Р=2·10−3 mm Hg nitrogen level decreases through the reducing efficiency of the nitrogen synthesis process. Consequences include increasing microdensity and decreasing microhardness. Ion energy impact on the condensates’ properties has been studied on the samples of DIN 1.2379 steel. Condensation process was carried out under the nitrogen pressure of Р1=6·10−3 mm Hg, Р2=1.5·10−3 mm Hg and accelerating potential values from –50 V to –300 V, while temperature of the samples was changing from 200 °C to 600 °C. Such changes in condensation conditions almost do not affect the microhardness value of obtained heterophasic (Р=6·10−3 mm Hg) and single-phase (Р =1.5·10−3 mm Hg) coatings. Condensation modes, especially temperature and condensation time, essentially affect the state of substrate’s material. In almost all modes ensuring to obtain quality coatings tempering of DIN 1.2379 steel occurs. Thus, the higher the ion energy is while condensing, and the longer the condensation time is while the sample rotates on its axis in order to obtain coatings with uniform thickness on both sides of the sample, the stronger the steel tempers. As studies have shown, forming Ti-based compounds require nitrogen pressure to be within the range of 3...4·10−1 Pa. Further studies of coating forming processes of various compositions were conducted in conditions that did not lead to the samples’ temperature rise over 200  °C. On the vacuum-plasma cleaning stage it was achieved through the use of treatment impulse mode, through selecting the ratio between work and pause intervals of the arc supplies, and selecting the total treatment time. While forming coatings with the use of titanium or alumi21Vacuum-plasma multilayer protective coatings for turbine bladesnum cathodes, as studies have shown, the close-to-optimal arc source mode involved 2 seconds of work and 4 seconds of pause with the total treatment time of 3–5 minutes and smoothly increasing accelerating potential from 30...50 V to the maximum value of 1000 V. While working with molybdenum cathode the pause time was increased to 6 seconds. On the stage of depositing coatings based on titanium and compounds with nitrogen, maintaining temperature within the limits of 180–200  °C was possible in the mode of continuously working vacuum-arc source with the potential of 30–40 V. There is a rather high correlation between changing of coatings’ phase composition and microhardness curve changing [20–22]. Despite the differences in microhardness absolute values provided by different authors, microhardness maximum (~28÷32 GPa) is in nitrogen concentration area that is consistent with the heterophasic coating composition (ε-Τі2Ν+δ-ΤіΝ). It is these coatings, which show maximum wear-resistance in dry-friction conditions, where the main reason of contacting surfaces destruction is abrasive wear [24–30]. But generally, coatings’ resistance under various operating conditions of the instruments, machine parts is not only defined by its microhardness value, but has a more complicated dependence on its composition, and also requires structural, orientation and other characteristics that determine coatings’ physical and mechanical properties in general, to be taken into account [26–30]. Coatings obtained by titanium plasma flow deposition in vacuum Р=10−3  mm  Hg have microhardness of 4·103 MPa, that is superior to the respective values for cast material due to fine dispersed structure and the impact of residual gases’ impurities. Titanium condensation under Р=7·10−3  Pа leads to the forming of nitrogen solid solutions in titanium with microhardness of Н=104 MPa. One of the multilayer coatings’ indicators that determine its properties in many aspects is the single layer thickness. When forming coating the necessary layer thickness is determined by working time of the relevant source that requires growth rate to be known. Generally, the coating growth rate depends on the power of the coating deposition source, on the distance from the source to substrate, on its orientation and position in relation to the axis of the diagram of coating source’s atomic flow direction, on the shape of the direction diagram itself, and on the offset potential applied to the substrate. The substrate can be fixed, rotating on its axis, or be planetary rotating. Table 3.1 shows the results of experiments to determine the growth rate of coatings.   Table 3.1  Growth rate of coatings with various composition No.CoatingThe growth rate, V, μm/hourNotes1Avinit C/P 100 (TiN)0.9Fixed position2Avinit C/P 100 (TiN)0.25Planetary rotation3Avinit C/P 110 (TiN)0.16-----х-----223 Experimental studies of Avinit coating processesBased on the coatings growth rate data the Avinit equipment was programmed for producing nanolayer Ti-TiN coatings with the recurrence interval of 10 nm and single nanolayers’ thickness of 2 and 8 nm respectively. These processes’ automated control system protocols are described in Fig. 3.1. Composition and some of the characteristics of the coatings studied by hardness, microhardness and roughness are described in Table 3.2.  Fig. 3.1  The fragment of the automated control system’s protocol of the Ti-TiN nanocoating deposition technological process with the recurrence interval of 10 nm and single nanolayers’ thickness of 2 and 8 nm  Table 3.2  Characteristics of the samples SubThe strate coating No. hardcomponess, sition HRC123Avinit C/P 100 59–60 (TiN) Avinit C/P 100 59–60 (TiN)Avinit C/P 110 59–60 (TiN)Technological parameters Properties of coatings Nitro- Coating RoughProgrammaCoating T, gen thickble composimicrohardness, ness, °C pressure ness, Ra, μm tion Hv, (MPa) μm Р, Ра Ti-N – based coatings Monolayer 0.70 12.0 15000–18000 without 250 1.5⋅10−1 (7с) separator Monolayer 0.040 1.0 15000–19000 with 250 1.5⋅10−1 (11с) separator Monolayer with the recurrence interval of 0.036 1.0 13000–18000 10 nm 250 1.5⋅10−1 (12a) and single nanolayers’ thickness of 2 and 8 nmMetallographic studies of the samples with coatings of various compositions showed that developed modes had ensured forming of the quality coatings. In the chosen modes, hardness and microhardness of the substrate material almost do not reduce compared to the initial state. Coatings had strong adhesion to the substrate material. Exposing samples to the scratch mesh did not reveal any coating detaches. 23Vacuum-plasma multilayer protective coatings for turbine bladesThe surface morphology of the coatings obtained through condensation from unseparated plasma flows is characterized by availability of the macroparticles (mostly metal drops), which quantity, size, and form depend on condensation physical and technological parameters. Studying roughness of the coated samples showed that its value is determined by both roughness of the initial surface value and coatings’ deposition modes. While processing the initial surface to the 6-7 finish class coating deposition did not reduce surface finish class and depending on the deposition mode could even enhance it by several points. Thus, after depositing coatings on initial surface of the 7 class surface finish steel sample in the mode of spherical structure formation, roughness value Ra was consistent with surface finish of 10 class. Without using the rectilinear separating device the coating surface finish, as profilographic studies have shown, deteriorates significantly (Fig. 3.2). Consequently, numerous macroparticles, common for condensation from unseparated plasma flows, emerge on the coating surface (mostly metal drops that depending on their formation time are covered with subsequent layers). Their quantity, size and form depend on technological parameters of the deposition process.ab  Fig. 3.2  TiN coating (×200): а - without separator; b - with a rectilinear separatorIn TiN coating obtained by usual deposition without separator initial surface roughness (class 12c) reduces sharply (class 7c, Table 3.1 paragraph 1). After depositing coatings on the samples with roughness of 12-13 surface finish class using a rectilinear separating device, surface roughness almost does not change or little roughness increasing can be seen that almost does not exceed the limits of one surface finish class, according to the surface roughness classification. While condensing, the heat load reduction due to decreasing ion current density, the usage of the rectilinear separator to get rid of drop phase, 243 Experimental studies of Avinit coating processesenhances the uniformity of condensate structure and ensure preservation of the surface finish class at the level of V13 (Fig. 3.3). V. U. 20,000  Fig. 3.3  Profilogram of the nanocomposite Ti-TiN coating3.2.2 Avinit C 200 coating (based on molybdenum nitrides) According to the state diagram in the Mo-N system at temperatures below 350 °C, depending on the nitrogen content, the α-Mo, α-Mo+β-Mo2N, β-Mo2N, and δ-MoN phases can be observed [31]. The β-Mo2N phase has a tetragonal crystal lattice with the parameter a=4.2 Å, c=8.01 Å, and the δ-MoN phase has a hexagonal crystal lattice with the parameter a=5.72 Å, c=5.608 Å. However, as evidenced by the results of many works, the vacuum-arc coating of coatings shows the presence instead of the phase β-Mo2N more high-temperature modification of γ-Mo2N, which has a friction lattice with parameters a=4.15…4.23 Å [31–34]. According to the work of [32] during vacuum-arc coating of molybdenum cathode in an air atmosphere at a pressure above 1.2·10−2 Pa in the coating near the phase α-Mo is observed phase γ-Mo2N. The amount of the latter increases with increasing pressure of the gas mixture in the chamber and at a pressure of more than 9.3·10−2 Pa and up to the maximum pressure in these studies 1.33·10−1 Pa coating has a single-phase structure of γ-Mo2N with lattice parameter a=4.204 Å and a microhardness of 29–30 GPa. In [33], when studying the dependence of the coating composition on nitrogen pressure, it was found that at pressures greater than 1 Pa and substrate voltages below 150 V, the coating also has a single-phase structure, but with δ-MoN. The increase in the pressure of the reaction gas in the spray chamber is accompanied by an increase in the microhardness of the coating from 31 GPa (at 0.4 Pa) to 51 GPa 25Vacuum-plasma multilayer protective coatings for turbine blades(at 1.9 Pa). With increasing voltage on the substrate or substrate temperature, the microhardness of the coatings decreases. In general, the nature of the change in the composition of the coating in the Mo-N system from the nitrogen pressure in the chamber has many features in common with the behavior of the Τi-system. The microhardness of coatings corresponding to the α-Mo+γ-Mo2N composition increases from ~13 GPa to 30–34 GPa with increasing γ-Mo2N phase content, which also coincides quite closely with the data for coatings of the Τi-composition. But there is one significant difference, which, in this consideration, it is advisable to pay attention, namely – much lower thermal stability of molybdenum nitrides compared to titanium nitrides. This, on the one hand, limits the allowable substrate temperatures and displacement potentials for the formation of coatings with sufficient microhardness [35], and on the other hand, is one of the reasons that makes it attractive for use in friction pairs. The latter is due to the fact that at high contact loads in friction pairs on micro-irregularities that accept the greatest local loads, and therefore primarily wear out, local temperatures can develop that are sufficient to cause the decay of molybdenum-nitrogen compounds. In this case, it will be accompanied by a decrease in the hardness of the coating in these local areas, which, in turn, will reduce the wear of the coating, improve the serviceability of friction surfaces, the formation of such a surface structure that will adapt to certain conditions. High tribological properties of coatings based on Mo-N are noted by the authors of many works [25, 36, 37]. As in the case of titanium nitride coatings, studies of the deposition of nitride vacuum arc coatings based on molybdenum were performed to determine the optimal parameters of the process of obtaining high quality Mo coatings on hardened steel with low tempering temperature, polished to V12 purity class. These data are necessary to obtain further composite nano- and microlayer coatings based on molybdenum. The coatings were obtained at an ionic current density I=10 mA/cm2, an accelerating substrate potential Un=–25 V and a substrate temperature Tn
https://ebin.pub/vacuum-plasma-multilayer-protective-coatings-for-turbine-blades-9789916951651-9789916951644.html
In Compliance Magazine | www.rfmentor.com In Compliance Magazine The electrical and electronics engineers source for all things design, testing, and compliance. URL: https://incompliancemag.com Updated: FCC Orders Blocking of Calls from Robocall Gateway Facilitator The U.S. Federal Communications Commission (FCC) has issued a Final Determination Order in its continuing effort to block illegal overseas robocalls being transmitted through a gateway voice service provider. Adopted by the Commission, the Final Determination Order targets One Eye LLC, a Wilmington, DE-based company, for failing to comply with FCC call-blocking rules applicable to gateway providers. Specifically, the Order requires any voice service provider that downstreams calls from One Eye to block all traffic from the company and to cease accepting traffic from the company within 30 days. The Final Determination Order follows an Initial Determination Order issued against One Eye by the Commission in early April. That Order cited the company for failing to respond to an FCC Notice of Suspected Illegal Robocall Traffic issued earlier this year involving phone calls impersonating representatives from Bank of American and Verizon with claims of “preauthorized orders” placed “on your name.” Under the terms of the Initial Determination Order, One Eye had 14 days to respond and verify compliance with the FCC rules. The FCC says that One Eye failed to respond to that Order, hence the basis for its decision to issue a Final Determination Order. Read the complete text of the Commission’s Final Determination Order in connection with One Eye. The postFCC Orders Blocking of Calls from Robocall Gateway Facilitatorappeared first onIn Compliance Magazine. FCC Proposes Expansion of Short-Range Radar Operation In an effort to support the growth of short-range, state-of-the-art radar technologies, the U.S. Federal Communications Commission (FCC) has adopted new rules that expand the legal operating band. According to a Report and Order, the new rules will allow the deployment of unlicensed field disturbance sensors (a kind of radar device) to operate in the 60 GHz band. Field disturbance sensors are increasingly being used in a variety of important applications, including sensors that alert users to children that have been left in dangerously hot motor vehicles, and mobility and health devices that can detect hand gestures and respiratory functions. The 60 GHz band has traditionally been available for unlicensed operation of indoor/outdoor communication devices based on the WiGig standard, as well as wireless local area networking devices. Prior to the issuance of its Report and Order, the FCC has issued waivers of its rules in selected cases. Allowing the use of the expanded band range is expected to foster the deployment of additional devices that leverage the benefits of field disturbance sensors and speed the introduction of new and advanced radar-based devices to market. Read the FCC’s Report and Order on expanding short-range radar operations. The postFCC Proposes Expansion of Short-Range Radar Operationappeared first onIn Compliance Magazine. FCC Threatens Fines for Illegal Use of Mobile Frequencies A Pennsylvania man has been ordered to cease operating surveillance cameras that are interfering with cellular service in his area. According to a Citation and Order issued by the U.S. Federal Communications Commission (FCC), officers of the FCC’s Enforcement Bureau launched an investigation in June 2022 into claims by T-Mobile that harmful interference to its cellular services in the York, PA area was emanating from surveillance security cameras installed at a single-family home in York, PA occupied by Luis Martinez. The Bureau’s investigation confirmed T-Mobile’s findings, and Enforcement Bureau officers instructed Martinez to either remove the cameras or readjust the camera’s settings so that the device operated within the 2.4 GHz band. Although Martinez reportedly disconnected the cameras, he eventually switched them back, reinitiating the interference. Under the terms of the Citation and Order, Martinez has 30 days to stop using the devices or face financial penalties for failing to do so. Read the FCC’s Citation and Order issued to Martinez. As a sidebar to this story, an article posted to TheDesk.net website raises the possibility that the security cameras might have been erroneously marked as working on the 2.4 GHz spectrum when they were, in fact, operating on the 2.5 GHz band (the same band being used by T-Mobile and other cellular service providers). The postFCC Threatens Fines for Illegal Use of Mobile Frequenciesappeared first onIn Compliance Magazine. FCC Chair Proposes Videoconferencing Accessibility Requirements The U.S. Federal Communications Commission (FCC) appears to be on the verge of developing accessibility requirements applicable to videoconferencing platforms and software. According to a press release issued by the Commission, FCC Chair Jessica Rosenworcel has recently shared with her fellow Commissioners a proposal that would require videoconferencing platforms to comply with current FCC accessibility requirements and other FCC rules applicable to interoperable video conferencing services. The details of Rosenworcel’s proposal as presented in the press release reference prior FCC-issued documents, including a Notice of Proposed Rulemaking (NPRM) that would amend Part 14 of Commission rules to include specific performance objectives for making interoperable videoconferencing services accessible to all regardless of their abilities. Enhancements specified in that NPRM include speech-to-text and text-to-speech capabilities and enabling the use of American Sign Language (ASL) interpretation. Read the press release announcing Rosenworcel’s plans for implementing accessibility requirements for videoconferencing platforms and applications. We’ll provide additional details on Rosenworcel’s proposal as they become available. The postFCC Chair Proposes Videoconferencing Accessibility Requirementsappeared first onIn Compliance Magazine. Selecting Your Next Oscilloscope: Why Deep Memory Matters Understanding memory depth attributes and benefits ensures selection of a specific oscilloscope matches the desired needs and applications This application note focuses on oscilloscope selection considerations associated with acquisition memory. Selecting an oscilloscope with deep memory can result in significant troubleshooting and debug time-saving. This offer is sponsored by Download now. hbspt.forms.create({ region: "na1", portalId: "517027", formId: "a484ab09-7303-47ff-b8d3-d011de33ca1f" }); The postSelecting Your Next Oscilloscope: Why Deep Memory Mattersappeared first onIn Compliance Magazine. Rohde & Schwarz to host RF Design Challenge at IMS2023 Tue, 05/23/2023 - 14:07 This year at the International Microwave Symposium (IMS), Rohde & Schwarz is presenting  a new way to experience and demonstrate solutions for RF and microwave applications. At the company’s booth (#735), attendees can put their design knowledge to test with the Rohde & Schwarz “Are you a genius?” RF Design challenge. The challenge takes place during the IMS exhibit hours and will incorporate a series of lab challenges that evaluate attendee’s knowledge in s-parameters, EVM, high power, and baseband measurements. In addition to the RF Design Challenge, Rohde & Schwarz will highlight multiple demonstrations at the company’s booth. These include the new 67 GHz noise figure measurement capability that further enhances theR&S ZNA vector network analyzerto provide a powerful and versatile test system for full characterization of amplifiers and converters. On the road to 6G, revolutionary technology components that demand new ways of testing are driving the next generation of wireless communication. Several highlights at the Rohde & Schwarz booth are the latest solutions for early sub-terahertz and 6G research applications. TheR&S FExx external frontendsextend the frequency ranges of Rohde & Schwarz signal and spectrum analyzers, and signal generators up to the D band (110 GHz to 170 GHz) so engineers can access the range they need to develop the next generation of mobile communications. Additionally, both theR&S ZNAvector network analyzers and theR&S FSWP phase noise analyzerwill be demonstrating 6G D-band system and component characterization. Show attendees can experience up close theR&S ATS1800CCATR based 5G and 6G mmWave Over-The-Air (OTA) test chamber, which provides the ideal environment for testing antennas, modules and devices from R&D to conformance. When equipped with the two side chamber extensions, a unique 3D quiet zone is formed, with which the test solution supports on a very small footprint RRM measurements, including multiple angles of arrival (AoA). Rohde & Schwarz is exhibiting at IMS2023 in booth #735 in San Diego, CA, from June 13-15, 2023. Open to all attendees, Rohde & Schwarz experts will be participating in the IMS2023 Micro App sessions and workshops from June 12-16. For  show updates from Rohde & Schwarz, followRohde & Schwarz solutions for Electronic Design on LinkedIn. Source:Rohde & Schwarz RF Design Challenge The postRohde & Schwarz to host RF Design Challenge at IMS2023appeared first onIn Compliance Magazine. New Waveguide Power Amps Support Frequency Bands from 26.5 to 96 GHz Fairview Microwave, an Infinite Electronics brand, has unveiled a new series of waveguide power amplifiers designed to cover high mm-wave frequency bands from 26.5 GHz to 96 GHz. This range of waveguide power amplifiers delivers exceptional performance and adaptability to address the needs of a wide range of sectors including SATCOM, radar, wireless infrastructure, 5G and more. These advanced waveguide power amplifiers employ state-of-the-art GaAs and GaN MMIC semiconductor techniques, guaranteeing exceptional efficiency in a space-efficient package. Featuring gain levels ranging from 25 dB to 35 dB and output Psat levels extending from 20 dBm to 31 dBm, these amplifiers ensure top-notch performance throughout the popular Ka, Q, U, V, E and W bands. Fairview Microwave’s waveguide power amplifiers are designed to endure demanding conditions, incorporating sturdy, compact, MIL-grade, gold-plated aluminum waveguide enclosures. They operate in temperatures from -40° F to +176 F (-40° C to +80°C) and can withstand exposure to 95% relative humidity and altitudes up to 10,000 feet. These waveguide power amplifiers are ideal for a range of applications, such as satellite communications, research and development, prototype/proof of concept, test and measurement applications, and both airborne and ground-based uses. “These new waveguide power amplifiers allow our customers to exploit the potential of high mm-wave frequencies for their diverse applications. We are confident they will significantly benefit industries requiring high-performance communication and networking systems,” said Tim Galla, Product Line Manager. Source: Fairview Microwave, anInfinite Electronicsbrand The postNew Waveguide Power Amps Support Frequency Bands from 26.5 to 96 GHzappeared first onIn Compliance Magazine. SIGLENT TECHNOLOGIES Introduces Handheld Spectrum and Vector Network Analyzer SIGLENT TECHNOLOGIES has introduced the SHA850A series, its first handheld spectrum and vector network analyzer. The SHA850A series is highly integrated and specifically designed for field operation. It is lightweight and portable with accurate measurements and flexible analysis capabilities. This handheld spectrum and vector network analyzer can easily handle advanced characterization or signal capture applications in harsh working environments. SIGLENT’S SHA850A series is a complete portable solution that provides professional accuracy with flexible analysis capabilities. In spectrum analyzer mode, it can measure up to 7.5 GHz. The DANL is as low as -165 dBm, which can effectively identify small signal levels. The single sideband phase noise is <-104 dBc/Hz @1 GHz with a 10 kHz offset. An independent full frequency source and a 25 dB preamplifier is standard, providing fast scanning speed and high sensitivity for a variety of applications. The SHA850A series’ measurable frequency range in vector network analyzer mode and cable and antenna measurement mode is from 100 kHz to 7.5 GHz with a dynamic range as high as 114 dB. This critical range makes the SHA850A series suitable for applications such as measuring the passband and out-of-band rejection performance of filters at the same time as well as measuring narrow-band devices with high rejection. Source:SIGLENT TECHNOLOGIES The postSIGLENT TECHNOLOGIES Introduces Handheld Spectrum and Vector Network Analyzerappeared first onIn Compliance Magazine. SelecTech, Inc. Expands Aerospace Division SelecTech, Inc. recently announced the expansion of its aerospace division to better serve its airline, aerospace and defense customers. The new division will include specialized product offerings and additional personnel trained to serve aerospace customers. In addition to its interlocking ESD flooring product, SelecTech’s expanded aerospace will offer its PolyStyle Factory ESD floor to aerospace customers. PolyStyle Factory ESD Floor is most often used for warehouse, factory, and other sensitive working environments and has been found to be very effective for airport hangars in need of ESD flooring to protect electronic equipment from the impacts of static electricity. “More and more of our aerospace customers are finding that they have a need for ESD flooring, particularly with the advancements in the electronics being used,” said Thomas Ricciardelli, president of SelecTech, Inc. “The new expanded aerospace division has significant experience with surfaces used in the aerospace industry and can quickly and accurately determine if those solutions are working.” Adds Ricciardelli, “Older styles of resinous ESD flooring systems are often inconsistent and often fail ESD audits.” PolyStyle uses the most advanced conductive additives to ensure that the finished floor has the most uniform electrical properties throughout the entire floor that are guaranteed for the life of the floor.  This gives flooring superior static control properties from the top layer through the bottom. SelecTech received the by Mexican Technology Award for Best New ESD Material in Mexico for 2021 specifically for its PolyStyle Factory ESD Floor product. They received the award at the Surface Mount Technology Association (SMTA) International held in Minneapolis, MN. In addition, SelecTech’s StaticStop ESD tiles employ a breakthrough interlocking technology that dramatically reduces installation times, completely bypassing the need for adhesives and floor prep to install or replace flooring. Because machinery does not have to be completely moved or removed for installation, downtime for businesses can be minimized or even eliminated altogether. In addition to being made largely from recycled materials, SelecTech’s products are 100 percent recyclable. These materials create a static-controlled environment that’s perfect for industries that significantly utilize electronics and sensitive data like electronics manufacturing, communications, aerospace, biotech, healthcare industries, and other high-tech industries. Made with 70 percent recycled materials and 100 percent recyclable, SelecTech flooring products meet CA 1350 Indoor Air Quality and is MAS Certified Green. Source:SelecTech, Inc. The postSelecTech, Inc. Expands Aerospace Divisionappeared first onIn Compliance Magazine. EU Commission Updates Recognized Standards List for PPE Regulation The Commission of the European Union (EU) has released an updated list of standards that can be used to demonstrate conformity with the essential requirements of its Regulation (EU) 2016/425 concerning personal protective equipment (or PPE). The PPE Regulation, which took effect in April 2018, replaced the EU’s original PPE Directive (89/686/EEC). The Regulation is aligned with the EU’s new Legislative Framework policy and includes slight modifications to the scope and risk categorization of products. Under the Regulation, personal protective equipment is defined as “equipment designed and manufactured to be worn or held by a person for protection against one or more risks to that person’s health and safety hazards.” Specifically excluded from the scope of the Regulation is equipment designed specifically for use by armed forces or law enforcement personnel, equipment to be used for self-defense (except for that intended for sporting activities), and equipment intended for the protection or rescue of individuals on vessels or aircraft. The extensive list of CEN and Cenelec standards was published in the Official Journal of the European Unionand replaces all previously published standards lists for the Regulation. Read the complete updated standards list for the EU’s PPE Regulation. The postEU Commission Updates Recognized Standards List for PPE Regulationappeared first onIn Compliance Magazine. FDA Releases New Video on Cybersecurity in Healthcare Facilities As part of its effort to protect healthcare workers and patients from equipment malfunction attributable to cybersecurity breaches, the U.S. Food and Drug Administration (FDA) has released a new video to help healthcare facilities prepare for a potential cybersecurity event. Posted to the FDA’s website, the brief (about 3 minutes) video, titled “Tips for Heath Care Facilities: Cybersecurity Incident Preparedness and Response,” provides an overview of how facilities can create an emergency preparedness plan for cybersecurity incidents. The video also provides suggestions for helping to ensure patient safety during a prolonged cybersecurity event. The new video is one of a series of three released to date on the issue of cybersecurity risks impacting medical devices. The previously released videos include “Cybersecurity Awareness for Connected Medical Devices” and “Tips for Clinicians: Keeping Your Patients’ Connected Medical Devices Safe.” View the FDA’s video on cybersecurity tips for healthcare facilities. View the video “Cybersecurity Awareness for Connected Medical Devices.” View the video “Tips for Clinicians.” Other resources are available on the FDA’s website on medical device cybersecurity. The postFDA Releases New Video on Cybersecurity in Healthcare Facilitiesappeared first onIn Compliance Magazine. FDA Updates Consumer Information on OTC Hearing Aids In a separate development, the U.S. Food and Drug Administration (FDA) has also updated its information webpage for consumers on over-the-counter (OTC) hearing aids. Authorized by the FDA for sale in October 2022, OTC hearing aids are expected to help address a condition experienced by nearly 30 million adults in the U.S. who live with a mild to moderate degree of hearing loss. OTC hearing aids can be purchased in stores and online and no longer require a prescription or a visit to a licensed healthcare professional, provided that the purchaser is 18 years of age or older. The FDA’s updated information page on OTC hearing aids provides detailed information on labeling requirements for hearing aid packaging, as well as detailed guidance on the factors that consumers should consider when purchasing them. It also provides a list of additional resources about OTC hearing aids available elsewhere on the FDA’s website. Visit the FDA’s webpage on OTC hearing aids. The postFDA Updates Consumer Information on OTC Hearing Aidsappeared first onIn Compliance Magazine. NIST Releases Cybersecurity Discussion Draft The U.S. National Institute of Standards and Technology (NIST) has recently published a discussion draft as part of its plans to update the current version of its Cybersecurity Framework (CSF) Published for public comment, the preliminary discussion draft, titled “Discussion Draft of the NIST Cybersecurity Framework 2.0 Core,” includes planned updates to the core elements of the framework presented in CSF 1.1. It specifically addresses cybersecurity outcomes across 6 Functions, 21 Categories, and 112 Subcategories, and includes new informative examples. The goal of the proposed changes is to help increase the clarity of the CSF and to bring the updated version in closer alignment with national and international cybersecurity standards and practices. NIST says that public comments on the discussion draft will be incorporated into a draft version of CSF 2.0, which is expected to be released later this year. NIST’s cybersecurity discussion draft is available for review. Comments and other feedback on the draft can be submitted [email protected]. The postNIST Releases Cybersecurity Discussion Draftappeared first onIn Compliance Magazine. Outdoor AC Panel Surge Protectors with High-Capacity MOV, 100-300 kA Options Transtector, an Infinite Electronics brand, hasreleased a new line of outdoor AC panel surge protectors with high-capacity metal oxide varistor (MOV) technology. They effectively protect AC power networks and local AC equipment from transient surges and EMI interference. The new line of outdoor MOV AC panel surge protectors was designed to especially meet the needs of the telecommunications industry, industrial facilities, and IT and data centers. Transtector’s new AC panel surge protectors include models for all common AC services. These include 120 Vac single-phase, 120/240 Vac split-phase, 208/120 Vac three-phase wye, 277/480 Vac three-phase wye, 240 Vac three-phase delta and 480 Vac three-phase wye. They are available with 100 kA, 200 kA or 300 kA surge capacity per phase. The new outdoor devices are dual listed to meet two sets of Underwriter Laboratories’ safety and performance standards. They satisfy UL 1449 requirements as Type 2 SPDs and UL 1283 certification as EMI filters. The new AC panel surge protectors are rugged enough for outdoor use. They are housed in watertight, corrosion-proof NEMA 4X enclosures that mount to a wall. Their operating temperature range is -40 degrees to +167 degrees Fahrenheit. “Our new line of outdoor AC panel SPDs with MOV technology do double duty in protecting AC power networks and local AC equipment from harmful transient surges as well as EMI interference,” said Transtector Product Line Manager Dan Rebeck. Source:Transtector, an Infinite Products brand The postOutdoor AC Panel Surge Protectors with High-Capacity MOV, 100-300 kA Optionsappeared first onIn Compliance Magazine. ETSI Releases First Use Cases for Reconfigurable Intelligent Surface Tue, 05/16/2023 - 08:00 ETSI has announced the release of the first Group Report developed by its Reconfigurable Intelligent Surface Industry Specification Group.The ETSI ReportETSIGRRIS-001identifies and defines relevant RIS use cases, with corresponding general Key Performance Indicators (KPIs). It also describes deployment scenarios as well as potential requirements for each identified use case, to enable interoperability with existing and upcoming wireless technologies and networks. RIS is a new wireless technology for the control of the radio signals between a transmitter and a receiver in a dynamic and goal-oriented way. This has motivated a host of potential new use cases targeting at the enhancement of various system Key Performance Indicators (KPIs) and the support of new wireless technology applications and capabilities. These use cases include enhancements to the capacity, coverage, positioning, security, and sustainability, as well as the support of further sensing, wireless power transfer, and ambient backscattering capabilities. The ETSI Report,ETSIGRRIS-001, specifies 11 concrete key use cases where RIS deployment may provide enhancements or new functionalities. “ In the future 5G-Advanced and 6G wireless networks, many new applications, such as in eHealth, strongly impose requirements on both the communication and sensing performance,” explains Arman Shojaeifard, Chair of the ETSI RIS group. “ As an example, a RIS can reconfigure the radio environment to sense human posture and detect someone falling, a useful application for elderly care”he adds . Providing coverage continues to be a challenge for operators commercializing 5G, and existing deployment solutions such as IAB (Integrated Access and Backhaul) and NCR (Network Controller Repeater) may not be economically viable in all cases, e.g., indoor scenarios. RIS can serve as a new low-cost energy-efficient deployment solution for enhancing coverage performance in 5G-Adv and future 6G systems, by intently reflecting signals to and from the end users. RIS corresponds to a planar surface composed of a certain arrangement of unit-cells, whose properties can be dynamically controlled to change its response in the electromagnetic domain. RIS can be controlled dynamically and/or semi-statically through control signalling such to tune the incident wireless signals through reflection, refraction, focusing, collimation, modulation, absorption or any combination of these. RIS can be implemented using mostly passive components without requiring high-cost active components such as power amplifiers, resulting in low implementation cost and energy consumption. This allows flexible deployment of RIS, with the possibility of RIS taking any shape and to be integrated onto objects (e.g. walls, buildings, lamp posts, etc.). RIS are supposed to run as nearly-passive devices and hence are unlikely to increase exposure to EMF, and they can even potentially be used to reduce EM pollution in legacy deployments. These associated characteristics suggest RIS may be considered as a sustainable environmentally friendly technology solution. RIS may have different structures with considerations of cost, form factor, design and integration. Source:ETSI The postETSI Releases First Use Cases for Reconfigurable Intelligent Surfaceappeared first onIn Compliance Magazine. FCC Enforcement Bureau Steps Up Action in NYC Against Pirate Radio Operations In what may be a record level of activity in a single day, the Enforcement Bureau of the U.S. Federal Communications Commission (FCC) issued more than a dozen warnings to property owners in the New York metro area for allowing pirate radio operations on their properties. According to a press release, 16 separate Notices of Illegal Pirate Radio Broadcasting were sent to individual property owners located in New York City and in the area of New Jersey bordering the City. The targeted properties were reportedly identified during so-called Pirate Sweeps conducted by Enforcement Bureau field agents in 2022 and 2023 to date. Recipients of the Notices were informed of their potential liability for permitting the pirate broadcasts and ordered to submit evidence that pirate operations are no longer being conducted on their property. Failure to comply with the terms of the FCC’s Notice could subject non-compliant property owners to a maximum of over $2.3 million in financial penalties. Read the Enforcement Bureau’s press release regarding its crackdown on pirate radio operations in the New York metro area. Read the list of the 16 individual Notices issued by the Enforcement Bureau. The postFCC Enforcement Bureau Steps Up Action in NYC Against Pirate Radio Operationsappeared first onIn Compliance Magazine. EU Commission Updates Regulation on Standby Energy Consumption of Electrical/Electronic Equipment The Commission of the European Union (EU) has updated its ecodesign requirements applicable to electrical and electronic household and office equipment to address energy use in standby and off modes. Published in the Official Journal of the European Union, Commission Regulation (EU) 2023/826 sets new, lower power consumption levels for electrical and electronic devices to reflect technological progress. The Regulation also expands the scope of products subject to these requirements, including motor-operated furniture such as standing desks and window blinds and curtains. Here’s a summary of the energy usage requirements presented in the new Regulation: From 2025 on, devices must not consume more than 0.5 Watts in standby or in off mode, or 0.8 Watts if they are in standby mode while displaying their status or other information; From 2027 on, devices must not consume more than 0.5 Watts in Standby, 0.3 Watts in off mode, or 0.8 Watts if they are in standby mode while displaying their status or other information; and From 2027 on, devices in network standby mode must not consume more than 2 to 7 Watts, depending on the product. The Commission says that the updated energy consumption requirements will save an additional 4 terawatt-hour (TWh)/year of energy, with greenhouse gas emissions (GHG) emission reductions of 1.36 metric tons (MT) of carbon dioxide equivalent (CO2eq)/year by 2030. Read the Commission’s Regulation updating the energy consumption of electrical and electronic devices in off mode and standby mode. The postEU Commission Updates Regulation on Standby Energy Consumption of Electrical/Electronic Equipmentappeared first onIn Compliance Magazine. FDA Releases Latest Third-Party Review Performance Report The U.S. Food and Drug Administration (FDA) has published its most recent data on the performance of accredited third parties conducting primary reviews of medical devices under the Agency’s 510(k) process. The FDA’s “Third Party Review Organization Performance Report” summarizes the activity of third parties accredited by the FDA’s Accredited Persons Program who completed at least five 510(k) submissions during the first six months of fiscal year 2023 (October 1, 2022, through March 31, 2023). Created under the scope of the FDA Modernization Act of 1997, the FDA’s Accredited Persons Program is intended to improve the efficiency and timeliness of medical device 510(k) reviews and help speed market access for medical devices. During the 6-month evaluation period, the FDA accepted 35 submissions from FDA-accredited third parties, with 24 (69%) ultimately receiving final decisions from the FDA, with 11 decisions pending by the conclusion of the evaluation period. Unlike prior review periods, none of the submissions made during the review period were withdrawn by the device manufacturer for unspecified reasons. For those submissions receiving a final FDA decision, 96% were achieved within 30 calendar days, with an average FDA total review time of just 23 days. Average review times in the lowest 25th percentile of submissions were as low as 19 calendar days, while the maximum review time reached as long as 70 days. Read the complete text of the FDA’s latest Performance Report on its Accredited Persons Program. The postFDA Releases Latest Third-Party Review Performance Reportappeared first onIn Compliance Magazine. FCC Establishes Spectrum Management Principles for Transmitters, Receivers The U.S. Federal Communications Commission (FCC) has published a set of high-level principles that it says will guide its management of the electromagnetic spectrum in the future. The FCC’s Policy Statement, “Principles for Promoting Efficient Use of Spectrum and Opportunities for New Services,” presents a framework designed to consider both transmitter and receiver components of wireless systems. The goal of the framework is reportedly to promote improved receiver performance as a key focal point in making more efficient use of the available spectrum and enabling new and advanced wireless technologies to be introduced to the market. According to the FCC, the Policy Statement is based largely on proceedings held last year by the Commission, as well as research conducted by the FCC’s Technological Advisory Council. Read the text of the FCC Policy Statement on spectrum management principles. The postFCC Establishes Spectrum Management Principles for Transmitters, Receiversappeared first onIn Compliance Magazine. EMC Standards Overview Overview of the Latest Applicable EMC Standards The tests for EMC are defined in various standards and adopted by numerous organizations. It is imperative that products meet the requirements set forth in these standards, because, among basic interoperability, public safety also relies on the products to perform as intended. With a sizable number of EMC test standards available, keeping track of and knowing which standards to apply can be a difficult task. Read EMC Standards Overviewto review some of the more common standards used across the industry. Learn about some of the more common standards used across the EMC industry Learn tips for picking the correct standard This offer is sponsored by Read now. hbspt.forms.create({ region: "na1", portalId: "517027", formId: "471e1942-9586-450a-a654-713e7f7e8745" }); The postEMC Standards Overviewappeared first onIn Compliance Magazine. RF Mentor Academy/Subscription Animated Mismatch and Reflection Calculator Reflectometer Applet
https://www.rfmentor.com/aggregator/sources/6
Manual therapy in Hamstring Injury - Clinical Trials Registry - ICH GCP Fatigue influences the kinematics of the knee. Decreasing the tone of the suboccipital musculature may decrease the tone of the knee flexors. Inhibition of the... Miodural Bridge Stretching in Posture Modification in Professional Footballers Efficacy of a Physiotherapy Intervention by Stretching the Miodural Bridge in the Modification of Posture in Professional Soccer Players. A Randomized Clinical Study. Fatigue influences the kinematics of the knee. Decreasing the tone of the suboccipital musculature may decrease the tone of the knee flexors. Inhibition of the suboccipital musculature is used to improve ischiosural muscle tension. The main objective of the study is to evaluate the effectiveness of the stretching of the miodural bridge in the modification of the posture in professional soccer players of 3rd division. Randomized clinical trial. 30 players will be randomized to the two study groups: experimental (technique of stretching technique of the miodural bridge) and control (without intervention). A blinded evaluator will perform three evaluations: pretreatment, post-treatment and follow-up. The study variables will be: modification of posture and weight distribution (plantar pressure platform). The sample distribution will be calculated using a Kolmogórov-Smirnov analysis. The changes after each evaluation will be analyzed with the t-student test of related samples and through an ANOVA of repeated measures the intra and intersubject effect will be observed. The effect size will be calculated using Cohen's formula. After stretching the miodural bridge, it is expected to see improvement in posture changes. Study Overview Status Withdrawn Conditions Hamstring Injury Intervention / Treatment Other: Manual therapy Study Type Interventional Phase Not Applicable Contacts and Locations This section provides the contact details for those conducting the study, and information on where this study is being conducted. Study Locations Spain Comunity Of Madrid Madrid, Comunity Of Madrid, Spain, 28670 Universidad Europea de Madrid Participation Criteria Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments. Eligibility Criteria Ages Eligible for Study 17 years to 22 years (Adult) Accepts Healthy Volunteers No Genders Eligible for Study Male Description Inclusion Criteria: Football players Male From 18 to 23 years old That have a federation file in 3rd division in the Region of Murcia That you don't have any acute lesions at the time of the study. Exclusion Criteria: Subjects that: present some relevant subacute or chronic pathology that may have a direct impact on the processes or structures related to the study who have neurological problems or related to the vestibular system That receive a specific Physiotherapy training on any of the study regions Not sign the informed consent document Study Plan This section provides details of the study plan, including how the study is designed and what the study is measuring. How is the study designed? Design Details Primary Purpose: Prevention Allocation: Randomized Interventional Model: Parallel Assignment Masking: Single 2 Arms and Interventions <table><tr><th> Participant Group / Arm</th><th> Intervention / Treatment</th></tr><tbody><tr><td> No Intervention: Control group Athletes included in the control group will not perform any intervention, continuing with their usual routine.</td><td></td></tr><tr><td> Experimental: Experimental group The intervention will take place over a period of 4 weeks, with 2 weekly sessions, with an estimated execution time of 1.50 to 3 minutes each. A manual therapy technique of inhibition of the suboccipital musculature and an axial traction of the upper hemiarchy will be performed</td><td> Other: Manual therapy The patient will be lying supine, relaxed. The physiotherapist, located at the patient's head, will cover the occipital bone with one hand while the palm of the hand will rest on the lambdoid suture, and the fingers will be introduced into the suboccipital space. The other hand, with a glove, will be inserted into the patient's oral cavity, resting respectively the index and middle fingers, each in an upper dental hemiarchy, on the chewing face of the tooth. An axial traction will be carried out until the three tension barriers of equal size between them are overcome, in an estimated time between 1.50 and 3 minutes. All manual therapy sessions will be performed by the same physiotherapist, following the same protocol and under the same conditions.</td></tr></tbody></table> What is the study measuring? Primary Outcome Measures <table><tr><th> Outcome Measure</th><th> Measure Description</th><th> Time Frame</th></tr><tbody><tr><td> Change from baseline posture modification after treatment and at month Time Frame: Screening visit, within the first seven days after treatment and after one month follow-up visit</td><td> An evaluation will be carried out with a pedometric platform. For the evaluation of plantar pressures, we use a plantar pressure platform (Podoprint® S10Pro model). This platform has 4,096 sensors, which allow a maximum pressure of 100 N / cm2 per sensor and has a sampling frequency of 150 Hz. All measurements will be made in accordance with international standards for anthropometric evaluation. All the evaluated players will adopt a relaxed and inert bipedal orthopedic position (arms held at the sides of the body, barefoot, with clothes that allowed to see the feet, legs and knees). With eyes open and looking at a fixed point, at a distance of 1.50 m for 20 seconds.</td><td> Screening visit, within the first seven days after treatment and after one month follow-up visit</td></tr></tbody></table> Secondary Outcome Measures <table><tr><th> Outcome Measure</th><th> Measure Description</th><th> Time Frame</th></tr><tbody><tr><td> Change from baseline modification of the weight distribution after treatment and at month Time Frame: Screening visit, within the first seven days after treatment and after one month follow-up visit</td><td> An evaluation will be carried out with a pedometric platform, to assess the distribution of body weight after the intervention by stretching the Miodural Bridge. The unit of measure will be the percentage of weight in each of the evaluations</td><td> Screening visit, within the first seven days after treatment and after one month follow-up visit</td></tr></tbody></table> Collaborators and Investigators This is where you will find people and organizations involved with this study. Sponsor Investigación en Hemofilia y Fisioterapia Study record dates These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website. Study Major Dates Study Start (Actual) March 2, 2020 Primary Completion (Actual) May 20, 2020 Study Completion (Actual) June 10, 2020 Study Registration Dates First Submitted February 27, 2020 First Submitted That Met QC Criteria February 27, 2020 First Posted (Actual) February 28, 2020 Study Record Updates Last Update Posted (Actual) September 5, 2021 Last Update Submitted That Met QC Criteria September 1, 2021 Last Verified September 1, 2021 More Information Terms related to this study Keywords Soccer Flexibility Hip joint Hamstring muscle Suboccipital muscles Other Study ID Numbers POST Drug and device information, study documents Studies a U.S. FDA-regulated drug product No Studies a U.S. FDA-regulated device product No This information was retrieved directly from the websiteclinicaltrials.govwithout any changes. If you have any requests to change, remove or update your study details, please [email protected]. As soon as a change is implemented onclinicaltrials.gov, this will be updated automatically on our website as well. Clinical Trials on Hamstring Injury NCT05786300 Not yet recruiting Effect of NMES+ on Hamstring Lesion (3a/3b) Hamstring Injury | Hamstring Sprain | Muscle Rupture NCT05727501 Recruiting Comparison of Post Isometric Relaxation and Post Facilitation Stretching on Hamstring Muscle Flexibility Hamstring Injury NCT05702593 Recruiting Immediate Effects of Hamstring Stretching Alone or Combined With Myofascial Release Temporomandibular Joint Disorders | Hamstring Injury | Masseter | Myofascial Release | Stretching | Surface EMG NCT05345015 Recruiting High Frequency RF Current Effects on Muscle Pain and Function Chronic Low-back Pain | Physical Therapy | Hamstring Injury | Transcutaneous Electric Nerve Stimulation | Muscle; Injury, Quadriceps (Thigh) | Calf Muscle Pulled NCT04246515 Recruiting The Effect of Blood Flow Restriction Training on Hamstring Elasticity After Injury Hamstring Injury NCT03868826 Recruiting Pain, Function and Quality of Life Before and After Treatment of Hamstring Avulsion Hamstring Injury NCT03373084 Recruiting Imaging Location of Hamstring Muscle Lesions in Sport and Relationships With Injury Mechanism. (HAMMER) Sport Injury | Hamstring Muscle Lesions NCT05655585 Completed Comparison of Mulligan Bent Leg Raise vs Active Release Technique in Patients With Hamstring Tightness Hamstring Injury NCT05904834 Completed Effect of a Flexibility Program on the Extensibility of the Hamstrings and the Thoracic and Lumbar Spinal Curvatures Spine Injury | Kyphosis | Hamstring Injury | Lumbar Hyperlordosis NCT05343052 Enrolling by invitation Hamstring Injury (HAMIR) Index Hamstring Injury Clinical Trials on Manual therapy NCT05917080 Recruiting Efficacy of Neuromuscular Training and Manual Therapy With Augmented Low-Dye Taping Technique for Correction of Pronated Foot in the Management of Anterior Knee Pain (AKPS NPRS FPI) Anterior Knee Pain Syndrome | Pronated Foot NCT05891704 Not yet recruiting The Efficacy of Hand Injuries Rehabilitation Intervention Program That Incorporated Ethnic and Cultural Reference Multiple Injuries of Hand (Disorder) NCT05883319 Recruiting The Effect Of Cervical Mobilization And Clinical Pilates in Cervicogenic Headache Exercise | Therapeutics | Headache, Cervicogenic NCT05861856 Not yet recruiting Manual Therapy and Virtual Reality Supported in Patient With Adolescent Idiopathic Scoliosis Adolescent Idiopathic Scoliosis NCT05851703 Not yet recruiting The Effects Of Instrument Cervical Manual Therapy Methods And Proprioceptive Neuromuscular Facilitation Techniques Neck Pain NCT05852314 Not yet recruiting A Problem-Solving Intervention for Women With Suicidal Ideation During Postnatal Period in Pakistan Postnatal Depression NCT05843149 Recruiting Manual Therapy/Exercises vs. Physiotherapy/Back School vs. Waiting List in Patients With Chronic Low Back Pain Chronic Low-back Pain NCT05823909 Not yet recruiting A Randomized, Multicenter Study of the Safety and Performance of Fabian PRICO for Saturation Targeting With Non-invasive Respiratory Support Respiratory Insufficiency Syndrome of Newborn NCT05781867 Not yet recruiting Selective Manual Therapy Techniques in Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease NCT05780593 Recruiting Effects of Manual Therapy and Inclined Board Standing on Low Back Pain Low Back Pain
https://ichgcp.net/clinical-trials-registry/NCT04290065
Oticon Agil Hearing Aid | Reviews and Prices Read real consumer reviews for the Oticon Agil and compare models like the Oticon Agil miniRITE, Oticon Agil RITE, Oticon Agil miniBTE, Oticon Agil BTE, Oticon Agil CIC/MIC, Oticon Agil ITC, Oticon Agil HS, and Oticon Agil LP/FS. The Oticon Agil may no longer be available.Show newer Oticon hearing aids. Oticon Agil Hearing Aid About the Oticon Agil The Oticon Agil is a family of hearing aids that includes at least 8 unique models and 2 unique technology levels . Models include the Agil miniRITE , the Agil RITE , the Agil miniBTE , the Agil BTE , the Agil CIC/MIC , the Agil ITC , the Agil HS , and the Agil LP/FS . Technology levels include the Agil and the Agil Pro . Oticon Agil Model Comparison Oticon Agil miniRITE Oticon Agil RITE Oticon Agil miniBTE Oticon Agil BTE Oticon Agil CIC/MIC Oticon Agil ITC Oticon Agil HS Oticon Agil LP/FS Rating 63% 13 reviews 58% 8 reviews 0% 0 reviews 71% 5 reviews 71% 2 reviews 0% 0 reviews 58% 2 reviews 0% 0 reviews Disposable Batteries Battery Size 312 Battery Size 312 Battery Size 312 Battery Size 13 Battery Size 10 Battery Size 312 Battery Size 312 Battery Size 312 IP Rating (Liquid) 7 7 7 7 IP Rating (Solid) 5 5 5 5 Push Button Telecoil Volume Rocker Model details listed above may be incomplete or inaccurate. For full specifications please refer to product specifications published by the original equipment manufacturer. To suggest a correction to the details listed, please email [email protected]. Oticon Agil Technology Levels Oticon Agil Oticon Agil Pro Rating 59% 7 reviews 64% 23 reviews Directionality Unavailable for CIC/MIC Adjustment Synchronization Unavailable for CIC/MIC Technology specifications listed above may be incomplete or inaccurate. For full specifications please refer to product specifications published by the original equipment manufacturer. To suggest a correction to the details listed, please email [email protected]. Oticon Agil Reviews Hearing aid reviews are fundamentally different from reviews for most other consumer electronic products. The reason is because individual factors, like degree of hearing loss, have a profound effect one's success and overall satisfaction with the product. When purchasing a hearing aid, you'll need to consider more than just your hearing outcome ...Continue reading Overall Ratings Hearing Tracker uses aten-question surveyto assess consumer feedback on hearing aids. The percentage bars below reflect the average ratings provided per question, averaged across all hearing aids belonging to this family of devices. Note: Original answers provided in star rating format. Benefit in Quiet No data available 78% Benefit in Noise No data available 46% Benefit on the Phone No data available 57% Clear and Natural No data available 70% Music Improvement No data available 60% Physical Comfort No data available 78% Reliability No data available No data available 57% Hearing Improvement No data available 70% Value No data available 60% 1.5 stars stars Oticon Agil Oticon Agil miniRITE Fair. My main problem is getting the connect line working. It seems of no value. I do not know how to use. 2.5 stars stars Oticon Agil Pro Oticon Agil RITE Updating possibly to phonak Marvels soon reply Oticon Agil Pro Oticon Agil RITE My life is so much better with the HAs. It's also much better for those around me. Oticon Agil Oticon Agil miniRITE These were expensive but lasted 8 years and are still working fine. They have accidentally dipped briefly in the swimming pool with no harm. Batteries last almost a week turning them off at night. Basically a very good product but I want new technology and hands free phone interconnect. I also use Oticon OPN1.  One of the main reasons to choose OPN1 was the promise that it has low power Bluetooth to connect directly to my mobile phone, after I had bought them I was told that this feature works with an IPhone only. It still doesn't work with Android 9, and it will never work with Android. The next-generation will work with Android... I feel really cheated! I hope, in near future self_programmable hearing aids will come, then I will never again enter an audiologistic car seller! Oticon Agil Pro Oticon Agil RITE I have had these Oticon Agils since 2009. Hoping to get a pair of Oticon Opns from the VA in 2018 Oticon Agil Pro Oticon Agil HS I've been very pleased with Oticon hearing aids. Very little problems with them. My Oticon Agil Pros were top of the line 8 years ago, but I'm looking to replace them with newer aids that can offer improved speech comprehension and iPhone compatibility. Oticon Agil Pro Oticon Agil CIC/MIC without hearing aids I'm not able to have any meaningful conversation, and with the aids I an function normally, so they are really a very big improvement reply Oticon Agil Pro Oticon Agil miniRITE Slight improvement of speech, big improvement feeling part of environment, hear birds etc. 1.5 stars stars Oticon Agil Pro Oticon Agil miniRITE My first HA, received them in 2012. Used open domes for 3 years then went to molds in 2016 to reduce feedback. Sounds were very unnatural, causing confusion at times, useless in noisy situations. Oticon Agil Pro Oticon Agil miniRITE I have hearing aids in both ears since about 15 years for 12 to 14 hours a day. Without hearing aids I cant't hear anything at all. For watching TV I have to use hearing aids and headphones. In normal situations, together with some family members at home i can understand quite well, in noisy environment with many talking people conversation is imposssible. 28 February 2018 These aids were the best (and most expensive) that Oticon made at the time I purchased them many years ago, however they are still going really well stop despite no longer being the latest and greatest. Looking to upgrade. Had to have the HA repaired both in and out of warranty. Overall the Agil Pro are adequate but not the best in noisy situations or when multiple conversations are going on. Lately been having difficulty at movie theaters with the dialog. I suffer from moderate hearing loss and tinnitus and tried out the OPN 1 earlier this year but found that my insurance no longer covered HA. Very pleased with the OPN 1 but at $6500 a little pricey with no insurance. Had them for 6 years. Have tinnitus in both ears. Have Meniere's disease focused on right ear. Eustachian tubes blocked frequently, reducing hearing. I would love to be able to program my aids myself, but fear to be unable to learn how. Have Genie software on PC, but no way to connect the Agil Pros. Also believe that new aids for $6,000 plus would not "pay for themselves." Wish that I was wrong in preceding assumptions. Audi's in past all seemed to want to to nothing but sell additional equipment, not refine HA programming. This has me reluctant to pay their high price for their HAs and promises. Also HA marketing has not changed in past 6 years. Still making same claims the the Agil Pros were not able to deliver. upgrading to oticon opn I didn't realize how much I was missing until I got my aids My Oticon Agil Pro BTE was purchased about 5 years ago. In that time I have experienced good to excellent results in most hearing environments. My choices of hearing aids is somewhat limited by the severity of my hearing loss. The inclusion of the Oticon Streamer and the Oticon TV Sound Transmitter were invaluable investments. So much so that an upgraded Streamer was purchased about 6 months ago. I am extremely fortunate to have health insurance that pays 80% of the cost thus making the Oticon affordable. My audiologist has been most helpful in keeping the aids working throughout the time I've had them. The audiologist is preferred by myself above all but one of the 6 or 8 that I have had association with. on-device buttons have failed on both aids intermittent short in one ear - after 5 years. The Agil Pro MiniRITE is a huge step up from the Resound BTEs that I had before. It has improved speech and noise processing to allow recognition of conversations. It also has a smaller form factor and has matching colors with the hair to allow inconspicuous usage. It also uses a new 312 battery type and still has the same battery life of 2-5 days. It comes with a Streamer that can be used with phones and laptops with Bluetooth, but the sound is monaural and not stereo. All in all, this is a great hearing aid for the sound quality. I find on many occasions that I don't need the hearing aids. When I'm in noisy situations, like a dinner party, it makes a difference, but not in too noisy of an environment. My hearing aids were provided by the VA and I use the streamer to adjust the hearing aids and receive telephone calls. I find the streamer helpful. The part I like best about these aids is the fact that the background noise is in the background where it should be. Voices are closer to my ears and more understandable since that the sound I want to hear the most. Noisy surroundings are much quieter, and sometimes the normal friends talk about how noisy the situation is, but I am comfortable. How, I wish I had these aids while I was working in the classroom setting and raising a family. Isn't technology great! Function pretty well with some problems with feedback in car and with phone. Sent for repair twice and issue fixed. I like my Oticon Agils quite a bit. They are a big improvement over my old Oticon Deltas. My main reason for upgrading was for connectivity to cell phones and my home and work phone. The bluetooth connections work with varying success, depending on the phone. I have one cell phone that connects 90% of the time. Another cell phone (a new Windows Nokia Phone) that has successfully connected with my Oticon Streamer Pro exactly once. I have very good luck with the streamer and my work/desk phone using an old Plantronics 500A box. I have had mixed results with the Streamer and the Connect Line phone connect box for my home phone. I have found the streamer to be really helpful to adjust volume when in meetings - allowing me to quickly turn the volume up and down, based on the location and volume of the person speaking. I have mixed success connecting the Streamer to an FM receiver in conference settings. I found that it is better to connect an FM receiver to a neck loop or ear hooks. While I had some initial issues with the programming, once that was figured out, I have been pretty happy with these aids. The Oticon rep was at my audiologist's office on one of my visits, and he felt like I was getting the maximum benefit from the instruments based on the degree of my loss. hearing aids generally good. wind noise is very bad. hearing in noise is poor. telecoil works very well. Great hearing aids generally, main pros are bluetooth phone capabilities and moisture resistance. The only would be their lack of performance in a noisy setting. Use the form below to leave a quick comment about the Oticon Agil. Alternatively, consider providing more thorough feedback using our hearing aid review system. If you review your hearing aids using our review system, we'll send you a$5 promotional creditfor use in ourhearing aid battery shopas a special thank you.Review your hearing aids now. Where can I get my Agil Pro Serial # 16386310 serviced in the St Louis Mo area? How different are all these various models? Just lost my right ear Ino Pro, and looking to find a used replacement. They were synchronized. Can a different but similar model synchronize? My ears aren't symmetric in their hearing loss, so I don't see that exactly matched hearing aids are a necessity otherwise.
https://www.hearingtracker.com/hearing-aids/archived/oticon-agil#deals
(PDF) Numerical studies of a second harmonic RF cavity for the IPNS RCS PDF | The Intense Pulsed Neutron Source (IPNS) Rapid Cycling Synchrotron (RCS) delivers 450-MeV protons in 70 ns pulses at 30 Hz to a heavy-metal target... | Find, read and cite all the research you need on ResearchGate Conference Paper PDF Available Numerical studies of a second harmonic RF cavity for the IPNS RCS February 1999 DOI: 10.1109/PAC.1999.792657 Source IEEE Xplore Conference: Particle Accelerator Conference, 1999. Proceedings of the 1999 Volume: 4 Authors: Argonne National Laboratory This person is not on ResearchGate, or hasn't claimed this research yet. US-ITER ORNL Abstract and Figures The Intense Pulsed Neutron Source (IPNS) Rapid Cycling Synchrotron (RCS) delivers 450-MeV protons in 70 ns pulses at 30 Hz to a heavy-metal target producing spallation neutrons for material science research. The average current extracted from the RCS is 15 μA with a peak intensity of 10 amps. The large circulating currents in the RCS generate oscillations in the bunch which are presently controlled by modulating the phase of the two RF cavities. By adding second harmonic (SH) rf, the bunch length can be increased reducing the peak current. Simulations suggest that a 20-40 percent increase in extracted current should be achievable. The simulation program allows for phasing between fundamental and SH RF voltages. Initial studies to optimize phase indicate the need to maximize bucket area early in the acceleration cycle, whereas the bunching factor is more significant later in the cycle Evolution of stable phase-space in the RCS showing the effect of SH rf and space-charge Longitudinal equations of motion for energy and phase may be written as, … Figures - uploaded by Jeffrey Craig Dooling NUMERICAL STUDIES OF A SECOND HARMONI C RF CAVITY FOR THE IPNS RCS * J. C. Dooling ✷ , F. R. Brumwell, G. E. McMichael, M. E. Middendorf, and R. A. Zolecki, ANL, Argonne, IL _______________________________________________________________________________ * Work suppor ted by U.S. D OE, Contract W -31-109- ENG- 38 ✷ Email: [email protected] Abstract The Intense Pulsed Ne utron Source (IPNS) Ra pid Cycling Synchrotron ( RCS) delive rs 450-Me V protons in 70 ns pulses at 30 Hz to a hea vy-meta l target pr oducing spallation neutrons for material science research. The average current extracted from the RC S is 15 µ A with a peak intensity of 10 Amps. The large circula ting currents in the RCS genera te oscillations in the bunch which a re presently controlle d by modulating the phase of the two rf cavities. By a dding second har monic (SH) rf , the bunch length can be increased red ucing the peak current. Simulations suggest that a 20-40 perce nt increa se in extracted current should be achievable. The sim ulation program allows f or phasing betw een f undamenta l and SH rf voltages. Initial studies to optimize phase indicate the need to maximize buck et area early in the acceleratio n cycle, whereas bunching factor is more significant later in the cycle. 1 INTRODUCTION During the 1998 Fiscal Ye ar, the I ntense Pulsed Neutr on Source ( IPNS) conducted 354 exper iments and w as oversubscr ibed by almost a factor of two. I PNS is looking at several optio ns to accommo date the deman d for neutrons. O ne option is to inc rease the neutron flux available f rom the sour ce by ra ising the incident pr oton beam c urrent. I nstalling a second ha rmonic (SH) rf cavity in the RCS will increase the current limit of the synchrot ron an d d ecrease capture losses. The SH rf cav ity should raise proton current to the ta rget by 20-40 pe rcent. Based upon this incr ease, IPNS c ould conduct an additional 100 experim ents annually. Alternatively, higher curre nt would improve the signal-to-noise ratio in collected da ta or provide better r esolution for expe riments. SH rf was first pr oposed for the IPNS in the early 1980’s but not pursued due to funding constra ints and loss of personne l[1]. E lsewhere , ISIS is preparing to insta ll a SH system which is expected to result in a 50 percent increase in curren t from their RC S[2,3]. 2 MODELING Several approach es are used to model capture and acceleration in the RCS. A longitudinal particle dynamics code, CAPT URE_SPC[4,5]( CAPT) is em ployed to study trapping and loss of injected be am including the effec ts of space ch arge. A predictor-co rrector algorithm is u sed to indepen dently comp are phase-space area to that calculated with CAPT for the case o f no space charg e. Both analyses yield essentially identical results for the bucket phase- space area. The evolu tion of RCS bu cket size during the acceleration cycle is sh own in Fig ure 1. Figure 1: Evo lution of stable p hase-space in the RCS showing the effect of SH rf an d space-charg e Longitudinal equa tions of motion f or ene rgy a nd phase may be written as, [] ) ( V ) , ( V ) , ( V 2 q E dt d sc s o φ + θ φ − θ φ π =       ω ∆ (1) s s 2 o E E h dt d ∆ β η ω = φ ∆ (2) where q is th e charge, V is the amplitu de of the rf vo ltage, φ is the phase of the bunch with r espect to the rf, h is the harm onic number (h=1, in the IPNS RCS), ω ο is the cyclotr on fre quency, η is the slip factor, β = v/c, E is the total energy of the particle, and the subscript s refers to the synchronous par ticle. I n the RCS β var ies f rom 0. 316 at injection to 0.737 at extraction c orresponding to a fre quency ra nge of 2. 21-5.14 M Hz. Allow ing for the presenc e of a se cond harm onic, 0-7803-5573-3/99/$10.00@1999 IEEE. 2274 Proceedings of the 1999 Particle Accelerator Conference, New York, 1999 [] ) 2 sin( ) sin( V ) , ( V θ + φ δ − φ = θ φ (3) where δ is the ratio of se cond to first ha rmonic a mplitudes and θ is phase shift. Th e space charge term may be expresse d as, 2 2 2 2 o o sc R 1 c L 2 Rg d ) ( d q V         β − γ ε φ φ λ − = (4) where λ is line density, g ο is the capacitive coupling factor , and L is tota l inductance per turn. CAPT tracks particles using a leap-frog algorithm to achieve second- order accu racy. Figure 2 p resents phase-sp ace and separa trix results f or the RCS with fundam ental-only r f, 8 ms after injection. A g aussian energy spread is assumed at injection with ∆ p/p=0.3 per cent, FWH M. Figure 2: a) B unch and ph ase-space from CAPT and b) current prof iles from CAPT ( ❑ ) and HP (  ) for fundam ental-only r f at t= 8 ms. 2.1 Bunch Factor With proper pha sing, SH r f raise s the bunch fa ctor ( BF) by flattening the longitudinal curr ent density pr ofile. Reducing the peak curre nt density is one me thod of delaying the onset of current-driven instabilities[6,7]. BF is define d as, ∫ φ φ π = φ φ 2 1 max d I ) ( I 2 1 BF (5) The original im pleme ntation of CAPT has been modified to allow for variation in θ to optimiz e BF. In Figure 3, CAPT results are presen ted with δ =0.55 and θ = -1.072 r ad, which maxim izes BF at 0. 487; for the funda mental- only case show n in Fig. 2, BF=0. 306. In both ca ses, the sam e rf voltage program is used. Figure 3: Sam e as Fig. 2 but with SH ( δ =0.55) and θ to maximize BF. 2.2 θ and Losses Modifying θ can h elp reduce acceleration losses. For the IPNS rf voltage progra m, the buc ket tends to shrink until reaching a minimum near B . max . CAPT predicts that after the initial trapping loss, particles continue to leave the bucket as the bunch is accelerated. The bunch fills the entire av ailable ph ase-space after capture; th erefore, any reduction in the bucket size will result in losses. The reduction in buc ket size betwe en 3 and 7 ms is evident in Fig. 1. For a given δ , maxim izing BF during the acceleration cycle b y vary ing θ , results in a smaller stable phase-space area (b ucket size) than with θ =0. The resulting loss can be seen in Figures 4 a) and b). Note that overall efficiency is improved relative to the θ profi le wh ere BF is max imi zed ( θ m ). However, to in crease the current limit of the machine, θ should be varie d to increa se the BF. The simulation shows that it should be possible to adjust θ to maximize bucket size early in the cycle, th en increase the BF to reduce the p eak currents during th e later stages of acceleration . One possible strategy is presented in Figur e 5. The SH pha se angle is kept at 0 until B . max (8 ms, jus t after the mini mum buck et size), then ramped to θ m at t=10 m s. T he BF is brought to its maximum value after B . max , where stable ph ase- space is increasing with time and , according to the analysis, acceleration lo sses cease. 2275 Proceedings of the 1999 Particle Accelerator Conference, New York, 1999 Figure 4a: Capt ure and acceleration losses Figure 4b: Integrated lo ss rate for three rf cases: δ =0.55, θ =0; δ =0.55, θ = θ m ; and fundam ental r f only. 3 CURRENT LIMITS Hoffman-Pedersen (HP) distribu tions[7 ] are used to examine current limits in the RCS. HP current profiles are shown in Figur es 2 and 3 along with CAPT results. For the case of funda mental- only rf, peak cur rent value s at 8 ms are 6.7 A and 7.1 A f rom H P and CAPT, respec tively; using SH rf with am plitude and phase a s shown in Fig. 3, the peak cur rents ar e 4.5 A a nd 5.1 A. HP analysis indicates a microwave instability current limit for the m achine in the range of 10- 11 A. In the fundame ntal case just pr ior to e xtraction, peak current has risen to 10.8 A accord ing to CAPT, in agreement with curre nt-toroid me asurem ents. With phased SH r f, near extraction time, calculations with CAPT predict a peak current of 7 .8 A for the same in jected charg e. Presently, the IPNS RCS is operating close to its current limit. By introducing SH rf with a third cavity, it should be possible to ra ise the curr ent delivere d to the target by 20-40 perc ent. Figure 5: Phasing of the SH rf f or a) m aximum BF a nd b) better transmission ( δ =0.55). Phase-sp ace conto urs before and after the ramp are also sho wn. 4 REFERENCES [1] J. Norem, F. Brandeber ry, and A. Rauchas, IEEE Tr ans. Nuc. Sci., 30 (4), 3490( 1983). . [2] C. R. Pr ior, Proc. of the Twelfth Meeting of the International Collaboration on Advanced N eutron Sour ces, Abingdon, May 1993, RAL 94-025, V ol. II, p. A -11. [3] M. R. Harold, M. G . Glover, I. S . K. Gar dner, and R. G. Bendal, “A Proposal to I mprove the Pe rform ance of ISI S,” ISI S Management Committee Report I MC/P16/96, 1996. [4] Y. Cho, E. Lessner, K . Symon, Proc. European Particle Accelerator Conf., p. 1228, (1994) . [5] E. Lessner and K. Symon, Com putational Accelerators Physics, Williamsbur g, Virginia, Se ptember 1996, AI P Conf. Proc. 391, p.185 (1997). [6] P. Bramham, S. Hansen, A . Hofmann, E. Peschardt, I EEE Trans. Nuc. Sci., 24 (3) , 1490(1977). [7] A. Hofm ann and F. Pedersen, IEEE Trans. N uc. Sci., 26 (3), 3526 (1979). 2276 Proceedings of the 1999 Particle Accelerator Conference, New York, 1999 ... Design and construction of a new predriver amplifier for a third rf system began in 1998. Simulation studies performed in 1999 suggested that a 20 to 40 percent increase in the extracted beam current could be realized with the addition of a second harmonic system capable of operating over the entire frequency sweep [2] . Funding was not available to develop a full second harmonic cavity, but adequate spare parts were available to assemble a third cavity identical to the original two cavities. ... ... Best operation for capture and initial acceleration is with the second harmonic at approximately zero phase relative to the fundamental (physically, the L6 cavity is 240 degrees around the ring from the reference cavity L2) and with the second-harmonic to fundamental voltage amplitude ratio equal to approximately 0.5. This agrees well with simulations [2] . Single-turn fundamental and second harmonic voltages, and the vector sum, at ~1.8 ms after injection, are shown in Figure 4. ... The IPNS second harmonic RF upgrade Conference Paper Full-text available Jul 2007 Mark Middendorf F.R. Brumwell Jeffrey Craig Dooling S. Wang The intense pulsed neutron source (IPNS) rapid cycling synchrotron (RCS) is used to accelerate protons from 50 MeV to 450 MeV, at a repetition rate of 30 Hz. The original ring design included two identical rf systems, each consisting of an accelerating cavity, cavity bias supply, power amplifiers and low-level analog electronics. The original cavities are located 180 degrees apart in the ring and provide a total peak accelerating voltage of ~21 kV over the 2.21-MHz to 5.14-MHz revolution frequency sweep. A third rf system has been constructed and installed in the RCS. The third rf system is capable of operating at the fundamental revolution frequency for the entire acceleration cycle, providing an additional peak accelerating voltage of up to ~11 kV, or at the second harmonic of the revolution frequency for the first ~4 ms of the acceleration cycle, providing an additional peak voltage of up to ~11 kV for bunch shape control. We describe here the hardware implementation and operation to date of the third rf cavity in the second harmonic mode. View ... Initially, the emphasis had to be on updating or replacing those subsystems that were becoming obsolete (spares no longer available or nearing end-of-life) and controlling losses so that operating hours could increase without increasing the activation of components. Calculations [6] showed that improving synchrotron rf system capabilities could reduce beam losses, and had the further advantage of providing redundancy to improve reliability. Thus, fifteen years after the original proposal, work started on a third rf system [7] for the RCS. ... Accelerator research on the rapid cycling synchrotron at IPNS Article Full-text available Jan 2006 G.E. McMichael F.R. Brumwell L.I. Donley M. R. Moser ... It was specified to provide 168 kW of unregulated DC power in either of two configurations; 24 A at 7 kV or 12 A at 14 kV. The two output configurations were specified with future second-harmonic RF [2] and cathode-follower amplifier studies in mind. ... The IPNS RCS RF-system third cavity upgrade Conference Paper Full-text available Feb 2001 Mark Middendorf F.R. Brumwell Jeffrey Craig Dooling G.E. McMichael The IPNS RCS is a rapid cycling synchrotron used to accelerate protons from 50 MeV to 450 MeV, 30 times per second. Currently, two single-gap, ferrite-loaded coaxial cavities, located 180° apart, provide a total peak accelerating voltage of approximately 21 kV over the 2.2 MHz to 5.1 MHz revolution frequency band. An amplifier chain, which includes a 2 kW predriver, a 20 kW driver and a 100 kW final, drives each cavity. A third RF system, consisting of a cavity, cavity bias supply, and amplifier chain, is currently under construction. When complete, this upgrade will provide flexibility in operation that is expected to enhance reliability (i.e., three cavity operation at higher total accelerating voltage, three cavity operation at lower voltage per cavity, or two cavity operation with an on-line spare). In addition, the third cavity will provide an experimental station for second harmonic RF cavity studies. We report progress to date Bunches with Local Elliptic Energy Distributions Article Full-text available Jul 1979 IEEE T NUCL SCI Albert Hofmann Flemming Pedersen This distribution fits well with distributions observed in proton synchrotrons and makes several analytical calculations for bunched beams in longitudinal phase space possible. For any shape of the focusing force the line density becomes proportional to the potential well. Self-forces caused by space-charge and inductive wall impedances are thus proportional to the external force, making calculation of bucket area reduction and bunch lengthening easy. The microwave instability threshold, as given by the Keil-Schnell criterion with local values for current and energy spread, is independent of the azimuthal position along the bunch, and again analytical formulae are possible even for strongly non-linear focusing forces. The relative magnitude of the self-force and the microwave threshold turn out to be closely related, as the self-force is always 40% of the external force when the microwave threshold is reached. The classical longitudinal space-charge limit can therefore only be reached within a factor of 0.4. Other calculations with this "natural" distribution include analytical formulae for the rigid dipole mode threshold, and creation of flat-topped bunches with reduced peak line density resulting in a higher transverse space-charge limit. A Proposed Second Harmonic Acceleration System for the Intense Pulsed Neutron Source Rapid Cycling Synchrotron Conference Paper Aug 1983 IEEE T NUCL SCI J. Norem F. Brandeberry A. Rauchas The Rapid Cycling Synchrotron (RCS) of the Intense Pulsed Neutron Source (IPNS) operating at Argonne National Laboratory is presently producing intensities of 2 to 2.5 x 10/sup 12/ protons per pulse (ppp) with the addition of a new ion source. This intensity is close to the space charge limit of the machine, estimated at approx.3 x 10/sup 12/ ppp, depending somewhat on the available aperture. With the present good performance in mind, accelerator improvements are being directed at: (1) increasing beam intensities for neutron science; (2) lowering acceleration losses to minimize activation; and (3) gaining better control of the beam so that losses can be made to occur when and where they can be most easily controlled. On the basis of preliminary measurements, we are now proposing a third cavity for the RF systems which would provide control of the longitudinal bunch shape during the cycle which would permit raising the effective space charge limit of the accelerator and reducing losses. View Longitudinal Instabilities of Bunched Beams in the ISR Article Jul 1977 IEEE T NUCL SCI P. Bramham S. Hansen Albert Hofmann E Peschardt Microwave instabilities occur in bunched beams in the ISR leading to a dilution of the phase space density and limiting the longitudinal density of the stacked beams. According to D. Boussard this instability can be described as a coasting beam instability inside bunches. Experimental investigations of this microwave instability support this theory and give a high frequency impedance |Z <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L</sub> |/n ≈ 14 ohms. Injecting large currents in bunches of large area increases the threshold of this instability. The larger currents can produce coupled bunch mode instabilities which can be cured by a higher harmonic cavity. Jan 1983 3490 J Norem F Brandeberry A Rauchas J. Norem, F. Brandeberry, and A. Rauchas, IEEE Trans. Nuc. Sci., 30(4), 3490(1983).. A Proposal to Improve the Performance of ISIS Jan 1996 M R Harold M G Glover I S K Gardner
https://www.researchgate.net/publication/3815745_Numerical_studies_of_a_second_harmonic_RF_cavity_for_the_IPNS_RCS
Refworld | U.S. Department of State Country Report on Human Rights Practices 1999 - Luxembourg Refworld is the leading source of information necessary for taking quality decisions on refugee status. Refworld contains a vast collection of reports relating to situations in countries of origin, policy documents and positions, and documents relating to international and national legal frameworks. The information has been carefully selected and compiled from UNHCR's global network of field offices, Governments, international, regional and non-governmental organizations, academic institutions and judicial bodies. U.S. Department of State Country Report on Human Rights Practices 1999 - Luxembourg Publisher United States Department of State Publication Date 25 February 2000 Cite as United States Department of State, U.S. Department of State Country Report on Human Rights Practices 1999 - Luxembourg , 25 February 2000, available at: https://www.refworld.org/docid/3ae6aa69c.html [accessed 11 June 2023] Disclaimer This is not a UNHCR publication. UNHCR is not responsible for, nor does it necessarily endorse, its content. Any views expressed are solely those of the author or publisher and do not necessarily reflect those of UNHCR, the United Nations or its Member States. Luxembourg Luxembourg is a constitutional monarchy with a democratic, parliamentary form of government. The role of the Grand Duke is mainly ceremonial and administrative. The Prime Minister is the leader of the dominant party in the popularly elected Parliament. The Council of State, whose members are appointed by the Grand Duke, serves as an advisory body to the Parliament. The judiciary is independent. The government effectively controls the security apparatus, which consists of the police and gendarmerie. Luxembourg has a prosperous market economy with active industrial and service sectors. The standard of living and the level of social benefits are high. The Government generally respects the human rights of its citizens, and the law and judiciary provide effective means of dealing with individual instances of abuse. Section 1. Respect for the Integrity of the Person, Including Freedom From: a. Political and Other Extrajudicial Killing b. Disappearance There were no reports of politically motivated disappearances. c. Torture and Other Cruel, Inhuman, or Degrading Treatment or Punishment The law prohibits such practices, and there were no reports that officials employed them. Prison conditions meet minimum international standards. The Government permits prison visits by human rights monitors. d. Arbitrary Arrest, Detention, or Exile The Constitution prohibits arbitrary arrest and detention, and the Government observes these prohibitions. Judicial warrants are required by law for arrests except in cases of hot pursuit. Within 24 hours of arrest, the police must lodge charges and bring suspects before a judge. Suspects are given immediate access to an attorney, at government expense for indigents. The presiding judge may order release on bail. The Constitution prohibits exile, and the Government respects this prohibition. e. Denial of Fair Public Trial The Constitution provides for an independent judiciary, and the Government respects this provision in practice. The judiciary provides citizens with a fair and efficient judicial process. The independent judiciary is headed by the Supreme Court, whose members are appointed by the Grand Duke. Defendants are presumed innocent. They have the right to public trials and are free to cross-examine witnesses and to present evidence. Either the defendant or the prosecutor can appeal a ruling; an appeal results in a completely new judicial procedure, with the possibility that a sentence may be increased or decreased. In response to a 1995 decision by the European Court of Human Rights, the government established an administrative court system to review citizen challenges to legislation. There were no reports of political prisoners. f. Arbitrary Interference with Privacy, Family, Home, or Correspondence The Constitution prohibits such practices, government authorities generally respect these prohibitions, and violations are subject to effective legal sanction. Section 2. Respect for Civil Liberties, Including: a. Freedom of Speech and Press The Constitution provides for freedom of speech and of the press, and the Government respects these rights in practice. In August the newly formed coalition Government promised legislation to reform an 1869 press law that requires journalists to reveal confidential sources. This commitment follows a 1998 case in which police searched the offices of a journalist who published a story alleging corruption on the part of the Interior Minister, but who declined to reveal his source. The stated goal of the new legislation is to find an appropriate balance between protecting journalists' sources and avoiding abuses. The 1869 law also is being challenged before the European Court of Human Rights. Print media are privately owned. Television broadcasting rights, previously held exclusively by the privately owned national radio and television company, were extended in 1997 to a regional cable television company. The Government issues licenses to private radio stations. Radio and television broadcasts from neighboring countries are freely available. Academic freedom is respected. The law provides for these rights, and the Government respects them in practice. c. Freedom of Religion The Constitution provides for freedom of religion, and the Government respects this right in practice. There is no state religion, but the State pays the salaries of Roman Catholic, Protestant, and Jewish clergy, and several local governments maintain sectarian religious facilities. Two additional religious institutions – the Anglican Church and an Islamic congregation – requested government funding and were awaiting a decision by the Department of Religion at year's end. d. Freedom of Movement Within the Country, Foreign Travel, Emigration, and Repatriation The law provides for these rights, and the Government respects them in practice. The government cooperates with the U.N. High Commissioner for Refugees and other humanitarian organizations in assisting refugees and provides first asylum. The law provides for the granting of refugee or asylee status in accordance with the 1951 U.N. Convention Relating to the Status of Refugees and its 1967 Protocol. The Government does not expel those having a valid claim to refugee status, and there were no reports of the forced return of persons to a country where they feared persecution. The Government received 2,930 requests for refugee status and 2,255 requests for asylum through the end of November. This represents a significant increase over the 1,709 total requests for refugee and asylum status that were received in 1998. During the year, 4,548 refugees were in the country, the vast majority from the former Yugoslavia. The Government began to apply the 1993 Dublin Convention and in November repatriated 36 refugees to Italy, their country of entry into the European Union (EU). The Government committed itself not to repatriate refugees to their country of origin during the winter and to provide financial and administrative assistance to the returning refugees. Section 3. Respect for Political Rights: The Right of Citizens to Change Their Government Luxembourg is a multiparty democracy. Suffrage is universal for citizens 18 years of age and above, and balloting is secret. National parliamentary elections are held every 5 years. Women are active in political life. Of 60 members of Parliament, 10 are women, as are 4 members of the Cabinet. Section 4. Governmental Attitude Regarding International and Nongovernmental Investigation of Alleged Violations of Human Rights Human rights groups operate without government restriction. Government officials are cooperative and responsive to their views. Section 5. Discrimination Based on Race, Sex, Religion, Disability, Language, or Social Status The law prohibits racial, sexual, or social discrimination, and the Government enforces these provisions. Blatant societal discrimination occurs only rarely. Women In 1998 women's shelters provided refuge to 421 women and 453 children. Women's organizations report that the increase over 1997 levels was almost entirely due to refugees from the former Yugoslavia. Information offices set up to respond to women in distress reported receiving a total of 4,752 telephone calls in 1998. Neither society nor the government is tolerant of violence against women, and the government prosecutes persons accused of such crimes. The government funds organizations providing shelter, counseling, and hot lines. Women enjoy the same property rights as men. In the absence of a prenuptial agreement, property is divided equally upon the dissolution of a marriage. The law mandates equal pay for equal work, and the Ministry for the Promotion of Women has a mandate to encourage a climate of equal treatment and opportunity. However, according to government reports, women are paid from 9 to 25 percent less than men for comparable work, depending on the profession. The differences are least in the highest paid professions and more substantial at lower salary levels. To date there have been no work-related discrimination lawsuits in the courts. Women constitute 38 percent of the work force. Children The Government demonstrates a strong commitment to children's rights and welfare through its well-funded systems of public education and medical care. The law mandates school attendance from the ages of 4 to 16. Schooling is free through the secondary level, and the Government provides some financial assistance for postsecondary education. There is no societal pattern of abuse of children. A physicians' organization estimates that approximately 200 cases of child abuse are treated in hospitals each year that result in legal proceedings. This group is working to reform judicial procedures to permit videotaped testimony in court proceedings and the testimony of child psychiatrists, as well as the coordination of hospital records in child abuse cases. In May the Government set up a hot line for young persons in distress; by the end of the year it had received 183 calls. In May the Government passed a comprehensive new law dealing with the sexual exploitation of children. The law increases penalties for adults who traffick in children, facilitate child prostitution, or exploit children through pornography. The law also extends the country's criminal jurisdiction over citizens and residents who engage in such activities abroad. No such trafficking was reported during the year. The law prohibits discrimination against people with disabilities in employment, education, and the provision of other state services. The law does not directly mandate accessibility for the disabled, but the government pays subsidies to builders to construct "disabled-friendly" structures. Despite government incentives, only a modest proportion of buildings and public transportation are modified to accommodate people with disabilities. The Government helps disabled persons obtain employment and professional education. Businesses and enterprises with at least 25 employees by law must fill a quota for hiring disabled workers and must pay them prevailing wages. The quotas are fixed according to the total number of employees; employers who do not fulfill them are subject to sizable monthly fines. The Government provides subsidies and tax breaks for employers who hire the disabled. There have been no known complaints of noncompliance with the disability laws. Despite strong legal protections, the Government acknowledged that laws establishing quotas for businesses that employ over 25 persons are not applied or enforced consistently, and there is a particular problem in the case of persons with mental disabilities. The Government is reviewing the effectiveness of the disability legislation, particularly the provisions that establish quotas. To attempt to remedy the problems of the mentally disabled, the Government established a pilot program through which it supports a private organization that owns and runs a children's amusement park. This park employs persons with mental disabilities, whose salaries are paid entirely by the Government. National/Racial/Ethnic Minorities Although noncitizens constitute approximately 35 percent of the total population, antiforeign incidents are infrequent. Resident citizens of EU member states have the right to vote and run in municipal elections. In May the Parliament enacted legislation to allow noncitizen EU nationals to be employed in certain public sector jobs. The Government promotes the integration of foreigners in society by providing support to private organizations for educational campaigns, cultural fairs, and publications. Section 6. Worker Rights a. The Right of Association All workers have the right to associate freely and choose their representatives. About 57 percent of the working population belong to a trade union. Membership is not mandatory. Unions operate free of governmental interference. The two largest labor federations are linked to, but organized independently of, major political parties. The law prohibits discrimination against strike leaders, and a labor tribunal deals with complaints. The Constitution provides for the right to strike, except for government employees such as the police, armed forces personnel, and hospital workers providing essential services. Legal strikes may occur only after a lengthy conciliation procedure between the parties. The Government's National Conciliation Office must certify that conciliation efforts have ended for a strike to be legal. On January 19-20, employees of the state railroad company, CFL, went on strike to oppose pension reform proposals announced by the Government. No illegal strikes took place during the year. Unions maintain unrestricted contact with international bodies. b. The Right to Organize and Bargain Collectively The law provides for and protects collective bargaining, which is conducted in periodic negotiations between centralized organizations of unions and employers. Enterprises having 15 or more employees must have worker representatives to conduct collective bargaining. Enterprises with over 150 employees must form joint works councils composed of equal numbers of management and employee representatives. In enterprises with more than 1,000 employees, one-third of the membership of the supervisory boards of directors must be employee representatives. The law provides for adjudication of employment-related complaints and authorizes labor tribunals to deal with them. A tribunal can fine an employer found guilty of antiunion discrimination, but it cannot require the employer to reinstate a worker fired for union activities. There are no export processing zones. c. Prohibition of Forced or Compulsory Labor The law prohibits forced or compulsory labor by children and adults, and it is not known to occur. d. Status of Child Labor Practices and Minimum Age for Employment The law prohibits the employment of children under the age of 16 and requires all children to remain in school until the age of 16. Apprentices who are 16 years old must attend school in addition to their job training. The Government prohibits forced and bonded child labor and enforces this prohibition effectively (see Section 6.c.). Workers under the age of 18 have additional legal protection, including limits on overtime and the number of hours that can be worked continuously. The Ministries of Labor and Education effectively monitor the enforcement of child labor and education laws. e. Acceptable Conditions of Work The law provides for minimum wage rates that vary according to the worker's age and number of dependents. The minimum wage for a single worker over the age of 18 is $7.32 (278 francs) per hour. Supporting a family is difficult on the minimum wage, but most employees earn more than the minimum. The law mandates a safe working environment. An inspection system provides severe penalties for infractions. The Labor Inspectorate of the Ministry of Labor and the Accident Insurance Agency of the Social Security Ministry carry out their inspections effectively. No laws or regulations specifically guarantee workers the right to remove themselves from dangerous work situations without jeopardy to continued employment, but every worker has the right to ask the Labor Inspectorate to make a determination, and the Inspectorate usually does so expeditiously. f. Trafficking in Persons In May the Government passed a law that criminalizes trafficking in persons and increases the penalties for adults who traffick in children. In March the Minister of Justice told Parliament that the Government was unaware of any trafficking rings operating in the country. His statement followed allegations by two prominent politicians – including Luxembourg's European Commissioner, Viviane Reding – that the country serves as a transit point for trafficking in women. According to the authorities, no arrests or prosecutions were made for trafficking in persons during the year. Moreover, local agencies assisting women in distress knew of no clear-cut cases of trafficking in women.
https://www.refworld.org/country,COI,USDOS,,LUX,,3ae6aa69c,0.html
Use of the Physician Orders for Life-Sustaining Treatment Program in the Clinical Setting: A Systematic Review of the Literature | Request PDF Request PDF | Use of the Physician Orders for Life-Sustaining Treatment Program in the Clinical Setting: A Systematic Review of the Literature | The Physician Orders for Life-Sustaining Treatment (POLST) form is a palliative care tool that contains standardized, actionable medical orders.... | Find, read and cite all the research you need on ResearchGate Article Literature Review Use of the Physician Orders for Life-Sustaining Treatment Program in the Clinical Setting: A Systematic Review of the Literature January 2015 Journal of the American Geriatrics Society63(2) DOI: 10.1111/jgs.13248 Authors: <here is a image b3fa91edb8de3534-e7cdd7c4dd7168a3> Susan E Hickman Indiana University-Purdue University Indianapolis <here is a image f2f62089ad6ff61c-d19572ff1996375a> Elisabeth Keevern Elisabeth Keevern <here is a image d966584e9f360732-0ccf3c4394d571df> Bernard Hammes Gundersen Health System, La Crosse, WI Abstract The Physician Orders for Life-Sustaining Treatment (POLST) form is a palliative care tool that contains standardized, actionable medical orders. It is designed to ensure that patient treatment preferences are elicited, communicated, and honored throughout the healthcare system. A systematic review of the literature was conducted to evaluate what is currently known about the POLST program and identify directions for future research. Twenty-three research studies focused on POLST use in the clinical setting were identified. A majority of studies have been conducted all or in part in Oregon, with chart review the most frequently used methodology. Research suggests that POLST is most commonly used in older, white patients who are near the end of life. A nonphysician facilitator usually prepares the POLST form for the physician to review and sign. The orders documented on POLST reflect a wide degree of individualization, with only approximately one-third of patients having orders reflecting the lowest level of treatment in all POLST form sections. Clinicians have generally positive attitudes regarding use of POLST yet report a wide range of challenges. POLST alters treatment in a way that is consistent with orders. However, evidence that POLST reflects patient or surrogate treatment preferences is lacking. Research is needed to evaluate the quality of POLST decisions, explore the experiences of patients and their surrogates, develop decision-support tools, improve clinician education, and assess the effect of POLST on care outcomes through intervention and population-based studies. ... From the mixture of EM residents and attending staff, we observed the following: a facility-level variation exists, a higher level of POLST knowledge is correlated with previous use, and EM residents report greater comfort with the POLST form and are more likely to have used it than attending staff. Hickman et al. conducted a systematic review on the POLST form and concluded that the evidence for POLST reflecting patient or surrogate treatment preferences is lacking, 8 Moss et al. conducted a state-wide survey and concluded that POLST education is necessary to improve any contradicting orders. 9 McGough et al. conducted a pre-and posttest to evaluate the nursing staff's knowledge of POLST and demonstrated the impact of the educational intervention. ... ... 20 Research is needed to evaluate the quality of POLST decisions, explore the experiences of patients and their surrogates, develop decision-support tools, improve clinician education, and assess the effect of POLST on care outcomes through intervention and population-based studies. 8 Our survey indicates that EM clinicians must understand the role of the POLST documents. ... Emergency medicine provider comfort with Physician Orders for Life Sustaining Treatment (POLST) advanced directive Article Full-text available Oct 2022 Katherine Briggie Kaitlin Sweeney Shannon Findlay <here is a image ddf9571493770321-b293f41dd507fd25> Sangil Lee ... During the conversation between the patient, the physician, and perhaps family members and nursing staff, the patient shares his or her values, beliefs, and goals for care, and the healthcare professional explains the patient's diagnosis, prognosis, and treatment alternatives, including the benefits and limitations of lifesustaining treatment. Together they reach an informed decision about the desired treatment, based on the patient's values, beliefs and goals for care, and their completed POLST form highlights the treatment preferences identified through the conversation [19] [20][21][22]. Patients in Oregon with POLST Comfort Measures Only orders were much less likely to die in hospitals than patients without POLST forms or with POLST orders for Full Treatment [20]. ... ... The POLST form is a medical order, but using a POLST form or other structured tools such as the PREPARE Advanced Directive [37], the ReSPECT [16], or the Respecting Choices ® [38] can help initiate the clarification. The POLST form is widely used in the US and prior research suggests that POLST facilitates concordance between medical orders and preferences for life-sustaining treatment [19] and that wishes documented on POLST forms are largely concordant with care delivered [39]. Critiques of the POLST include the risk of it being filled in without a conversation about values and goals, not allowing for changes in preferences, and lack of clarity in interpretation of preferences [40]. ... Discussing patient preferences for levels of life-sustaining treatment: development and pilot testing of a Danish POLST form Article Full-text available Jan 2022 BMC Palliat Care Lone Doris Tuesen <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hans-Henrik Bülow Anne Sophie Ågård Hanne Irene Jensen Background Medically frail and/or chronically ill patients are often admitted to Danish hospitals without documentation of patient preferences. This may lead to inappropriate care. Modelled on the American Physician Orders for Life-Sustaining Treatment (POLST) form, the purpose of the study was to develop and pilot test a Danish POLST form to ensure that patients’ preferences for levels of life-sustaining treatment are known and documented. Methods The study was a mixed methods study. In the initial phase, a Danish POLST form was developed on the basis of literature and recommendations from the National POLST organisation in the US. A pilot test of the Danish POLST form was conducted in hospital wards, general practitioners’ clinics, and nursing homes. Patients were eligible for inclusion if death was assessed as likely within 12 months. The patient and his/her physician engaged in a conversation where patient values, beliefs, goals for care, diagnosis, prognosis, and treatment alternatives were discussed. The POLST form was completed based on the patient’s values and preferences. Family members and/or nursing staff could participate. Participants’ assessments of the POLST form were evaluated using questionnaires, and in-depth interviews were conducted to explore experiences with the POLST form and the conversation. Results In total, 25 patients participated, 45 questionnaires were completed and 14 interviews were conducted. Most participants found the POLST form readable and understandable, and 93% found the POLST form usable to a high or very high degree for discussing preferences regarding life-sustaining treatment. Three themes emerged from the interviews: (a) an understandable document is essential for the conversation, (b) handling and discussing wishes, and (c) significance for the future. Conclusion The Danish version of the POLST form is assessed by patients, families, physicians, and nurses as a useful model for obtaining and documenting Danish patients’ preferences for life-sustaining treatment. However, this needs to be confirmed in a larger-scale study. ... However, ACP is a concept yet to be implemented in many countries (Meeussen et al., 2011;Gjerberg et al., 2015;Petri et al., 2020). One of the most used and researched ACP tools is the American Physician Orders for Life-Sustaining Treatment (POLST) (Hickman et al., 2015; Moss et al., 2017). The POLST form is designed for seriously ill or medically frail patients. ... ... During the conversation, the patient shares his or her values, belief, and goals for care, and the healthcare professional elucidates the patient's diagnosis, prognosis and treatment alternatives, including the benefits and burdens of life-sustaining treatment. Together, they then reach an informed decision about desired treatment (Hickman et al., 2015) . ... Patient–physician conversations about life-sustaining treatment: Treatment preferences and participant assessments Article Full-text available Dec 2021 Lone Doris Tuesen <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hans-Henrik Bülow Anne Sophie Ågård Hanne Irene Jensen Objective In 2019, the Danish parliament issued legislation requiring Danish physicians to clarify and honor seriously ill patients’ treatment preferences. The American POLST (Physician Orders for Life-Sustaining Treatment) document could be a valuable model for this process. The aim of the study was to examine patients' preferences for life-sustaining treatment and participant assessment of a Danish POLST form. Methods The study is a prospective intervention based on a pilot-tested Danish POLST form. Participant assessments were examined using questionnaire surveys. Patients with serious illness and/or frailty from seven hospital wards, two general practitioners, and four nursing homes were included. The patients and their physicians completed the POLST form based on a process of shared decision-making. Results A total of 95 patients (aged 41–95) participated. Hereof, 88% declined cardiopulmonary resuscitation, 83% preferred limited medical interventions or comfort care, and 74% did not require artificial nutrition. The preferences were similar within age groups, genders, and locations, but with a tendency toward younger patients being more in favor of full treatment and nursing home residents being more in favor of cardiopulmonary resuscitation. Questionnaire response rates were 69% (66/95) for patients, 79% (22/28) for physicians, and 31% (9/29) for nurses. Hereof, the majority of patients, physicians, and nurses found that the POLST form was usable for conversations and decision-making about life-sustaining treatment to either a high or very high degree. Significance of results The majority of seriously ill patients did not want a resuscitation attempt and opted for selected treatments. The majority of participants found that the Danish POLST was usable for conversations and decisions about life-sustaining treatment to either a high or a very high degree, and that the POLST form facilitated an opportunity to openly discuss life-sustaining treatment. ... ACP has been shown to have many benefits for individuals, their families, and health care providers. The benefits to the individual include an increased sense of selfcontrol over their treatment, consideration and respect for their wishes about the treatment, place of care and endof-life care, and increased dialogue with family and health care providers (2)(3)(4)(5)(6)(7) (8) . The benefits to the family include their reduced decision-making burden and the reduced stress, anxiety, and depression experienced after their family member's death (9). ... ... The contents of the program are shown in Table 1. These contents were selected through discussions within the working group based on a review of previous studies and the Guidelines for Decision-Making about End-of-Life Care developed by the Ministry of Health, Labour and Welfare (1)(2)(3)(4)(5)(6)(7) (8) (9)(10)(11)(12)(13)(14)(15)33). Some of the members of this group were also the developers of the guidelines. ... Health care providers’ knowledge, confidence, difficulties, and practices after completing a communication skills training program for advance care planning discussion in Japan Jul 2021 Hiroko Okada Tatsuya Morita <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Takahiro Kiuchi <here is a image 640955454aaa9776-8c0c323bccda1ad4> Yoshiyuki Kizawa Background: Advance care planning (ACP) is an important factor that affects the quality of end-oflife. However, health care providers are not able to sufficiently support patients' ACP due to their lack of knowledge and psychological burden. This study investigated how the knowledge, attitudes, and practices of health care providers who completed a communication skills training (CST) program for ACP discussion changed before and after the course. Methods: Health care providers who participated in the Education for Implementing End of Life Discussion (E-FIELD) CST training program in Japan were surveyed at three time points: before, immediately after, and 6 months after training. The number of participants who completed all three surveys was 306. Knowledge, confidence, communication difficulties, number of discussions and completions of ACP were measured using a questionnaire. Results: Participants' knowledge and confidence increased right after training compared with before training. The number of ACP discussions and completions increased significantly 6 months after training compared with before training and difficulties tended to decrease. Physicians maintained their confidence, which increased immediately after training until 6 months after training and their number of ACP discussions and completions also increased significantly 6 months after training compared with before training. Conclusions: The CST program for ACP, E-FIELD, has the potential to increase the knowledge, confidence, and number of ACP discussions and completions used by physicians, nurses, and social workers, and also lower their difficulties. ... POLST is used in nursing homes and residential long-term care settings across the country, likely in part reflecting the high proportion of POLST-appropriate patients within that care setting. 4 Research suggests POLST is used to guide the care of hundreds of thousands of geriatric patients throughout the United States. A California study found that almost half of all nursing home residents (n ¼ 142,672) had a POLST form in 2011. ... ... 8 These findings highlight program and policy issues with POLST use in nursing homes and are consistent with a series of studies that have identified issues with nursing home use, including staff difficulty understanding and explaining the form, discomfort with issues raised by the form, and problems using the form to guide treatment. 4, 9 One specific problematic practice that contributes to these difficulties is use of POLST as a universal code status order form to document CPR orders. In a recent National POLST survey of state POLST programs, almost half of program representatives who responded to the survey (15 of 33 or 45.4%) reported that POLST is at least sometimes used as a code status order form in their state and 9 (60%) of 15 who reported this occurs describe the practice as "very widespread" or "common" in their state. ... POLST Is More Than a Code Status Order Form: Suggestions for Appropriate POLST Use in Long-term Care Article Full-text available May 2021 J AM MED DIR ASSOC <here is a image a431b053ac7ba2b6-a04185e83dd50944> Karl E. Steinberg <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> John Carney <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hillary D Lum <here is a image b3fa91edb8de3534-e7cdd7c4dd7168a3> Susan E Hickman POLST (Physician Orders for Life-Sustaining Treatment) is a medical order form used to document preferences about cardiopulmonary resuscitation (CPR), medical interventions such as hospitalization, care in the intensive care unit, and/or ventilation, as well as artificial nutrition. Programs based on the POLST paradigm are used in virtually every state under names that include POST (Physician Orders for Scope of Treatment), MOLST (Medical Orders for Life-Sustaining Treatment), and MOST (Medical Orders for Scope of Treatment), and these forms are used in the care of hundreds of thousands of geriatric patients every year. Although POLST is intended for persons who are at risk of a life-threatening clinical event due to a serious life-limiting medical condition, some nursing homes and residential care settings use POLST to document CPR preferences for all residents, resulting in potentially inappropriate use with patients who are ineligible because they are too healthy. This article focuses on reasons that POLST is used as a default code status order form, the risks associated with this practice, and recommendations for nursing homes to implement appropriate use of POLST. ... Along with this law, the physician orders for life-sustaining treatment (POLST) program was developed in Oregon and is now actively applied in 43 states [14] . Studies reported that the majority of the patients are involved in POLST discussions in settings ranging from hospitals and hospice to communities in the United States [14,15]. ... ... Along with this law, the physician orders for life-sustaining treatment (POLST) program was developed in Oregon and is now actively applied in 43 states [14]. Studies reported that the majority of the patients are involved in POLST discussions in settings ranging from hospitals and hospice to communities in the United States [14, 15]. These findings seem to be affected 4 Korean Cancer Association This article is protected by copyright. ... Analysis of Cancer Patient Decision-Making and Health Service Utilization after Enforcement of the Life-Sustaining Treatment Decision-Making Act in Korea Article Full-text available Apr 2021 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Dal Yong Kim <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Shin Hye Yoo Seyoung Seo Chae-Man Lim Purpose: This study aimed to confirm the decision-making patterns for life-sustaining treatment and analyze medical service utilization changes after enforcement of the Life-Sustaining Treatment Decision-Making Act. Materials and methods: Of 1,237 patients who completed legal forms for life-sustaining treatment (hereafter called the life-sustaining treatment [LST] form) at three academic hospitals and died at the same institutions, 1,018 cancer patients were included. Medical service utilization and costs were analyzed using claims data. Results: The median time to death from completion of the LST form was three days (range, 0 to 248 days). Of these, 517 people died within two days of completing the document, and 36.1% of all patients prepared the LST form themselves. The frequency of use of the intensive care unit, continuous renal replacement therapy, and mechanical ventilation was significantly higher when the families filled out the form without knowing the patient's intention. In the top 10% of the medical expense groups, the decision-makers for LST were family members rather than patients (28% patients vs. 32% family members who knew and 40% family members who did not know the patient's intention). Conclusion: The cancer patient's own decision-making rather than the family's decision was associated with earlier decision-making, less use of some critical treatments (except chemotherapy) and expensive evaluations, and a trend toward lower medical costs. ... 7,8 A systematic review of POLST found evidence that medical orders in POLST forms are more likely to influence care at the end of life than advance directives alone and acknowledged the lack of studies assessing the quality of those medical orders as a critical knowledge gap deserving high priority in future studies. 9 Furthermore, few studies assessed the psychometric properties of the POLST form, 10 and we are not aware of any study that addressed its construct validity. Therefore, the purpose of this study was to assess the construct validity of the POLST form by comparing medical orders documented in POLST forms with the content of free-form documentation of an advance care planning conversation performed by an independent researcher. ... ... Second, our sample was small and restricted to inpatients from a single university hospital in a middleincome country, which does not reflect other contexts where POLST has been used, as most studies about POLST were conducted in longterm care facilities in the USA. 9 Third, the training level of our researchers and the quality of advance care planning discussions performed within our study may differ from usual practice in several locations. Hence, our results may not be generalizable to other areas and populations. ... To What Extent Do Physician Orders for Life-Sustaining Treatment (POLST) Reflect Patients' Preferences for Care at the End of Life? Article <here is a image 78e9a2c9a05f9ebc-e9551e7f9d1f0a66> Gustavo Lovadini <here is a image 48c08c34fa02504b-c57cc719bd0d2223> Fernanda Bono Fukushima Joao Francisco Lindenberg Schoueri <here is a image f757b6a75aacdec3-7a4924013763c11a> Edison Vidal Objective To assess whether medical orders within Physician Orders for Life-Sustaining Treatment (POLST) forms reflect patients' preferences for care at the end of life. Design This cross-sectional study assessed the agreement between medical orders in POLST forms and the free-form text documentation of an advance care planning conversation performed by an independent researcher during a single episode of hospitalization. Setting and Participants Inpatients at a single public university hospital, aged 21 years or older, and for whom one of their attending physicians provided a negative answer to the following question: “Would I be surprised if this patient died in the next year?” Data collection occurred between October 2016 and September 2017. Measures Agreement between medical orders in POLST forms and the free-form text documentation of an advance care planning conversation was measured by kappa statistics. Results Sixty-two patients were interviewed. Patients' median (interquartile range) age was 62 (56-70) years, and 21 patients (34%) were women. Overall, in 7 (11%) cases, disagreement in at least 1 medical order for life-sustaining treatment was found between POLST forms and the content of the independent advance care planning conversation. The kappa statistic for cardiopulmonary resuscitation was 0.92 [95% confidence interval (CI): 0.82-1.00]; for level of medical intervention, 0.90 (95% CI: 0.81-0.99); and for artificially administered nutrition, 0.87 (95% CI: 0.75-0.98). Conclusions and Implications The high level of agreement between medical orders in POLST forms and the documentation in an independent advance care planning conversation offers further support for the POLST paradigm. In addition, the finding that the agreement was not 100% underscores the need to confirm frequently that POLST medical orders accurately reflect patients' current values and preferences of care. ... The distribution of ACDs is unequal across racial lines, as has been demonstrated and confirmed in numerous reports. 15,19,[53] [54] [55][56] These studies seem to convey the same message in different ways: in one, that racial minorities in the US are less likely to have ACDs than white patients 53 ; in another, that most people with ACDs are elderly, white, and critically ill 54 ; and in yet another, that non-white patients with lower socioeconomic status were less likely to have documented preferences. 15 These inequalities in utilization may be driven by experiences of discrimination, which contribute to mistrust of providers. ... ... The distribution of ACDs is unequal across racial lines, as has been demonstrated and confirmed in numerous reports. 15,19,[53][54][55][56] These studies seem to convey the same message in different ways: in one, that racial minorities in the US are less likely to have ACDs than white patients 53 ; in another, that most people with ACDs are elderly, white, and critically ill 54 ; and in yet another, that non-white patients with lower socioeconomic status were less likely to have documented preferences. 15 These inequalities in utilization may be driven by experiences of discrimination, which contribute to mistrust of providers. ... Value of Advance Care Directives for Patients With Serious Illness in the Era of COVID Pandemic: A Review of Challenges and Solutions Article Amol Gupta <here is a image 03177aa0034af44b-b004b4bbbb26b3f8> Bhavyaa Bahl Saher Rabadi Viswanath Vasudevan Advance care directives (ACDs) are instructions regarding what types of medical treatments a patient desires and/or who they would like to designate as a healthcare surrogate to make important healthcare decisions when the patient is mentally incapacitated. At end-of-life, when faced with poor prognosis for a meaningful health-related quality of life, most patients indicate their preference to abstain from aggressive, life-sustaining treatments. Patients whose wishes are left unsaid often receive burdensome life sustain therapy by default, prolonging patient suffering. The CoVID pandemic has strained our healthcare resources and raised the need for prioritization of life-sustaining therapy. This highlights the urgency of ACDs more than ever. Despite ACDs' potential to provide patients with care that aligns with their values and preferences and reduce resource competition, there has been relatively little conversation regarding the overlap of ACDs and CoVID-19. There is low uptake among patients, lack of training for healthcare professionals, and inequitable adoption in vulnerable populations. However, solutions are forthcoming and may include electronic medical record completion, patient outreach efforts, healthcare worker programs to increase awareness of at-risk minority patients, and restructuring of incentives and reimbursement policies. This review carefully describes the above challenges and unique opportunities to address them in the CoVID-19 era. If solutions are leveraged appropriately, ACDs have the potential to address the described challenges and ethically resolve resource conflicts during the current crisis and beyond. ... Patients with POLST comfort measures orders are 59-71% less likely to receive life-sustaining medical interventions than patients with code status orders alone and no POLST. 10 Given the effectiveness of POLST at altering treatment outcomes, 15 it is especially important that POLST orders match current preferences. However, information about POLST concordance is limited to a few descriptive studies with small sample sizes and no comparison groups. ... ... In this study, nursing facility residents with POLST forms were over three times as likely to have their current treatment preferences match the orders in their medical record as residents without POLST forms. In combination with prior research, 15 our results indicate POLST helps increase the likelihood that current patient preferences are known and honored. However, only 59.1% of POLST forms matched current preferences and further work is clearly needed to improve concordance. ... Do Life-sustaining Treatment Orders Match Patient and Surrogate Preferences? The Role of POLST Article Oct 2020 <here is a image de622dea9d695dd0-1cc0dc83a700e1a0> Greg Sachs <here is a image d966584e9f360732-0ccf3c4394d571df> Bernard Hammes <here is a image b3fa91edb8de3534-e7cdd7c4dd7168a3> Susan E Hickman Alexia M. Torke Background It is essential to high-quality medical care that life-sustaining treatment orders match the current, values-based preferences of patients or their surrogate decision-makers. It is unknown whether concordance between orders and current preferences is higher when a POLST form is used compared to standard documentation practices. Objective To assess concordance between existing orders and current preferences for nursing facility residents with and without POLST forms. Design Chart review and interviews. Setting Forty Indiana nursing facilities (29 where POLST is used and 11 where POLST is not in use). Participants One hundred sixty-one residents able to provide consent and 197 surrogate decision-makers of incapacitated residents with and without POLST forms. Main Measurements Concordance was measured by comparing life-sustaining treatment orders in the medical record (e.g., orders about resuscitation, intubation, and hospitalization) with current preferences. Concordance was analyzed using population-averaged binary logistic regression. Inverse probability weighting techniques were used to account for non-response. We hypothesized that concordance would be higher in residents with POLST (n = 275) in comparison to residents without POLST (n = 83). Key Results Concordance was higher for residents with POLST than without POLST (59.3% versus 34.9%). In a model adjusted for resident, surrogate, and facility characteristics, the odds were 3.05 times higher that residents with POLST had orders for life-sustaining treatment match current preferences in comparison to residents without POLST (OR 3.05 95% CI 1.67–5.58, p < 0.001). No other variables were significantly associated with concordance. Conclusions Nursing facility residents with POLST are significantly more likely than residents without POLST to have concordance between orders in their medical records and current preferences for life-sustaining treatments, increasing the likelihood that their treatment preferences will be known and honored. However, findings indicate further systems change and clinical training are needed to improve POLST concordance. ... Although the POLST Paradigm is believed to represent an important progress in this field in the United States [7,[24] [25] [26], there is evidence that it is not perfect [18][19][27][28][29], and that, as any other instrument, its appropriate use depends on how well it is operated (e.g., how ACP conversations are performed) and on the quality of the training the healthcare professionals involved in completing POLST forms and acting upon those orders. Hence, if the POLST Paradigm is to be effectively implemented in Brazil will depend on substantial and concerted support of major stakeholders in the country. ... Schwerpunkt / Special Issue "Advance Care Planning around the World: Evidence and Experiences, Programmes and Perspectives'' Advance Care Planning in Brazil Advance Care Planning in Brasilien Article Jun 2023 <here is a image 3e9569034e21fa70-fc9b786a364eb88f> Natália Rocha Tardelli Daniel Neves Forte <here is a image f757b6a75aacdec3-7a4924013763c11a> Edison Vidal Brazil is a country of continental size marked by extreme social inequalities. Its regulation of Advance Directives (AD) was not enacted by law but within the scope of the norms that govern the relationships between patients and physicians, as a resolution of the Federal Medical Council without any specific requirement for notarization. Despite this innovative starting point, most of the debate regarding Advance Care Planning (ACP) in Brazil has been dominated by a legal transactional approach focused on making decisions in advance and the creation of AD. Yet, other novel ACP models have recently emerged in the country with a focus on the creation of a specific quality of relationship between patients, families, and physicians aiming at the facilitating future decision-making. Most of the education on ACP in Brazil happens in the context of palliative care courses. As such, most ACP conversations are performed within palliative care services or by healthcare professionals with training in that area. Hence, the scarce access to palliative care services in the country means that ACP is still rare and that those conversations usually happen late in the course of disease. The authors posit that the existing paternalistic healthcare culture is one of the most important barriers to ACP in Brazil and envision with great concern the risk that its combination with extreme health inequalities and the lack of healthcare professionals' education on shared decision-making could lead to the misuse of ACP as a form of coercive practice to reduce healthcare use by vulnerable populations. ... 43 Research suggests that ECTP forms facilitate conversations between clinicians and patients. 47 The ReSPECT process is supported by the ReSPECT form, which, in the community, is a patient-held document that is completed by clinicians. 43 The ReSPECT form is designed to prompt clinicians to discuss emergency treatment options with patients to (1) structure the documentation of decisionmaking for greater transparency and (2) be carried by patients across medical settings. ... Recommended summary plan for emergency care and treatment: ReSPECT a mixed-methods study Article Full-text available Dec 2022 <here is a image 1262fd4ba456c859-e8a62cb7971f2d6a> Gavin David Perkins <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Claire A Hawkes Karin Eli Anne-Marie Slowther Background Do not attempt cardiopulmonary resuscitation decisions have been widely criticised. The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process was developed to facilitate shared decisions between patients and clinicians in relation to emergency treatments, including cardiopulmonary resuscitation. Objective To explore how, when and why ReSPECT plans are made and what effects the plans have on patient outcomes. Design A mixed-methods evaluation, comprising (1) a qualitative study of ReSPECT decision-making processes, (2) an interrupted time series examining process and survival outcomes following in-hospital cardiac arrest and (3) a retrospective observational study examining factors associated with ReSPECT recommendations and patient outcomes. Setting NHS acute hospitals and primary care and community services in England (2017–2020). Participants Hospital doctors, general practitioners, nurses, patients and families. Data sources The following sources were used: (1) observations of ReSPECT conversations at six hospitals and conversations with clinicians, patient, families and general practitioners, (2) survey and freedom of information data from hospitals participating in the National Cardiac Arrest Audit and (3) a review of inpatient medical records, ReSPECT forms and NHS Safety Thermometer data. Results By December 2019, the ReSPECT process was being used in 40 of 186 (22%) acute hospitals. In total, 792 of 3439 (23%) inpatients, usually those identified at risk of deterioration, had a ReSPECT form. Involvement of the patient and/or family was recorded on 513 of 706 (73%) ReSPECT forms reviewed. Clinicians said that lack of time prevented more conversations. Observed conversations focused on resuscitation, but also included other treatments and the patient’s values and preferences. Conversation types included open-ended conversations, with clinicians actively eliciting the patients’ wishes and preferences, a persuasive approach, swaying the conversation towards a decision aligned with medical opinion, and simply informing the patient/relative about a medical decision that had already been made. The frequency of harms reported on the NHS Safety Thermometer was similar among patients with or without a ReSPECT form. Hospital doctors and general practitioners gave different views on the purpose of the ReSPECT process and the type of recommendations they would record. Limitations The research was undertaken within the first 2 years following the implementation of ReSPECT. Local policies meant that doctors led these conversations. Most patients were seriously ill, which limited opportunities for interviews. Incomplete adoption of the ReSPECT process and problems associated with the NHS Safety Thermometer tool affected the evaluation on clinical outcomes. Conclusions Patients and families were involved in most ReSPECT conversations. Conversations focused on resuscitation, but also included other emergency treatments. Respect for patient autonomy and duty to protect from harm informed clinicians’ approach to varying degrees, depending on the clinical situation and their views of ReSPECT as a shared decision-making process. The complexity of these conversations and the clinical, emotional and organisational barriers observed suggest that a nuanced and multifaceted approach will be necessary to support good ReSPECT processes. Future work Further research is needed to understand the advantages and disadvantages to the adoption of a national emergency care and treatment plan system, the most effective national and local implementation approaches, and whether or not shared decision-making approaches in the context of emergency care and treatment plans could further enhance patient and family engagement. Study registration This study is registered as ISRCTN11112933. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research ; Vol. 10, No. 40. See the NIHR Journals Library website for further project information. ... 12,13 Advance directives are also not medical orders but statements about preferred care that can be too general to guide treatment decisions in the moment. 14 SAPOs are typically used only by nursing homes and first responders 15 and are less well suited to other clinical contexts. Patients may also have difficulty envisioning future health states and imagining what they might want under those circumstances. ... The VA Life‐Sustaining Treatment Decisions Initiative: A qualitative analysis of veterans with advanced kidney disease Article Full-text available Apr 2022 Susan P.Y. Wong Jennifer Cohen Ann M O'Hare <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mary Beth Foglia Background: Documentation of patients' goals of care is integral to promoting goal-concordant care. In 2017, the Department of Veterans Affairs (VA) launched a system-wide initiative to standardize documentation of patients' preferences for life-sustaining treatments (LST) and related goals-of-care conversations (GoCC) that included using a note template in its national electronic medical record system. We describe implementation of the LST note based on documentation in the medical records of patients with advanced kidney disease, a group that has traditionally experienced highly intensive patterns of care. Methods: We performed a qualitative analysis of documentation in the VA electronic medical record for a national random sample of 500 adults with advanced kidney disease for whom at least one LST note was completed between July 2018 and March 2019 to identify prominent themes pertaining to the content and context of LST notes. Results: During the observation period, a total of 723 (mean 1.5, range 1-6) LST notes were completed for this cohort. Two themes emerged from the analysis: (1) Reactive approach: LST notes were largely completed in response to medical crises, in which they focused on short-term goals and preferences rather than patients' broader health and goals, or certain clinical encounters designated by the initiative as "triggering events" for LST note completion; (2) Practitioner-driven: Documentation suggested that practitioners would attempt to engage patients/surrogates in GoCC to lay out treatment options in order to move care forward, but patients/surrogates sometimes appeared reluctant to engage in GoCC and had difficulty communicating in ways that practitioners could understand. Conclusions: Standardized documentation of patients' treatment preferences and related GoCC was used to inform in-the-moment decision-making during acute illness and certain junctures in care. There is opportunity to expand standardized documentation practices and related GoCC to address patients'/surrogates' broader health concerns and goals and to enhance their engagement in these processes. ... Less aggressive EOL care has been observed when health care professionals discuss approaching EOL and preferences about life-sustaining treatments with nursing home residents or their families [12]. However, little is known about how these conversations are experienced by patients and physicians in hospitals and nursing homes [13] . Applying strategies to make patient preferences known to healthcare providers and support persons while the patient still has the capacity for this is a critical step in improving the quality of EOL care [14]. ... Decision-making conversations for life-sustaining treatment with seriously ill patients using a Danish version of the US POLST: a qualitative study of patient and physician experiences Article Full-text available Feb 2022 Lone Doris Tuesen Anne Sophie Ågård <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hans-Henrik Bülow Hanne Irene Jensen Objective: To explore patients' and physicians' perspectives on a decision-making conversation for life-sustaining treatment, based on the Danish model of the American Physician Orders for Life Sustaining Treatment (POLST) form. Design: Semi-structured interviews following a conversation about preferences for life-sustaining treatment. Setting: Danish hospitals, nursing homes, and general practitioners' clinics. Subjects: Patients and physicians. Main outcome measures: Qualitative analyses of interview data. Findings: After participating in a conversation about life-sustaining treatment using the Danish POLST form, a total of six patients and five physicians representing different settings and age groups participated in an interview about their experience of the process. Within the main research questions, six subthemes were identified: Timing, relatives are key persons, clarifying treatment preferences, documentation across settings, strengthening patient autonomy, and structure influences conversations. Most patients and physicians found having a conversation about levels of life-sustaining treatment valuable but also complicated due to the different levels of knowledge and attending to individual patient needs and medical necessities. Relatives were considered as key persons to ensure the understanding of the treatment trajectory and the ability to advocate for the patient in case of a medical crisis. The majority of participants found that the conversation strengthened patient autonomy. Conclusion: Patients and physicians found having a conversation about levels of life-sustaining treatment valuable, especially for strengthening patient autonomy. Relatives were considered key persons. The timing of the conversation and securing sufficient knowledge for shared decision-making were the main perceived challenges.KEY POINTSConversations about preferences for life-sustaining treatment are important, but not performed systematically.When planning a conversation about preferences for life-sustaining treatment, the timing of the conversation and the inclusion of relatives are key elements.Decision-making conversations can help patients feel in charge and less alone, and make it easier for health professionals to provide goal-concordant care.Using a model like the Danish POLST form may help to initiate, conduct and structure conversations about preferences for life-sustaining treatment. ... Although clinicians report that POLST reliably expresses patients' preferences and guides care, existing data about whether POLST accurately represents patient preferences are weak. There is however a high rate of consistency between the withholding of CPR and the POLST orders. 362 According to an anonymous survey in one of the 42 US states where POLST is used, the emergency medical technicians changed their standard treatment plan in 45% of the situations in which a POLST form was present, including not starting or stopping CPR. ... Perception of inappropriateness of cardiopulmonary resuscitation : prevalence, associated factors and impact on emergency clinicians Thesis Jan 2021 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Patrick Druwé ... The number of deaths due to the discontinuation of life-sustaining treatments (LSTs) is gradually increasing worldwide [1][2][3] [4] . In South Korea, the "Act on Hospice and Palliative Care and Decisions on Life-sustaining Treatment for Patients at the End of Life" was enacted in February 2016, and based on this law, the LST decision system has been implemented since February 4, 2018 [5]. ... The Future Direction of the Organ Donation System After Legislation of the Life-Sustaining Treatment Decision Act Article Full-text available Oct 2021 ANN TRANSPL Seung Min Baik Jin Park Tae Yoon Kim <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Kyung Sook Hong Background The transplant community is seeking ways to encourage organ donation after cardiac arrest to solve the problem of the insufficiency of organs available for the increasing number of people awaiting transplantation. This study aimed to determine whether the life-sustaining treatment (LST) decision system, implemented in Korea on February 4, 2018, can address the shortage of organ donations. Material/Methods We retrospectively analyzed the medical records of the 442 patients who had filled out forms for the LST decision at Ewha Womans University Mokdong Hospital from April 2018 to December 2019, and classified the eligibility of organ and tissue donation according to the Korean Organ Donation Agency criteria. Results We included 442 patients in this study. Among them, 238 (53.8%) were men, and 204 (46.2%) were women. The average age of the patients was 71.8 years (the youngest and oldest were aged 23 years and 103 years, respectively). Of these, 110 patients (24.9%) decided on their own to discontinue LST, whereas 332 (75.1%) decided to discontinue with their family’s consent. This study demonstrated that 50% of patients who were not brain-dead and discontinued LST were eligible for organ donation. However, the patients and caregivers were not aware of this option because the current law does not allow the discussion of such donations. Conclusions A discussion regarding donation after circulatory death is recommended to solve the problem of insufficient organ donation. ... 23 For example, several surveys of physicians and emergency medical services providers raise concerns about the interpretability of POLST and whether they accurately reflect patients' preferences. [24][25][26][27] Two prior systematic reviews of POLST have been published, with one describing its use in clinical settings 28 and the other evaluating the concordance between documented treatment preferences on POLST with actual care delivered. 29 However, neither study assessed the quality or strength of available evidence or the breadth of studies. ... The influence of POLST on treatment intensity at the end of life: A systematic review Article Sep 2021 <here is a image 3236fe701bcb3bc1-8c893679697e15f8> Kelly Vranas Wesley Plinke Donald Bourne <here is a image 11a2e415bd1ccc7e-af0d48154e511156> Donald R Sullivan Background: Despite its widespread implementation, it is unclear whether Physician Orders for Life-Sustaining Treatment (POLST) are safe and improve the delivery of care that patients desire. We sought to systematically review the influence of POLST on treatment intensity among patients with serious illness and/or frailty. Methods: We performed a systematic review of POLST and similar programs using MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database for Systematic Reviews, and PsycINFO, from inception through February 28, 2020. We included adults with serious illness and/or frailty with life expectancy <1 year. Primary outcomes included place of death and receipt of high-intensity treatment (i.e., hospitalization in the last 30- and 90-days of life, ICU admission in the last 30-days of life, and number of care setting transitions in last week of life). Results: Among 104,554 patients across 20 observational studies, 27,090 had POLST. No randomized controlled trials were identified. The mean age of POLST users was 78.7 years, 55.3% were female, and 93.0% were white. The majority of POLST users (55.3%) had orders for comfort measures only. Most studies showed that, compared to full treatment orders on POLST, treatment limitations were associated with decreased in-hospital death and receipt of high-intensity treatment, particularly in pre-hospital settings. However, in the acute care setting, a sizable number of patients likely received POLST-discordant care. The overall strength of evidence was moderate based on eight retrospective cohort studies of good quality that showed a consistent, similar direction of outcomes with moderate-to-large effect sizes. Conclusion: We found moderate strength of evidence that treatment limitations on POLST may reduce treatment intensity among patients with serious illness. However, the evidence base is limited and demonstrates potential unintended consequences of POLST. We identify several important knowledge gaps that should be addressed to help maximize benefits and minimize risks of POLST. ... 91 In some Asian countries, death is considered unlucky, the topic of death is sensitive and is believed to have a negative impact on patients, contributing to the difficulties in discussing EOL care openly. 92 ACP conducted by trained health professionals could reduce the anxiety of talking about death. 11 ACP should not only include patients' EOL care preferences toward hypothetical clinical scenarios, but also focus on patients' values, goals of EOL care, and the education on the benefits and risks of different treatments. ... The Compliance of End-of-Life Care Preferences Among Older Adults and Its Facilitators and Barriers: A Scoping Review Objectives To explore the compliance of end-of-life (EOL) care preferences, and the facilitators and barriers of promoting quality of EOL care among older adults. Design A scoping review was used to identify key themes in the compliance of EOL care preferences among older adults. Setting and Participants Studies published between 2009 and 2020 were identified from the Medline and Cochrane libraries. Eligible articles containing components related to the compliance of EOL care preferences among older adults were selected. Measures The eligible articles were thematically synthesized. Factors that affected the compliance of EOL care preferences among older adults were identified from the key components. Results In total, 35 articles were included to identify the key components in the compliance of EOL care preferences: (1) supportive policy, (2) supportive environment, (3) cultural characteristics, (4) advance care planning (ACP), (5) the concordance of EOL care preferences between patients and surrogate decision makers, (6) prognosis awareness, and (7) patient's health status and the type of disease. Facilitators for the compliance of EOL care preferences included enactment of relevant policy, sufficient care institutions, the utilization of ACP, and poor health status. Barriers included lack of supportive policy, different culture, and low utilization of ACP. Conclusions/Implications The compliance of EOL care preferences was low among older adults. The compliance of EOL care preferences can be improved through relevant policy development and the utilization of ACP. ... Although resuscitation decisions need to be taken across the spectrum of medical care, we chose to focus on a hospital setting, assuming that the majority of resuscitation attempts occur in the in-patient sector, rendering resuscitation status particularly important, and that digital documentation was most advanced. We chose a university hospital in the region for our exploration, for various reasons: 1) Code status is systematically collected from all patients and documented in the electronic hospital information system (since 2013), 2) The hospital has got a large number of documented resuscitation decisions (120'000 in total), spread across the different departments, 3) Unlike many other healthcare institutions, the hospital offers advance care planning (ACP) for patients by trained professionals including so-called physician orders for life-sustaining treatment (POLST, "an approach to end-of-life planning based on conversations between patients, loved ones and health care professionals" 2 ) [27] , so that the decisions resulting from this process can be considered fairly well informed and well reflected [28]. A significant part of healthcare providers also receive obligatory training on the ethical and procedural rules governing resuscitation [29], which are defined by national guidelines. ... AI support for ethical decision-making around resuscitation: Proceed with care Artificial intelligence (AI) systems are increasingly being used in healthcare, thanks to the high level of performance that these systems have proven to deliver. So far, clinical applications have focused on diagnosis and on prediction of outcomes. It is less clear in what way AI can or should support complex clinical decisions that crucially depend on patient preferences. In this paper, we focus on the ethical questions arising from the design, development and deployment of AI systems to support decision-making around cardiopulmonary resuscitation and the determination of a patient’s Do Not Attempt to Resuscitate status (also known as code status). The COVID-19 pandemic has made us keenly aware of the difficulties physicians encounter when they have to act quickly in stressful situations without knowing what their patient would have wanted. We discuss the results of an interview study conducted with healthcare professionals in a university hospital aimed at understanding the status quo of resuscitation decision processes while exploring a potential role for AI systems in decision-making around code status. Our data suggest that (1) current practices are fraught with challenges such as insufficient knowledge regarding patient preferences, time pressure and personal bias guiding care considerations and (2) there is considerable openness among clinicians to consider the use of AI-based decision support. We suggest a model for how AI can contribute to improve decision-making around resuscitation and propose a set of ethically relevant preconditions—conceptual, methodological and procedural—that need to be considered in further development and implementation efforts. ... As a person enters the final phase of their life, and they can see more clearly how their life might end and which medical treatments will be helpful and which may not, the DMOST medical order form (for Delaware residents) with its clarity and specificity, has been shown to be effective in aligning a person's medical care to their preferences. 5 A person or their surrogate decision maker (when the person no longer has decisional capacity) may complete this medical order form with their health care provider. This order can be modified or voided and should be consistent with previous AD. ... The Increasing Importance of Advance Care Planning ... 5 POLST usage has resulted in high consistency between treatment and patient preferences for resuscitation, hospitalization, and antibiotics administration, [22][23][24] POLST has resulted in state variation in content and rates of adoption. 25, 26 For example, out of 51 POLST state forms, only 32 were found to have asked about antibiotic preferences. 27 To strengthen overall healthcare quality including infection control programs in NHs, the Centers for Medicare & Medicaid Services (CMS) funded 14 regional collaboratives known as Quality Innovation Network-Quality Improvement Organizations (QIN-QIOs). ... The Role of Regional and State Initiatives in Nursing Home Advance Care Planning Policies Objective Antibiotic use at the end of life (EoL) may introduce physiological as well as psychological stress and be incongruent with patients’ goals of care. Advance care planning (ACP) related to antibiotic use at the EoL helps improve goal-concordant care. Many nursing home (NH) residents are seriously ill. Therefore, we aimed to examine whether state and regional ACP initiatives play a role in the presence of “do not administer antibiotics” orders for NH residents at the EoL. Methods We surveyed a random, representative national sample of 810 U.S. NHs (weighted n = 13,983). The NH survey included items on “do not administer antibiotics” orders in place and participation in infection prevention collaboratives. The survey was linked to state Physician Orders for Life-Sustaining Treatment (POLST) adoption status and resident, facility, and county characteristics data. We conducted multivariable regression models with state fixed effects, stratified by state POLST designation. Results NHs in mature POLST states reported higher rates of “do not administer antibiotics” orders compared to developing POLST states (10.1% vs. 4.6%, respectively, p = 0.004). In mature POLST states, participation in regional collaboratives and smaller NH facilities (<100 beds) were associated with having “do not administer antibiotics” orders for seriously ill residents (β = 0.11, p = 0.006 and β = 0.12, p = 0.003, respectively). Discussion NHs in states with mature POLST adoption that participated in infection control collaboratives were more likely to have “do not administer antibiotics” orders. State ACP initiatives combined with regional antibiotic stewardship initiatives may improve inappropriate antibiotic use at the EoL for NH residents. ... Although resuscitation decisions need to be taken across the spectrum of medical care, we chose to focus on a hospital setting, assuming that the majority of resuscitation attempts occur in the in-patient sector, rendering resuscitation status particularly important, and that digital documentation was most advanced. We chose a university hospital in the region for our exploration, for various reasons: 1) Code status is systematically collected from all patients and documented in the electronic hospital information system (since 2013), 2) The hospital has got a large number of documented resuscitation decisions (120'000 in total), spread across the different departments, 3) Unlike many other healthcare institutions, the hospital offers advance care planning (ACP) for patients by trained professionals including so-called physician orders for life-sustaining treatment (POLST, "an approach to end-of-life planning based on conversations between patients, loved ones and health care professionals" 2 ) [27] , so that the decisions resulting from this process can be considered fairly well informed and well reflected [28]. A significant part of healthcare providers also receive obligatory training on the ethical and procedural rules governing resuscitation [29], which are defined by national guidelines. ... AI support for ethical decision-making around resuscitation: proceed with care Artificial intelligence (AI) systems are increasingly being used in healthcare, thanks to the high level of performance that these systems have proven to deliver. So far, clinical applications have focused on diagnosis and on prediction of outcomes. It is less clear in what way AI can or should support complex clinical decisions that crucially depend on patient preferences. In this paper, we focus on the ethical questions arising from the design, development and deployment of AI systems to support decision-making around cardio-pulmonary resuscitation leading to the determination of a patient's Do Not Attempt to Resuscitate (DNAR) status (also known as code status). The COVID-19 pandemic has made us keenly aware of the difficulties physicians encounter when they have to act quickly in stressful situations without knowing what their patient would have wanted. We discuss the results of an interview study conducted with healthcare professionals in a university hospital aimed at understanding the status quo of resuscitation decision processes while exploring a potential role for AI systems in decision-making around code status. Our data suggest that 1) current practices are fraught with challenges such as insufficient knowledge regarding patient preferences, time pressure and personal bias guiding care considerations and 2) there is considerable openness among clinicians to consider the use of AI-based decision support. We suggest a model for how AI can contribute to improve decision-making around resuscitation and propose a set of ethically relevant preconditions - conceptual, methodological and procedural - that need to be considered in further development and implementation efforts. ... 10 Prior studies have evaluated various types of discordance, including patient perceptions that the plan of care was concordant with their wishes and concordance between clinicians' and patients' preferences, between patient and surrogate decision-maker preferences, [11][12][13][14] and between advance care planning interventions and treatments received. 15, 16 Treatment discordant with the patient's goals has been shown to increase medical costs and prolong end-of-life difficulties. [6][7][8][9][10][11] In contrast, treatment that is concordant or aligned with the patient's goals decreases anxiety, depression, trauma, and regret while improving trust, peacefulness, and satisfaction. ... Discordance Between Surrogate Goals of Care and Medical Treatments Received by Hospitalized Older Adults (GP717) ... [14] Health care providers generally found the POLST to be helpful in guiding discussions, but a number of challenges exist with understanding the form. [15] For example, there is a lack of consistency in form interpretation by out of hospital personnel and emergency room physicians [16] and concern that the form may decrease patient centered decision making. [17] A chart review investigating use of the Maryland MOLST found contradictions between health care provider responses on page one and two of the MOLST form, in line with our study results which found physicians to be confused regarding the first and second page of the form. ... Housestaff perceptions on training and discussing the Maryland Orders for Life Sustaining Treatment Form (MOLST) Background On-line tutorials are being increasingly used in medical education, including in teaching housestaff skills regarding end of life care. Recently an on-line tutorial incorporating interactive clinical vignettes and communication skills was used to prepare housestaff at Johns Hopkins Hospital to use the Maryland Orders for Life Sustaining Treatment (MOLST) form, which documents patient preferences regarding end of life care. 40% of housestaff who viewed the module felt less than comfortable discussing choices on the MOLST with patients. We sought to understand factors beyond knowledge that contributed to housestaff discomfort in MOLST discussions despite successfully completing an on-line tutorial. Methods We conducted semi-structured telephone interviews with 18 housestaff who completed the on-line MOLST training module. Housestaff participants demonstrated good knowledge of legal and regulatory issues related to the MOLST compared to their peers, but reported feeling less than comfortable discussing the MOLST with patients. Transcripts of interviews were coded using thematic analysis to describe barriers to using the MOLST and suggestions for improving housestaff education about end of life care discussions. Results Qualitative analysis showed three major factors contributing to lack of housestaff comfort completing the MOLST form: [1] physician barriers to completion of the MOLST, [2] perceived patient barriers to completion of the MOLST, and [3] design characteristics of the MOLST form. Housestaff recommended a number of adaptations for improvement, including in-person training to improve their skills conducting conversations regarding end of life preferences with patients. Conclusions Some housestaff who scored highly on knowledge tests after completing a formal on-line curriculum on the MOLST form reported barriers to using a mandated form despite receiving training. On-line modules may be insufficient for teaching communication skills to housestaff. Additional training opportunities including in-person training mechanisms should be incorporated into housestaff communication skills training related to end of life care. ... (8) There are various methods of documenting treatment preferences. (9, 10) Documenting treatment preferences that arise from ACP conversations in a manner accessible to SDMs could help align care to a person's wishes. (11) Unfortunately, the existing prevalence of ACP documentation in LTC ranges from 11% to 44%. ... The Impact of Prior Advance Care Planning Documentation on End-of-Life Care Provision in Long-Term Care Background The impact of prior advance care planning (ACP) documentation on substitute decision-makers’ (SDMs) knowledge of values for end-of-life (EOL) care, and its correlation with SDM satisfaction with EOL care provision, have not been assessed in long-term care (LTC). Methods A cross-sectional survey of 2,595 SDMs from 27 LTC homes assessed: 1) knowledge of pre-existing ACP documentation and values for EOL care, and 2) the importance and satisfaction of EOL care provision in LTC. Knowledge of values for EOL care was compared to administrative documentation. Importance and satisfaction were plotted on a performance-importance grid. Multiple linear regression assessed whether knowledge of pre-existing ACP documentation correlated with satisfaction. Results The response rate was 25% (658/2,595); 69% of LTC residents had pre-existing ACP documentation. Discordance was noted between SDMs’ knowledge of values for EOL care and administrative documentation. Pre-existing knowledge of ACP documentation was not correlated with EOL care provision satisfaction. Priority areas for increasing satisfaction include illness management, SDM communication, and relationships with LTC clinicians. Conclusions The discordance between SDMs’ knowledge of values for EOL care and formal documentation needs to be addressed. Although pre-existing ACP documentation does not impact satisfaction, EOL care provision could be improved by targeting illness management, SDM communication, and relationships with LTC clinicians. ... 10 Prior studies have evaluated various types of discordance, including patient perceptions that the plan of care was concordant with their wishes and concordance between clinicians' and patients' preferences, between patient and surrogate decision-maker preferences, [11][12][13][14] and between advance care planning interventions and treatments received. 15, 16 Treatment discordant with the patient's goals has been shown to increase medical costs and prolong end-of-life difficulties. [6][7][8][9][10][11] In contrast, treatment that is concordant or aligned with the patient's goals decreases anxiety, depression, trauma, and regret while improving trust, peacefulness, and satisfaction. ... Assessment of Discordance Between Surrogate Care Goals and Medical Treatment Provided to Older Adults With Serious Illness Importance An important aspect of high-quality care is ensuring that treatments are in alignment with patient or surrogate decision-maker goals. Treatment discordant with patient goals has been shown to increase medical costs and prolong end-of-life difficulties. Objectives To evaluate discordance between surrogate decision-maker goals of care and medical orders and treatments provided to hospitalized, incapacitated older patients. Design, Setting, and Participants This prospective cohort study included 363 patient-surrogate dyads. Patients were 65 years or older and faced at least 1 major medical decision in the medical and medical intensive care unit services in 3 tertiary care hospitals in an urban Midwestern area. Data were collected from April 27, 2012, through July 10, 2015, and analyzed from October 5, 2018, to December 5, 2019. Main Outcomes and Measures Each surrogate’s preferred goal of care was determined via interview during initial hospitalization and 6 to 8 weeks after discharge. Surrogates were asked to select the goal of care for the patient from 3 options: comfort-focused care, life-sustaining treatment, or an intermediate option. To assess discordance, the preferred goal of care as determined by the surrogate was compared with data from medical record review outlining the medical treatment received during the target hospitalization. Results A total of 363 dyads consisting of patients (223 women [61.4%]; mean [SD] age, 81.8 [8.3] years) and their surrogates (257 women [70.8%]; mean [SD] age, 58.3 [11.2] years) were included in the analysis. One hundred sixty-nine patients (46.6%) received at least 1 medical treatment discordant from their surrogate’s identified goals of care. The most common type of discordance involved full-code orders for patients with a goal of comfort (n = 41) or an intermediate option (n = 93). More frequent in-person contact between surrogate and patient (adjusted odds ratio [AOR], 0.43; 95% CI, 0.23-0.82), patient residence in an institution (AOR, 0.44; 95% CI, 0.23-0.82), and surrogate-rated quality of communication (AOR, 0.98; 95% CI, 0.96-0.99) were associated with lower discordance. Surrogate marital status (AOR for single vs married, 1.92; 95% CI, 1.01-3.66), number of family members involved in decisions (AOR for ≥2 vs 0-1, 1.84; 95% CI, 1.05-3.21), and religious affiliation (AOR for none vs any, 4.87; 95% CI, 1.12-21.09) were associated with higher discordance. Conclusions and Relevance This study found that discordance between surrogate goals of care and medical treatments for hospitalized, incapacitated patients was common. Communication quality is a modifiable factor associated with discordance that may be an avenue for future interventions. ... 5 Treatment-limiting POLSTs have been associated with less in-hospital death, hospitalization, and unwanted cardiopulmonary resuscitation (CPR) and with a low incidence of intensive care in nursing home residents. 6 However, the associations between POLST order for medical interventions and measures of intensive care in other populations are less studied. ... Association of Physician Orders for Life-Sustaining Treatment With ICU Admission Among Patients Hospitalized Near the End of Life Importance Patients with chronic illness frequently use Physician Orders for Life-Sustaining Treatment (POLST) to document treatment limitations. Objectives To evaluate the association between POLST order for medical interventions and intensive care unit (ICU) admission for patients hospitalized near the end of life. Design, Setting, and Participants Retrospective cohort study of patients with POLSTs and with chronic illness who died between January 1, 2010, and December 31, 2017, and were hospitalized 6 months or less before death in a 2-hospital academic health care system. Exposures POLST order for medical interventions (“comfort measures only” vs “limited additional interventions” vs “full treatment”), age, race/ethnicity, education, days from POLST completion to admission, histories of cancer or dementia, and admission for traumatic injury. Main Outcomes and Measures The primary outcome was the association between POLST order and ICU admission during the last hospitalization of life; the secondary outcome was receipt of a composite of 4 life-sustaining treatments: mechanical ventilation, vasopressors, dialysis, and cardiopulmonary resuscitation. For evaluating factors associated with POLST-discordant care, the outcome was ICU admission contrary to POLST order for medical interventions during the last hospitalization of life. Results Among 1818 decedents (mean age, 70.8 [SD, 14.7] years; 41% women), 401 (22%) had POLST orders for comfort measures only, 761 (42%) had orders for limited additional interventions, and 656 (36%) had orders for full treatment. ICU admissions occurred in 31% (95% CI, 26%-35%) of patients with comfort-only orders, 46% (95% CI, 42%-49%) with limited-interventions orders, and 62% (95% CI, 58%-66%) with full-treatment orders. One or more life-sustaining treatments were delivered to 14% (95% CI, 11%-17%) of patients with comfort-only orders and to 20% (95% CI, 17%-23%) of patients with limited-interventions orders. Compared with patients with full-treatment POLSTs, those with comfort-only and limited-interventions orders were significantly less likely to receive ICU admission (comfort only: 123/401 [31%] vs 406/656 [62%], aRR, 0.53 [95% CI, 0.45-0.62]; limited interventions: 349/761 [46%] vs 406/656 [62%], aRR, 0.79 [95% CI, 0.71-0.87]). Across patients with comfort-only and limited-interventions POLSTs, 38% (95% CI, 35%-40%) received POLST-discordant care. Patients with cancer were significantly less likely to receive POLST-discordant care than those without cancer (comfort only: 41/181 [23%] vs 80/220 [36%], aRR, 0.60 [95% CI, 0.43-0.85]; limited interventions: 100/321 [31%] vs 215/440 [49%], aRR, 0.63 [95% CI, 0.51-0.78]). Patients with dementia and comfort-only orders were significantly less likely to receive POLST-discordant care than those without dementia (23/111 [21%] vs 98/290 [34%], aRR, 0.44 [95% CI, 0.29-0.67]). Patients admitted for traumatic injury were significantly more likely to receive POLST-discordant care (comfort only: 29/64 [45%] vs 92/337 [27%], aRR, 1.52 [95% CI, 1.08-2.14]; limited interventions: 51/91 [56%] vs 264/670 [39%], aRR, 1.36 [95% CI, 1.09-1.68]). In patients with limited-interventions orders, older age was significantly associated with less POLST-discordant care (aRR, 0.93 per 10 years [95% CI, 0.88-1.00]). Conclusions and Relevance Among patients with POLSTs and with chronic life-limiting illness who were hospitalized within 6 months of death, treatment-limiting POLSTs were significantly associated with lower rates of ICU admission compared with full-treatment POLSTs. However, 38% of patients with treatment-limiting POLSTs received intensive care that was potentially discordant with their POLST. Reliability and Validity of the Chinese Version of Advance Care Planning Self-efficacy Scale for Physicians Background: Chinese patients prefer physicians to initiate advance care planning (ACP) conversations, but there is no appropriate tool to evaluate physicians' ACP self-efficacy level in mainland China. This study aimed to translate the ACP self-efficacy scale into Chinese (ACP-SEc) and measure its psychometric properties among clinical physicians. Method: The original scale was translated by literal translation, synthesis, and reverse translation, according to Brislin's translation model. Seven experts were invited to further revise the scale and evaluate the content validity. 348 physicians were conveniently sampled to evaluate the reliability and validity of the scale from May to June 2021 in 7 tertiary hospitals. Results: The ACP-SEc contained 17 items, 1 dimension, with a total score of 17 to 85 points. In this study, the critical ratios of the items ranged from 12.533 to 23.306, the item-total correlation coefficients ranged from 0.619 to 0.839. The item-content validity index ranged from 0.86 to 1.00, and the average scale-level content validity index was 0.98. In total, 75.507% of the total variance was explained by 1 common factor. The results of confirmatory factor analysis showed that the fitting indices of the modified model were desirable. The ACP-SEc was moderately correlated with General Self-Efficacy Scale (r = 0.675, P < .001), and it differentiated between physician groups based on the knowledge level of ACP, palliative care or ACP-related training experience, attitude toward ACP, willingness to initiate ACP discussions with patients, and experience of discussing ACP with family and friends, willingness to initiate ACP discussions with family and friends (P <.05). The total Cronbach's α and test-retest reliability of the scale were .960 and .976, respectively. Conclusion: The ACP-SEc shows good reliability and validity, and it can be used to assess the ACP self-efficacy level of physicians. Don't Throw the Baby Out With the Bathwater: Meta-Analysis of Advance Care Planning and End-of-life Cancer Care Context: There is ongoing discourse about the impact of advance care planning (ACP) on end-of-life (EOL) care. No meta-analysis exists to clarify ACP's impact on patients with cancer. Objective: To investigate the association between, and moderators of, ACP and aggressive versus comfort-focused EOL care outcomes among patients with cancer. Methods: Five databases were searched for peer-reviewed observational/experimental ACP-specific studies that were published between 1990-2022 that focused on samples of patients with cancer. Odds ratios were pooled to estimate overall effects using inverse variance weighting. Results: Of 8,673 articles, 21 met criteria, representing 33,541 participants and 68 effect sizes (54 aggressive, 14 comfort-focused). ACP was associated with significantly lower odds of chemotherapy, intensive care, hospital admissions, hospice use fewer than seven days, hospital death, and aggressive care composite measures. ACP was associated with 1.51 times greater odds of do-not-resuscitate orders. Other outcomes-cardiopulmonary resuscitation, emergency department admissions, mechanical ventilation, and hospice use-were not impacted. Tests of moderation revealed that the communication components of ACP produced greater reductions in the odds of hospital admissions compared to other components of ACP (e.g., documents); and, observational studies, not experimental, produced greater odds of hospice use. Conclusion: This meta-analysis demonstrated mixed evidence of the association between ACP and EOL cancer care, where tests of moderation suggested that the communication components of ACP carry more weight in influencing outcomes. Further disease-specific efforts to clarify models and components of ACP that work and matter to patients and caregivers will advance the field. Manejo das demências em fase avançada: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia Alzheimer’s disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers. Keywords: Dementia; Palliative Care; Behavior; Cognition Management in severe dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology Alzheimer’s disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers. Keywords: Dementia; Palliative Care; Behavior; Cognition Association between Goals of Care Designation orders and health care resource use among seriously ill older adults in acute care: a multicentre prospective cohort study Executive summary: With increased therapeutic capabilities in healthcare today, many patients with multiple progressive comorbidities are living longer. They experience recurrent hospitalizations and often undergo procedures that are not aligned with their personal goals. That is why it is essential to discuss and document healthcare preferences prior to an acute event when significant interventions could occur, especially for patients with serious and progressive illness. Completion of an advance directive and a physician order for life-sustaining treatment (POLST) supports provision of goal-concordant care. Further, for patients who have do not attempt resuscitation (DNAR) orders or are diagnosed with advanced dementia, having a POLST is essential. This may be best accomplished with hospitalization discharge plans. Our 896-bed academic medical center, Cedars-Sinai Medical Center, launched a quality initiative in 2015 to complete POLSTs for patients being discharged with DNAR status or with dementia returning to a skilled nursing facility. As part of interdisciplinary progression of care rounds, emphasis was placed on those patients for whom POLST completion was indicated. Proactive, facilitated discussions with patients, family members, and attending physicians were initiated to support POLST completion. The completed forms were then uploaded to the electronic health record. Individual units and physicians received regular feedback on POLST completion rates, and the data were later shared at medical staff quality improvement meetings.During the initiative, POLST completion rates for DNAR patients discharged alive rose from 41% in fiscal year (FY) 2014 to 75% in FY 2019. Similar improvement was seen for patients with dementia discharged to skilled nursing facilities, regardless of code status (rising from 14% in FY 2014 to 54% in FY 2019). Subsequently, we have expanded our efforts to include early discussion and completion of these advanced care planning documents for patients recently diagnosed with high mortality cancers (ovarian, pancreatic, lung, glioblastoma), focusing on the completion of advanced care planning documentation and palliative care referrals. Background US hospitals typically provide a set of code status options that includes Full Code and Do Not Resuscitate (DNR) but often includes additional options. Although US hospitals differ in the design of code status options, this variation and its impacts have not been empirically studied. Design and methods Multi-institutional qualitative study at 7 US hospitals selected for variability in geographical location, type of institution and design of code status options. We triangulated across three data sources (policy documents, code status ordering menus and in-depth physician interviews) to characterise the code status options available at each hospital. Using inductive qualitative methods, we investigated design differences in hospital code status options and the perceived impacts of these differences. Results The code status options at each hospital varied widely with regard to the number of code status options, the names and definitions of code status options, and the formatting and capabilities of code status ordering menus. DNR orders were named and defined differently at each hospital studied. We identified five key design characteristics that impact the function of a code status order. Each hospital’s code status options were unique with respect to these characteristics, indicating that code status plays differing roles in each hospital. Physician participants perceived that the design of code status options shapes communication and decision-making practices about resuscitation and life-sustaining treatments, especially at the end of life. We identified four potential mechanisms through which this may occur: framing conversations, prompting decisions, shaping inferences and creating categories. Conclusions There are substantive differences in the design of hospital code status options that may contribute to known variability in end-of-life care and treatment intensity among US hospitals. Our framework can be used to design hospital code status options or evaluate their function. Background/objectives: Many older persons with chronic illness use Physician Orders for Life-Sustaining Treatment (POLST) to document portable medical orders for emergency care. However, some POLSTs contain combinations of orders that do not translate into a cohesive care plan (eg, cardiopulmonary resuscitation [CPR] without intensive care, or intensive care without antibiotics). This study characterizes the prevalence and predictors of POLSTs with conflicting orders. Design: Retrospective cohort study. Setting: Large academic health system. Participants: A total of 3,123 POLST users with chronic life-limiting illness who died between 2010 and 2015 (mean age = 69.7 years). Measurements: In a retrospective review of all POLSTs in participants' electronic health records, we describe the prevalence of POLSTs with conflicting orders for cardiac arrest and medical interventions, and use clustered logistic regression to evaluate potential predictors of conflicting orders. We also examine the prevalence of conflicts between POLST orders for antibiotics and artificial nutrition with orders for cardiac arrest or medical interventions. Results: Among 3,924 complete POLSTs belonging to 3,123 decedents, 209 (5.3%) POLSTs contained orders to "attempt CPR" paired with orders for "limited interventions" or "comfort measures only"; 745/3169 (23.5%) POLSTs paired orders to restrict antibiotics with orders to deliver non-comfort-only care; and, 170/3098 (5.5%) POLSTs paired orders to withhold artificial nutrition with orders to deliver CPR or intensive care. Among POLSTs with orders to avoid intensive care, orders to attempt CPR were more likely to be present in POLSTs completed earlier in the patient's illness course (adjusted odds ratio = 1.27 per twofold increase in days from POLST to death; 95% confidence interval = 1.18-1.36; P < .001). Conclusion: Although most POLSTs are actionable by clinicians, 5% had conflicting orders for cardiac arrest and medical interventions, and 24% had one or more conflicts between orders for cardiac arrest, medical interventions, antibiotics, and artificial nutrition. These conflicting orders make implementation of POLST challenging for clinicians in acute care settings. Context As part of its Life-Sustaining Treatment (LST) Decisions Initiative, the Veterans Health Administration (VA) in January 2017 began requiring electronic documentation of goals of care and preferences for Veterans with serious illness and at high risk for life-threatening events. Objectives To evaluate whether goals of “to be comfortable” were associated with greater palliative care (PC) use and lesser acute care use. Methods We identified Veterans with VA inpatient or nursing home stays overlapping July 2018–January 2019, with LST templates documented by January 31, 2019, and who died by April 30, 2019 (N = 18,163). From template documentation, we identified a “to be comfortable” goal. Using VA and Medicare data, we determined PC use (consultations and hospice) and hospital, intensive care unit, and emergency department use 7 and 30 days before death. Multivariate logistic regression examined the associations of interest. Results Sixty-four percent of the 18,163 Veterans had comfort-care goals; 80% with comfort care goals received hospice and 57% PC consultations (versus 57% and 46%, respectively, for decedents without comfort-care goals). In adjusted analyses, comfort care documented on the LST template prior to death was associated with significantly lower odds of hospital, intensive care unit, and emergency department use near the end of life. In the last 30 days of life, Veterans with a comfort care goal had 44% lower odds (adjusted odds ratio 0.57; 95% CI: 0.51, 0.63) of being hospitalized. Conclusion Findings support the VA's commitment to honoring of Veterans' preferences post introduction of its Life Sustaining Treatment Decisions Initiative. In Reply We agree with Drs Mehta and Blackhall that a POLST may not always accurately reflect a patient’s goals of care at the time of completion for a number of reasons, and that this inaccuracy is one potential cause of POLST-discordant intensive care.¹ The fact that patients and surrogates do not always recall or even agree with their own POLSTs² strongly suggests that there is room for improvement in the initial completion of POLSTs. Additionally, there are emerging data that mapping patients’ values (eg, prioritization of comfort over longevity) to discrete treatment preferences (eg, no cardiopulmonary resuscitation or intensive care) is a complicated and perhaps error-prone process for many patients.³,4 We also agree that the process of completing a POLST form should be closely guided by clinicians and that there is a need for more education of clinicians so that they can help patients and surrogates complete POLSTs that both accurately reflect goals and can be implemented during acute illness. However, effective implementation of POLSTs may require more than simple educational interventions. The enormous variability in the reported efficacies of advance care planning interventions⁵ suggests that effective interventions may have key features for success that are often not replicated with fidelity in clinical practice. Such differences in implementation may arise because of limitations in resources, time, and effective point-of-care tools. Background/Objectives Physician Orders for Life-Sustaining Treatment (POLST) is recommended as a preferred practice for advance care planning with seriously ill patients. Decision aids can assist patients in advance care planning, but there are limited studies on their use for POLST decisions. We hypothesized that after viewing a POLST video, decision aid participants would demonstrate increased knowledge and satisfaction and decreased decisional conflict. Design Pre-and postintervention with no control group. Setting/Participants Fifty community-dwelling adults aged 65 and older asked to complete a POLST based on a hypothetical condition. Interventions Video decision aid for Sections A and B of the POLST form. Measurements Pre- and postintervention participant knowledge, decisional satisfaction, decisional conflict, and acceptability of video decision aid. Results Use of the video decision aid increased knowledge scores from 11.24 ± 2.77 to 14.32 ± 2.89, P < .001, improved decisional satisfaction 10.14 ± 3.73 to 8.70 ± 3.00, P = .001, and decreased decisional conflict 12 ± 9.42 to 8.15 ± 9.13, P < .001. All participants reported that they were comfortable using the video decision aid, that they would recommend it to others, and that it clarified POLST decisions. Conclusions Participants endorsed the use of a POLST video decision aid, which increased their knowledge of POLST form options and satisfaction with their decisions, and decreased their decisional conflict in POLST completion. This pilot study provides preliminary support for the use of video decision aids for POLST decision-making. Future research should evaluate a decision aid for the entire POLST form and identify patient preferences for implementing POLST decision aids into clinical practice. Objectives: To determine for each basic, instrumental, and mobility activity after hospitalization for acute medical illness: (1) disability prevalence immediately before and monthly for 6 months after hospitalization; (2) disability incidence 1 month after hospitalization; and (3) recovery time from incident disability during months 2 to 6 after hospitalization. Design: Prospective cohort study. Setting: New Haven, Connecticut. Participants: A total of 515 community-living persons, mean age 82.7 years, hospitalized for acute noncritical medical illness and alive within 1 month of hospital discharge. Measurements: Disability was defined monthly for each basic (bathing, dressing, walking, transferring), instrumental (shopping, housework, meal preparation, taking medications, managing finances), and mobility activity (walking a quarter mile, climbing flight of stairs, lifting/carrying 10 pounds, driving) if help was needed to perform the activity or if a car was not driven in the prior month. Results: Disability was common 1 and 6 months after hospitalization for activities frequently involved in leaving the home to access care including walking a quarter mile (prevalence 65% and 53%, respectively) and driving (65% and 61%). Disability was also common for activities involved in self-managing chronic health conditions including meal preparation (53% and 41%) and taking medications (41% and 31%). New disability was common and often prolonged. For example, 43% had new disability walking a quarter mile, and 30% had new disability taking medications, with mean recovery time of 1.9 months and 1.7 months, respectively. Findings were similar for the subgroup of persons residing at home (ie, not in a nursing home) at the first monthly follow-up interview after hospitalization. Conclusion: Disability in specific functional activities important to leaving home to access care and self-managing health conditions is common, often new, and present for prolonged time periods after hospitalization for acute medical illness. Post-discharge care should support patients through extended periods of vulnerability beyond the immediate transitional period.
https://www.researchgate.net/publication/271649462_Use_of_the_Physician_Orders_for_Life-Sustaining_Treatment_Program_in_the_Clinical_Setting_A_Systematic_Review_of_the_Literature
Multiple Sclerosis and Gene Expression Profiling | Request PDF Request PDF | Multiple Sclerosis and Gene Expression Profiling | In gene microarray studies on MS brain, my lab has been studying mRNA from active MS brain lesions from MS brains, and comparing them to three... | Find, read and cite all the research you need on ResearchGate Multiple Sclerosis and Gene Expression Profiling February 2001 Advances in Experimental Medicine and Biology 490:109-12 DOI: 10.1007/978-1-4615-1243-1_11 Authors: Abstract In gene microarray studies on MS brain, my lab has been studying mRNA from active MS brain lesions from MS brains, and comparing them to three control brains, as well as four brains with Huntington’s Disease, and four brains with Parkinson’s Disease.1, 2 Using a 6800 gene Affymetrix microarray, large increases in transcription of genes encoding key components of the immune response have been seen.1, 2, 3 Microarray gene expression profiling of chronic active and inactive lesions in multiple sclerosis Article May 2004 CLIN NEUROL NEUROSUR Marcin P Mycko Multiple sclerosis, a primary autoimmune disease of the central nervous system has been characterized by the presence of the demyelinating lesions (plaques) in the CNS. To further understand the gene transcription status of the two most common lesions, chronic active and chronic inactive, we have performed a cDNA microarray analysis of these two lesion type. Comparative analysis of differential gene expression of chronic active and inactive lesions have confirmed the existence of a significant difference in the transcriptional profiles of these two lesion types in both marginal and central areas. Different sets of genes were highlighted, including genes of inflammatory characteristics, apoptosis related and stress-induced, indicating their potential role in MS pathogenesis. Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (Fingolimod) in multiple sclerosis Article Oct 2010 Chang-Wook Lee Ji Woong Choi Jerold Chun FTY720 (fingolimod, Novartis) is a promising investigational drug for relapsing forms of multiple sclerosis (MS), an autoimmune and neurodegenerative disorder of the central nervous system. It is currently under FDA review in the United States, and could represent the first approved oral treatment for MS. Extensive, ongoing clinical trials in Phase II/III have supported both the efficacy and safety of FTY720. FTY720 itself is not bioactive, but when phosphorylated (FTY720-P) by sphingosine kinase 2, it becomes active through modulation of 4 of the 5 known G protein-coupled sphingosine 1-phosphate (S1P) receptors. The mechanism of action (MOA) is thought to be immunological, where FTY720 alters lymphocyte trafficking via S1P1. However, MOA for FTY720 in MS may also involve a direct, neurological action within the central nervous system in view of documented S1P receptor-mediated signaling influences in the brain, and this review considers observations that support an emerging neurological MOA. Microarray gene expression profiling of chronic active and inactive lesions in multiple sclerosis Article Jul 2004 CLIN NEUROL NEUROSUR Marcin P Mycko Ruben Papoian Ursula Boschert Krzysztof Selmaj Multiple sclerosis, a primary autoimmune disease of the central nervous system has been characterized by the presence of the demyelinating lesions (plaques) in the CNS. To further understand the gene transcription status of the two most common lesions, chronic active and chronic inactive, we have performed a cDNA microarray analysis of these two lesion type. Comparative analysis of differential gene expression of chronic active and inactive lesions have confirmed the existence of a significant difference in the transcriptional profiles of these two lesion types in both marginal and central areas. Different sets of genes were highlighted, including genes of inflammatory characteristics, apoptosis related and stress-induced, indicating their potential role in MS pathogenesis. Microarray Analysis of Human Nervous System Gene Expression in Neurological Disease Article Feb 2004 INT REV NEUROBIOL Steven A Greenberg This chapter focuses on the use of microarrays applied to human tissues for the study of neurological disease, the unique challenges relating to the isolation of RNA from individual cells by laser capture microdissection, and on issues relating to the experimental design and data analysis. Microarrays can be used to study disease pathophysiology and disease classification. Microarray-based disease classification studies use class methods applied to expression profiles to compare diagnostic categories, discover disease subtypes, correlate phenotypical variables with gene expression patterns, and build models that predict clinically relevant variables that may include diagnosis or prognosis. Understanding of disease pathophysiology requires accurate identification of the genes that are differentially expressed across different conditions. Studying the role of these genes helps to understand the molecular mechanisms behind the disease. The most frequently used measure of differential gene expression is the fold ratio. In class comparison analysis, the data set consists of labeled specimens and each of them has a predefined class assignment. Their goal is to understand whether different classes have different expression profiles, and to compare and contrast the gene expression differences among the classes. Computational approaches to disease classification include cluster analysis and supervised learning techniques. The chapter outlines the human neurological diseases studied by microarray technology, such as multiple sclerosis, brain tumors, neuromuscular disorders, and alzheimer's disease. View Discovery and analysis of inflammatory disease-related genes using cDNA microarrays Article Mar 1997 P NATL ACAD SCI USA Renu A. Heller Mark Schena Andrew Chai Ronald Davis cDNA microarray technology is used to profile complex diseases and discover novel disease-related genes. In inflammatory disease such as rheumatoid arthritis, expression patterns of diverse cell types contribute to the pathology. We have monitored gene expression in this disease state with a microarray of selected human genes of probable significance in inflammation as well as with genes expressed in peripheral human blood cells. Messenger RNA from cultured macrophages, chondrocyte cell lines, primary chondrocytes, and synoviocytes provided expression profiles for the selected cytokines, chemokines, DNA binding proteins, and matrix-degrading metalloproteinases. Comparisons between tissue samples of rheumatoid arthritis and inflammatory bowel disease verified the involvement of many genes and revealed novel participation of the cytokine interleukin 3, chemokine Groα and the metalloproteinase matrix metallo-elastase in both diseases. From the peripheral blood library, tissue inhibitor of metalloproteinase 1, ferritin light chain, and manganese superoxide dismutase genes were identified as expressed differentially in rheumatoid arthritis compared with inflammatory bowel disease. These results successfully demonstrate the use of the cDNA microarray system as a general approach for dissecting human diseases. Multiple approaches to multiple sclerosis Article Full-text available Jan 2000 Lawrence Steinman Multiple sclerosis results from the failure of several different regulatory mechanisms designed to protect against autoimmunity, suggesting multiple targets for therapeutic intervention. Three papers in this issue suggest that if tolerance to components of the nervous system is not maintained in the thymus and autoimmunity ensues, the extent of brain damage can be checked by blockade of glutamate receptors on neurons and oligodendrocytes (pages 56-70). Multiple Sclerosis: A Coordinated Immunological Attack against Myelin in the Central Nervous System Article Jun 1996 Lawrence Steinman The role of TNFα and lymphotoxin in demyelinating disease Dec 1999 Christopher Lock Jorge R Oksenberg Larry Steinman Multiple sclerosis (MS) is an inflammatory demyelinating disease of central nervous system (CNS) white matter.1 The aetiology is unknown but the condition is probably the result of a misdirected immune response against myelin antigens. Pathologically there are multiple plaques or areas of white matter inflammation, demyelination, and glial scarring or sclerosis. In addition to myelin damage, axon loss may occur as there is a close relation between myelin and axon.2 The inflammatory lesions are disseminated in time and space, and clinically the illness is characterised by relapsing episodes of neurological dysfunction. In a commonly proposed sequence of events, autoreactive myelin specific CD4+ Th1 are activated in the periphery, probably by non-self antigens with a resemblance to myelin proteins.3 T cells interact with adhesion molecules, such as selectins and integrins, on the capillary endothelium and then migrate into the brain parenchyma in response to chemotactic signals. Matrix metalloproteases (MMPs) are important in facilitating T cell penetration through the endothelial basement membrane. Microglia and astrocytes reactivate T cells locally in the CNS by presentation of myelin proteins bound to class II MHC molecules. T cells stimulate macrophage activity by release of proinflammatory cytokines such as IL2, IFNγ, tumour necrosis factor α (TNFα) and lymphotoxin (LT). Activated macrophages phagocytose myelin, and damage myelin by release of proteases, nitric oxide metabolites, reactive oxygen species, eicosanoids, complement components and TNFα. Autoantibodies directed against myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) are involved in myelin damage.4 5 Experimental allergic (or autoimmune) encephalomyelitis (EAE) can be induced in a variety of animal species, including non-human primates, by immunisation with spinal cord homogenates, myelin proteins or their peptide derivatives. A number of different myelin proteins can induce EAE, including proteolipid protein (PLP), MBP, MOG, myelin associated glycoprotein (MAG), and 2'3' cyclic nucleotide … Assessment of Animal Models for MS and Demyelinating Disease in the Design of Rational Therapy Dec 1999 NEURON Larry Steinman Transcriptional profile of Huntington disease brain with gene microarrays Jan 1999 541 M V Karpuj L Steinman Large-scale expression analysis of MS lesions using gene microarrays NEUROLOGY C Lock J Oksenberg C Raine
https://www.researchgate.net/publication/11839039_Multiple_Sclerosis_and_Gene_Expression_Profiling
Impact of childhood bullying still evident after 40 years | EurekAlert! Science News The negative social, physical and mental health effects of childhood bullying are still evident nearly 40 years later, according to new research by King's College London. The study is the first to look at the effects of bullying beyond early adulthood, and is published in the American Journal of Psychiatry. Impact of childhood bullying still evident after 40 years Negative impact of bullying was found to be persistent and pervasive, with health, social and economic consequences lasting well into adulthood The negative social, physical and mental health effects of childhood bullying are still evident nearly 40 years later, according to new research by King's College London. The study is the first to look at the effects of bullying beyond early adulthood, and is published in the American Journal of Psychiatry. The findings come from the British National Child Development Study which includes data on all children born in England, Scotland and Wales during one week in 1958. The study published today includes 7,771 children whose parents provided information on their child's exposure to bullying when they were aged 7 and 11. The children were then followed up until the age of 50. Dr Ryu Takizawa, lead author of the paper from the Institute of Psychiatry at King's College London, says: "Our study shows that the effects of bullying are still visible nearly four decades later. The impact of bullying is persistent and pervasive, with health, social and economic consequences lasting well into adulthood." Just over a quarter of children in the study (28%) had been bullied occasionally, and 15% bullied frequently - similar to rates in the UK today. Individuals who were bullied in childhood were more likely to have poorer physical and psychological health and cognitive functioning at age 50. Individuals who were frequently bullied in childhood were at an increased risk of depression, anxiety disorders, and suicidal thoughts. Individuals who were bullied in childhood were also more likely to have lower educational levels, with men who were bullied more likely to be unemployed and earn less. Social relationships and well-being were also affected. Individuals who had been bullied were less likely to be in a relationship, to have good social support, and were more likely to report lower quality of life and life satisfaction. Professor Louise Arseneault, senior author, also from the Institute of Psychiatry at King's adds: "We need to move away from any perception that bullying is just an inevitable part of growing-up. Teachers, parents and policy-makers should be aware that what happens in the school playground can have long-term repercussions for children. Programmes to stop bullying are extremely important, but we also need to focus our efforts on early intervention to prevent potential problems persisting into adolescence and adulthood." Bullying is characterized by repeated hurtful actions by children of a similar age, where the victim finds it difficult to defend themselves. The harmful effect of bullying remained even when other factors including childhood IQ, emotional and behavioural problems, parents' socioeconomic status and low parental involvement, were taken into account. Professor Arseneault adds: "40 years is a long time, so there will no doubt be additional experiences during the course of these young people's lives which may either protect them against the effects of bullying, or make things worse. Our next step is to investigate what these are." ### The study was funded by the British Academy and the Royal Society. For a copy of the paper, or interviews with the author, please contact Seil Collins, Press Officer, Institute of Psychiatry, King's College [email protected]/ (+44) 0207 848 5377 / (+44) 07718 697 176 Paper reference: Takizawa R, Maughan B, Arseneault L. "Adult health outcomes of childhood bullying victimization: Evidence from a 5-decade longitudinal British cohort" will be published in the American Journal of Psychiatry About the National Child Development Study: The National Child Development Study (NCDS) follows the lives of 17,000 people born in England, Scotland and Wales in a single week of 1958. Also known as the 1958 Birth Cohort Study, it collects information on physical and educational development, economic circumstances, employment, family life, health behaviour, wellbeing, social participation and attitudes. The NCDS is run by the Centre for Longitudinal Studies, an Economic and Social Research Council resource centre based at the Institute of Education, University of London.http://www. cls. ioe. ac. uk/ page. aspx?&sitesectionid= 724&sitesectiontitle= Welcome+to+the+1958+National+Child+Development+Study About King's College London: King's College London is one of the top 20 universities in the world (2013/14 QS World University Rankings) and the fourth oldest in England. It is The Sunday Times 'Best University for Graduate Employment 2012/13'. A research-led university based in the heart of London, King's has more than 25,000 students (of whom more than 10,000 are graduate students) from nearly 140 countries, and more than 6,500 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate. King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £554 million. King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit:http://www. kingshealthpartners.org . The College is in the midst of a five-year, £500 million fundraising campaign - World questions|King's answers - created to address some of the most pressing challenges facing humanity as quickly as feasible. The campaign's five priority areas are neuroscience and mental health, leadership and society, cancer, global power and children's health. More information about the campaign is available athttp://www. kcl.ac. uk/ kingsanswers . Keywords
https://archive.eurekalert.org/pub_releases/2014-04/kcl-ioc041614.php
Perceptual Fusion of Infrared and Visible Image through Variational Multiscale with Guide Filtering Perceptual Fusion of Infrared and Visible Image through Variational Multiscale with Guide Filtering Perceptual Fusion of Infrared and Visible Image through Variational Multiscale with Guide Filtering Xin Feng*,Kaiqun Hu* Article Information Corresponding Author: Xin Feng* ([email protected]) Xin Feng*, College of Mechanical Engineering, Chongqing Technology and Business University, Chongqing, China; and Key Laboratory of ManufacturingEquipment Mechanism Design and Control of Chongqing, Chongqing, China, [email protected] Kaiqun Hu*, College of Mechanical Engineering, Chongqing Technology and Business University, Chongqing, China; and Key Laboratory of ManufacturingEquipment Mechanism Design and Control of Chongqing, Chongqing, China, [email protected] Published (Print):December 31 2019 Published (Electronic):December 31 2019 Abstract Abstract:To solve the problem of poor noise suppression capability and frequent loss of edge contour and detailed information in current fusion methods, an infrared and visible light image fusion method based on variational multiscale decomposition is proposed. Firstly, the fused images are separately processed through variational multiscale decomposition to obtain texture components and structural components. The method of guided filter is used to carry out the fusion of the texture components of the fused image. In the structural component fusion, a method is proposed to measure the fused weights with phase consistency, sharpness, and brightness comprehensive information. Finally, the texture components of the two images are fused. The structure components are added to obtain the final fused image. The experimental results show that the proposed method displays very good noise robustness, and it also helps realize better fusion quality. Keywords: Image Fusion , Guided Filter , Phase Consistency , Variational Multiscale Decomposition 1. Introduction Infrared sensors are important to the reflection of real scenes. The resulting images are featured by low resolution and low signal-to-noise ratio. The details of the scene under certain conditions can be reflected clearly using visible light sensor, and the imaging is susceptible to the natural conditions such as illumination and weather [1]. Currently, infrared and visible light image fusion is based on various improved multi-scale analysis methods. Meng et al. [2] proposed an infrared and visible image fusion based on object region detection and the non-subsampled contourlet transform (NSCT), and by using the model that had proposed, objects and be clarified and details and visual artifacts in the fused image can be preserved. Zhu et al. [3] proposed an infrared and visible image fusion method based on an improved multi-scale top-hat transform model; this model highlights the target of infrared images and preserves the details of visible images, and its performance is better than certain conventional multi-scale transform image methods in this respect. Liu et al. [4] proposed a multi-scale geometric analysis combined with image fusion method in sparse representation (SR), and they obtained better results than that of solely SR or multi-scale geometric analysis. Zhang et al. [5] proposed a multi-exposure image fusion algorithm based on time-domain median filtering. Although the traditional multi-scale method has certain noise robustness, the performance will decrease linearly when the noise is serious. In general, the structural components of infrared and visible light images mainly depict the basic contour structure of the image, and are most susceptible to noise interference. If the fusion rule is capable of filtering and maintaining the edge of the image, a clear structural fusion result can be obtained; and the texture components can reduce the effect of noise on the fusion results on infrared and visible light images by discarding the texture components on the smallest scale. Fig. 1. The block diagram of this paper. 2. Variational Multi-scale Decomposition Variational multiscale decomposition is frequently adopted to recover real images from noise images. It is an important research content in the domain of image processing research. It can be seen as a decomposition of the image f ⋅ f = u + v f ⋅ f = u + v denotes that the former mainly represents the image structure component, and the latter mainly represents the texture component of the image [ 6 ]. For the input infrared light image f A f A with the initial scale λ = 0.0005 λ = 0.0005 , the following energy functional is defined: (1) ( f A u λ , f A v λ ) = arginf ⎧ ⎪ ⎪ ⎨ ⎪ ⎪ ⎩ E λ ( f A , λ ; f A u , f A v ) = ∥ ∥ f A u ∥ ∥ + λ ∥ ∥ f A − f A u − f A v ∥ ∥ + ∥ ∥ f A v ∥ ∥ , ∫ Ω f A u = ∫ Ω f A ( f u λ A , f v λ A ) = arginf ⁡ { E λ ( f A , λ ; f u A , f v A ) = ‖ f u A ‖ + λ ‖ f A − f u A − f v A ‖ + ‖ f v A ‖ , ∫ Ω f u A = ∫ Ω f A where λ λ denotes the initial decomposition scale. f A u λ f u λ A denotes the structural component of the infrared light image at the scale λ λ , and f A v λ f v λ A λ λ . arginf() is the independent variable corresponding to the maximum likelihood function, f A u f u A is the structural component of the input infrared light image, f A v f v A is the texture component of the input infrared light image, and the residual of the image can be expressed as: (2) f A r = f A − f A u − f A v f r A = f A − f u A − f v A According to the above rules, constantly decomposition is performed to establish a multi-scale decomposition form, and obtain the structural components, texture components, and residual components of the final infrared light image: (3) f A = f A u 1 + f A u 2 + f A u 3 + … + f A u m + f A v 1 + f A v 2 + f A v 3 + … + f A v m + f A r m f A = f u 1 A + f u 2 A + f u 3 A + … + f u m A + f v 1 A + f v 2 A + f v 3 A + … + f v m A + f r m A Among them, m denotes the number of decomposition layers, f A u m f u m A and f A v m f v m A are the structural components and texture components of the m-layer decomposition of the visible light image, and f A r m f r m A is the residual difference component of the input infrared image after m-layer decomposition. Similarly, by taking the above steps for the visible light image, the corresponding structural component f B u m f u m B , texture component f B v m f v m B , and residual difference component f B r m f r m B of the visible light image can be obtained: (4) f B = f B u 0 + f B u 1 + f B u 2 + … + f B u m + f B v 0 + f B v 1 + f B v 2 + … + f B v m + f B r m f B = f u 0 B + f u 1 B + f u 2 B + … + f u m B + f v 0 B + f v 1 B + f v 2 B + … + f v m B + f r m B By discarding the texture components at the lowest two scales, the effect of noise on the fused image is reduced. The overall structural components f A u f u A and f B u f u B of infrared and visible light images are f A u = m ∑ i = 0 f A u i f u A = ∑ i = 0 m f u i A and f B u = m ∑ i = 0 f B u i f u B = ∑ i = 0 m f u i B , respectively, and the overall texture components f A v f v A and f B v f v B are f A v = m ∑ i = 2 f A v i f v A = ∑ i = 2 m f v i A and f B v = m ∑ i = 2 f B v i f v B = ∑ i = 2 m f v i B , respectively. 3. Structural Component Fusion Guided filtering refers to a filtering algorithm based on the local linear model. It was proposed by He et al. [7] in 2013. It is a local multi-point filter and an effective boundary-preserving filter. Its main advantage including its function of maintaining the edge of the image while filtering, and the algorithm complexity is linear and efficient. Therefore, the fusion rule is an ideal choice for the setting of the structural components. It is assumed that, in a window ( 2 r + 1 ) × ( 2 r + 1 ) ( 2 r + 1 ) × ( 2 r + 1 ) of size ω, the output O of the filter is always represented as the linear transformation of the pilot image I: (5) O i = a j I i + b j , ∀ i ∈ ω j O i = a j I i + b j , ∀ i ∈ ω j In the fusion process, the structural components on different scales are respectively fused to obtain the fused structural components at different scales. f A u f u A and f B u f u B are the structural components of infrared and visible light images at a certain scale, and then f A u f u A and f B u f u B are compared based on each pixel to obtain weight maps w 1 w 1 and w 2 w 2 : (6) w 1 = { 0 , otherelse 1 , if f A u > f B u w 1 = { 0 , otherelse 1 , if f u A > f u B (7) w 2 = { 0 , otherelse 1 , if f B u > f A u w 2 = { 0 , otherelse 1 , if f u B > f u A The structural component is obtained by through the calculation and the noise and the edges are not uniform in this respect. Then, guided filtering is performed on the weighted graphs w 1 w 1 and w 2 w 2 and f A u f u A and f B u f u B are respectively acting as the infrared and visible guiding images to obtain new weighted graphs m 1 m 1 and m 2 m 2 : (8) m 1 = G r , ε ( w 1 , f A u ) m 1 = G r , ε ( w 1 , f u A ) (9) m 2 = G r , s ( w 2 , f B u ) m 2 = G r , s ( w 2 , f u B ) And the filter core is expressed as: (10) G r , s = 1 | Ω | 2 ∑ k : ( i , j ) ∈ Ω k [ 1 + ( G i − μ k ) ( G j − μ k ) σ 2 k + ζ ] G r , s = 1 | Ω | 2 ∑ k : ( i , j ) ∈ Ω k [ 1 + ( G i − μ k ) ( G j − μ k ) σ k 2 + ζ ] where Ω Ω is the radius of the pilot filter and is set to r=3, which ζ ζ is the regularized adjustment parameter of the pilot filter and is set to ζ = 10 − 6 , σ 2 k ζ = 10 − 6 , σ k 2 and μ k μ k represent the average and variance of the guide image within the radius respectively. With the new weight graphs m1 and m2, the fused structure component f u f u is obtained: (11) f u = f A u × m 1 + f B u × m 2 f u = f u A × m 1 + f u B × m 2 4. Texture Component Fusion The texture component includes a large amount of texture information and detail information in the image. Considering the relationship between the intensity of the current subband coefficient and the different subband coefficients in the same area, phase coherence information is adopted on the subbands of the infrared light and visible light texture components. Definition and image brightness information and other comprehensive information are adopted to calculate the texture component information of the image to be fused. First of all, for the infrared and visible light component subbands, the phase consistency information is obtained as: (12) M m A ( x , y ) = ∑ k E m A , θ ( x , y ) ε + ∑ n ∑ k S m A , n , θ ( x , y ) M A m ( x , y ) = ∑ k E A , θ m ( x , y ) ε + ∑ n ∑ k S A , n , θ m ( x , y ) (13) M m B ( x , y ) = ∑ k E m B , θ ( x , y ) ε + ∑ n ∑ k S m B , n , θ ( x , y ) M B m ( x , y ) = ∑ k E B , θ m ( x , y ) ε + ∑ n ∑ k S B , n , θ m ( x , y ) where m is the decomposition scale of the subband of the texture component, and M m A ( x , y ) , M m B ( x , y ) M A m ( x , y ) , M B m ( x , y ) are the phase coherence information of infrared and visible light images on the m-scale at the point ( x , y ) ; E m A , θ ( x , y ) ( x , y ) ; E A , θ m ( x , y ) and E m B , θ ( x , y ) E B , θ m ( x , y ) denote the local energy information of the Fourier domain in the m-scale and θ θ -direction angles of the texture component sub-bands of the infrared and visible light images at the point ( x , y ) ; S m A , n , θ ( x , y ) ( x , y ) ; S A , n , θ m ( x , y ) and S m B , n , θ ( x , y ) S B , n , θ m ( x , y ) denote the local amplitude information of the Fourier region of the infrared component and the visible light image at the point (x, y) in the m-scale and θ-direction angular subbands; E E is a very small positive value, which is adopted in case the denominator is zero. The sliding window is set as ϕ ϕ , and it is assumed that the center of the window is (x, y), when the image is traversed to an arbitrary position. The definition information of the sub-band of the texture component of the visible light and infrared light image in the window is calculated as: (14) C m A ( x 0 , y 0 ) = [ I m h , A ( x , y ) − I m h , A ( x 0 , y 0 ) ] 2 ( x 0 , y 0 ) ∈ ϕ C A m ( x 0 , y 0 ) = [ I h , A m ( x , y ) − I h , A m ( x 0 , y 0 ) ] 2 ( x 0 , y 0 ) ∈ ϕ (15) C m B ( x 0 , y 0 ) = [ I m h , B ( x , y ) − I m h , B ( x 0 , y 0 ) ] 2 ( x 0 , y 0 ) ∈ ϕ C B m ( x 0 , y 0 ) = [ I h , B m ( x , y ) − I h , B m ( x 0 , y 0 ) ] 2 ( x 0 , y 0 ) ∈ ϕ I m h , A ( x , y ) I h , A m ( x , y ) and I m h , B ( x , y ) I h , B m ( x , y ) are the texture component subbands of the m-scale at the point (x, y) of the infrared and visible light images respectively. C m A ( x 0 , y 0 ) C A m ( x 0 , y 0 ) amd C m B ( x 0 , y 0 ) C B m ( x 0 , y 0 ) denote the amount of definition information of the texture component sub-bands at the m-scale dimension of the pixel point ( x 0 , y 0 ) ( x 0 , y 0 ) respectively. At the same time, ( x 0 , y 0 ) ( x 0 , y 0 ) is an arbitrary point within the sliding window ϕ ϕ . In this paper, according to the experience ϕ ϕ , the value is 11 × 11 11 × 11 . Through the comprehensive analysis of the phase consistency and the factors such as definition and image brightness, the rules for subband fusion of the texture components are obtained as follows. The activity of the subband of the texture component is defined as: (16) H m A ( x , y ) = ∑ ( x , y ) ∈ ϕ [ M m A ( x 0 , y 0 ) ] α 1 × [ C m A ( x 0 , y 0 ) ] β 1 × ∣ ∣ I m A ( x , y ) ∣ ∣ γ 1 H A m ( x , y ) = ∑ ( x , y ) ∈ ϕ [ M A m ( x 0 , y 0 ) ] α 1 × [ C A m ( x 0 , y 0 ) ] β 1 × | I A m ( x , y ) | γ 1 (17) H m B ( x , y ) = ∑ ( x , y ) ∈ ϕ [ M m B ( x 0 , y 0 ) ] α 1 × [ C m B ( x 0 , y 0 ) ] β 1 × ∣ ∣ I m B ( x , y ) ∣ ∣ γ 1 H B m ( x , y ) = ∑ ( x , y ) ∈ ϕ [ M B m ( x 0 , y 0 ) ] α 1 × [ C B m ( x 0 , y 0 ) ] β 1 × | I B m ( x , y ) | γ 1 H m A ( x , y ) H A m ( x , y ) and H m B ( x , y ) H B m ( x , y ) denote the active level of the texture component of the infrared and visible light images on the m-scale, and ∣ ∣ I m A ( x , y ) ∣ ∣ γ 1 | I A m ( x , y ) | γ 1 and ∣ ∣ I m B ( x , y ) ∣ ∣ γ 1 | I B m ( x , y ) | γ 1 denote the brightness of the subbands of the texture component. a 1 , β 1 a 1 , β 1 and γ 1 γ 1 denote the weight information of phase consistency information, sharpness, and image brightness information respectively. Based on the experience values, the weight coefficient in experiment were 0.001, 1, and 1, respectively. Then the weight of the fused texture components of infrared and visible light images is calculated: (18) Q m A ( x , y ) = { 0 , otherelse 1 , Q S m , p A ( x , y ) ≥ x × y 2 Q A m ( x , y ) = { 0 , otherelse 1 , Q S A m , p ( x , y ) ≥ x × y 2 (19) Q m B ( x , y ) = { 0 , otherelse 1 , Q S m , p B ( x , y ) ≥ x × y 2 Q B m ( x , y ) = { 0 , otherelse 1 , Q S B m , p ( x , y ) ≥ x × y 2 Q S m , p A ( x , y ) Q S A m , p ( x , y ) and Q S m , p B ( x , y ) Q S B m , p ( x , y ) are the number of active pixels in the sliding window of the infrared and visible light images at the point (x, y) m-scale, where x × y x × y is the size of the sliding window, and the expression of Q S m , p A ( x , y ) Q S A m , p ( x , y ) and Q S m , p B ( x , y ) Q S B m , p ( x , y ) are: (20) Q S m , p A ( x , y ) = { ( x 0 , y 0 ) ∈ ϕ | H m , p A ( x 0 , y 0 ) ≥ max { H m , p B ( x 0 , y 0 ) , H m , p A ( x 0 , y 0 ) } } Q S A m , p ( x , y ) = { ( x 0 , y 0 ) ∈ ϕ | H A m , p ( x 0 , y 0 ) ≥ max { H B m , p ( x 0 , y 0 ) , H A m , p ( x 0 , y 0 ) } } (21) | Q S m , p B ( x , y ) = { ( x 0 , y 0 ) ∈ ϕ | H m , p B ( x 0 , y 0 ) ≥ max { H m , p B ( x 0 , y 0 ) , H m , p A ( x 0 , y 0 ) } } | Q S B m , p ( x , y ) = { ( x 0 , y 0 ) ∈ ϕ | H B m , p ( x 0 , y 0 ) ≥ max { H B m , p ( x 0 , y 0 ) , H A m , p ( x 0 , y 0 ) } } Finally, texture component fusion is performed: (22) I m H , F ( x , y ) = I m H , A ( x , y ) × Q A ( x , y ) + I m H , B ( x , y ) × Q B ( x , y ) I H , F m ( x , y ) = I H , A m ( x , y ) × Q A ( x , y ) + I H , B m ( x , y ) × Q B ( x , y ) 5. Fusion Results In this experiment, the simulation experiment platform uses Intel Xeon CPU E3-1231 v3 @ 3.40 G 3.40 GHZ and its memory is 16 G, with PC Win7 and programming language MATLAB2010a. Due to the limited length of the paper, only a set of infrared visible images were adopted to verify the experimental results. At the same time, Gaussian white noise was artificially added to all images. The standard deviation was 10, 20. It can naturally introduce the denoising process into the fusion process, and has somehow denoising capability by adopting the transform domain method. Therefore, in this paper, it is mainly compared with the transform domain fusion method. Three representative methods for transform domain fusion are compared with the proposed method. That is, NSCT fusion method, SR fusion method, Shearlet transform (ST) fusion method, respectively. Among them, discrete wavelet transform (DWT), NSCT, ST decomposition layer is set to 4 layers, and wavelet base db4 is used in DWT method. In NSCT method, the direction filter is set to "vk", decomposition filter is set to "pyrexc", and the direction of 4 layers decomposition are 4, 8, 8, and 16, respectively. The SR method image block size is set to 8 × 8 8 × 8 , the reconstruction error is set to 0.1, k-singular value decomposition (K-SVD) is used for training dictionary, and the dictionary size is 256. In terms of fusion rules, NSCT method, RT method, and ST method integrate the fusion rules in literature [ 8 , 9 ] and [ 10 ], respectively. Fig. 2 is the result of the experiment in this paper when the noise standard deviation is 10. Fig. 2(a) and 2(b) are the original images of the third group of samples to be fused. Fig. 2(c) and 2(d) are schematic diagrams of the third group of samples to be fused after adding 10 standard deviation Gaussian white noise; Fig. 2(e)–2(i) are the four fusion methods for the purpose of comparison, and the fusion of the paper as a result of the method. It can be seen that due to the small amount of added noise, the fusion results of several methods are relatively ideal, as they are basically capable of maintaining the edges and details, and all of them have displayed certain capacity of noise suppression. The NSCT method, the Shearlet method, and the method mentioned in this paper are relatively smooth and have displayed relatively better visual effects. Fig. 2. Comparison of the third group of fusion results (noise standard deviation is 10): (a) original visible light image, (b) original infrared light image, (c) visible light and noise image, (d) infrared light and noise image, (e) NSCT method fusion result, (f) RT method fusion result, (g) Shearlet method fusion result, (h) fusion results of proposed method in this paper. In order to highlight the noise suppression effect of this method, the standard deviation of Gaussian white noise added is increased to 20 and the others remain unchanged as shown in Fig. 3. Since the serious noises can be effectively suppressed by adopting most of existing methods for multi-scale fusion methods, the guide filtering is adopted in the method to set the fusion rules on the structural components, which effectively removes noise pollution at the edges, and discards the lowest two in the texture component. The texture components on the scale have shown the best noise suppression performance compared to the other types. It can be seen that the fusion results of the DWT method, the ST method and the NSCT method are very poor, and the noise particles have been heavily contaminated to the structural edge and texture information of the fusion result. The fusion of the method in this paper is obviously outperform other methods for transform domain fusion. It can effectively suppress the noise while retaining the edge and texture information and has the best visual effect. And after the partial amplification of the fusion results of the above four methods can be clearly seen (as shown in Fig. 4), and the image obtained through this method looks significantly smoother than that obtained using other methods, and edge and texture information is much better. In summary, the visual effect of this method is better than the traditional transform domain method in the presence of noise pollution, especially when the noise is greater than 20 standard deviations, namely, the fusion method of this paper is more prominent when the original image is seriously polluted by noise. Fig. 3. Comparison of the third group of fusion results (noise standard deviation is 20): (a) original visible light image, (b) original infrared light image, (c) visible light and noise image, (d) infrared light and noise image, (e) NSCT method fusion result, (f) RT method fusion result, (g) Shearlet method fusion result, and (h) fusion results of proposed method in this paper. Fig. 4. The partially enlarged views of the fusion results in Fig. 3. In terms of the objective evaluation indicators, five common fusion indicators are adopted to evaluate the objective quality of various fusion methods. In the aspect of the information theory, the mutual information index is adopted, and the gradient-based fusion index is adopted for the image feature. As for the structure, the fusion index based on structural similarity is adopted and the index in human visual sensitivity is also used. The objective evaluation results of the quality of the three sets of image fusion results are shown in Table 1. Table 1. Fusion evaluation index From the above Table 1, we can see that when 10 standard deviation Gaussian white noise is added, this method has shown a few advantages in aspect of fusion index comparison, followed by RT fusion method and NSCT fusion method. However, when the noise is increased to 20 standard deviations, the advantages of the method become obvious in terms of gradient, structural similarity, visual sensitivity, and mutual information indicators. The merits of the method is obvious for the traditional transform domain when dealing with noise-contaminated original images. Meanwhile, as the complexity of the pilot filter algorithm is linear, regardless of the size of the set window, it has high efficiency. In terms of subjective and objective synthesis, this method can be applied to the fusion of noisy infrared and visible light images, and it has certain advantages over traditional transform domain fusion methods. 6. Conclusions In this paper, an infrared and visible light image fusion method based on variational multiscale decomposition is proposed. Guided filtering was used to fuse the structural components. The fusion weight rules were constructed using the phase consistency, definition, and brightness synthesis information on the texture components. Compared with the traditional methods for infrared and visible image fusion, it not only effectively overcomes the noise interference in the fusion process, but also obtains better texture details while maintaining the edge structure, and displays certain subjective and objective quality by adopting the method. However, due to the complexity of the guided filtering algorithm, it takes a long time if the algorithm is used. In the case of high real-time demand, the algorithm is difficult to meet the requirements, so the next study needs to further improve the computational efficiency of the algorithm. Acknowledgement The paper is supported by National Natural Science Foundation of China (No. 31501229, 61861025), Chongqing Nature Science Foundation for Fundamental Science and Frontier Technologies (No. cstc2018jcyjAX0483), Key Laboratory of Chongqing Technology and Business University (No. KFJJ2019076), and project of science and technology research program of Chongqing Education Commission of China (No. KJQN201900821). Biography Xin Feng https://orcid.org/0000-0001-8793-3775 He received Ph.D. degrees in School of Computer Science and Engineering from Lanzhou University of Technology in 2012. Since March 2013, he has been teaching in the School of Chongqing Technology and Business University. Biography Kaiqun Hu https://orcid.org/0000-0002-5590-2584 She received her Ph.D. degree from China Agriculture University in 2011. Now she is a lecturer in Chongqing Technology and Business University. Her main research direction is the technology of computer control and image processing. References 1 . J. Ma, Y. Ma, C. Li, "Infrared and visible image fusion methods and applications: a survey," Information Fusion , vol. 45, pp. 153-178, 2019. Cited By 2 . F. Meng, M. Song, B. Guo, R. Shi, D. Shan, "Image fusion based on object region detection and non-subsampled contourlet transform," Computers & Electrical Engineering , vol. 62, pp. 375-383, 2017. Cited By 3 . P. Zhu, X. Ma, Z. Huang, "Fusion of infrared-visible images using improved multi-scale top-hat transform and suitable fusion rules," Infrared Physics & Technology , vol. 81, pp. 282-295, 2017. Cited By 4 . Y. Liu, X. Chen, H. Peng, Z. Wang, "Multi-focus image fusion with a deep convolutional neural network," Information Fusion , vol. 36, pp. 191-207, 2017. Cited By 5 . B. Zhang, X. Lu, H. Pei, H. Liu, Y. Zhao, W. Zhou, "Multi-focus image fusion algorithm based on focused region extraction," Neurocomputing , vol. 174, pp. 733-748, 2016. Cited By 6 . J. Ma, C. Chen, C. Li, J. Huang, "Infrared and visible image fusion via gradient transfer and total variation minimization," Information Fusion , vol. 31, pp. 100-109, 2016. Cited By 7 . K. He, J. Sun, X. Tang, "Guided image filtering," IEEE Transactions on Pattern Analysis and Machine Intelligence , vol. 35, no. 6, pp. 1397-1409, 2013. Cited By 8 . Q. Zhang, B. L. Guo, "Multifocus image fusion using the nonsubsampled contourlet transform," Signal Processing , vol. 89, no. 7, pp. 1334-1346, 2009. Cited By 9 . B. Y ang, S. Li, "Multifocus image fusion and restoration with sparse representation," IEEE Transactions on Instrumentation and Measurement , vol. 59, no. 4, pp. 884-892, 2010. Cited By 10 . Q. G. Miao, C. Shi, P. F. Xu, M. Y ang, Y. B. Shi, "A novel algorithm of image fusion using shearlets," Optics Communications , vol. 284, no. 6, pp. 1540-1547, 2011. Cited By Table 1. Fusion evaluation index Fusion method QMI QG QY QCB Time (s) Noise standard deviation is 10 NSCT 0.791 0.679 0.839 0.769 54 RT 0.780 0.680 0.856 0.799 98 ST 0.699 0.690 0.817 0.776 43 This paper 0.743 0.685 0.829 0.756 34 Noise standard deviation is 20 NSCT 0.597 0.499 0.638 0.568 78 RT 0.569 0.548 0.667 0.594 116 ST 0.540 0.498 0.624 0.574 59 This paper 0.695 0.640 0.791 0.656 61 The block diagram of this paper. Comparison of the third group of fusion results (noise standard deviation is 10): (a) original visible light image, (b) original infrared light image, (c) visible light and noise image, (d) infrared light and noise image, (e) NSCT method fusion result, (f) RT method fusion result, (g) Shearlet method fusion result, (h) fusion results of proposed method in this paper. Comparison of the third group of fusion results (noise standard deviation is 20): (a) original visible light image, (b) original infrared light image, (c) visible light and noise image, (d) infrared light and noise image, (e) NSCT method fusion result, (f) RT method fusion result, (g) Shearlet method fusion result, and (h) fusion results of proposed method in this paper. The partially enlarged views of the fusion results in Fig. 3.
http://jips-k.org/pub-reader/view?doi=10.3745%2FJIPS.04.0144
Court Decisions | OIP | Department of Justice Court Decisions Displaying 2731 - 2740 of 3209 Garvey v. DOJ, No. 14-201, 2014 WL 4178290 (D.D.C. Aug. 22, 2014) (Leon, J.) Garvey v. DOJ, No. 14-201, 2014 WL 4178290 (D.D.C. Aug. 22, 2014) (Leon, J.) Re:Request for ethics opinion requested by and provided to prosecutor in plaintiff's prior criminal case Disposition:Denying plaintiff's motion for summary judgment Exemption 6: The court "conclude[s] that although the government's assertions are not detailed, they suffice at least to create a genuine issue of material fact as to whether the information warrants withholding under Exemption 6, and [plaintiff] is not entitled to summary judgment."  The court notes that "EOUSA determined that there was no public interest in disclosure, 'because the dissemination of this personal information would not help to explain the activities and the operations of the USAO,' . . . and [plaintiff] has not argued or offered any evidence to the contrary." Judicial Watch, Inc. v. DOJ, No. 13-01344, 2014 WL 4178291 (D.D.C. Aug. 22, 2014) (Leon, J.) Judicial Watch, Inc. v. DOJ, No. 13-01344, 2014 WL 4178291 (D.D.C. Aug. 22, 2014) (Leon, J.) Re: Request for records related to settlement discussions in Committee on Oversight and Government Reform v. Holder Disposition:Granting defendant's motion for summary judgment; denying plaintiff's cross-motion for summary judgment Exemption 3: The court holds that "the withholding of those documents was clearly proper."  The court first notes that "D.C. Local Rule 84.9 states that the District Court 'prohibits the mediator, all counsel and parties and any other persons attending the mediation from disclosing any written or oral communications made in connection with or during any mediation session.'"  "Plaintiff argues, however, that because the responsive documents were created before the parties were formally ordered into mediation by Judge Jackson, Local Rule 84.9 does not apply."  The court finds that "it strains credulity for plaintiff to argue that these communications were not 'made in connection' with mediation, given that the parties were strongly encouraged to engage in settlement discussions, and were reminded that court-ordered mediation might be ordered at any time."  The court holds that "[p]laintiff's narrow interpretation of Local Rule 84.9's applicability is simply inconsistent with both the case law and the purpose of the Rule."  Second, the court holds that "[e]ven assuming, arguendo, that Local Rule 84.9 does not apply, however, DOJ did not abuse its discretion in refusing to disclose the responsive settlement communications because it was honoring a court-imposed restriction, and thus there 'simply [was] no discretion for the agency to exercise.'"  The court notes that there is "an explicit statement from Judge Jackson instructing the parties to keep the substance of their settlement discussions private , . . . extrinsic evidence that the parties believed there was a court-imposed restriction prohibiting the disclosure of the substance of their settlement negotiations, . . . and a court rule prohibiting the disclosure of 'any written or oral communications made in connection with or during any mediation session.'"  Therefore, the court holds that "[b]ased on the above, there can be no doubt that there was a valid court-imposed restriction prohibiting disclosure of confidential settlement communications between the parties." Sack v. DOJ, No. 12-01755, 2014 WL 4100407 (D.D.C. Aug. 21, 2014) (Cooper, J.) Sack v. DOJ, No. 12-01755, 2014 WL 4100407 (D.D.C. Aug. 21, 2014) (Cooper, J.) Re:Request for records concerning polygraph bias Disposition:Granting in part and denying in part defendant's motion for summary judgment Litigation Considerations, Adequacy of Search: The court holds that "[the FBI] declaration does not describe any searches specific to [plaintiff's Defense Academy for Credibility Assessment] request, or outline the FBI's general search process in such a way that might lead to a reasonable inference that the Bureau responded specifically to this request."  The court finds that "[t]he government is correct that a FOIA plaintiff cannot succeed in challenging the adequacy of the government's search by hypothesizing that additional records should have been discovered, . . . but this does not end the matter."  "It remains the government's burden to provide affidavits demonstrating that it conducted an adequate search."  "The Court concludes it has failed to do so here."  Additionally, the court finds that "the government's description of its search indicates it may have misconstrued [plaintiff's] request." Exemption 2: The court holds that "construing Exemption 2 narrowly, it cannot extend to ATF's polygraph program because this is not trivial personnel information."  The court notes that "the relevant inquiry is whether the policies and procedures the DOJ uses to screen applicants for law enforcement positions is trivial personnel information."  The court finds that "[t]he public may well want to know, as [plaintiff] does, how agencies employ somewhat-controversial polygraph techniques to screen job applicants." Exemption 5, Deliberative Process Privilege: The court holds that "ATF cannot redact portions of the email under Exemption 5."  The court relates that "ATF redacted a portion of the email to OMB quoting and interpreting Order 2123.1."  The court finds that "[i]t is well established that an agency's regulations and settled regulatory interpretations are not covered by the deliberative process privilege" and, "[a]t face value, then, the redacted portion of the email cannot be withheld under Exemption 5 because it provides ATF's interpretation of its regulation, and nothing indicates that this interpretation was in any way novel."  The court also disagrees with ATF's argument "that it sent OMB the information contained in the email to help it decide whether to re-approve Order 2123.1, and . . . that these deliberations on future regulation make the document deliberative and pre-decisional," instead finding "that a document explaining existing policy 'cannot be considered deliberative' simply because it was created to help make decisions about future policies." Exemption 7(E): The court holds that "[g]iven that the Court has determined that ATF may not withhold Order 2123.1 and the OMB email under Exemptions 2 or 5, it will defer ruling on ATF's withholdings under Exemption 7(E) in order to provide ATF an opportunity to determine whether, in light of this opinion, any portions of the withheld material are reasonably segregable from properly withheld material."  The court notes that "[i]n doing so, the agency should keep in mind that there must be 'a rational nexus between the withheld material and a legitimate law enforcement purpose[.]'" Richardson v. U.S., No. 13-1202, 2014 WL 4114089 (D.D.C. Aug. 21, 2014) (Huvelle, J.) Richardson v. U.S., No. 13-1202, 2014 WL 4114089 (D.D.C. Aug. 21, 2014) (Huvelle, J.) Re:Request for records concerning plaintiff Disposition:Granting defendant's motion for summary judgment Litigation Considerations: The court holds that "plaintiff has obtained all of the relief he seeks, and defendant is entitled to judgment as a matter of law."  The court notes that "Federal Rule of Civil Procedure 56(a) states that '[t]he court shall grant summary judgment if the movant shows that there is no genuine dispute as to any material fact and the movant is entitled to judgment as a matter of law.'"  "Here, defendant has satisfied this standard" and, "[d]ue to plaintiff's failure to respond to defendant's motion, it is undisputed that defendant has conducted the 'further processing' required by the OIP remand order." Cofield v. U.S., No. 14-0055, 2014 WL 4087501 (D.D.C. Aug. 20, 2014) (Jackson, J.) Cofield v. U.S., No. 14-0055, 2014 WL 4087501 (D.D.C. Aug. 20, 2014) (Jackson, J.) Re:Request for records concerning Internet Corporation for Assigned Names and Numbers Disposition:Granting federal defendants' motion to dismiss claims against them; remanding remainder to Superior Court of the District of Columbia Litigation Considerations, Pleadings: The court "concludes that there is no legal basis upon which Plaintiff can sue the defendants named in this lawsuit in their personal capacities." Litigation Considerations, Relief: The court holds that "[p]laintiff cannot state any tort claim for monetary damages regarding any FOIA request he may have made because 'no money damages are available under FOIA.'" Litigation Considerations, Jurisdiction: The court holds that "[t]he federal courts . . . have exclusive jurisdiction over any claim Plaintiff may be asserting under the FOIA and the Privacy Act."  "This means that the Superior Court did not have jurisdiction over Plaintiffs' claims against the Federal Defendants in the first place, and given that this matter was removed to federal court under 28 U.S.C. §§ 1442 and 1446, this Court cannot assert jurisdiction over them on removal." North v. DOJ, No. 08-1439, 2014 WL 4079927 (D.D.C. Aug. 19, 2014) (Kollar-Kotelly, J.) North v. DOJ, No. 08-1439, 2014 WL 4079927 (D.D.C. Aug. 19, 2014) (Kollar-Kotelly, J.) Re:Request for records concerning purported DEA informant Disposition:Denying plaintiff's second motion for reconsideration Litigation Considerations, Adequacy of Search: The court holds that "[t]he fact that the DEA averred that it found three criminal investigative files containing information about Plaintiff does not necessarily suggest that those files contained documents that were responsive to Plaintiff's FOIA request, which specifically requested documents referencing Plaintiff and [the alleged informant]."  The court further holds that "even though the DEA did not have enough information to positively identify the [alleged informant] for whom the DEA located files as the [alleged informant] identified by Plaintiff, the DEA's search looked at the files associated with all [individuals with the same name as the alleged informant] and found that none of them also referenced or otherwise corresponded with Plaintiff." Clemente v. FBI, No. 08-1252, 2014 WL 4066222 (D.D.C. Aug. 18, 2014) (Rothstein, J.) Clemente v. FBI, No. 08-1252, 2014 WL 4066222 (D.D.C. Aug. 18, 2014) (Rothstein, J.) Re:Request for FBI's file on late high-ranking Mafia member who served as FBI informant Disposition:Granting in part and denying in part defendant's second renewed motion for summary judgment Litigation Considerations, Adequacy of Search: The court holds that "[p]laintiff's Rule 54(b) motion is denied."  The court relates that plaintiff requests that the court "reconsider the Court's earlier determination that the FBI's search for documents responsive to Plaintiff's FOIA request was sufficient."  The court finds that "[p]laintiff's arguments regarding the adequacy of the FBI's search have been addressed on three separate occasions" and "[e]ach time, the Court affirmed that the FBI's search was adequate because it was 'reasonably calculated to uncover all relevant documents.'" Exemption 7, Threshold: The court "agrees with Judge Friedman's assessment of the records and will not disturb his decision on this issue."  The court relates that "Judge Friedman . . . held that even if the 'Court were to assume that the FBI's deployment of [the informant] sometimes contravened the law, there is no evidence that the records were compiled for any purpose other than that supplied by the FBI: documenting the activities of a criminal informant.'"  "'Such documentation advances the FBI's interest in monitoring the behavior and interactions of an important source of information and so serves a law enforcement purpose.'" Exemption 7(C): The court first addresses the FBI's efforts to ascertain the life status of individuals identified in the responsive documents.  The court holds that "the FBI is instructed to supplement its Vaughn Index to address [certain] concerns."  The court finds that "[t]he FBI fails to address [plaintiff's] objections in any manner whatsoever."  These objections include concerns over "the manner in which the FBI searched its Automated Case Support System to locate identifiable dates of birth and/or social security numbers for those individuals for whom such information is not contained in the responsive documents," the fact "that the FBI 'does not indicate whether the search of the ACS employed the Electronic Case File' . . . something that Plaintiff alleges 'would presumably be far more effective in determining life status,'" the fact "that the FBI does 'not mention using the Social Security Death Index' . . . an index that [plaintiff] claims 'is most likely to be effective in determining whether someone has died,'" and "the manner in which the FBI conducted its search on the Consolidated Lead Evaluation and Reporting . . . database and Google."  "Without input from the Government, this Court is unable to ascertain the validity of Plaintiff's concerns, nor determine, as a matter of law, that the FBI 'has made a reasonable effort to account for the death of a person on whose behalf the FBI invokes exemption 7(C).'" Second, the court addresses disclosure of identifying information.  The court finds "that the individuals whose identifying information is redacted from the documents that are responsive to Plaintiff's FOIA request have a substantial interest in keeping their information private."  "However, as noted above, the FBI must address Plaintiff's concerns regarding its attempt to ascertain the life status of these individuals."  "The Court is unable to appropriately balance the privacy interest at stake against the public interest in disclosure until this Court knows the life status of the affected individuals." Third, regarding the withholding of certain FBI agent names, the court holds that "[g]iven the facts of this particular FOIA request—namely that Plaintiff implicates FBI agents in wrongdoing and that the document in question dates back to 1965—this Court finds that the public's interest in disclosure [of certain FBI agent names] outweighs the FBI agent's privacy interest."  The court holds that "[t]he FBI shall disclose this information." The court also directs "the FBI . . . to supplement its VaughnIndex to address Plaintiff's arguments" that "'five or six lines . . . of material includes more than just a name and basic identifying information, yet the FBI has failed to provide any description of the nature of the withheld material.'"  Similarly, "the Court instructs the FBI to re-examine [one document] to determine whether more information may be disclosed, and if it determines that further information may not be disclosed without revealing identifying information, explain why that is the case." Finally, the court finds that "where the information relates to individuals who are associated with the Mafia, disclosing the job could very well reveal the identity of the individual" and, "[t]herefore, the Court finds that the FBI has satisfied its burden under Exemption 7(C) and the information shall remain redacted." Exemption 7(D):The court holds that "the FBI is entitled, pursuant to Exemption 7(D), to withhold information provided by 'source symbol numbered informants' and the names and information of third parties who were interviewed under an implied grant of confidentiality."  The court finds that "'[a]s to "source symbol numbered informants," [defendant] explains in [its] declaration that it is the FBI's practice to assign source symbols to informants only if those individuals "report information to the FBI on a regular basis pursuant to an 'express' grant of confidentiality.'"  "This averment is sufficient to demonstrate that those informants qualify as 'confidential source[s]' within the meaning of the FOIA.'"  Additionally, the court finds that "'[i]ndividuals who provide information on the Mafia to the FBI . . . are to be considered confidential sources.'" Exemption 7(E):The court holds that "the FBI's redactions were appropriate."  The court relates that the FBI "avers that '[r]eleasing the details of these specific law enforcement techniques and procedures in the context of these records will provide criminals with a vivid picture of the context and circumstances in which a specific technique is employed, what actions and/or circumstances would trigger the use of specific techniques, the reasoning behind the use of the techniques, and specific information about the implementation of the techniques.'"  "The FBI further asserts that disclosure of this information may 'aid individuals in circumventing the law by promoting the invention and implementation of countermeasures, development of methods to more effectively cover their criminal activities thus avoiding detection, adjustment of behavior to mislead investigations, concealment of evidence, and prevention of future infiltration of informants into criminal organizations .... disclosure ... [could] divert FBI investigative methods from intended targets, severely hamper the ability to effectively investigate and prosecute criminals, and endanger the life and/or physical integrity of informants.'"  The court relates that the FBI also stated that "'the techniques employed by confidential informants and their handlers [during the time that [the informant at issue] was an FBI informant] are still effectively used by informants and their handlers in current investigations.'" The court finds that "[a]lthough the FBI does not directly state that the techniques are not publicly known, the Court infers that they are not, otherwise the techniques could not be 'effectively used' by the FBI in 'current investigations.'"  The court holds that "[t]his is sufficient to satisfy the FBI's burden of proof under Exemption 7(E)." Kollock v. Glunt, No. 13-656, 2014 WL 4080757 (D.D.C. Aug. 18, 2014) (Diamond, J.) Kollock v. Glunt, No. 13-656, 2014 WL 4080757 (D.D.C. Aug. 18, 2014) (Diamond, J.) Re:Request for presentence investigation report Disposition:Approving and adopting Magistrate Judge's report and recommendation; denying petition for writ of habeas corpus Procedural Considerations, Entities Subject to the FOIA: Regarding plaintiff's argument "that trial counsel was ineffective for failing to provide him with the pre-sentence investigation report, resulting in a violation of his due process rights," the court adopted the magistrate's holding that "[t]o the extent Petitioner argues that counsel's failure to provide him with the presentence investigation report violated the Freedom of Information Act, . . . such a claim fails because the Act applies to federal, not state, agencies." Hawthorne v. Gibson, No. 14-81, 2014 WL 4102375 (N.D. W.Va. Aug. 18, 2014) (Groth, J.) Hawthorne v. Gibson, No. 14-81, 2014 WL 4102375 (N.D. W.Va. Aug. 18, 2014) (Groth, J.) Re:Request for number of complaints made by certain employees of Office of Resolution Management Disposition:Dismissing plaintiff's claim Litigation Considerations, Pleadings: The court holds that "[p]laintiff has . . . failed to allege that the Office of Resolution Management received his FOIA request and failed to provide a response within twenty days of receipt of the request."  "Therefore, Plaintiff's Complaint does not make factual allegations sufficient to state a claim for relief." Whitaker v. CIA, No. 12-316, 2014 WL 3973865 (D.D.C. Aug. 15, 2014) (Kollar-Kotelly, J.) Whitaker v. CIA, No. 12-316, 2014 WL 3973865 (D.D.C. Aug. 15, 2014) (Kollar-Kotelly, J.) Re:Request for records concerning disappearance of planes, plaintiff's father, and other individuals Disposition:Granting defendants' renewed motion for summary judgment Exemption 3: The court grants the CIA's motion for summary judgment.  The court notes that "[h]ere, the CIA has invoked two statutes—the CIA Act of 1949 and the National Security Act of 1947."  The court explains that "Section 6 of the CIA Act states that 'the Agency shall be exempted from the provisions of ... any other law which require the publication or disclosure of the organization, functions, names, official titles, salaries, or numbers of personnel employed by the Agency.'"  The court finds "that '[t]he CIA Act has been invoked to protect the names and other information that would identify CIA personnel, such as their initials, email addresses, telephone numbers, and office locations.'"  Therefore, "the Court concludes that the CIA has properly applied the CIA Act in response to the Court's previous Order, and summary judgment on this issue is appropriate."  The court explains that "[t]he National Security Act of 1947 vests the Director of National Intelligence with the authority to protect 'intelligence sources and methods.'"  The court finds that "the CIA has stated that the document processing materials either themselves discuss intelligence sources and methods or contain information that would reveal intelligence sources and methods which the CIA has sought to protect through its Glomar response."  Based on this information, and "[i]n light of the 'great deference' afforded the CIA pursuant to this provision, the Court concludes that this material may be withheld pursuant to the National Security Act and Exemption (b)(3)." Procedural Requirements, Searching for Responsive Records: The court explains that it previously found that the State Department's "search was inadequate because the State Department had not searched for records about . . . the co-pilot of the plane containing Plaintiff's father."  The court notes that "[t]he State Department now represents that it has searched for records relating to [the co-pilot] as requested by Plaintiff and released the one document located in response to Plaintiff, thus curing the defects in its previous search." Litigation Considerations, Reasonably Segregable Requirements: The court "does not find segregability concerns sufficient to deny summary judgment to Defendants."  The court relates that "the CIA evaluated the documents potentially responsive to Plaintiff's request and determined that any documents responsive to Plaintiff's requests were exempt from disclosure in their entirety."
https://www.justice.gov/oip/court-decisions?p=763&page=273
(PDF) Tell it in Gath Studies in the History and Archaeology of Israel Essays in Honor of Aren M. Maeir on the Occasion of his Sixtieth Birthday PDF | On Nov 15, 2018, Itzhaq Shai and others published Tell it in Gath Studies in the History and Archaeology of Israel Essays in Honor of Aren M. Maeir on the Occasion of his Sixtieth Birthday | Find, read and cite all the research you need on ResearchGate Tell it in Gath Studies in the History and Archaeology of Israel Essays in Honor of Aren M. Maeir on the Occasion of his Sixtieth Birthday November 2018 Publisher: Zaphon ISBN: 978-3-96327-032-1 Authors: Tell it in Gath Studies in the History and Archaeology of Israel Essays in Honor of Aren M. Maeir on the Occasion of his Sixtieth Birthday Edited by Itzhaq Shai, J effrey R. Chadwick, Louise Hitchcock, Amit D agan, Chris McKinny and Joe Uziel ÄGYPTEN UND ALTES TESTAMENT Studien zu Geschichte, Kultur u nd Religion Ägyptens und des Alt en Testaments Band 90 Gegründet von Manfred Görg Herausgegeben von Stefan Jakob Wimmer und Wolfgang Zwickel Tell it in Gath Studies in the History and Archaeology of Israel Essays in Honor of Aren M. Maeir on the Occasion of his Sixtieth Birthday Edited by Itzhaq Shai, J effrey R. Chadwick, Louise Hitchcock, Amit D agan, Chris McKinny Münster Ägypten und Altes Testament, Band 90 Tell it in Gath:Studies in the History and Archaeology of Israe l: Essays in Honor of Aren M. Maei r on the Occasion of his Sixtiet h Birthday Lily Singer-Av itz – Tel Aviv Un iversity Philipp W. S tockhammer – Institut für Vor- und Früh ges chichtliche Archäologi e und Provinzialrömische Archäologie , Ludwig-Maximilians- Universität M ünchen, Germany xi L IST OF C ONTRIBUTORS Marvin A. Sw eeney – Profes sor of Hebrew Bible, Claremont School o f Theology Nahshon Szanton – Israe l Antiquities Authority Eitan Tchernov ( z”l) – Israel Antiquities Authority David Ussishkin – Professor Emeritus, Tel Aviv University Joe Uziel – Israel Antiquities Authority Josephine A. Verducci – University of Melbourne Paula Waiman-Barak – University of Haifa Ehud Wei ss – Archaeobotanical la b, Institu te o f Archaeology, The Martin (Szu sz) Department of Land of Israel Studies and Archa eology Bar-Ilan University Stefan Ja kob Wimmer – Ludwig-Maximilians-Universität München Samuel R. Wolff – W.F. Albright Institute o f Archaeological Res earch Naama Yahalom- Mack – The Hebrew University of Jerusalem Joseph Yellin – Th e Hebrew University of Jerusalem K. Laws on Younger Jr. – Trinity Inter national University – Divinity School Irit Ziffer – Eretz Israel Museum, Tel Aviv Sharon Zuc kerman (z”l) – The Hebrew University of Jerusalem Wolfgang Zwickel – Johannes Gutenberg University Mainz xii INTRODUCTION We are delighted and privileged to present this Festschrift volume in honor of our friend, teacher and colleague, Aren M. Maeir, on the occasion of his sixtieth birthday in March of 2018. The lengthy collection herein features over sixty studies by more than ninety authors from a wide variety of academic fields, including archaeology, history, bible and other areas of scientific and ancient studies. Each contributor is one of Aren’s many friends and collaborators, and quite a few have also been his students or have benefited from his unique style of mentoring. To a woman, and to a man, the list of contributors in our Table of Contents join the Festschrift editors in congratulating Aren on a remarkable career and a life well lived, thus far, with our best wishes for many happy and productive years to come. To us, and to his many other friends everywhere, indeed to all who know him, Aren is the quintessential example of “a real Mensch.” Aren Maeir Maeir was born in Rochester, New York, and made aliyah to Israel with his family at age 11 . He grew up in Jerusalem, served his country honorably in the Israel Defense Force s , and married Adina Hartman, with whom he has shared a wonderful life in Israel , rai sed three remarkable sons, and now enjoys his grandchildren. After his military service, Aren graduated from the Hebrew University of Jerusalem with a BA, MA, and PhD in Archaeology. His field experience included work at several sites around Israel, most notably Beit Shean where he excavated with his “archaeology father” mentor and friend Amihai Mazar. He then began teaching at Bar-Ilan University in Ramat Gan, advancin g from lecturer to full professor of archaeology in a dozen years. There he presides over his renowned subterranean archaeology lab and continues teaching twenty years on, having become an “archaeology father” himself. Many of his students have completed their own MA and PhD programs, and gone on to make their own contributions in the profession, the academy , and the field including three of the editors of this volume (IS. AD and JU). In 1996, Professor Maeir launched his major life’s work – a long term archaeological expedition at Tel Tzafit (Tell es -Sa fi) , the massive mound of ancient Gath, situated where the Shephelah of Judah meets the southern coastal plain. The Tell es-Safi/Gath Archaeological Project, also known as the Ackerman Family Bar -Il an University Expedition to Gath, has excavated annually, each summer, for over twenty years at the ancient Canaanite and Philistine citadel. And “the dig” is still going. Aren has gradually gathered and deftly led an international staff of experts, great friends who are fiercely loyal to him and to “Safi,” as we call both the site and the project. And literally thousands of students from Israel and around the world have trained in archaeological technique at “Safi” under his directorship. Everyone who works with Aren comes to know and admire his unique blend of light hearted and even comic exchange, blended with his serious and cutting edge scientific scholarship. And that combination manifests itself both in personal relationships and professional matters. He is the power source of the dynamic and open-minded atmosphere of his excavation project, and it is his own approach and personality, as much as the remarkable site of Tel Tzafit, which has attracted his staff and the other multitudes of scholars and students to the expedition. Many of these, who start out as young volunteers, are encouraged by him to conduct their own research on materials from the excavation or on related topics. These studies often cross the boundaries of traditional archaeological inquiry, moving into topics such as historical sources, historical geography, geomorphology, ethnoarchaeology, and the application of laboratory science to the excavation field. I NTRODUCTION The broad scope of “Safi related” research is a natural outcome of another remarkable fact: successfully working with Aren requires efforts beyond those which archaeology normall y demands. His management style is to designate crucial roles for team members, both younger and older, and to leave ample space for their own personal performance, expression, and even error. To put it su ccinctly , Aren doesn’t just do archaeology, he makes archaeologists. And he approaches it with his own philosophical attitude which is perhaps best expressed in his own frequent quip, well known to all who work with him: “There’s no sense in doing archaeology if we’re not having fun!” Over the course of two decades, Professor Maeir has become recognized as a world class scholar and expert on the archaeology of ancient Israel, Philistia, and the Bronze and Iron ages. He is sought out for interviews by television, radio, and print media whenever a new discovery makes the headlines. His international teaching experience includes a post-doctoral fellowship at M.I.T. in Cambridge MA, an appointment as a distinguished visiting professor at the University of California, San Diego, and lectu res and workshops at dozens of universities and other venues across America, Europe, Asia, and Australia. He has received a dozen other fellowships and grants for his academic and research efforts, and was recently presented with the 2016 Distinguished Researcher Award from the Rector of Ba r -Ilan University. At age sixty, Aren is also the author of a vast amount of scholarly publications, including his two monographs: Bronze and Iron Age Tombs at Tel Gezer (2004) and In the Midst of the Jordan: The Jordan Valley During the Middle Bronze Age (2010). The eight contributor volumes he has edited or co-edited include his most recent effort s , The She ph elah During the Iron Age: Recent Archaeological Studies (with Oded Lipschits, 2017) and Wandering Arameans: Arameans Outside Syria – Textual and Archaeological Perspectives (with Angelika Berlejung, 2017) as well as the BAS award winning first volume of his excavation report series, Tell es-Safi/Gath I: Report on the 1996–2005 Seasons (2012) and the forthcoming second volume, Tell es -Safi/Gath II: Excavation Reports and Studies (with Joe Uziel, now in press). These are joined by scores of academic articles, solely and co-authored, spanning an impressive variety of archaeological, historical, biblical, and scientific subjects. These articles were published in various academic journals including the most prestigious peer -reviewed journals and all the way to popular stages. Aren seems to know something about almost everything. Many of the contributors to this present volume have been co -authors of other articles with Aren. Their diverse studies here are divided into ten thematic sections, each inspired by subjects of Aren’s own interest, and most with a biblical quotation as part of the section title. Section 1, “The Rising Urban Entities,” focuses on the Early Bronze Age in Canaan, an essentially protohistoric period locally, but which is well represented in Aren’s work at Tel Tzafit. Section 2, “The Canaanite was then in the land …,” moves to the Middle and Late Bronze Ages, also well represented at “Safi,” and the focus of a great deal of Aren’s own work, including his PhD dissertation. Section 3 highlights “The Origins, Material Culture, and Interactions of the Philistines” – when Aren began his career he could not have guessed it would focus so much on the Sea Peoples and their descendants in Philistia. Section 4 continues that theme, “Entering the third decade of the Tell es-Sa fi / Gath Archaeological Project.” Section 5 moves to an area of Aren’s more recent exploration, “The Aramean Realm.” Section 6 proceeds to “New Perspectives on the Biblical Accounts,” an d Section 7 explores “Textual and Archaeological Research of the Iron Age.” Section 8, with emphasis on “Methodological Approaches” to archaeology, and the “Reports on Archaeological Excavations and Finds” of Section 9, lead naturally into the concluding theme of Section 10: “Discover how to visit the past and bring yesterday’s stories into our lives today.” The editors offer our sincere thanks to these contributing scholars from Israel and around the world who took of their time and talent to present our discipline with a few valuable gems for each xiv I NTRODUCTION section, in honor of our teacher, mentor, colleague, friend, and real Mensch, Aren Maeir. In addition, this book could not have been made possible without the help of many other individuals, who assisted in its production: Edna Sachar, who language edited selected articles, Dr. Eli Even of the Bar Ilan University Research Authority and private individuals for financial support, and Profs. Stefan Wimmer and Wolfgang Zwickel for their help in the publication project and agreeing to publish the volume in the AAT series. We would also like to thank Dr. Kai A. Metzler for his editorial comments and guidance throughout the editing process. For all of those involved, it was a pleasure to be able to be part of such a project for such a special scholar and individual! The Editors xv OVER TWO DECADE S OF FRIENDSHIP, FIELDWORK , AND COMRADERY WITH ARE N MAEIR Ahuva Ho In the spring of 1995 while I was w orking on my PhD in Hebrew Bible, I joined my professor Ta mmy Schneider of the Cla r emont Graduate S chool in California on the survey of Tell es-Safi or T el Tzafit (the name was not yet determined, but I shall refer to it here as Te ll Gath). It was a preliminary introduction in the hope that it would lau nch the r enewal of an organized archaeological e xcavation th e following year based on our survey. The excavation was set to be in cooperation with Prof. Aren Maeir of Bar- Il an University. This is where I first met Aren. Unfortunately, the coll aboration w a s called o f f and A ren returned to the tell forging proj ects with other institutes. I joined Prof . Schn eider on other excavations in Israel because of m y commit ment to my ac ademic program. However, once free from my obligations I contacted Aren and he was more tha n happy to have me back. The two of us are the only survivors left from that first year of survey, and e ver since, for over twenty y ears, I have been volunteering at Tell Gath and enjoying every moment. We have spent many ho ur s deep into the night in the field to se c ure the countless finds that n eeded to b e unearthed, recorded, measured, photographed, a nd boxed. Aren ha s been an inspiration as a scholar and a friend. He has enriched our knowledge of the Philistines in ge neral and Gath in particular by employing a pl ethora of scientific m e dia and collaborating with top scientists from Israel a nd abroad (as noted in a n interview by Heidi J. Gleit: “The Science of Archaeology,” E r etz M a gazine 150 (2015): 20-27). H e has brought excitement to t he field and an enthusiasm that ke e ps volunteers c oming back. It is my delight to congratulate Aren on his 6 0th birthday, who has made my twenty-plus ye ars at Gath educational a nd enjoyable. Here’s to you Aren! Happy 60 th ! ResearchGate has not been able to resolve any citations for this publication. Section 3 highlights "The Origins, Material Culture, and Interactions of the Philistines" -when Aren began his career he could not have guessed it would focus so much on the Sea Peoples and their descendants in Philistia. Section 4 continues that theme Aren Aren. Their diverse studies here are divided into ten thematic sections, each inspired by subjects of Aren's own interest, and most with a biblical quotation as part of the section title. Section 1, "The Rising Urban Entities," focuses on the Early Bronze Age in Canaan, an essentially protohistoric period locally, but which is well represented in Aren's work at Tel Tzafit. Section 2, "The Canaanite was then in the land …," moves to the Middle and Late Bronze Ages, also well represented at "Safi," and the focus of a great deal of Aren's own work, including his PhD dissertation. Section 3 highlights "The Origins, Material Culture, and Interactions of the Philistines" -when Aren began his career he could not have guessed it would focus so much on the Sea Peoples and their descendants in Philistia. Section 4 continues that theme, "Entering the third decade of the Tell es-Safi/ Gath Archaeological Project." Section 5 moves to an area of Aren's more recent exploration, "The Aramean Realm." Section 6 proceeds to "New Perspectives on the Biblical Accounts," and Section 7 explores "Textual and Archaeological Research of the Iron Age." Section 8, with emphasis on "Methodological Approaches" to archaeology, and the "Reports on Archaeological Excavations and Finds" of Section 9, lead naturally into the concluding theme of Section 10: "Discover how to visit the past and bring yesterday's stories into our lives today." The editors offer our sincere thanks to these contributing scholars from Israel and around the world who took of their time and talent to present our discipline with a few valuable gems for each Chapter Full-text available Y. Garfinkel and S. Ganor 2018. Khirbet al-Ra'i near Lachish. In Shai, I., Chadwick, J.R., Hitchcock... July 2018 Amit Dagan
https://www.researchgate.net/publication/328968669_Tell_it_in_Gath_Studies_in_the_History_and_Archaeology_of_Israel_Essays_in_Honor_of_Aren_M_Maeir_on_the_Occasion_of_his_Sixtieth_Birthday
EWG's Food Scores | Raley's Purely Made Organic Oats & Honey Granola, Oats & Honey Check out the food score for Raley's Purely Made Organic Oats & Honey Granola, Oats & Honey from EWG's Food Scores! EWG's Food Scores rates more than 80,000 foods in a simple, searchable online format to empower you to shop smarter and eat healthier. Raley's Purely Made Organic Oats & Honey Granola, Oats & Honey Lower scores accompany better foods. Image source: Brand Logo EWG Overall Score Breakdown The product score is based on weighted scores for nutrition, ingredient and processing concerns. Generally, nutrition counts most, ingredient concerns next and degree of processing least. The weighted scores are added together to determine the final score.Read more about scores here. EWG Overall Score Breakdown EWG scored on three factors: nutrition, ingredient concerns, and the degree of processing.Read the full scoring methodology. Lower concern N I P Lower concern Higher concern N Nutrition Concern I Ingredient Concern P Processing Concern Nutrition Concern Details Considers calories, saturated fat, trans fat, sugar, sodium, protein, fiber and fruit, vegetable and nut content to differentiate between healthful and less healthful foods. For more information on nutrition concerns,read our full methodology. Contains ingredients that may contribute small amounts of unhealthy artificial trans fats: Canola Oil (Expeller Pressed) (Organic) [read more] Per gram, high in protein [read more] The nutrition factors used for scoring Raley's Purely Made Organic Oats & Honey Granola, Oats & Honey Positive factors Fruit, vegetable, bean or nut content Protein content Fiber content Omega-3 fatty acids Negative factors Calorie density Sugar/low-calorie sweetener content Sodium content Saturated fat content Trans fat content Ingredient Concern Details Considers food additives, pesticides, hormones, antibiotics and contaminants like mercury and BPA, which can affect human health and the environment. For more information on ingredient concerns,read methodology. Certified organic product [read more] May contain high arsenic levels from rice and rice-based ingredients [read more] This product has some contamination concerns: Arsenic Contamination from Rice (Brown) (Organic) and Rice Syrup (Organic) This contaminant is of moderate concern in food. Learn why. Processing Concern Details Estimates how much the food has been processed. Considers many factors, chief among them, modification of individual ingredients from whole foods and number of artificial ingredients. For more information on processing concerns,read our full methodology. Product has been classified as having moderate processing concerns Products with moderate and high processing concerns generally have more artificial ingredients, more ingredients that have been significantly modified from whole foods, and more ingredients overall. EWG's Top Findings Certified organic product [read more] Certified organic product Certified organic food is produced without the use of synthetic pesticides and fertilizers, and free of genetically engineered ingredients. Certified organic meat and dairy must also be produced without antibiotics and artificial growth promoters or hormones. May contain high arsenic levels from rice and rice-based ingredients [read more] May contain high arsenic levels from rice and r... Rice and rice-based ingredients often have high concentrations of arsenic, which is a carcinogen and cardiovascular toxicant. http://www.ewg.org/foodscores/content/arsenic-contamination-in-rice Contains ingredients that may contribute small amounts of unhealthy artificial trans fats: Canola Oil (Expeller Pressed) (Organic) [read more] Contains ingredients that may contribute small ... Both refined oils and fully hydrogenated oils contain small amounts of unhealthy artificial trans fats and contribute to the total intake of trans fat in the diet (Biofortis 2014). Artificial trans fats are generated in refined oils when they are processed at high temperatures from the crude oil into a bland, odorless, colorless oil (Greyt 1999). A 2012 study conducted by FDA scientists estimated that refined oil contributes an average 0.6 grams of trans fat a day (Doell 2012). The World Health Organization recommends limits on trans fat of less than 1 to 2 grams a day—in this context, it’s easy to see that 0.6 grams is not an insignificant contribution. In the case of fully hydrogenated oils, they should theoretically be free of trans fat, but since no hydrogenation process is 100 percent efficient, trans fats are often found in fully hydrogenated oils at low levels (FDA 2013). The United States Department of Agriculture National Nutrition Database has tested refined, partially hydrogenated and fully hydrogenated oils and found trans fats in all of them (USDA 2013). Textbooks for food scientists reveal that the mono and di-glycerides and other emulsifiers are often made from hydrogenated fats (Hasenhuettl and Hartel 2008) and at temperatures above 220°C (Sikorski and Kolakowka 2011). Emulsifiers produced from hydrogenated fats “contain measurable concentrations" of trans fats (Hasenhuettl and Hartel 2008). Unfortunately, due to lack of label disclosure and the trans fat labeling loophole, only the food scientists will ever know just how much trans fat these refined oils and emulsifiers are contributing to foods and the American diet. Does not contain artificial or industrial ingredients [read more] Does not contain artificial or industrial ingre... EWG has not identified any artificial or industrial ingredients in this product. Contains 92% more sugar per serving than the average cold cereal [read more] Contains 92% more sugar per serving than the av... This cereal contains more sugar per serving than the average adult cold cereal, which has 7.3 grams per serving. Read EWG's 2014 report on sugar in the cereal aisle to find healthier options: http://www.ewg.org/research/children's-cereals Per gram, high in protein [read more] Per gram, high in protein Protein is a source of amino acids that are required for the proper growth, maintenance and repair of tissues. It also provides the building blocks for important enzymes and hormones. Protein provides calories and if eaten in excess will be stored as fat. Protein is found in high amounts in beans, nuts, eggs, seafood and meat. Protein is essential to health, but eating too much also carries an environmental and health cost. Learn more: http://www.ewg.org/meateatersguide/ Product has been classified as having moderate processing concerns EWG Food Reports How Much is Too Much? Excess Vitamins and Minerals in Food Can Harm Kids' Health Children's Cereal: Sugar by the Pound EWG's Good Food On A Tight Budget EWG's Shopper's Guide to Pesticide in Produce Meat Eater's Guide to Climate Change + Health Ingredient List From the Package ORGANIC WHOLE ROLLED OATS, ORGANIC MILLED CANE SUGAR, ORGANIC CRISP BROWN RICE (ORGANIC BROWN RICE, ORGANIC BROWN RICE SYRUP, SALT), ORGANIC EXPELLER PRESSED CANOLA OIL, ORGANIC WHOLE OAT FLOUR, ORGANIC HONEY, ORGANIC MOLASSES, ORGANIC VANILLA EXTRACT, SALT, MIXED TOCOPHEROLS (NATURAL VITAMIN E TO MAINTAIN FRESHNESS). * Older Product Products remain in the database for two years after their label information is recorded in stores. A product with label information last recorded more than a year ago is marked with an * identifying it as an older product. * Discontinued Product Product Images Please note that EWG obtains the displayed images of products from third parties and that the product's manufacturer or packager may change the product's packaging at any point in time. Therefore, EWG assumes no responsibility for the accuracy of images presented. Selected Certifications and Seals USDA Organic Other Information This product is certified organic and, therefore, was produced without the use of synthetic pesticides and fertilizers, and free of genetically engineered ingredients. [read more] This product is certified organic and, therefor... Certified organic food must be produced without synthetic pesticides and fertilizers. Genetically engineered ingredients are not allowed. Synthetic preservatives and artificial colors are not allowed in processed foods. Meat and dairy ingredients must be produced without antibiotics and artificial growth promoters or hormones. Nutrition Facts 0.0 servings per containerServing Size 1.0 cup 2.0 cup (1x) 3.0 cup 4.0 cup (2x) 6.0 cup (3x) 8.0 cup (4x)( 57g) Amount Per 2/3 cup Calories 250 % Daily Value (based on a 2,000 calorie diet and adult bodyweight) Update the values for someone: -age- 1-3 years 4-8 years 9-13 years 14-18 years 19-30 years 31-50 years 51-70 years over 70 years -gender/life stage- male female pregnant female lactating female goQUICK FACTS: 9.0 9.0 % Total Fat 7 g 15.0 15.0 % Total Carbs 42 g % Protein 5 gAVOID TOO MUCH: 3.0 3.0 % Saturated Fat 0 g Trans Fat 0.0g 0.0 0.0 % Cholesterol 0 mg 4.0 4.0 % Sodium 85 mg Added Sugar Ingredients: Rice Syrup (Organic), Honey (Organic), Molasses (Organic), and Cane Sugar (Organic)NUTRIENTS: 11.0 11.0 % Dietary Fiber 3 g Vitamin D (no value on present label) 2.0 2.0 % Calcium 8.0 8.0 % Iron 4.0 4.0 % Potassium 160 mg† Institute of Medicine. 2010. "Dietary Reference Intakes Tables and Application." Accessed April 8, 2014:link The Eat Well Guide helps consumers find locally grown and sustainably produced food. Listings include farms, restaurants, stores, farmers' markets, and CSAs throughout the United States. About EWG's Food Scores
https://www.ewg.org/foodscores/products/046567039718-RaleysPurelyMadeOrganicOatsHoneyGranolaOatsHoney/
View - Tasmanian Legislation Online Skip to main content Tasmanian Legislation Tasmania's consolidated legislation online Toggle navigation www.tas.gov.au Home (current) About Related Links Help Search Browse In Force Legislation Legislation As Made Repealed Legislation Preferences Contact Copyright and Disclaimer Feedback Submit Table Of Contents Toggle navigation Loading.. Return to standard view Statutory Rules Legislative history Search Search Act Find Component Find Legislation Atom Feeds Current Document Amendments SRs A Results: match 0 of 0 provisions Previous Hit Next Hit Return to search results 0 hits in page: First Last Land Titles Act 1980 Loading.. Loading.. Land Titles Act 1980 An Act to consolidate and amend the law relating to the registration of title to land, easements and possessory titles [The long title Amended by No. 4 of 2001, s. 4, Applied:12 Apr 2001] [Royal Assent 21 May 1980] Be it enacted by His Excellency the Governor of Tasmania, by and with the advice and consent of the Legislative Council and House of Assembly, in Parliament assembled, as follows: PART I - General 1. Short title This Act may be cited as the Land Titles Act 1980 . 2. Commencement (1) This section and section 1 shall commence on the date of assent to this Act. (2) Except as provided in subsection (1) , this Act shall commence on such date as may be fixed by proclamation. 3. Interpretation [Section 3 Subsection (1) amended by No. 29 of 1984, s. 3 and Sched. 1 ] [Section 3 Subsection (1) amended by No. 2 of 1987, s. 4 ] [Section 3 Subsection (1) amended by No. 11 of 1990, s. 11 and Sched. 1 ] [Section 3 Subsection (1) amended by No. 48 of 1990, s. 4 ] [Section 3 Subsection (1) amended by No. 68 of 1994, s. 3 and Sched. 1 ] [Section 3 Subsection (1) amended by No. 21 of 1996, s. 4 ] (1) [Section 3 Subsection (1) amended by No. 46 of 1981, s. 4 ] In this Act, except in so far as the context or subject matter otherwise indicates or requires – approved form means a form approved by the Recorder under section 169A ; Assistant Recorder of Titles means an Assistant Recorder of Titles appointed pursuant to section 4 (3A) ; assurance fund means the assurance fund referred to in section 150 ; caveator means the person by whom or on whose behalf a caveat has been lodged; [Section 3 Subsection (1) amended by No. 4 of 2001, s. 5, Applied:12 Apr 2001] [Section 3 Subsection (1) amended by No. 4 of 2001, s. 5, Applied:12 Apr 2001] dealing means any document in writing (other than a grant) which is registrable or capable of being made registrable under this Act or in respect of which any recording in the Register is by this or any other Act required or permitted to be made and includes a priority notice, but for the purposes of Part IX does not include a caveat or a withdrawal of a caveat; Deputy Recorder means the Deputy Recorder of Titles appointed pursuant to section 4 (3) ; duplicate registered dealing means the duplicate of a registered dealing delivered pursuant to section 48 (6) ; [Section 3 Subsection (1) amended by No. 36 of 2012, s. 4, Applied:13 Nov 2012] electronic communication has the same meaning as in the Electronic Transactions Act 2000 ; [Section 3 Subsection (1) amended by No. 36 of 2012, s. 4, Applied:13 Nov 2012] electronic dealing means a dealing that is an electronic communication; [Section 3 Subsection (1) amended by No. 36 of 2012, s. 4, Applied:13 Nov 2012] encumbrance means any charge on land created for the purpose of securing a current, future or contingent payment of an annuity, rent-charge, or sum of money other than a debt; encumbrancee means the proprietor of an encumbrance; encumbrancer means the registered proprietor of land subject to an encumbrance; forestry right has the meaning assigned to that expression in the Forestry Rights Registration Act 1990 ; grant means the grant of any land of the Crown; [Section 3 Subsection (1) amended by No. 36 of 2012, s. 4, Applied:13 Nov 2012] instrument includes any grant, certificate of title, conveyance, assurance, deed, map, plan, survey, will, probate, or exemplification of will or probate, or any other document in writing relating to the disposition, devolution, or acquisition of land or evidencing title to land; land includes – (a) messuages, tenements and hereditaments, corporeal and incorporeal, of every kind and description (whatever may be the estate or interest in them), together with all paths, passages, ways, waters, watercourses, liberties, privileges, easements, plantations, gardens, mines, minerals and quarries and all trees and timber on land or lying or being under land; and (b) any structure which is above land but permanently anchored to, or otherwise kept in place above, the land; [Section 3 Subsection (1) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] [Section 3 Subsection (1) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] legal practitioner means an Australian legal practitioner; lessee means the registered proprietor of a lease; lessor means the registered proprietor of the reversion immediately expectant upon the expiration of a registered lease; mortgage means any charge on land created merely for securing a debt; mortgagee means the proprietor of a mortgage; mortgagor means the registered proprietor of land subject to a mortgage; [Section 3 Subsection (1) amended by No. 36 of 2012, s. 4, Applied:13 Nov 2012] newspaper does not include a newspaper published solely in electronic form; [Section 3 Subsection (1) amended by No. 36 of 2012, s. 4, Applied:13 Nov 2012] office copy , in relation to an order, means a copy of the order that is certified by a legal practitioner, a justice or a Commissioner for Declarations to be a true copy of the order; proclaimed date means the date fixed by proclamation under section 2 (2) ; proprietor means any person seised or possessed of any estate or interest in land at law or in equity, in possession, in futurity, or in expectancy; public record means a public record referred to in section 36 ; qualified title means a folio of the Register on which is recorded a caution in accordance with section 21 (2) ; Recorder means the Recorder of Titles appointed pursuant to section 4 (1) ; Register means the register of title referred to in section 33 ; registered means registered under this Act or any of the Acts specified in Schedule 2 ; registered land means land which is subject to this Act; registered proprietor means any person appearing by a folio of the Register, or by any registered dealing, to be the proprietor of any estate or interest in registered land; repealed Act means the Real Property Act 1862 ; transfer means the passing of any estate or interest in land under this Act, whether for valuable consideration or otherwise; transmission means the acquisition of title to, or an interest in, land, consequent on the death, will, intestacy, or bankruptcy of a proprietor. (2) [Section 3 Subsection (2) amended by No. 4 of 2001, s. 5, Applied:12 Apr 2001] The describing of any person as owner, proprietor, transferor, transferee, mortgagor, mortgagee, encumbrancer, encumbrancee, lessor, or lessee, or as seised of or having or taking any estate or interest in any land, shall include the executors, administrators, and assigns of that person. 3A. Crown to be bound [Section 3A Inserted by No. 4 of 2001, s. 6, Applied:12 Apr 2001] This Act binds the Crown, not only in right of Tasmania but also, so far as the legislative power of Parliament permits, the Crown in all its other capacities. PART II - Administration 4. Appointment of Recorder, &c. [Section 4 Substituted by No. 29 of 1984, s. 3 and Sched. 1 ] (1) [Section 4 Subsection (1) substituted by No. 5 of 1990, s. 3 and Sched. 1 ] [Section 4 Subsection (1) substituted by No. 86 of 2000, Sched. 1, Applied:01 May 2001] The Governor may appoint a State Service officer or State Service employee to be Recorder of Titles, and that officer or employee is to hold that office in conjunction with State Service employment. (2) [Section 4 Subsection (2) substituted by No. 2 of 1987, s. 5 ] A person is not eligible for appointment as Recorder of Titles unless he is – (a) a legal practitioner of not less than 5 years' standing; or (b) [Section 4 Subsection (2) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] an Australian lawyer who has been a legal practitioner for at least 5 years. (3) [Section 4 Subsection (3) substituted by No. 5 of 1990, s. 3 and Sched. 1 ] [Section 4 Subsection (3) substituted by No. 86 of 2000, Sched. 1, Applied:01 May 2001] The Governor may appoint a State Service officer or State Service employee to be Deputy Recorder of Titles, and that officer or employee is to hold that office in conjunction with State Service employment. (3A) [Section 4 Subsection (3A) inserted by No. 48 of 1990, s. 5 ] [Section 4 Subsection (3A) substituted by No. 86 of 2000, Sched. 1, Applied:01 May 2001] The Governor may appoint State Service officers and State Service employees to an office of Assistant Recorder of Titles and officers and employees so appointed are to hold office in conjunction with State Service employment. (4) [Section 4 Subsection (4) amended by No. 86 of 2000, Sched. 1, Applied:01 May 2001] [Section 4 Subsection (4) amended by No. 68 of 2000, s. 62, Applied:04 Apr 2001] [Section 4 Subsection (4) added by No. 5 of 1990, s. 3 and Sched. 1 ] Subject to and in accordance with the State Service Act 2000 , such persons as may be considered necessary may be appointed or employed for the purposes of this or any other Act. 5. Seal of office The Recorder shall have and use a seal of office, bearing the impression of the arms of the State, and having inscribed in the margin thereof the words "Recorder of Titles, Tasmania" . 6. Powers and immunities of Deputy Recorder, &c. [Section 6 Amended by No. 48 of 1990, s. 6 ] Anything that is by law or practice appointed, authorized, or required to be done by the Recorder may lawfully be done by the Deputy Recorder or a person appointed to the office of Assistant Recorder of Titles who when so doing has the same immunities and protection from suits as the Recorder. 7. Documents purporting to be sealed or signed by Recorder or Deputy Recorder, &c., to be received in evidence [Section 7 Amended by No. 48 of 1990, s. 7 ] All documents, whether purporting to be issued or written by or under the direction of the Recorder, and purporting either to be sealed with his seal of office or signed by him or by the Deputy Recorder or a person appointed to the office of Assistant Recorder of Titles, shall, if admissible, be received in evidence, and shall be deemed to have been issued or written by or under the direction of the Recorder, without further proof, unless the contrary is shown. 8. Facsimile signature of Recorder or Deputy Recorder, &c. [Section 8 Amended by No. 48 of 1990, s. 8 ] Whenever it is required or permitted by this or any other Act that the Recorder, the Deputy Recorder or an Assistant Recorder of Titles sign any document, memorial, recording, certificate, endorsement, or plan, the Recorder, Deputy Recorder or an Assistant Recorder may – (a) himself attach; or (b) authorize an officer to attach – a facsimile of his signature to the document, memorial, recording, certificate, endorsement, or plan and the facsimile so attached has the same force and effect as if the Recorder, Deputy Recorder or an Assistant Recorder, as the case may be, had personally signed his name in the place of the facsimile signature, and all courts and judges shall take judicial notice of the facsimile signature of the Recorder, Deputy Recorder and Assistant Recorder and shall presume that it was properly attached. PART III - Bringing land under this Act Division 1 - Crown grant 9. Unalienated land, when alienated in fee, to be subject to this Act Except as provided in section 10 (3) , all unalienated lands of the Crown, when alienated in fee, become subject to this Act. 10. Transfers to be used instead of grant deeds (1) [Section 10 Subsection (1) amended by No. 21 of 1996, s. 19 ] Except as provided in subsection (3) , land of the Crown that is not under this Act shall not be granted by letters patent but shall be granted by transfer in an approved form as if it had already been brought under this Act. (2) The Recorder, upon receiving a transfer under subsection (1) , shall create a folio of the Register for the land comprised in the transfer, and upon a folio being created the transfer shall be deemed to be duly registered, and duly enrolled of record. (3) When the Crown grants an easement to be appurtenant only to land that is not registered land, the grant shall be effected by letters patent as if this section had not been enacted. (4) Where an easement is granted by letters patent in pursuance of subsection (3) , the letters patent shall be registered under the Registration of Deeds Act 1935 as an instrument and delivered to the grantee. (5) On the registration of letters patent as provided in subsection (4) , the letters patent shall be deemed to have been duly enrolled of record. Division 2 - Application 11. Applications to bring land under this Act (1) [Section 11 Subsection (1) amended by No. 21 of 1996, s. 19 ] Subject to subsection (2) , land may be brought under this Act on the application in writing in an approved form of any of the following persons: (a) the person claiming to be the owner of the fee simple either at law or in equity; (b) the person claiming to be entitled to a grant in fee from the Crown of any land under or by virtue of a contract with the Crown (other than a contract under any Act relating to the sale of Crown lands), or in equity and good conscience; (c) the tenant for life, or person having the powers of a tenant for life, under the Settled Land Act 1884 ; (d) [Section 11 Subsection (1) amended by No. 33 of 1996, Sched. 1, Applied:01 Sep 1997] the guardian of an infant or the administrator of the estate of a person under the Guardianship and Administration Act 1995 , if – (i) the infant or patient would have been entitled, if not under disability, to apply under paragraph (a) , paragraph (b) , or paragraph (c) ; and (ii) the application contains a direction that the infant or patient shall be registered as proprietor; (e) [Section 11 Subsection (1) amended by No. 36 of 2012, s. 5, Applied:13 Nov 2012] a person holding power of attorney authorizing the sale of a freehold estate in the land in the name of the proprietor of that land, unless the power expressly prohibits his making such an application; (f) [Section 11 Subsection (1) amended by No. 36 of 2012, s. 5, Applied:13 Nov 2012] the legal practitioner acting for a person referred to in paragraph (a) , (b) , (c) , (d) or (e) . (2) An application under this section shall not be made by – (a) a person claiming to be entitled to an undivided share of any land, unless the person who appears to be entitled to the other undivided shares of the land joins in the application with a view to bringing the entirety under this Act; or (b) a tenant for life, or person having the powers of a tenant for life, under the Settled Land Act 1884 unless – (i) he is selling or exchanging the fee simple pursuant to a provision of that Act or the Settled Land Act 1911 and directs that the purchaser or person to whom the fee simple is given in exchange shall be registered as proprietor; or (ii) in the case of a life tenant in possession – (A) where there is a vested estate in expectancy in the land (other than an estate vested in an infant), the application contains a direction that the person entitled to that estate shall be registered as proprietor of that estate; or (B) where there is a vested estate in expectancy in the land to which an infant is entitled, or there is an estate in expectancy in the land capable of taking effect on the happening of a future event, the application contains a direction that the trustee of the settlement under which the estate in expectancy was created shall be registered as proprietor of that estate – so that upon the granting of the application and compliance with the direction, all the vested estates in the land are brought under this Act. (3) A person who lodges an application under this section or a mortgagee or other person who has in his possession or under his control instruments constituting or in any way affecting the title of the land to which the application relates shall lodge those instruments and also, if required, an abstract of the title to that land with the Recorder. (4) A person referred to in subsection (3) shall not lodge with the Recorder any instruments which a purchaser of the land to which the application relates would not be entitled to require pursuant to section 35 of the Conveyancing and Law of Property Act 1884 . (5) A chamber in a building standing on land that is not under this Act shall not be brought under this Act separately from the land and building. 12. How application dealt with (1) The Recorder may – (a) do or require to be done such things as will, in his opinion, justify him in bringing the land to which an application under section 11 relates under this Act; and (b) subject to sections 13 and 14 , bring the land under this Act by creating a folio of the Register for the land. (2) In considering an application under section 11 in respect of land unalienated in fee from the Crown, the Recorder shall be guided by equity and good conscience and by the best evidence that can or may be procured, even though it is not such as he might require in other cases. (3) Where, on considering an application under section 11 , the Recorder is of the opinion that the applicant's title is open to objection but is nevertheless a title the holding under which will not be disturbed, he may bring the land under this Act with a title other than a qualified title. (4) Where an application under section 11 by a person claiming a life estate in possession directs that the person entitled to a vested estate in expectancy in the land shall be registered as proprietor of the estate in expectancy, the Recorder may refuse to bring the land to which the application relates under this Act unless he approves the title to the life estate and the vested estate in expectancy, and brings all the vested estates in the land under this Act. 13. Notices (1) [Section 13 Subsection (1) amended by No. 4 of 2001, s. 7, Applied:12 Apr 2001] [Section 13 Subsection (1) substituted by No. 36 of 2012, s. 6, Applied:13 Nov 2012] Where an application under section 11 is based on a claim by possession under a statute of limitations (other than a claim against the Crown), the applicant is to – (a) post on the land, or at such place as the Recorder directs, and keep so posted for not less than one month before the granting of the application; and (b) publish, not less than one month before the granting of the application, in at least one newspaper that is published, and circulating generally, in Tasmania and that is available in the locality in which the relevant land is situated – a notice of the application in such form as the Recorder directs. (2) The Recorder may refuse to bring land under this Act in a case to which subsection (1) applies until it has been proved to his satisfaction that the requirements of that subsection have been complied with. (3) [Section 13 Subsection (3) amended by No. 4 of 2001, s. 7, Applied:12 Apr 2001] A notice under this section shall specify a time (being not less than one month) after the expiration of which the Recorder may, unless a caveat is lodged forbidding it, bring the land under this Act. 14. Caveat forbidding the bringing of land under this Act (1) [Section 14 Subsection (1) amended by No. 21 of 1996, s. 19 ] A person who claims an estate or interest in land that is the subject of an application under section 11 may, before the creation of a folio of the Register for that land, lodge a caveat with the Recorder in accordance with an approved form forbidding the bringing of the land under this Act. (2) The Recorder, on the lodgment of a caveat pursuant to subsection (1) , shall notify the person who lodged an application under section 11 in respect of the land and shall not proceed with the application until – (a) the caveat has been withdrawn or has lapsed as provided in subsection (3) ; or (b) [Section 14 Subsection (2) amended by No. 36 of 2012, s. 7, Applied:13 Nov 2012] a judgment or order in the matter has been obtained from a court of competent jurisdiction. (3) On the expiration of 30 days after lodgment, a caveat lodged pursuant to subsection (1) lapses and ceases to have any effect unless the caveator has, within that period – (a) commenced proceedings in a court of competent jurisdiction to establish his title to the estate or interest specified in the caveat and has given written notice that he has commenced proceedings to the Recorder, in which case the Recorder shall not proceed with the application until those proceedings have been determined; or (b) [Section 14 Subsection (3) amended by No. 36 of 2012, s. 7, Applied:13 Nov 2012] obtained and served on the Recorder an injunction or order of a court of competent jurisdiction restraining the Recorder from bringing the land under this Act, in which case the Recorder shall not proceed with the application while that injunction or order is in force. (4) [Section 14 Subsection (4) substituted by No. 36 of 2012, s. 7, Applied:13 Nov 2012] Unless permitted by a Supreme Court order, a caveat that has lapsed under subsection (3) may not be renewed and a new caveat may not be lodged by or on behalf of the same person in respect of the same estate or interest. (5) Section 133 (5) and (6) and section 135 apply to a caveat lodged pursuant to subsection (1) . 15. Withdrawal of application to bring land under Act An applicant may withdraw his application to bring land under this Act at any time before the creation of a folio of the Register for that land, and on the withdrawal of the application the Recorder shall return the muniments of title lodged in support of the application to the person from whom he received them. Division 3 - Completing the Register 16. Appointed day (1) The expression appointed day , in relation to a provision of this Division, means such day as the Governor, by order, declares to be the appointed day for the purposes of that provision. (2) The Governor may declare different appointed days in respect of the provisions of this Division. 17. Land may be brought under this Act on registration of instruments under the Registration of Deeds Act 1935 [Section 17 Subsection (1) amended by No. 21 of 1996, s. 19 ] (1) [Section 17 Subsection (1) amended by No. 36 of 2012, s. 8, Applied:13 Nov 2012] [Section 17 Subsection (1) amended by No. 46 of 1981, s. 5 ] A person who lodges for registration under the Registration of Deeds Act 1935 – (a) a conveyance on sale; or (b) [Section 17 Subsection (1) amended by No. 36 of 2012, s. 8, Applied:13 Nov 2012] a legal mortgage by conveyance of the fee simple; or (ba) [Section 17 Subsection (1) amended by No. 36 of 2012, s. 8, Applied:13 Nov 2012] any other instrument that affects land – shall leave with the Recorder, in addition to the documents required by section 12 of that Act – (c) [Section 17 Subsection (1) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] a statement in an approved form signed by the purchaser or mortgagor or by the legal practitioner acting for and on behalf of the purchaser or mortgagor and addressed to the Recorder, which shall state the facts of the ownership of the land and such further information as may be required by the form; and (d) all instruments in his possession or under his control constituting or in any way affecting the title to the land except any instruments which a purchaser of the land to which the statement relates would not be entitled to require pursuant to section 35 of the Conveyancing and Law of Property Act 1884 , and also, if required, an abstract of that title. (1A) [Section 17 Subsection (1A) amended by No. 36 of 2012, s. 8, Applied:13 Nov 2012] [Section 17 Subsection (1A) inserted by No. 11 of 1990, s. 11 and Sched. 1 ] A person who lodges for registration under the Registration of Deeds Act 1935 a forestry right shall leave with the Recorder, in addition to the documents required by section 12 of that Act – (a) [Section 17 Subsection (1A) amended by No. 66 of 2007, Applied:31 Dec 2008] a statement in a form approved by the Recorder signed by the owner of the land over which the forestry right is granted or by the legal practitioner acting for and on behalf of that owner and addressed to the Recorder, which shall state the facts of the ownership of the land and such further information as may be required by the form; and (b) all instruments in his possession or under his control constituting or in any way affecting the title to the land except any instruments which a purchaser of the land to which the statement relates would not be entitled to require pursuant to section 35 of the Conveyancing and Law of Property Act 1884 , and also, if required, an abstract of that title. (2) [Section 17 Subsection (2) amended by No. 36 of 2012, s. 8, Applied:13 Nov 2012] [Section 17 Subsection (2) substituted by No. 11 of 1990, s. 11 and Sched. 1 ] The Recorder may refuse to register a conveyance on sale, a legal mortgage by conveyance of the fee simple, another instrument that affects land or a forestry right unless it is accompanied by a statement and other instruments as required by subsection (1) or (1A) . (3) [Section 17 Subsection (3) amended by No. 36 of 2012, s. 8, Applied:13 Nov 2012] [Section 17 Subsection (3) amended by No. 11 of 1990, s. 11 and Sched. 1 ] On registering under the Registration of Deeds Act 1935 a conveyance, mortgage, other instrument or forestry right to which subsection (1) or (1A) applies the Recorder may, if he thinks fit – (a) [Section 17 Subsection (3) amended by No. 36 of 2012, s. 8, Applied:13 Nov 2012] bring the land comprised in the conveyance, mortgage, other instrument or forestry right under this Act by creating a folio of the Register for that land; and (b) [Section 17 Subsection (3) amended by No. 36 of 2012, s. 8, Applied:13 Nov 2012] for the purposes of so bringing the land under this Act, return the conveyance, mortgage, other instrument or forestry right and any other instruments in his custody to the lodging party. (4) [Section 17 Subsection (4) amended by No. 11 of 1990, s. 11 and Sched. 1 ] [Section 17 Subsection (4) omitted by No. 36 of 2012, s. 8, Applied:13 Nov 2012] . . . . . . . . 17A. Land to be brought under this Act upon subdivision [Section 17A Inserted by No. 48 of 1990, s. 9 ] (1) On and after the appointed day the owner of land which is not registered land shall not subdivide any land – (a) held under the same title; or (b) included in one subsisting legal mortgage by conveyance of the fee simple – unless the owner has made an application under section 11 to bring the land under this Act. Penalty: Fine not exceeding 20 penalty units. (2) In subsection (1) subdivide , in respect of land, means to divide the surface of that land legally by creating estates or interests giving separate rights of occupation. 18. Land may be brought under this Act upon subdivision [Section 18 Amended by No. 30 of 1995, s. 3 and Sched. 1 ] The Recorder may refuse to accept a sealed plan under Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 that is lodged with him on or after the appointed day and that includes land which is not registered land until all the land – (a) held under the same title as any of the land included in the plan; or (b) included in one subsisting legal mortgage by conveyance of the fee simple with any of the land included in the plan – whichever the Recorder, in his discretion, directs, is brought under this Act. 19. Land may be brought under this Act at the instance of the Recorder (1) [Section 19 Subsection (1) amended by No. 21 of 1996, s. 19 ] The Recorder may on or after the appointed day cause notice to be given to any person requiring him, within a time specified in the notice, not being a time less than 30 days from the date of the notice – (a) to inform the Recorder in writing whether he claims an estate or interest in land (not being registered land) specified in the notice; (b) where he claims an estate or interest by virtue of an assurance or other disposition or by devolution in law – (i) to furnish to the Recorder a statement in an approved form; and (ii) to produce to the Recorder all instruments constituting or in any way affecting his title to the land which are in his possession or under his control or in the possession or under the control of the mortgagee of the land except any instruments which a purchaser would not be entitled to require pursuant to section 35 of the Conveyancing and Law of Property Act 1884 ; and (c) where he claims an estate by the operation of a statute of limitations, to furnish to the Recorder such evidence in support of that claim as he possesses. (2) Where the Recorder has given notice under subsection (1) he may bring any land specified in the notice under this Act by creating a folio of the Register for that land. (3) [Section 19 Subsection (3) amended by No. 36 of 2012, s. 9, Applied:13 Nov 2012] The Recorder shall, as far as possible, use his powers under this section so that by the operation of sections 17 and 18 and this section all land (other than Crown land) which is not registered land shall be brought under this Act. 20. Refusal to comply with notice under section 19; making false or misleading statement, &c. (1) [Section 20 Subsection (1) amended by No. 43 of 1991, s. 5 and Sched. 1 ] Any person who wilfully refuses or neglects to comply with any requirement of a notice given to him under section 19 is guilty of an offence and is liable on summary conviction to a fine not exceeding 5 penalty units and a daily fine not exceeding one penalty unit. (2) [Section 20 Subsection (2) amended by No. 43 of 1991, s. 5 and Sched. 1 ] Any person who makes a statement under section 17 (1) (c) or section 19 (1) (b) , or furnishes the Recorder with evidence under section 19 (1) (c) , that to his knowledge is false or misleading in a material particular is guilty of an offence and liable on summary conviction to a fine not exceeding 50 penalty units or to imprisonment for a term not exceeding 2 years. Division 4 - Qualified title 21. Qualified title (1) Land may be brought under this Act with a qualified title where – (a) an applicant under section 11 – (i) fails to satisfy the Recorder that he is entitled to the estate he claims; (ii) fails to do or prove to the Recorder's satisfaction such things or matters as the Recorder may have required him to do or prove in order to justify the bringing of the land under this Act; or (iii) requests the Recorder to register a qualified title; (b) the proprietor of land to which section 17 applies or a person to whom the Recorder has given notice under section 19 requests the Recorder to register a qualified title; (c) the Recorder is doubtful whether the title of any person to whom any provision of Division 3 of this Part applies is a title the holding under which will not be disturbed; or (d) under any Act the Recorder is directed or empowered to register a qualified title. (2) Where land is brought under this Act with a qualified title a caution shall be recorded on the folio of the Register for that land and may be – (a) a general caution, that is to say, a caution that the registered proprietor holds his estate subject to all estates and interests in the land created before the land was brought under this Act; or (b) a particular caution, that is to say, a caution that the registered proprietor holds his estate subject to any defect in title or the estate or interest of any person the existence or probable or possible existence of which is indicated in a minute signed by the Recorder and filed in his office. (3) The Recorder's minute for the purpose of subsection (2) (b) – (a) shall set forth any defect in the title or any estate or interest or probable or possible estate or interest of any person in the land and the acts or matters that ought to be done or proved and the requisitions that ought to be complied with in order to justify the cancellation of the caution recorded on the folio of the Register; (b) does not form part of the Register; and (c) shall be made available for inspection by any person on payment of the prescribed fee (if any). (4) The Recorder may revise and amend a minute under subsection (2) so as to indicate which of the defects, estates, or interests referred to in the minute have been removed or resolved and which of the acts, matters, or requisitions so referred to have been done, proved, or complied with. (5) Where a general caution is recorded on a folio of the Register, the Recorder may at any time cancel that caution and substitute a particular caution. (6) The Recorder may, upon production to him of such evidence of title as he deems sufficient, cancel a caution recorded on a folio of the Register. 22. Subsisting estates and interests to be recorded on qualified title (1) When bringing land under this Act with qualified title, the Recorder shall record on the relevant folio of the Register any subsisting estate or interest then apparent to him, but shall not be concerned to make searches or inquiries as to the existence of any such interest. (2) The Recorder may, at any time after the creation of a qualified title – (a) if a general caution is recorded on the qualified title, record on that qualified title any additional subsisting estate or interest in the land comprised in the title; or (b) if a particular caution is recorded on the qualified title, record on that qualified title any additional subsisting estate or interest the existence or probable or possible existence of which is indicated in the relevant Recorder's minute – and, in either case, in such a manner as to preserve the priority that the additional estate or interest would have had if it had been recorded on the relevant folio of the Register when the land was first brought under this Act. 23. Certain informal dealings may be registered [Section 23 Amended by No. 21 of 1996, s. 5 ] [Section 23 Amended by No. 29 of 1997, s. 4, Applied:06 Nov 1997] An instrument that affects any land brought under this Act and that might have been registered under the Registration of Deeds Act 1935 if the land had not been brought under this Act may, in the discretion of the Recorder, be registered under this Act notwithstanding that it is not an instrument in an approved form, and when registered has effect for all purposes as if it were such an instrument. 24. Qualified title may be cancelled or corrected in certain circumstances (1) If, on application made to him for that purpose, it appears to the Recorder that the proprietor of an estate or interest in the land comprised in a qualified title has suffered judgment for the recovery of the land or a declaration, injunction, or other judgment destructive of that proprietor's estate or interest wholly or in part, the Recorder shall – (a) cancel or correct the folio of the Register relating to that land; and (b) call in and cancel or correct the corresponding certificate of title, as the circumstances may require. (2) Subject to subsection (3) , a person who claims an estate of freehold in the whole or any part of the land comprised in a qualified title of which some other person is the registered proprietor may apply to have the land brought under this Act as if that qualified title had not been created, and the Recorder, if satisfied of the grounds of his claim, shall – (a) correct the folio of the Register; or (b) cancel the folio of the Register constituting the qualified title and create a folio of the Register in the name of the applicant – and shall call in the certificate of title corresponding to the corrected or cancelled folio of the Register and correct or cancel it as the circumstances require. (3) Where a particular caution is recorded on a folio of the Register, a person may apply under subsection (2) only if he claims an estate or interest the existence or probable or possible existence of which is indicated in the Recorder's minute or arising from a defect in title indicated in the minute. 25. Caution to lapse after 20 years (1) A caution lapses, unless it sooner ceases to have effect, at the expiration of a period of 20 years after the date on which the land was brought under this Act or the repealed Act . (2) Where a caution lapses under this section the Recorder shall as soon as practicable cancel the caution. (3) [Section 25 Subsection (3) amended by No. 36 of 2012, s. 10, Applied:13 Nov 2012] The lapsing of a caution under this section operates to free the land in respect of which it lapsed from any estates and interests that affected the land at the date on which it was brought under this Act or the repealed Act , except an estate or interest which is preserved by section 40 , section 46 , section 138W(4) or section 138X(4) or which was immediately before the lapsing – (a) recorded on the relevant folio of the Register; or (b) the subject of a caveat affecting the land comprised in that folio. 26. Application of this Act to land in qualified title The provisions of this Act apply in respect of land comprised in a qualified title in like manner as if that qualified title were a title to the land comprised in a folio of the Register upon which no caution is recorded except that – (a) if a general caution is recorded on the qualified title and the caution has not lapsed, the land comprised in the title is subject to every estate and interest in the land created before the date on which the land was brought under this Act or the repealed Act ; and (b) if a particular caution is recorded on the qualified title and the caution has not lapsed, the land comprised in the title is subject to any defect in title or any estate or interest of any person the existence or probable or possible existence of which is indicated in the Recorder's minute. Division 5 - General provisions 27. Land not alienated from the Crown may be brought under this Act Land may be brought under this Act pursuant to Division 2 or Division 3 whether or not it has been alienated from the Crown and, where there appears to be no deed of grant or transfer from the Crown, no such deed or transfer is necessary before the Recorder brings the land under this Act. 27A. Certain Crown land may be brought under this Act [Section 27A Inserted by No. 98 of 1986, s. 4 ] (1) This section does not apply to, or in relation to, any land in respect of which an application under section 11 has been made. (2) The Recorder may, on the application of the Director-General of Lands, bring under this Act any land of the Crown by creating a folio of the Register for the land. (3) Where land is brought under this Act pursuant to subsection (2) – (a) the Crown shall be registered as the proprietor of the land for an estate in fee simple; (b) the land remains subject to any limitation, exception, reservation, condition, or restriction to which it was subject immediately before it was so brought under this Act; and (c) the Recorder may record on the folio created under that subsection such particulars as he considers appropriate relating to any matter affecting the land in force under the Crown Lands Act 1976 or any other Act. (4) The Recorder may at any time cancel or amend in such manner as he considers appropriate an endorsement made on a folio under subsection (3) (c) . (5) Where particulars of a lease are recorded in the folio of the Register under subsection (3) (c) , the Recorder may – (a) create a folio of the Register for the lease; and (b) record in that folio as the registered proprietor of the lease the name of a person who, in the opinion of the Recorder, is so entitled. (6) [Section 27A Subsection (6) inserted by No. 87 of 1997, Sched. 3, Applied:15 Jan 1998] [Section 27A Subsection (6) substituted by No. 36 of 2012, s. 11, Applied:13 Nov 2012] In an application made under subsection (2) , the Director-General of Lands may – (a) create any easement, covenant, limitation, exception, reservation, condition or restriction that he or she considers appropriate; and (b) request the Recorder to note the creation of that new interest on the relevant folio of the Register for the land and any other limitation, exception, reservation, condition or restriction to which the land is subject in accordance with the Crown Lands Act 1976 . (7) [Section 27A Subsection (7) inserted by No. 87 of 1997, Sched. 3, Applied:15 Jan 1998] Where on the commencement of the Crown Lands (Shack Sites) Act 1997 the Crown is the registered proprietor of any land, that land is subject to any limitation, exception, reservation, condition or restriction that is noted on the relevant folio. (8) [Section 27A Subsection (8) amended by No. 36 of 2012, s. 11, Applied:13 Nov 2012] [Section 27A Subsection (8) inserted by No. 87 of 1997, Sched. 3, Applied:15 Jan 1998] On application by the Director-General of Lands, the Recorder may amend any easement, covenant, limitation, exception, reservation, condition or restriction noted on the folio. (9) [Section 27A Subsection (9) inserted by No. 87 of 1997, Sched. 3, Applied:15 Jan 1998] A transfer of any land of which the Crown is the registered proprietor is, unless the parties otherwise agree, to be subject to any limitation, exception, reservation, condition, restriction, covenant or easement that is noted on the relevant folio under this section. (10) [Section 27A Subsection (10) inserted by No. 87 of 1997, Sched. 3, Applied:15 Jan 1998] Where the Recorder brings land under this Act pursuant to an application made under subsection (2) , the application is taken to be a registered dealing. 28. How certain estates and interests dealt with when land brought under this Act (1AA) [Section 28 Subsection (1AA) inserted by No. 29 of 1997, s. 5, Applied:06 Nov 1997] In this section, instrument means any deed, judgment, will, letters of administration or other document or writing affecting or intended to affect land in this State. (1) [Section 28 Subsection (1) amended by No. 98 of 1986, s. 5 ] When – (a) on the bringing of land under this Act, it appears to the Recorder that the land is subject to a legal mortgage by conveyance of the fee simple; (b) a legal mortgage by conveyance of the fee simple is to be recorded in the Register pursuant to section 22 ; or (c) in the case of land of the Crown for which a folio of the Register is created under section 27A (2) , it appears to the Recorder that the land is subject to a legal mortgage – the Recorder shall register the mortgage on the relevant folio of the Register notwithstanding that it is not an instrument in the form of a memorandum of mortgage under this Act, and when so registered it has effect for all purposes as if it were such an instrument registered under this Act at the time the land was brought under this Act. (2) [Section 28 Subsection (2) amended by No. 9 of 1982, s. 7 and Sched. 10 ] Where – (a) [Section 28 Subsection (2) amended by No. 42 of 2001, Sched. 1, Applied:15 Jul 2001] on the bringing of land under this Act, it appears to the Recorder that an instrument registered under the Registration of Deeds Act 1935 or Part 2K.2 of the Corporations Act creates an estate or interest in that land (other than the estate claimed by the person making application to bring land under this Act or the person who is to be registered as proprietor) that could have been created by an instrument registered under this Act if at the time of its creation the land were under this Act; or (b) he is required to record the estate or interest referred to in paragraph (a) on the relevant folio of the Register pursuant to section 22 – he may record that instrument as if it were the appropriate instrument under this Act to create the estate or interest, notwithstanding that – (c) it is not in the form of an appropriate instrument; and (d) it discloses the existence of other estates or interests that may not otherwise be registered under this Act. (3) Subsection (2) allows the recording of an equitable mortgage or charge as a legal mortgage or encumbrance. (4) [Section 28 Subsection (4) amended by No. 29 of 1997, s. 5, Applied:06 Nov 1997] Where an instrument is recorded on a folio of the Register pursuant to this section or is referred to on the folio – (a) the Recorder shall – (i) certify on the instrument that it is so recorded; (ii) [Section 28 Subsection (4) amended by No. 29 of 1997, s. 5, Applied:06 Nov 1997] make a copy of the instrument, which he shall retain, and which shall for all purposes be deemed to be the original instrument; and (iii) return the instrument to the person from whom he received it, and that instrument shall be produced to the Recorder whenever the duplicate instrument is required by this Act to be produced to him; (b) dealings with the estate or interest so recorded are subject to this Act; and (c) the proprietor of the estate or interest so recorded has all the rights of a registered proprietor of such an estate or interest instead of any rights of a like nature enjoyed by him before that registration. (5) [Section 28 Subsection (5) amended by No. 42 of 2001, Sched. 1, Applied:15 Jul 2001] [Section 28 Subsection (5) amended by No. 9 of 1982, s. 7 and Sched. 10 ] Where an instrument is registered under the Registration of Deeds Act 1935 or Part 2K.2 of the Corporations Act, the Recorder is not bound to require production of the instrument or to comply with subsection (4) (a) (i) . (6) In registering instruments under this section the Recorder shall, in the absence of proof to the contrary, preserve such priority as they appear to have by virtue of the Registration of Deeds Act 1935 and for that purpose may assume that all instruments registered under that Act have been executed or taken in good faith by the purchasers. (7) A power of sale arising from an instrument registered pursuant to this section shall be exercised, and the estate or interest sold shall be transferred, in accordance with this Act and not otherwise. (8) Foreclosure of a mortgage registered pursuant to this section shall be effected by an application under section 85 and an order made and registered pursuant to section 86 , and not otherwise. (9) Where a person is aggrieved by a decision of the Recorder – (a) to register or refrain from registering an instrument under subsection (1) or subsection (2) ; or (b) on the priority of an instrument so registered – section 144 applies as if the decision were a refusal as mentioned in subsection (1) (a) of that section. (10) Where – (a) on the bringing of land under this Act, it appears to the Recorder that the land is subject to an equitable interest incapable of registration under this Act; or (b) the Recorder is required under section 22 to record on a qualified title an equitable interest incapable of registration under this Act – he shall record a caveat to protect the interest of the person entitled in equity and shall give notice of the caveat to that person and to the registered proprietor. (11) A caveat recorded pursuant to subsection (10) – (a) may be withdrawn by the Recorder, upon proof to his satisfaction that the equitable interest no longer exists, or by the person protected by the caveat; and (b) is otherwise subject to the same provisions as if it were a caveat lodged by that person. (12) [Section 28 Subsection (12) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] Where – (a) on the bringing of land under this Act, it appears to the Recorder that a judgment registered under the Registration of Deeds Act 1935 affects that land; or (b) the Recorder is required under section 22 to record the interest of the judgment creditor under such a judgment – the Recorder shall record a caveat to protect the interest of the judgment creditor, and shall give notice of the caveat to the judgment creditor or to the legal practitioner who registered the judgment, and to the registered proprietor. (13) A caveat recorded pursuant to subsection (12) – (a) [Section 28 Subsection (13) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] may be withdrawn by the Recorder upon proof to his satisfaction that the judgment has been satisfied, or by the person to whom the money payable under the judgment is payable or by his legal practitioner for him and on his behalf; (b) unless sooner withdrawn or lapsed, lapses at the expiration of 5 years after the date of the first registration of the judgment, or the latest re-registration of the judgment before the land was brought under this Act, whichever is the later date; and (c) is otherwise subject to the same provisions as if it were a caveat lodged by a judgment creditor. (14) [Section 28 Subsection (14) inserted by No. 29 of 1997, s. 5, Applied:06 Nov 1997] On recording an estate or interest referred to in subsection (2) , (10) or (12) , it is sufficient compliance with this section if the Recorder refers to an instrument registered under the Registration of Deeds Act 1935 which records that estate or interest, whether it was created in that instrument or in another instrument registered in the Registry of Deeds. 28A. Restraining orders not affected when land brought under Act [Section 28A Inserted by No. 47 of 1996, s. 8 and Sched. 1 ] If land that is brought under this Act is subject to a restraining order within the meaning of the Criminal Injuries Compensation Act 1976 , the Recorder is to record particulars of the restraining order on the relevant folio of the Register. 29. Notice to be given in Registry of Deeds [Section 29 Amended by No. 98 of 1986, s. 6 ] When land is brought under this Act (otherwise than pursuant to Division 1 or section 27A ), the Recorder shall give notice of that fact in the Registry of Deeds in the prescribed manner. 30. Disposal of antecedent documents of title [Section 30 Subsection (1) amended by No. 68 of 1994, s. 3 and Sched. 1 ] (1) [Section 30 Subsection (1) amended by No. 48 of 1990, s. 10 ] Where land is brought under this Act or the repealed Act , the Recorder – (a) shall return to the person from whom he received them documents relating to any property other than the land included in the relevant folio of the Register; and (b) may, in relation to any other documents – (i) retain them in his office; (ii) transfer them to the Tasmanian Library Board, to be dealt with as if they were State records within the meaning of the Archives Act 1983 ; or (iii) subject to subsection (2) , sell or destroy them. (2) The Recorder shall not destroy a document pursuant to subsection (1) unless – (a) where the land was brought under this Act or the repealed Act with a title other than a qualified title, a period of at least 12 years has expired since the land was brought under this Act or the repealed Act ; or (b) where the land was brought under this Act or the repealed Act with a qualified title, the title has ceased to be qualified and a period of at least 12 years has expired since it ceased to be qualified. (3) [Section 30 Subsection (3) amended by No. 48 of 1990, s. 10 ] Instead of selling or destroying a document under the authority of subsection (1) , the Recorder may deliver it to any person who satisfies the Recorder that he intends to preserve the document for historical purposes. (3A) [Section 30 Subsection (3A) inserted by No. 48 of 1990, s. 10 ] If an application is made by a person who had an estate or interest in the land specified in a document at the time that document was lodged or deposited with the Recorder, the Recorder shall, if the Recorder considers that the document is of no value for the purpose of the Register, give possession of the document to that person free of charge. (4) [Section 30 Subsection (4) amended by No. 48 of 1990, s. 10 ] Before selling, returning or delivering a document pursuant to this section, the Recorder shall mark the document as cancelled so far as it relates to land brought under this Act or the repealed Act . (5) A person is not entitled to the production of a document retained by the Recorder, or transferred to the Tasmanian Library Board, pursuant to subsection (1) , except upon the order of the Recorder or of the Supreme Court. (6) In this section, document means, in relation to land brought under this Act or the repealed Act , an instrument constituting, or in any way affecting, the title to the land, being an instrument that is left with or surrendered to the Recorder by the applicant or any other person, other than an instrument that is registered pursuant to section 28 . 31. Persons to produce deeds (1) Where, by any provision of this Part, a proprietor is required to produce to the Recorder instruments constituting, or in any way affecting, his title, a mortgagee or other person who holds those instruments shall, upon being requested to do so by the proprietor, at the cost of the proprietor, produce those instruments to the Recorder. (2) The Supreme Court may, on the application of the Recorder or of a person who is required by any provision of this Part to produce it to the Recorder, order any specified person who has in his possession or under his control an instrument evidencing title to land to which that person claims title, within such time as may be limited by the order, to produce and leave that instrument at the office of the Recorder, upon such terms and subject to such conditions as to costs or otherwise as the Court considers necessary. (3) Production of instruments to the Recorder under subsection (1) does not affect a lien which the person producing the instruments may have, and an order made under subsection (2) may preserve a lien. (4) A person producing instruments to the Recorder under subsection (1) may do so subject to the condition that the Recorder shall deliver to that person the certificate of title issued upon the bringing of the land, or any part of the land, to which the instruments relate under this Act, and an order made under subsection (2) may contain a similar condition. 32. Land may be described by verbal description if no survey available, &c. [Section 32 Subsection (2) amended by No. 26 of 1992, s. 4 ] (1) [Section 32 Subsection (1) amended by No. 26 of 1992, s. 4 ] Where, on the bringing of land under this Act pursuant to this Part (other than Division 1 ), there is not available to the Recorder a survey such as he could require under section 162 , the land may be described by a verbal description or by a plan prepared from information contained in a verbal description. (2) [Section 32 Subsection (2) amended by No. 48 of 1990, s. 11 ] Where, pursuant to subsection (1) , land is described by a verbal description or by a plan prepared from information contained in a verbal description, or where, under section 143E (1) , the remainder of any land included in a title is described by a plan prepared from information contained in a verbal description – (a) subject to subsection (2A) , an action is not to be brought against – (i) the Recorder; or (ii) the assurance fund; or (iii) in the case of a plan prepared by a surveyor – that surveyor – by reason or in respect of any difference between the area of land or the position or dimensions of the boundaries so described and the actual area, position or dimensions as found by survey; and (b) [Section 32 Subsection (2) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] a legal practitioner who acts for any party taking or proposing to take any estate or interest in the land is not under any duty to check that that description agrees with the description in the antecedent documents of title; and (c) on such evidence of boundaries as he deems sufficient, the Recorder may alter the description to accord with that evidence. (2A) [Section 32 Subsection (2A) inserted by No. 26 of 1992, s. 4 ] Where, pursuant to subsection (1) , the Recorder describes land by – (a) a verbal description; or (b) a plan prepared from information contained in a verbal description – subsection (2) (a) does not exempt the Recorder from any liability under section 153 as a result of any omission, mistake or misfeasance of the Recorder or any of the Recorder's officers in respect of that description. (3) [Section 32 Subsection (3) amended by No. 26 of 1992, s. 4 ] The fact that land comprised in a folio of the Register is described by a verbal description or by a plan prepared from information contained in a verbal description shall be conclusive evidence that at the time the verbal description or plan was first inserted in that folio no survey such as he could require under section 162 was available to the Recorder. (4) [Section 32 Subsection (4) substituted by No. 26 of 1992, s. 4 ] The Recorder may, at any time – (a) add to a verbal description a plan prepared from information contained in that description; or (b) replace a verbal description with a plan prepared from information contained in that description or with a plan from actual survey; or (c) replace a plan prepared from information contained in a verbal description with an amended or corrected plan of the same kind or with a plan from actual survey. (4A) [Section 32 Subsection (4A) substituted by No. 26 of 1992, s. 4 ] A plan prepared from – (a) information contained in a verbal description; or (b) a plan prepared from information contained in a verbal description – is to be endorsed "sketch by way of illustration only" . (5) [Section 32 Subsection (5) amended by No. 26 of 1992, s. 4 ] A plan or sketch by way of illustration only shall not in any way govern, control, restrict, or enlarge the verbal description from which it has been prepared. (6) In this section verbal description means a description – (a) by metes and bounds; or (b) in such form as may be prescribed. PART IV - The Register and Certificates of Title 33. The Register, certificates of title and registration (1) Subject to this section, the Recorder shall keep or cause to be kept a register of title to land which is subject to this Act. (2) Regulations may prescribe the manner in which the Register is to be kept. (3) [Section 33 Subsection (3) amended by No. 21 of 1996, s. 6 ] Subject to any regulation under this section the Register may be kept wholly or partly – (a) on paper, on microfilm, or in or on such other medium as may be approved by the Recorder; or (b) in such device for storing or processing information as may be approved by the Recorder. (4) The Register shall comprise – (a) the folios of the Register; (b) the dealings registered under this Act and any of the Acts specified in Schedule 2 ; and (c) [Section 33 Subsection (4) amended by No. 10 of 2000, s. 10, Applied:28 Apr 2000] schemes under the Strata Titles Act 1998 – but shall not include any other maps and plans or documents deposited with the Recorder. (5) Each folio of the Register shall – (a) be the record of the title to one or more parcels of land, or to an estate in one or more parcels of land being an estate of a kind referred to in subsection (6) ; (b) be numbered or otherwise identified as prescribed; (c) contain a record of such matters as the Recorder is, by or under this or any other Act, required to record on the folio; and (d) contain such other particulars as may be prescribed. (6) [Section 33 Subsection (6) amended by No. 36 of 2012, s. 12, Applied:13 Nov 2012] The Recorder may, if he deems it convenient to do so, create a folio of the Register for any of the following: (a) a leasehold estate created by a lease registered under this Act; (b) a life estate; (c) [Section 33 Subsection (6) amended by No. 36 of 2012, s. 12, Applied:13 Nov 2012] an estate in remainder or other future estate; (d) [Section 33 Subsection (6) amended by No. 36 of 2012, s. 12, Applied:13 Nov 2012] an undivided share in land; (e) [Section 33 Subsection (6) amended by No. 36 of 2012, s. 12, Applied:13 Nov 2012] any other estate or interest in land. (7) Land becomes subject to this Act when the Recorder creates a folio of the Register for it. (8) [Section 33 Subsection (8) amended by No. 36 of 2012, s. 12, Applied:13 Nov 2012] Except as may otherwise be prescribed, when the Recorder creates a folio of the Register, the Recorder may in the prescribed manner prepare a certificate of title to the same land. (9) [Section 33 Subsection (9) amended by No. 21 of 1996, s. 19 ] A certificate of title shall be in an approved form and contain the prescribed particulars. (10) [Section 33 Subsection (10) amended by No. 36 of 2012, s. 12, Applied:13 Nov 2012] On the lodgment of a dealing, the Recorder is to ensure it is marked with a distinctive number, letter or code or marked in some other manner approved by the Recorder. (11) The Recorder shall register a dealing by making such recording or alteration on the folio of the Register or registered dealing to be affected thereby as, in his opinion, may be necessary to give effect to the dealing. (12) Where land is removed from a title, the Recorder shall create a new folio of the Register for that land, and shall cancel the folio from which the land is removed, so far as it relates to that land. (13) The Recorder may at any time, if he thinks fit, rearrange parts of the Register by creating a new folio containing the whole or part of land in one or more existing folios or in such other manner as may appear to him to be convenient. (14) [Section 33 Subsection (14) amended by No. 30 of 1995, s. 3 and Sched. 1 ] In exercising his powers under subsection (13) , the Recorder – (a) shall not create a new folio so as to permit the subdivision of land contrary to the provisions of Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 ; and (b) in creating a new folio, shall distinguish the parcels comprised in the new folio which may lawfully be separately alienated immediately before the proclaimed date. (15) Any parcels comprised in a new folio created pursuant to subsection (13) which may lawfully be separately alienated immediately before the proclaimed date may, on and after that date, be separately alienated. (16) Where the Recorder creates a new folio of the Register pursuant to subsection (13) , he shall cancel the folio of the Register from which the land comprised in the new folio is taken, so far as it relates to that land. (17) Where the Recorder creates a new folio of the Register pursuant to subsection (12) or subsection (13) , he may call in any certificate of title or grant referring to the same land and cancel it to the same extent as he has cancelled the corresponding folio of the Register. (18) The Recorder may, upon registering a dealing, or whenever he considers it convenient to do so – (a) create a new edition of a folio of the Register containing the subsisting recordings only; (b) prepare a new edition of a certificate of title containing the subsisting recordings only, whether or not he has created a new edition of the relevant folio pursuant to paragraph (a) ; and (c) destroy the superseded edition of a certificate of title – but shall retain a record of the registration of dealings which have ceased to affect the land comprised in that folio which record shall remain part of the Register. (19) [Section 33 Subsection (19) omitted by No. 15 of 2001, Sched. 2, Applied:01 Jul 2001] . . . . . . . . 34. Power of Recorder to make transparencies (1) [Section 34 Subsection (1) amended by No. 68 of 1994, s. 3 and Sched. 1 ] The Recorder may cause to be made a transparency of any dealing, map, plan, or document that is in his possession or custody or under his control and may, subject to the Archives Act 1983 , keep that transparency in lieu of, or in addition to, the dealing, map, plan, or document of which it is a transparency. (2) Where the Recorder, pursuant to subsection (1) , keeps a transparency in lieu of a dealing, map, plan, or document, he may – (a) deliver the dealing, map, plan, or document to any person who satisfies the Recorder that he intends to preserve it for historical purposes; or (b) destroy the dealing, map, plan, or document. (3) [Section 34 Subsection (3) substituted by No. 80 of 2001, Sched. 1, Applied:01 Jul 2002] In this section, transparency , in relation to any dealing, map, plan or document, means – (a) a developed negative or positive photograph of that dealing, map, plan or document (in this definition referred to as an original photograph) made on a transparent base by means of light reflected from, or transmitted through, the dealing, map, plan or document; or (b) a copy of an original photograph made by the use of photosensitive material on a transparent base placed in surface contact with the original photograph; or (c) any one of a series of copies of an original photograph, the first of the series being made by the use of photosensitive material on a transparent base placed in surface contact with a copy referred to in paragraph (b) , and each succeeding copy in the series being made in the same manner from any preceding copy in the series. 34A. Power to sell, destroy or otherwise dispose of certain documents [Section 34A Inserted by No. 48 of 1990, s. 12 ] (1) The Recorder may, with the written permission of the State Archivist given in accordance with section 20 (2) (b) of the Archives Act 1983 , sell, destroy or otherwise dispose of any document or any class of document in the possession of the Recorder which the Recorder considers to be of no value for the purposes of the Register. (2) Before selling or disposing of a document the Recorder shall mark it as no longer valid. (3) For the purposes of this Act the Recorder is the Head of Agency for the purpose of section 3 of the Archives Act 1983 . (4) If an application is made by a person who had an estate or interest in the land specified in a document at the time that document was lodged or deposited with the Recorder, the Recorder shall, if the Recorder considers that the document is of no value for the purpose of the Register, give possession of the document to that person free of charge. (5) In this section document includes an instrument, a dealing, map, plan and transparency made in accordance with section 34 . 35. Lost certificate of title, folio of the Register, or duplicate registered dealing (1) The Recorder, on application for that purpose and proof to his satisfaction that a certificate of title or duplicate grant has been lost, mislaid, or destroyed, may, subject to such advertisement, notice, or indemnity as he requires, issue a new certificate of title, and where he issues a new certificate of title he shall record on the relevant folio of the Register that he has done so pursuant to this section. (2) Where a new certificate of title is issued under subsection (1) , the new certificate of title shall be produced to the Recorder whenever production of the certificate of title or duplicate grant is required. (3) If a folio of the Register or registered dealing forming part of the Register is lost or destroyed, or so obliterated as to become illegible, the Recorder may create a substituted folio or dealing from such evidence as is available to him as to the contents of and entries upon the original, and where he creates a substituted folio or dealing he shall record on it that it is a substituted folio or dealing. (4) Where a substituted folio or dealing is created under subsection (3) , the substituted folio or dealing shall be used for all purposes in place of the original folio or dealing. (5) The Recorder, on application for that purpose and proof to his satisfaction that a duplicate registered dealing has been lost or destroyed, may, subject to such advertisement, notice, or indemnity as he requires, issue a substituted duplicate registered dealing in place of the lost duplicate, and where he issues a substituted duplicate registered dealing he shall record on the original dealing that the substituted duplicate has been issued. (6) Where a substituted duplicate registered dealing is issued under subsection (5) , the substituted duplicate shall be produced to the Recorder whenever production of the duplicate registered dealing is required. 36. Searches of public records [Section 36 Subsection (1) amended by No. 21 of 1996, s. 7 ] (1) [Section 36 Subsection (1) amended by No. 48 of 1990, s. 13 ] The following records are public records: (a) the Register; (b) dealings in the office of the Recorder awaiting registration, or re-execution, completion, or correction to make them registrable and instruments and documents lodged, deposited or filed in support of a dealing or instrument; (c) caveats and priority notices; (d) [Section 36 Subsection (1) amended by No. 36 of 2012, s. 13, Applied:13 Nov 2012] maps, plans and surveys deposited with the Recorder under this or any other Act whether or not they are capable of being withdrawn or rejected; (e) any index of unregistered dealings kept in the office of the Recorder. (2) Any information in a public record shall be available at the prescribed times, in the prescribed manner, and upon payment of the prescribed fee (if any). 37. Copies of public records (1) The Recorder shall, on application and payment of the prescribed fee, furnish a person with a certified copy of any public record in his custody. (2) [Section 37 Subsection (2) amended by No. 48 of 1990, s. 14 ] A copy for the purposes of this section may, in the Recorder's discretion, be – (a) in writing; (b) made by such photocopying, facsimile or electronic transmission process as the Recorder determines; or (c) made partly in accordance with paragraph (a) and partly in accordance with paragraph (b) . (3) [Section 37 Subsection (3) amended by No. 48 of 1990, s. 14 ] In this section – certified copy in relation to a public record, means a copy of that public record that – (a) is certified by the Recorder or some officer acting on the Recorder's behalf to be a copy of the public record; or (b) in the case of a copy created by a facsimile or electronic transmission process – has recorded upon it by that process an indication that the transmission creating the copy was initiated in an office of the Recorder and a record of the time and date of the transmission; [Section 37 Subsection (3) amended by No. 80 of 2001, Sched. 1, Applied:01 Jul 2002] [Section 37 Subsection (3) amended by No. 80 of 2001, Sched. 1, Applied:01 Jul 2002] machine copy , in relation to a public record, means a copy of the record made by – (a) a machine in which, or a process by which, a latent image of the contents of the document is produced from surface contact with the document or by the use of photosensitive material other than transparent photographic film; or (b) the electrostatic process known as Xerography or any similar process; photocopying process , in relation to a copy of a public record, means the process of making a photographic copy or machine copy of the public record; photographic copy , in relation to a public record, means a print made from a transparency of the public record; [Section 37 Subsection (3) amended by No. 80 of 2001, Sched. 1, Applied:01 Jul 2002] transparency , in relation to a public record, means transparency as defined in section 34(3) . (4) [Section 37 Subsection (4) added by No. 48 of 1990, s. 14 ] [Section 37 Subsection (4) omitted by No. 80 of 2001, Sched. 1, Applied:01 Jul 2002] . . . . . . . . 38. [Section 38 Subsection (1) amended by No. 48 of 1990, s. 15 ] [Section 38 Repealed by No. 80 of 2001, Sched. 1, Applied:01 Jul 2002] . . . . . . . . PART V - The Effect of Registration 39. Folio of the Register conclusive evidence of title, &c. (1) A folio of the Register is evidence of the particulars recorded in the folio. (2) Except as otherwise provided in this Act, a folio of the Register is conclusive evidence that – (a) the person named in the folio as registered proprietor of or as taking an estate or interest in the land described in the folio is entitled to that land for that estate or interest; and (b) that land has been duly brought under this Act. 40. Estate of registered proprietor indefeasible (1) For the purposes of this section indefeasible , in relation to the title of a registered proprietor of land, means subject only to such estates and interests as are recorded on the folio of the Register or registered dealing evidencing title to the land. (2) Subject to subsections (3) and (4) , the title of a registered proprietor of land is indefeasible. (3) [Section 40 Subsection (3) amended by No. 24 of 1993, s. 3 and Sched. 1 ] The title of a registered proprietor of land is not indefeasible – (a) in the case of fraud, in which case the person defrauded has, except as otherwise provided in sections 41 and 42 , all rights and remedies that he would have had if the land were not registered land; (b) where 2 or more folios of the Register subsist for conflicting estates in respect of the same land, in which case the title which was first brought under this Act or the repealed Act defeats the titles subsequently brought under this Act or the repealed Act ; (c) so far as regards the omission or misdescription of any reservations, exceptions, conditions, and powers contained in the Crown grant of the land, or of any right to the use and flow of water in a river, stream, watercourse, lake, pond, or marsh, or of any public right of way; (d) so far as regards the interest of a tenant under – (i) a periodic tenancy; (ii) a lease taking effect in possession for a term not exceeding 3 years (whether or not the lessee is given power to extend the term) at the best rent that can be reasonably obtained without taking a fine; and (iii) [Section 40 Subsection (3) amended by No. 67 of 2003, s. 28, Applied:05 Mar 2004] a lease capable of taking effect in equity only, except as against a bona fide purchaser for value without notice of the lease who has lodged a transfer for registration; and (iv) [Section 40 Subsection (3) amended by No. 67 of 2003, s. 28, Applied:05 Mar 2004] a residential tenancy agreement to which the Residential Tenancy Act 1997 applies; (e) so far as regards – (i) [Section 40 Subsection (3) amended by No. 36 of 2012, s. 14, Applied:13 Nov 2012] an easement arising by implication or under a statute which would have given rise to a legal interest if the servient land had not been registered land; or (ia) [Section 40 Subsection (3) amended by No. 29 of 1997, s. 6, Applied:06 Nov 1997] [Section 40 Subsection (3) amended by No. 36 of 2012, s. 14, Applied:13 Nov 2012] an easement created by deed but unintentionally omitted from the folio of the Register for the servient land when that servient land was brought under this Act or the repealed Act; or (ib) [Section 40 Subsection (3) amended by No. 36 of 2012, s. 14, Applied:13 Nov 2012] an easement that has been created under this Act but unintentionally omitted from the folio of the Register for the servient land; or (ii) an equitable easement, except as against a bona fide purchaser for value without notice of the easement who has lodged a transfer for registration; (f) so far as regards any portion of land that may be erroneously included in the folio of the Register or registered dealing evidencing the title of that registered proprietor by a wrong description of parcels or boundaries; (g) so far as regards any money charged on land under any Act; and (h) [Section 40 Subsection (3) amended by No. 36 of 2012, s. 14, Applied:13 Nov 2012] subject to section 138W , so far as regards rights acquired, or in the course of being acquired, under a statute of limitations; and (i) so far as regards land which under the Land Acquisition Act 1993 has vested in an acquiring authority, within the meaning of that Act, and in respect of which that authority has not been registered as proprietor. (3A) [Section 40 Subsection (3A) inserted by No. 29 of 1997, s. 6, Applied:06 Nov 1997] The application of subsection (3)(e)(ia) extends to any land that was brought under this Act or the repealed Act before the commencement of the Land Titles Amendment (General Law Easements and Records) Act 1997 . (4) If the estate of a registered proprietor is a leasehold estate, his estate is subject also to the provisions of the lease and of this Act affecting leases, lessors, and lessees, and subleases, sublessors, and sublessees. (5) In every case, other than those mentioned in subsections (2) , (3) , and (4) , the title of a registered proprietor of land prevails, notwithstanding – (a) the existence in any other person of any estate or interest, whether derived by grant from the Crown or otherwise, which, but for this Act, might be held to be paramount, or to have priority; and (b) any want of notice or insufficient notice of any application, or any error, omission, or informality in any application or proceedings under this Act. (6) In this section, interest means – (a) any interest, mortgage, encumbrance, charge, reservation, or right in respect of land; (b) any covenant, the burden of which runs with freehold land; or (c) any claim or demand in respect of land – whether at law or in equity. 41. Purchaser from registered proprietor not to be affected by notice (1) Subject to section 40 (3) (d) (iii) and to section 40 (3) (e) (ii) , except in the case of fraud, a person contracting or dealing with, or taking, or proposing to take a transfer from, the registered proprietor of any registered estate or interest shall not be required to inquire or ascertain the circumstances in or the consideration for which the registered proprietor or any previous registered proprietor of the estate or interest in question is or was registered, or to see to the application of the purchase-money, or of any part of that money, or shall not be affected by notice direct or constructive of any trust or unregistered interest. (2) The knowledge that any trust or unregistered interest is in existence shall not of itself be imputed as fraud. 42. Purchasers and mortgagees protected Nothing in this Act shall be so interpreted as to leave subject to action for recovery of damages as provided in section 152 , or to action of ejectment as provided in section 149 , or to deprivation of the estate or interest in respect to which he is registered as proprietor, any purchaser or mortgagee in good faith for valuable consideration of registered land on the plea that his vendor or mortgagor may have been registered as proprietor through fraud or error, or under any void or voidable instrument, or may have derived from or through a person registered as proprietor through fraud or error, or under any void or voidable instrument, whether that fraud or error consists in wrong description of the boundaries or of the parcels of any land or otherwise. 43. Validity of registration in name of deceased person The creation of a folio of the Register, or registration of a grant or a dealing, in a case where the person named in the folio as registered proprietor or the person taking an estate or interest under the grant or dealing died before the date of creation of the folio or registration of the grant or dealing, is as valid and effectual, and the estate and interest of that registered proprietor or person devolves in like manner, as if the creation or registration had been effected before the death of that registered proprietor or person. 44. Persons jointly registered to be joint tenants Two or more persons who are named in a dealing as transferees or proprietors of an estate or interest shall, in the absence of words of severance, be entitled as joint tenants, and every such dealing, when registered, takes effect accordingly. 45. In suit for specific performance, folio of the Register conclusive evidence of title, &c. In any action for specific performance brought by a registered proprietor of registered land against a person who not having notice of any fraud affecting the title of the vendor may have contracted to purchase that land, the folio of the Register certifying the title of the registered proprietor is conclusive evidence that the registered proprietor has a good and valid title to the land, and for the estate or interest mentioned or described in the folio. 46. Folio of the Register void in certain cases Any folio of the Register – (a) [Section 46 Amended by No. 36 of 2012, s. 15, Applied:13 Nov 2012] created upon the first bringing of land under this Act or of the repealed Act other than a folio created upon the registration of a grant or transfer from the Crown under section 10 ; or (b) [Section 46 Amended by No. 36 of 2012, s. 15, Applied:13 Nov 2012] which names an applicant under section 138W(4) as proprietor pursuant to a vesting order made under section 138X ; or (c) [Section 46 Amended by No. 36 of 2012, s. 15, Applied:13 Nov 2012] which names an applicant under section 138D as proprietor pursuant to that section – and every folio or new edition of a folio created in respect of the same land, or any part of the land, which names as proprietor of the land any person claiming or deriving title under or through the applicant proprietor, shall be void as against the title of any person adversely in actual occupation of, and rightfully entitled to, that land, or any part of that land, at the time when that land was so brought under this Act or the repealed Act , or the applicant was so registered as proprietor, and continuing in that occupation at the time of any subsequent folio or new edition of a folio being created in respect of the land. 47. Certificate, recording, &c., procured by fraud void as between all parties to fraud If any person – (a) fraudulently procures, assists in fraudulently procuring, or is privy to the fraudulent procurement of any certificate of title or recording in the Register or of any cancellation or alteration in any recording in the Register, or in any instrument or form issued by the Recorder; (b) fraudulently uses, assists in fraudulently using, or is privy to the fraudulent use of, any form purporting to be issued or sanctioned by the Recorder; or (c) knowingly misleads or deceives any person authorized by this Act to demand explanation or information in respect of any land or the title to any land which is the subject of an application to bring it under this Act, or in respect of which any dealing or transmission is proposed to be registered or recorded – any certificate of title, recording, cancellation, or alteration so procured or made by fraud is void as between all parties or privies to that fraud. PART VI - Estates and Interests in Land and Registration of Dealings Division 1 - General provisions 48. Dealings to be attested; order of registration; priority of dealings (1) Every dealing lodged for registration shall – (a) except as may otherwise be prescribed, be attested by a witness who is not a party to the dealing; (b) be lodged singly, in duplicate, or otherwise as prescribed; and (c) comply with the prescribed requirements. (1A) [Section 48 Subsection (1A) inserted by No. 21 of 1996, s. 8 ] A dealing or instrument is taken to be lodged with the Recorder when a record is made in a device for storing or processing information approved under section 33 (3) (b) or 143A (3) (b) . (2) Where two or more dealings affecting the same land are lodged for registration at the same time by the same person and are awaiting registration, the Recorder shall register the dealings in the order in which he is requested in writing to do so by the person lodging the dealings. (3) [Section 48 Subsection (3) amended by No. 36 of 2012, s. 16, Applied:13 Nov 2012] [Section 48 Subsection (3) amended by No. 21 of 1996, s. 8 ] Where two or more dealings, lodged by different persons, or lodged by the same person at different times, affect the same land, the Recorder shall, subject to subsection (4) , register them in the order which will give effect to the intentions of the parties as expressed in, or apparent to him from, the dealings. (4) [Section 48 Subsection (4) amended by No. 21 of 1996, s. 8 ] Where the intentions of the parties referred to in subsection (3) appear to the Recorder to conflict, the order of registration shall be determined in the order in which a record is made in a device for storing or processing information approved under section 33 (3) (b) or 143A (3) (b) . (5) When registered, dealings affecting the same estate or interest shall, notwithstanding any express, implied, or constructive notice, be entitled in priority the one over the other according to the order in which they are registered and not according to the date of each dealing itself. (6) The Recorder, upon registering a dealing, shall deliver any duplicate of the dealing to the person appearing to him pursuant to section 54 to be entitled to the duplicate. (7) When registered, a dealing shall have the effect of a deed duly executed by the parties who signed it. 48A. Lodgment of dealings and instruments [Section 48A Inserted by No. 21 of 1996, s. 9 ] [Section 48A Amended by No. 4 of 2001, Sched. 1, Applied:12 Apr 2001] [Section 48A Substituted by No. 36 of 2012, s. 17, Applied:13 Nov 2012] A dealing or instrument that may be lodged with the Recorder under this or another Act may be so lodged – (a) by delivery of the original dealing or instrument; or (b) if authorised by the Recorder, by the transmission, by electronic communication, of a copy of the original dealing or instrument; or (c) by the lodgment of an electronic communication that – (i) is set out in a format approved by the Recorder; and (ii) allows the Recorder to produce the appropriate dealing or instrument in the approved form, the form approved by the Recorder or other form required by, or allowed under, this or another Act; or (d) in any other manner approved by the Recorder. 48B. Authority for lodgment by electronic process [Section 48B Inserted by No. 21 of 1996, s. 9 ] (1) [Section 48B Subsection (1) amended by No. 4 of 2001, Sched. 1, Applied:12 Apr 2001] [Section 48B Subsection (1) substituted by No. 36 of 2012, s. 18, Applied:13 Nov 2012] The Recorder may make an agreement with a person authorising the person to prepare, lodge or prepare and lodge any dealing or instrument that may be lodged with the Recorder under this or another Act otherwise than by production of the original dealing or instrument. (2) An agreement must provide that the procedures to be followed – (a) are comparable with the normal procedures adopted by the Recorder and will not adversely affect the register of title referred to in section 33 or the register of plans; and (b) [Section 48B Subsection (2) amended by No. 4 of 2001, Sched. 1, Applied:12 Apr 2001] [Section 48B Subsection (2) amended by No. 36 of 2012, s. 18, Applied:13 Nov 2012] will ensure the accurate transmission by electronic communication of the dealing or instrument. (3) [Section 48B Subsection (3) amended by No. 36 of 2012, s. 18, Applied:13 Nov 2012] [Section 48B Subsection (3) amended by No. 4 of 2001, Sched. 1, Applied:12 Apr 2001] The Recorder may require a person seeking to lodge a dealing or instrument by electronic means to produce documentary evidence that he or she is authorised to do so. 48C. Lodgment of supporting documents [Section 48C Inserted by No. 21 of 1996, s. 9 ] [Section 48C Amended by No. 4 of 2001, Sched. 1, Applied:12 Apr 2001] [Section 48C Amended by No. 36 of 2012, s. 19, Applied:13 Nov 2012] The application of sections 48A and 48B extend to the preparation and lodgment by electronic means of any document required by the Recorder in support of the dealing or instrument. 49. Instruments not effectual until registered (1) An instrument shall not be effectual to pass any estate or interest in registered land, or to render that land liable as security for the payment of money; but upon the registration of any instrument in accordance with this Act the estate or interest specified in the instrument shall pass, or the land shall become liable as security, in the manner and subject to the covenants, conditions, and contingencies set forth and specified in the instrument or by this Act declared to be implied in instruments of a like nature. (2) A person on whom the right to be registered as the proprietor of registered land has – (a) devolved by reason of the death or bankruptcy of the registered proprietor or otherwise by operation of law; or (b) been conferred by a dealing – may, subject to such conditions (if any) as may be prescribed, execute and lodge for registration instruments dealing with the land before he is himself registered as proprietor. (3) An instrument lodged for registration pursuant to subsection (2) is, when registered, as valid and effectual as if the person executing it had been registered as proprietor at the date of execution of the instrument. (4) Where two or more dealings which affect the same land are awaiting registration the Recorder may, if he thinks fit, register those dealings by making a single recording in the Register, referring in the recording to the lodgment numbers of those dealings or otherwise identifying them. (5) For the purposes of Part XI , a person expressed in a dealing registered pursuant to subsection (4) as taking an estate or interest in registered land shall be deemed to have become registered as proprietor of that estate or interest according to the tenor of the dealing. 50. Dealings not to be registered except in accordance with this Act (1) Subject to this section, the Recorder shall not register any dealing except as provided in this Act and unless the dealing is in accordance with this Act. (2) Where a dealing that is not in accordance with this Act is lodged for registration, the Recorder shall – (a) require it to be amended as provided in subsection (4) ; (b) himself amend it as provided in subsection (6) ; or (c) refuse to register it. (3) Notwithstanding any other provision of this Act, the Recorder may, in his discretion, register a dealing notwithstanding any error in or omission from the dealing and where a dealing is so registered the error or omission does not invalidate its registration. (4) If, in the opinion of the Recorder, a dealing which is lodged with the Recorder for registration is erroneous, incomplete, or defective in any particular, the Recorder may by notice in writing require the person by whom the dealing was lodged, or his agent, to re-execute, complete, or correct the dealing or procure the re-execution, completion, or correction of the dealing in such manner as may be specified in the notice. (5) If a person to whom a notice under subsection (4) is forwarded fails, within the prescribed period, to re-execute, complete, or correct the dealing, or to procure the re-execution, completion, or correction of the dealing in accordance with the notice, the Recorder shall, after such delay (if any) as he thinks proper, deal with the dealing as if he had not required any amendment. (6) [Section 50 Subsection (6) amended by No. 36 of 2012, s. 20, Applied:13 Nov 2012] The Recorder may, of his own motion, correct a patent error in a dealing lodged for registration by notation, and after an error is so corrected the dealing has the same validity and effect as if the error so corrected had not been made. (7) The Recorder may refuse to register a dealing which in his opinion cannot be registered because another dealing is required to be registered before it, and that other dealing has not been lodged, or is not in order, for registration. (8) Where the Recorder refuses to register a dealing, he shall notify the person by whom the dealing was lodged or his agent of his refusal, and may retain one-half of the fees paid on the lodging of the dealing. (9) Where the Recorder refuses to register a dealing, he may also refuse to register a dealing which appears to him to be intended to be registered subsequent to the first-mentioned dealing, or which, in his opinion, could only be registered after the registration of the first-mentioned dealing. (10) [Section 50 Subsection (10) amended by No. 9 of 2003, Sched. 1, Applied:16 Apr 2003] All fees retained by the Recorder in accordance with subsection (8) shall be paid into the Consolidated Fund. (11) [Section 50 Subsection (11) amended by No. 68 of 2000, s. 62, Applied:04 Apr 2001] [Section 50 Subsection (11) substituted by No. 36 of 2012, s. 20, Applied:13 Nov 2012] The Recorder is not to register a dealing that purports to be executed under or in pursuance of a power of attorney unless he or she is satisfied that – (a) the power of attorney is registered under the Powers of Attorney Act 2000 ; or (b) in the case of a foreign power of attorney within the meaning of the Powers of Attorney Act 2000 , the foreign power of attorney is registered under, or taken to be registered in Tasmania for the purposes of, that Act. (11A) [Section 50 Subsection (11A) inserted by No. 36 of 2012, s. 20, Applied:13 Nov 2012] If satisfied as specified in subsection (11) , the Recorder is entitled to assume that the execution of the dealing is within the powers conferred on the attorney by the relevant power of attorney or foreign power of attorney. (12) If the Recorder is of the opinion that by reason of amendments made or to be made in a dealing the dealing will be inconvenient for subsequent use, he may require the person by whom it was lodged, or his agent, to lodge within 30 days from the date of the requisition a fresh dealing to the same effect as the original dealing has, or would have, after amendment. (13) A dealing lodged pursuant to subsection (12) has effect as if it had been lodged in place of the original dealing, and if validly made in fact is not invalid merely because it could not have been validly made at the date of lodgment of the original dealing. (14) A requirement or refusal made by the Recorder under this section in respect of a dealing shall be notified in writing to the person by whom the dealing was lodged or his agent. (15) [Section 50 Subsection (15) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] Where a legal practitioner is acting as or for the agent referred to in subsection (14) the notification shall be sent to that legal practitioner. (16) For the purposes of this section – registration includes all methods of recording in the office of the Recorder; the prescribed period means – (a) in the case of a caveat, or a writ referred to in section 61 , a period of 21 days; and (b) in any other case, a period of 3 months – after the date of the notice under subsection (4) . 51. Recording of dealing on certificate of title, &c. (1) The Recorder shall not register a dealing unless the certificate of title, grant, or duplicate registered dealing to be affected by the dealing has been lodged with him for the purpose of registering that dealing. (2) Subsection (1) does not apply to the following dealings: (a) the recording of a writ (referred to in section 61 ) and the registration of a transfer pursuant to a writ under section 61 ; (b) discharges of mortgages pursuant to section 90 , and discharges of mortgages or encumbrances pursuant to sections 91 and 148 ; (ba) [Section 51 Subsection (2) amended by No. 36 of 2012, s. 21, Applied:13 Nov 2012] in respect of the registration of a transfer on the exercise of a power of sale by a mortgagee or encumbrancee under section 78 , the memorandum of mortgage or the memorandum of encumbrance; (c) satisfactions of encumbrances pursuant to section 94 ; (d) orders under section 110 after notice has been given under subsection (4) of that section; (e) [Section 51 Subsection (2) amended by No. 36 of 2012, s. 21, Applied:13 Nov 2012] action taken by the Recorder under section 138A , section 138B , section 138D or section 138X ; (f) [Section 51 Subsection (2) amended by No. 36 of 2012, s. 21, Applied:13 Nov 2012] any other dealing where the Recorder considers that the production of the certificate of title, grant or registered dealing is not required. (3) Subsection (1) does not apply – (a) where the Recorder dispenses with production of a certificate of title, grant, or duplicate registered dealing pursuant to section 160 (5) ; or (b) where by the provisions of this or any other Act the Recorder is, expressly or by necessary implication, required or authorized to make the recording without production of a certificate of title, grant, or duplicate registered dealing. (4) [Section 51 Subsection (4) amended by No. 36 of 2012, s. 21, Applied:13 Nov 2012] On registering a dealing, the Recorder shall note on the dealing the fact and date of its registration, and that notation shall be conclusive evidence that the dealing was duly registered on that date. (5) Where under subsection (1) a certificate of title, grant, or duplicate registered dealing is required to be lodged with the Recorder before he registers a dealing, the Recorder shall, except as may otherwise be prescribed – (a) make the same recording on the relevant certificate of title, grant, or duplicate registered dealing as he has made on the folio of the Register or registered dealing to give effect to the dealing; or (b) issue a certificate of title, or a new edition of the certificate of title, in accordance with the folio of the Register. (6) Where the Recorder has registered a dealing without the certificate of title, grant, or duplicate registered dealing being produced to him, he may act as provided in subsection (5) when the certificate of title, grant, or duplicate registered dealing is next produced to him for any purpose. (7) Nothing in this section affects any power of the Recorder to compel production to him of the certificate of title, grant, or duplicate registered dealing. (8) A failure by the Recorder to comply with any of the requirements of subsections (1) , (5) , and (6) does not invalidate the registration of a dealing. (9) Nothing in this section requires the Recorder to record – (a) on a certificate of title or grant – (i) a caveat; (ii) a priority notice; or (iii) a dealing of a prescribed kind; or (b) on a registered dealing or duplicate registered dealing, any dealing – which is recorded on the folio of the Register constituting the title to the land affected by the caveat, priority notice, or dealing. 52. Priority notices (1) [Section 52 Subsection (1) amended by No. 47 of 1996, s. 8 and Sched. 1 ] Any of the following persons may lodge with the Recorder a priority notice in accordance with subsection (2) : (a) a registered proprietor; (b) a person entitled to deal with registered land; (c) a person who has contracted in good faith and for value to deal with a person referred to in paragraph (a) or paragraph (b) or is entitled to execute and lodge dealings as and in the cases prescribed under section 49 (2) ; (d) [Section 52 Subsection (1) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] the legal practitioner for a person referred to in paragraph (a) , paragraph (b) , or paragraph (c) ; and (e) a person authorized in writing to do so by any of the persons referred to in paragraphs (a) , (b) , (c) , and (d) ; and (f) the Director of Public Prosecutions where a restraining order has been made under section 18 of the Criminal Injuries Compensation Act 1976 . (2) [Section 52 Subsection (2) amended by No. 48 of 1990, s. 16 ] [Section 52 Subsection (2) amended by No. 21 of 1996, s. 19 ] [Section 52 Subsection (2) amended by No. 47 of 1996, s. 8 and Sched. 1 ] A priority notice – (a) shall be in an approved form; (b) except as provided by subsection (5A) , limits a period, not exceeding 60 days, after the day on which the notice is lodged with the Recorder during which priority shall be reserved for lodgment of the dealing specified in the notice; (c) shall, when lodged, be dealt with by the Recorder in the prescribed manner; and (d) operates to prevent registration or recording of any dealing lodged with, or served on, the Recorder after the lodgment of the priority notice, except as is otherwise provided in subsections (3) , (5) , (5A) and (7) . (3) [Section 52 Subsection (3) amended by No. 47 of 1996, s. 8 and Sched. 1 ] If a dealing specified in a priority notice is lodged with the Recorder within the period limited in the priority notice or, if that period expires on a day on which the office of the Recorder is closed, on the next day on which the office is open, that dealing shall, subject to subsections (4) , (5) , (5A) and (6) be registered, notwithstanding the lodgment with the Recorder of any other dealing after the lodgment of the priority notice. (4) Subsection (3) does not authorize the registration of a dealing executed by a person entitled to be registered as the proprietor of registered land otherwise than as and in the cases prescribed under section 49 (2) . (5) [Section 52 Subsection (5) amended by No. 47 of 1996, s. 8 and Sched. 1 ] Except as provided by subsection (5A) , a priority notice ceases to have effect – (a) if no dealing specified in the priority notice is lodged with the Recorder within the period limited in the priority notice, at the expiration of that period; or (b) if a dealing specified in the priority notice is lodged within the period limited in the priority notice, when all dealings – (i) which are specified in the priority notice; and (ii) which have been lodged with the Recorder within the period limited in the priority notice – have been registered, have been withdrawn from registration, or have been refused registration. (5A) [Section 52 Subsection (5A) inserted by No. 47 of 1996, s. 8 and Sched. 1 ] A priority notice lodged by the Director of Public Prosecutions under subsection (1) (f) – (a) reserves priority, for the period commencing after the day on which the notice is lodged with the Recorder and ending on the day on which the notice ceases to have effect, for lodgment of the dealing specified in the notice; and (b) ceases to have effect when – (i) the restraining order to which the notice relates ceases to have effect under section 23 of the Criminal Injuries Compensation Act 1976 ; or (ii) the notice is withdrawn; or (iii) the notice is otherwise removed under this section; or (iv) if the dealing specified in the notice is lodged – the dealing is registered, withdrawn from registration or refused registration. (5B) [Section 52 Subsection (5B) inserted by No. 47 of 1996, s. 8 and Sched. 1 ] If a judge extends the period during which a restraining order to which a priority notice lodged under subsection (1) (f) relates is in force the Director may apply to the Recorder, on a form approved by the Recorder, to record particulars of the extension on the priority notice. (5C) [Section 52 Subsection (5C) inserted by No. 47 of 1996, s. 8 and Sched. 1 ] The Recorder may, if satisfied that an application under subsection (5B) is in order, record particulars of the extension on the relevant priority notice. (6) [Section 52 Subsection (6) amended by No. 47 of 1996, s. 8 and Sched. 1 ] After a priority notice ceases to have effect pursuant to subsection (5) or (5A) , dealings lodged with, or served on, the Recorder while the priority notice was effective in respect of the land to which the priority notice relates shall be dealt with in the same manner, shall have the same priority as between themselves, and shall be as effectual, as if the priority notice had not been lodged. (7) A priority notice does not prevent the registration or recording of a dealing lodged by the Crown or a public or local authority – (a) pursuant to a power – (i) to resume or take land; (ii) to restrict the use or alienation of land; (iii) to erect works on land; or (iv) to give notice of its intention to do any one or more of the things referred to in subparagraphs (i) , (ii) , and (iii) ; or (b) in prescribed circumstances or subject to prescribed conditions. (8) Where a dealing is lodged for registration but its registration is prevented by a priority notice, the Recorder shall, as soon as practicable, notify the person who has lodged the dealing that it is so affected. (9) Notwithstanding any other provision of this section, a person by whom or on whose behalf a priority notice has been lodged may, notwithstanding the notice, consent to the registration of a specified dealing, and the dealing to the registration of which he has consented may, if the consent is lodged with it, be registered as if the priority notice had not been lodged. (10) [Section 52 Subsection (10) amended by No. 21 of 1996, s. 19 ] A person who has lodged a priority notice may withdraw it by lodging with the Recorder a notice of withdrawal in an approved form. (11) The Recorder shall not be concerned to satisfy himself that a person lodging a priority notice is a person entitled or authorized to do so pursuant to subsection (1) . (12) A person who lodges a priority notice with the Recorder and who is not entitled or authorized to do so under this section is liable to any person who may have sustained damage as a result of the priority notice being lodged for such compensation as a judge, on a summons in chambers, deems just. (13) The cost of a summons referred to in subsection (12) and all proceedings in connection with the summons shall be in the discretion of the judge, and execution may issue for the amount of compensation, if any, and of costs ordered by him to be paid in the same manner as if the amount of compensation and costs had been recovered by a judgment in an action in the Supreme Court. (14) A person having an interest in land to which a priority notice relates may take out a summons requiring the person who lodged the notice to show cause to a judge in chambers why the priority notice should not be removed. (15) On the return of a summons under subsection (14) , the judge may refer the matter to the Supreme Court, and the judge or the Court may make such an order as to him or it seems just, and may provide for the costs of the proceedings. (16) The Recorder shall, upon being served with an order made under subsection (15) , give effect to the order so far as it relates to matters under his control. 52A. Attorney-General to give notice of forfeiture orders [Section 52A Inserted by No. 47 of 1996, s. 8 and Sched. 1 ] Where, pursuant to section 29 of the Criminal Injuries Compensation Act 1976 , the State is registered as the owner of land under this Act, the Attorney-General is, within 30 days of the registration, to give notice of the registration to each person who appears to the Attorney-General, from the Register, to have an interest in that land. 53. Dealing may be registered prior to grant from the Crown (1) [Section 53 Subsection (1) amended by No. 46 of 1991, s. 4 and Sched. 2 ] [Section 53 Subsection (1) amended by No. 27 of 2000, s. 4, Applied:01 Jul 1995] Where a dealing is lodged with the Recorder for registration, accompanied by a receipt of, or a receipt purporting to be signed on behalf of the Treasurer, the Director-General of Lands, the Surveyor-General, or the managing director of Tasmania Development and Resources acknowledging payment of all money required to be paid for a grant in fee of land affected by the dealing from the Crown to the person executing the dealing, the Recorder shall, subject to subsection (4) , record upon the receipt particulars of the dealing. (2) Where particulars of a dealing are recorded pursuant to subsection (1) – (a) the dealing shall be held to be duly registered under this Act; and (b) the person named in the recording shall be held to be duly registered as proprietor of the estate or interest specified in the recording. (3) On registering a dealing pursuant to subsection (1) , the Recorder shall retain the receipt and dealing in his office until a transfer granting the land by the Crown is registered; and the Recorder shall then record on the folio of the Register created pursuant to that transfer every dealing recorded upon the receipt. (4) The Recorder is not bound to record under subsection (1) any dealing relating to part of the land to which the receipt relates. 54. Delivery of certificate of title or duplicate registered dealing (1) The Recorder – (a) where he considers it proper to do so, may deliver a certificate of title or duplicate registered dealing in his custody to the person by whom it was lodged unless that person has given written instructions to the Recorder to deliver the certificate or duplicate to some other person; (b) shall not, where written instructions have been given as mentioned in paragraph (a) , deliver the certificate or duplicate otherwise than in accordance with those instructions or by order of the Supreme Court; and (c) where he is unable to determine to whom a certificate of title or duplicate registered dealing should be delivered, may deliver it to the person he considers best entitled to the certificate of title or duplicate registered dealing, or may retain it in his office. (2) [Section 54 Subsection (2) amended by No. 36 of 2012, s. 22, Applied:13 Nov 2012] A person who lodges any dealing or other document with the Recorder is taken to have authority from all persons claiming under, or having an interest in, the dealing or document – (a) to lodge it with the Recorder; (b) to collect it from the Recorder for amendment or to withdraw it from registration, and in either case to give a receipt for it; and (c) to receive communications and notices in respect of it. 55. Effect of reference to plan [Section 55 Substituted by No. 21 of 1996, s. 10 ] (1) Where land is described in a folio of the Register by reference to a plan filed, lodged or deposited with the Recorder under Division 3 of Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 , the Registration of Deeds Act 1935 or any other law, a transfer, mortgage, encumbrance or lease of that land or any other dealing, instrument or plan is taken to import a statement that the land is similarly described by reference to that plan. (2) For the purposes of subsection (1) , a document is taken to be a plan if it incorporates by reference any information contained in another plan or document filed, deposited or lodged with the Recorder under this Act. (3) The application of this section extends to a plan prepared by the Recorder. 56. General covenants implied in dealings In every dealing charging, creating, or transferring an estate or interest in registered land, there shall be implied a covenant by the party charging, creating, or transferring the estate or interest that he will do such acts and execute such dealings as may be necessary to give effect to all covenants, conditions, and purposes expressly set forth in the dealing, or by this Act declared to be implied against that party in dealings of a like nature. 57. Implied covenants may be modified or negatived (1) Every covenant and power implied in any dealing by virtue of this Act may be negatived or modified by express declaration in the dealing or endorsed on the dealing. (2) In a declaration in an action for an alleged breach of a covenant referred to in subsection (1) , the covenant alleged to be broken may be set forth; and it may be alleged that the party against whom the action is brought did so covenant precisely in the same manner as if that covenant had been expressed in words in that dealing. (3) Every implied covenant referred to in this section has the same force and effect and is enforced in the same manner as if it had been set out at length in the dealing. (4) Where any dealing is executed by more parties than one, such covenants as are by this Act declared to be implied in dealings of the like nature shall be construed to bind the parties jointly and severally. Division 2 - Transfers 58. Transfer (1) [Section 58 Subsection (1) amended by No. 21 of 1996, s. 19 ] A registered proprietor may transfer his estate or interest in land by a memorandum of transfer in an approved form. (2) [Section 58 Subsection (2) amended by No. 36 of 2012, s. 23, Applied:13 Nov 2012] On a transfer referred to in subsection (1) being registered, the estate or interest of the transferor, as set forth in the transfer, with all rights, powers, privileges, requirements and liabilities belonging or appertaining to that estate or interest, shall pass to the transferee. (3) A registered proprietor may surrender land to the Crown by the form of transfer mentioned in subsection (1) , and when registered the transfer shall be deemed to have been duly enrolled of record. 59. Transferee of land subject to mortgage or encumbrance to indemnify transferor In every memorandum of transfer of an estate or interest in registered land which is subject to a mortgage or encumbrance, there shall be implied a covenant by the transferee – (a) with the transferor and the mortgagee or encumbrancee, that he will pay the interest, annuity, and principal sum secured by that mortgage or encumbrance in the manner and at the time specified in the memorandum of mortgage and encumbrance; and (b) with the transferor, that he will indemnify and keep harmless the transferor from and against all moneys secured by the memorandum of mortgage or encumbrance and from and against all liability in respect of any of the covenants contained in the memorandum, or by this Act implied, on the part of the transferor. 60. Transfers of mortgages, encumbrances, and leases (1) On the registration of a transfer of a registered mortgage, a registered lease, or a registered encumbrance, the transferee shall become subject to and liable for the same requirements and liabilities to which he would have been subject and liable if named in that instrument originally as mortgagee, encumbrancee, or lessee. (2) By virtue of every transfer referred to in subsection (1) – (a) the right to sue upon a memorandum of mortgage or other dealing, and to recover any debt, sum of money, annuity, or damages under the memorandum of mortgage or other dealing (notwithstanding the same may be deemed or held to constitute a chose in action); and (b) all interest in the debt, sum of money, annuity, or damages referred to in paragraph (a) – shall be transferred so as to vest the same at law as well as in equity in the transferee. (3) Nothing contained in this section shall prevent a court from giving effect to any trusts affecting the debt, sum of money, annuity, or damages referred to in subsection (2) , where the transferee holds the same as a trustee for any other person. 61. Sale under writ (1) In this section, writ means – (a) a writ of fieri facias issued out of the High Court of Australia or out of the Supreme Court; (b) [Section 61 Subsection (1) amended by No. 73 of 1993, Sched. 1, Applied:30 Mar 1998] a writ enforcing a judgment or order issued under the Magistrates Court (Civil Division) Act 1992 ; or (c) a direction, decree, or order of the High Court of Australia, the Supreme Court, the Family Court of Australia, or any court of competent jurisdiction directing or authorizing the sale of any estate or interest in land. (2) No execution of any writ shall bind, charge, or affect any estate or interest in registered land except within the period of 3 months after it has been recorded in accordance with subsection (3) . (3) [Section 61 Subsection (3) amended by No. 21 of 1996, s. 19 ] The Recorder, pursuant to an application in an approved form which – (a) is accompanied by a copy of a writ; (b) identifies, by reference to a folio of the Register or to a registered dealing, the land sought to be affected by that writ; and (c) incorporates, or is supported by, a statutory declaration that, to the Recorder's satisfaction, identifies the judgment debtor named in the writ with the registered proprietor of the land comprised in that folio or registered dealing – shall record the writ on that folio or registered dealing. (4) Subject to this section, where a writ recorded pursuant to subsection (3) is executed by sale of all or part of the land to which the recording relates, and a transfer pursuant to the sale is lodged for registration within 3 months after that recording, the Recorder shall register the transfer, notwithstanding that a dealing with the land by the registered proprietor has already been lodged for registration, and for that purpose may call in the relevant certificate of title or duplicate registered dealing or use the certificate of title or duplicate if it is in his possession. (5) After a writ has been recorded pursuant to subsection (3) , the Recorder shall not register on that folio or registered dealing a dealing executed by the registered proprietor of the folio or registered dealing until – (a) a period of 3 months has elapsed since the writ was so recorded; or (b) satisfaction of the writ has been registered. (6) [Section 61 Subsection (6) substituted by No. 36 of 2012, s. 24, Applied:13 Nov 2012] After a writ is issued but before it is recorded in accordance with subsection (3) , a person dealing with the registered proprietor or with a mortgagee or encumbrancee exercising a power of sale may lodge a transfer for registration and, if that transfer is registered, the person is entitled to take his or her interest in priority even if the person had actual or constructive notice of the issue of the writ. (7) The Recorder, on such evidence as he considers sufficient, may record on the relevant folio of the Register or registered dealing the satisfaction of any writ recorded under this section, and upon the satisfaction of any writ being recorded that writ shall cease to bind, charge, or affect the estate or interest sought to be affected by the writ. (8) On the expiration of 3 months after a writ has been recorded in accordance with subsection (3) , and if no transfer pursuant to a sale under the writ has within that period been lodged for registration – (a) the writ ceases to bind, charge, or affect the estate or interest sought to be affected by the writ; and (b) the Recorder may cancel the recording of the writ. (9) For the purposes of calculating time under this section, a writ which is recorded pursuant to subsection (3) shall be deemed to have been recorded on the day on which the application to record it was lodged with the Recorder. 62. Dealings with lands of the Crown under Act (1) A transfer under the hand of the Minister administering the Crown Lands Act 1976 of any land of which Her Majesty is registered proprietor, witnessed by the Director-General of Lands or an officer of his department, and duly registered, has the effect, for all purposes, of letters patent issued under the seal of the State and duly enrolled of record. (2) The Recorder shall not record on a folio of the Register a notice of statutory duties or restrictions affecting lands of which Her Majesty is registered proprietor, and no reference in the Register to a notification in the Gazette shall be deemed to be notice of any subsisting statutory duty or restriction. (3) Except where the contrary is expressly enacted, no statutory duty or restriction referred to in subsection (2) has, as against any registered estate or interest, any greater effect than if it were enforceable only in equity and not at law. Division 3 - Severance of joint tenancy 63. Severance of joint tenancy (1) [Section 63 Subsection (1) amended by No. 21 of 1996, s. 19 ] A joint tenant of registered land may sever his joint tenancy by a declaration of severance in an approved form and registered under this Act. (2) On registering a declaration of severance in accordance with subsection (1) , the Recorder shall notify every other joint tenant of the land by notice in writing. (3) The mode of severance prescribed by this section is in addition to, and not in substitution for, any other mode available before the proclaimed date to a joint tenant of registered land. (4) [Section 63 Subsection (4) inserted by No. 36 of 2012, s. 25, Applied:13 Nov 2012] On the registration of a declaration of severance of a joint tenancy under this section, the joint tenants become tenants in common with equal shares in the land. (5) [Section 63 Subsection (5) inserted by No. 36 of 2012, s. 25, Applied:13 Nov 2012] Nothing in subsection (4) prevents the tenants in common referred to in that subsection executing a transfer so as to provide that the shares in the land are held by them in other than equal shares. Division 4 - Leases 64. Leases (1) [Section 64 Subsection (1) amended by No. 21 of 1996, s. 19 ] The registered proprietor of land may lease it for any term exceeding 3 years by a memorandum of lease in an approved form. (2) A lease for a term of 3 years or less is not registrable under this Act. (3) A lease of mortgaged or encumbered land shall not be valid and binding against the mortgagee or encumbrancee unless the mortgagee or encumbrancee has consented in writing to the lease prior to the registration of the lease. 65. Surrender of lease (1) [Section 65 Subsection (1) amended by No. 21 of 1996, s. 19 ] The lessee may surrender a registered lease by a memorandum of surrender in an approved form accepted by the lessor. (2) When a memorandum of surrender of lease has been registered under this Act, the estate or interest of the lessee in that land ceases. (3) A lease subject to mortgage or encumbrance shall not be surrendered in accordance with this section without the consent of the mortgagee or encumbrancee. 66. Covenants implied in every lease against lessee In every memorandum of lease the following covenants shall be implied against the lessee, unless otherwise provided in that memorandum: (a) the lessee will pay the rent reserved by the lease, at the times mentioned in the lease, and all rates and taxes which may be payable in respect of the demised property during the continuance of the lease; (b) the lessee will keep and yield up the demised property in good and tenantable repair, damage by fire, storm, tempest, act of Her Majesty's enemies, and reasonable wear and tear excepted. 67. Powers in lessor In every memorandum of lease the following powers shall be implied in the lessor, unless otherwise provided in that memorandum: (a) the lessor may by himself or his agents, at all reasonable times, enter upon the demised property, and view the state of repair of the demised property, and may serve upon the lessee, or leave at his last or usual place of abode, or upon the demised property, a notice in writing of any defect, requiring him, within a reasonable time to be specified in the notice, to repair the demised property; (b) where the rent or any part of the rent is in arrears for 3 months, or where default is made in the fulfilment of any covenant, whether expressed or implied in that lease, on the part of the lessee, and is continued for 3 months, or where the repairs required by the notice referred to in paragraph (a) have not been completed within the time specified in the notice, the lessor may re-enter upon and take possession of the demised property. 68. Recovery of possession and determination of lease (1) The Recorder, on proof to his satisfaction – (a) of lawful re-entry and recovery of possession by a lessor; or (b) that the lessee has abandoned the demised property, and that the lessor has re-entered and occupied the property by himself or tenants undisturbed by the lessee – shall record the re-entry as prescribed. (2) Where a re-entry is recorded pursuant to subsection (1) the lease shall determine without prejudice to any action or cause of action previously commenced or accrued in respect of any breach or non-observance of any covenant expressed or implied in the lease. 69. Provisions of Act as to leases to apply, with necessary modifications, to subleases (1) The provisions of this Act affecting leases, lessors, and lessees apply to subleases, sublessors, and sublessees, with such modifications and exceptions as the difference between a lease and sublease require. (2) If a lease is determined by forfeiture of a superior lease or otherwise by operation of law, the assurance fund shall not be liable for compensation for any loss, damage, or deprivation occasioned by that determination. (3) In addition to the covenants specified by this Act to be implied in leases, there shall be implied in every sublease under this Act a covenant that the sublessor will during the term granted by the sublease pay the rent reserved by and perform and observe the covenants and agreements contained in the sublessor's lease and on his part to be paid, performed, and observed. 70. Extension or variation of lease (1) [Section 70 Subsection (1) amended by No. 21 of 1996, s. 19 ] The term of a registered lease may be extended by a memorandum of extension in an approved form signed by the lessor and lessee and lodged for registration before the expiry of that term. (2) Subject to this section, on the registration of a memorandum of extension – (a) the memorandum shall have the same effect as if it were a memorandum of lease for the extended term subject to the same covenants, conditions, and restrictions, with the necessary modifications, as are contained or implied in the lease; (b) the estate of the lessee under the extended term of the lease shall be subject to all mortgages, encumbrances, and interests to which the lease is subject at the time of registration of the memorandum of extension; and (c) all references in any Act or in any agreement, deed, instrument, notice, or other document to the lease or to the estate of the lessee under the lease shall, unless inconsistent with the context of this section, be deemed to be references to the lease as varied by the memorandum of extension or to the estate of the lessee under the extended term of the lease, as the case may be. (3) The covenants, conditions, and restrictions contained or implied in a lease may be expressly varied, negatived, or added to by a memorandum of extension. (4) [Section 70 Subsection (4) amended by No. 21 of 1996, s. 19 ] Notwithstanding that the term of a lease is not extended, the covenants, conditions, and restrictions contained or implied in a registered lease may be expressly varied, negatived, or added to by a memorandum in an approved form signed by the lessor and the lessee and lodged for registration before the expiry of the term of the lease. (5) On the registration of a memorandum of extension of a lease in respect of which a separate folio of the Register has been created, that folio shall have full validity and effect during the extended term. (6) If the land affected by a lease is at the time of registration of a memorandum of extension or variation subject to a mortgage or an encumbrance, the memorandum shall not be binding on the mortgagee or encumbrancee unless he has consented to the memorandum of extension or variation in writing on the memorandum. 71. Folio of the Register for a leasehold estate (1) When a folio of the Register has been created for a leasehold estate, the Recorder – (a) [Section 71 Subsection (1) amended by No. 36 of 2012, s. 26, Applied:13 Nov 2012] is to record the creation of that folio on the folio of the Register evidencing the lessor's title; and (b) [Section 71 Subsection (1) amended by No. 36 of 2012, s. 26, Applied:13 Nov 2012] is to register on that leasehold folio all dealings with the lease. (c) [Section 71 Subsection (1) amended by No. 36 of 2012, s. 26, Applied:13 Nov 2012] . . . . . . . . (2) [Section 71 Subsection (2) amended by No. 36 of 2012, s. 26, Applied:13 Nov 2012] On the determination of a lease, otherwise than by effluxion of time, the Recorder shall cancel the folio of the Register, or the edition of the folio of the Register, for the leasehold estate, and on the expiry of the term of the lease the folio, or the edition of the folio, of the Register for the leasehold estate shall be deemed to be so cancelled. Division 5 - Mortgages and encumbrances 72. Creation of mortgage or encumbrance [Section 72 Amended by No. 21 of 1996, s. 19 ] The registered proprietor of a freehold or leasehold estate in registered land – (a) may mortgage it by a memorandum of mortgage in an approved form; and (b) may charge it with the payment of an annuity, rent-charge, or other sum of money by a memorandum of encumbrance in an approved form. 73. Mortgage or encumbrance not to operate as transfer A mortgage or encumbrance when registered has effect as security, and is an interest in land, but does not operate as a transfer of the land mortgaged or charged. 74. Covenants implied in every memorandum of mortgage In every memorandum of mortgage there is implied against the mortgagor a covenant that he will repair and keep in repair all buildings or other improvements erected and made upon the land; and that the mortgagee may at all convenient times, until the mortgage is redeemed, be at liberty, with or without surveyors or others, to enter into and upon the land, to view and inspect the state of repair of the buildings or improvements. 75. Submortgages (1) [Section 75 Subsection (1) amended by No. 21 of 1996, s. 19 ] A mortgagee may create a submortgage in favour of a person by executing a transfer of mortgage by way of security in an approved form. (2) Section 60 applies to a transfer of mortgage under this section, but nothing in that section prevents a court from giving effect to a covenant contained in a transfer of mortgage that the transferee will execute a registrable transfer of the mortgage to the transferor by way of discharge of the security. 76. Postponement of mortgages and encumbrances (1) [Section 76 Subsection (1) amended by No. 21 of 1996, s. 19 ] The priority between themselves of the mortgages or encumbrances appearing by the Register to affect any land may from time to time be varied by an instrument in an approved form registered under this Act. (2) [Section 76 Subsection (2) substituted by No. 36 of 2012, s. 27, Applied:13 Nov 2012] An instrument referred to in subsection (1) that postpones the priority of a mortgage or encumbrance must be executed by the registered proprietor of the mortgage or encumbrance that is postponed. 77. Procedure in case of default (1) Where default is made in the payment of any money secured by any registered mortgage or encumbrance, or in the observance of any covenant expressed or by this Act declared to be implied in any registered mortgage or encumbrance, and that default is continued for one month, or for such other period as may be expressly limited for that purpose in the mortgage or encumbrance, the mortgagee or encumbrancee may – (a) give to the mortgagor or encumbrancer written notice in accordance with subsection (2) ; or (b) leave that notice on the mortgaged or encumbered land or at the usual or last known place of abode in the State of the mortgagor or encumbrancer or other person claiming to be then entitled to the land. (2) A notice referred to in subsection (1) shall – (a) require the mortgagor or encumbrancer to pay the money then due or owing under the mortgage or encumbrance or to observe the covenants expressed or implied in the mortgage or encumbrance; and (b) state that sale will be effected if default in payment of the money referred to in paragraph (a) , or in the observance of covenants referred to in that paragraph, is continued. (3) A purchaser under a sale referred to in subsection (2) (b) shall not be bound to inquire whether default has been made or continued as provided in this section or whether the notice referred to in subsection (1) has been given, or otherwise as to the propriety or regularity of the sale of the land. (4) Where the trustee of the mortgagor or encumbrancer under the law relating to bankruptcy has disclaimed, or has notified the Recorder that he does not intend to claim, any land subject to mortgage or encumbrance, the mortgagee or encumbrancee, in lieu of giving notice to the mortgagor or encumbrancer as provided by this section, may publish in a newspaper a similar notice to all persons concerned. 78. Power to sell and appropriation of proceeds (1) [Section 78 Subsection (1) amended by No. 36 of 2012, s. 28, Applied:13 Nov 2012] After default in payment or in observance of covenants continuing for the further period of 30 days from the date of service or publication of the notice pursuant to section 77 , or for such other period as may be limited for that purpose in the memorandum of mortgage or memorandum of encumbrance, the mortgagee or encumbrancee may, in good faith and having regard to the interests of the mortgagor, encumbrancer, and other persons – (a) sell or concur with any other person in selling the mortgaged or encumbered land or any part of that land, altogether or in lots, in such manner and subject to such terms and conditions as he thinks fit; and (b) for the purpose of making a sale of the land or any part of the land at the best price, do anything that the mortgagor or encumbrancer could do in relation to the land. (2) [Section 78 Subsection (2) amended by No. 30 of 1995, s. 3 and Sched. 1 ] Without limiting the generality of subsection (1) (b) , the mortgagee or encumbrancee may – (a) subdivide, change the use of, or otherwise develop the land; (b) carry out works upon the land; (c) set aside part of the land for purposes other than sale, in the course of subdivision; (d) execute schedules of easements for the purposes of Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 , as if he were the owner; and (e) [Section 78 Subsection (2) amended by No. 36 of 2012, s. 28, Applied:13 Nov 2012] grant and reserve easements and profits à prendre , and enter into restrictive covenants; and (f) [Section 78 Subsection (2) amended by No. 36 of 2012, s. 28, Applied:13 Nov 2012] enter into an agreement under Part 5 of the Land Use Planning and Approvals Act 1993 . (3) Anything made, done, or executed by the mortgagee or encumbrancee in pursuance of this section shall be as valid and effectual as if made, done, or executed by the mortgagor or encumbrancer. (4) The receipt in writing of the mortgagee or encumbrancee shall be a sufficient discharge to the purchaser of the land or any portion of the land for so much of his purchase-money as may be expressed to be received by the receipt. (5) A purchaser referred to in subsection (4) shall not be answerable for the loss, misapplication, or non-application, or be obliged to see to the application, of the purchase-money paid by him, and shall not be concerned to inquire whether any default or notice has been made or given. (6) A memorandum of transfer by a registered mortgagee or encumbrancee expressed to be in exercise of the power of sale conferred by this Act may be accepted by the Recorder as sufficient evidence that the power of sale has been duly exercised. (7) The purchase-money received by a mortgagee who has exercised the power of sale conferred by this section, after discharge of prior mortgages and encumbrances to which the sale is not made subject (if any), shall be applied – (a) firstly, in payment of all costs, charges, and expenses properly incurred, incidental to or for the purpose of the sale, or any attempted sale, or otherwise consequent on the default; (b) secondly, in payment of the money which is due and owing on the mortgage; (c) thirdly, in payment of subsequent mortgages and encumbrances (if any) in the order of their priority; (d) fourthly, in satisfaction of the claims of all persons who have lodged caveats subsisting when the power of sale was exercised, in accordance with their respective rights and priorities; and (e) fifthly, in payment of the residue (if any) to the mortgagor. (8) The purchase-money received by an encumbrancee who has exercised the power of sale conferred by this section, after discharge of prior mortgages and encumbrances to which the sale is not made subject (if any), shall be applied – (a) firstly, in payment of all costs, charges, and expenses properly incurred, incidental to or for the purpose of the sale, or any attempted sale, or otherwise consequent on the default; (b) secondly, in accordance with any express provision in the memorandum of encumbrance for disposing of the money (either by setting aside the proceeds of sale or part of the proceeds of sale on investment to meet future periodical payments, or by payment to the encumbrancee out of the proceeds of a sum being the estimated capital value of the encumbrancee's interest, or otherwise); and in the absence of any provision in the memorandum of encumbrance for disposing of the money, in payment of the money which is due and owing on the encumbrance at the date of the sale; (c) thirdly, in payment of subsequent mortgages and encumbrances (if any) in the order of their priority; (d) fourthly, in satisfaction of the claims of all persons who have lodged caveats subsisting when the power of sale was exercised in accordance with their respective rights and priorities; and (e) fifthly, in payment of the residue (if any) to the encumbrancer. (9) Where by this section a mortgagee or encumbrancee is required to account to a subsequent encumbrancee for money arising on a sale, the money shall be paid or applied in accordance with the express provision (if any) in the memorandum of encumbrance for disposing of the money, and, in the absence of express provision, in discharge of the money due to the subsequent encumbrancee at the date of the sale. (10) Notwithstanding anything contained in subsection (9) , where by this section a mortgagee or encumbrancee is required to account to a subsequent mortgagee or encumbrancee for money arising on a sale – (a) he may pay to the subsequent mortgagee or encumbrancee such sum as the subsequent mortgagee or encumbrancee claims in writing is owing upon the security of the subsequent mortgage or encumbrance; and (b) the subsequent mortgagee or encumbrancee, and not the mortgagee or encumbrancee making the payment, is accountable to the mortgagor or encumbrancer for any amount in fact overpaid. (11) Where a mortgagee or encumbrancee cannot reasonably ascertain how he is to satisfy claims of persons who have lodged caveats, he may pay all money available to satisfy those claims into the Supreme Court, and the receipt or certificate of the proper officer of the Supreme Court is a sufficient discharge to the mortgagee or encumbrancee for the money so paid in, and that money shall be dealt with in accordance with the orders of the Supreme Court. 79. Power of mortgagee to sell or lease mortgaged land and other land together (1) In the exercise by the mortgagee of a power of sale or lease contained or implied in a mortgage, the mortgaged land may be sold or leased together with any other land of whatever nature or tenure and whether registered land or not that is the subject of the mortgage or of any other mortgage from the mortgagor to the mortgagee by one sale or lease at one price or rent; and the mortgagee shall fairly and equitably apportion all costs, expenses, purchase-money, and rent between the lands so sold or leased. (2) A failure by the mortgagee to make the apportionment required by this section does not affect the purchaser or lessee or the title to any land in his hands. 80. Notice or lapse of time may be dispensed with (1) Any notice or lapse of time prescribed by section 77 or section 78 may, by agreement expressed in the mortgage or encumbrance or otherwise in writing, be dispensed with, and in that case section 78 operates as if no notice or lapse of time were required. (2) This section applies to mortgages and encumbrances made before or after the proclaimed date. 81. Effect of registration of sale by mortgagee or encumbrancee (1) On the registration of a memorandum of transfer executed by a registered mortgagee or encumbrancee for the purpose of a sale pursuant to section 78 , the estate or interest of the mortgagor or encumbrancer described in that memorandum of transfer to be conveyed shall pass to and vest in the purchaser, freed and discharged from all liability on account of – (a) the mortgage or encumbrance; (b) any mortgage or encumbrance registered subsequent to the mortgage or encumbrance; or (c) any caveat that if not removed would forbid the registration of any dealing by the purchaser. (2) Where a memorandum of transfer to which subsection (1) relates is registered – (a) the title of the purchaser is not impeachable on the ground that – (i) a case had not arisen to authorize the sale; (ii) due notice to pay the money due or owing to the mortgagee or encumbrancee as required by this Act was not given by the mortgagee or encumbrancee to the mortgagor or encumbrancer; or (iii) the power of sale was otherwise improperly or irregularly exercised; (b) a person who suffers any loss or damage by reason of the registration of the memorandum of transfer is entitled to recover damages, by action in a court of competent jurisdiction, from the person who exercised the power of sale; and (c) the purchaser shall, for the purposes of section 41 , be deemed to have contracted, or dealt with, or taken a transfer from, the registered proprietor of the land. 82. Remedies of mortgagee or encumbrancee upon default The mortgagee or encumbrancee, upon default in the payment of any money secured by the mortgage or encumbrance, may – (a) enter into possession of the mortgaged or encumbered land by receiving the rents and profits of that land; (b) distrain upon the occupier or tenant of the mortgaged or encumbered land under the power to distrain contained in section 83 ; or (c) pursue the remedy provided by section 146 to obtain possession of the mortgaged or encumbered land – and a registered mortgagee shall be entitled to foreclose the right of the mortgagor to redeem the mortgaged land as provided by sections 85 and 86 . 83. Mortgagee or encumbrancee may distrain for arrears of money secured under mortgage or encumbrance When the payment of any money secured by a mortgage or encumbrance has been in arrears for 21 days, and 7 days have elapsed since demand was made for payment, the mortgagee or encumbrancee may distrain on the goods and chattels on the mortgaged or encumbered land, and Part V of the Landlord and Tenant Act 1935 applies as if the mortgagee or encumbrancee were a landlord and the mortgagor or encumbrancer were his tenant. 84. Mortgagee or encumbrancee of leasehold entering into possession of rent and profits becomes liable to lessor Any mortgagee or encumbrancee of leasehold land under this Act, or any person claiming that land as a purchaser or otherwise from or under the mortgagee or encumbrancee, after entering into possession of that land or the rents and profits of that land, shall, during that possession and to the extent of any rents and profits which may be received by him, become and be subject and liable to the lessor of that land to the same extent as the lessee or tenant was subject and liable to the lessor prior to the mortgagee, encumbrancee, or other person entering into possession of that land, or the rents and profits of that land. 85. Mortgagee may apply to Recorder for order for foreclosure (1) When default has been made for 6 months in the payment of any money secured by a registered memorandum of mortgage, the mortgagee may make application in writing to the Recorder for an order for foreclosure. (2) An application under subsection (1) shall state that – (a) default has been made for 6 months in the payment of the money secured by a registered memorandum of mortgage; (b) the land, estate, or interest mortgaged has been offered for sale at a lawfully conducted public auction; (c) prior to the attempted sale by public auction, notice of intention to sell had been given to the mortgagor pursuant to section 77 , unless the notice of intention has been dispensed with in accordance with section 80 ; (d) the amount of the highest bid at the sale was not sufficient to satisfy the money secured by the mortgage, together with the expenses occasioned by the sale; and (e) notice in writing of the intention of the mortgagee to make an application for an order for foreclosure has been served on the mortgagor in the manner provided in the mortgage for service of notices, or posted on the mortgaged land, or left at the usual or last known place of abode of the mortgagor. (3) An application under subsection (1) shall be supported by a certificate of the person conducting the public auction at which the land was put up for sale, and such other proof of matters material to the application as the Recorder may require. (4) The statements made in an application under subsection (1) shall be verified by the statutory declaration of the applicant. 86. Order for foreclosure (1) The Recorder, if he does not reject an application under section 85 , shall direct notice to be published once in a newspaper, published in this State, circulating in the locality in which the mortgaged land is situated offering the mortgaged land for sale, and shall appoint a time in the notice, not less than one month from the date of the advertisement in that newspaper, on or after which the Recorder may make and register an order for foreclosure in favour of the applicant unless in the interval a sufficient amount has been realized by the sale of land to satisfy the money due, and all expenses occasioned by the sale and proceedings. (2) An order for foreclosure under the hand of the Recorder shall when registered have the effect of vesting in the mortgagee all the estate and interest of the mortgagor in the land mentioned in that order, free from all right and equity of redemption on the part of the mortgagor or of any person claiming through or under him. 87. First mortgagee or encumbrancee to produce title for registration of subsequent dealing When a dealing subsequent to a first mortgage or encumbrance is made, the first mortgagee or encumbrancee, if he holds the certificate of title or duplicate registered dealing evidencing title to the land affected, shall, upon being requested to do so by the person entitled to the benefit of the subsequent dealing but at the cost of that person, produce the certificate of title or duplicate to the Recorder so that the subsequent dealing may be registered. 88. Variation of terms of mortgage and encumbrance (1) [Section 88 Subsection (1) amended by No. 21 of 1996, s. 19 ] A registered mortgage or encumbrance may be varied in any of the following ways: (a) the amount secured by the mortgage or encumbrance may be increased or reduced; (b) the rate of interest may be increased or reduced; (c) the term or currency of the mortgage or encumbrance may be shortened, extended, or renewed; (d) the covenants, conditions, and powers contained or implied in the mortgage or encumbrance may be varied, negatived, or added to – by an instrument in an approved form, executed by the respective parties or their successors in title, and registered under this Act. (2) Notwithstanding anything in subsection (1) , it is not necessary for – (a) a mortgagor or encumbrancer to execute an instrument which reduces; or (b) a mortgagee or encumbrancee to execute an instrument which increases – the mortgage debt, or the money payable under an encumbrance, or the rate of interest payable under a mortgage or encumbrance, without otherwise varying the mortgage or encumbrance. (3) An instrument under this section varying a mortgage or encumbrance affecting land subject to a subsequent mortgage or encumbrance is not binding on a subsequent mortgagee or encumbrancee unless he has consented to the variation in writing on that instrument, but that consent renders the instrument binding on the subsequent mortgagee or encumbrancee so consenting, and is binding on all persons who may subsequently derive from him any interest in the mortgaged or encumbered property. 89. Discharge of mortgage and encumbrance (1) [Section 89 Subsection (1) amended by No. 21 of 1996, s. 19 ] Whenever a registered mortgage or encumbrance is intended to be discharged wholly or partially, the registered mortgagee or encumbrancee shall execute a discharge in an approved form. (2) On the registration of a discharge of mortgage or encumbrance, the mortgaged or encumbered estate or interest shall, to the extent specified in the discharge, cease to be charged with any money secured by the mortgage or encumbrance. 90. Recorder may facilitate discharge of mortgage in certain cases (1) The Recorder, on proof to his satisfaction that all money secured by a registered mortgage has been paid, may record on the relevant folio of the Register or registered dealing that the mortgage is discharged, and upon that recording the mortgaged estate or interest ceases to be charged with any money secured by the mortgage. (2) In any of the cases mentioned in subsection (3) , the Recorder may, if he considers that there is sufficient cause for so doing – (a) on proof to his satisfaction of the amount of the debt owing under a registered mortgage, direct that amount to be paid to the Treasurer; and (b) on production to him of the receipt of the Treasurer for that amount, proceed as if he had been satisfied, under subsection (1) , that all money secured by that mortgage had been paid. (3) The cases in which the Recorder may act under subsection (2) are – (a) when – (i) a person who is entitled to receive payment of money secured by a mortgage – (A) is out of the State; (B) cannot be found; or (C) is unknown; or (ii) it is uncertain who is entitled to receive payment of money secured by a mortgage; and (b) when the mortgagee or one of several mortgagees is dead, and there is no person within the State presently entitled to discharge the mortgage. (4) Between the person who is liable to pay money by reason of a mortgage affected by a recording made pursuant to this section and the person entitled to be paid it, any amount in fact outstanding at the time of the making of the recording shall be deemed to be a specialty debt created by the instrument under which, but for the operation of this section, it would be payable. (5) The Recorder may, if he thinks fit, hold an inquiry in order to satisfy himself as to any fact or matter of which he may require proof for the purposes of this section, and may make such order as to the costs of any person attending such an inquiry as he thinks fit. (6) An order as to costs made under subsection (5) may be registered in the Supreme Court, and, on being so registered, is enforceable as if it were a judgment of that Court. 91. Application for order declaring mortgage, &c., discharged (1) Subject to this section and section 92 , where on the application of the registered proprietor of any land which appears by the Register to be subject to a mortgage or encumbrance, the Recorder is satisfied that by virtue of the operation of a statute of limitation no action may be brought to recover the money secured by the mortgage or encumbrance, he may make an order declaring that the mortgage or encumbrance is discharged. (2) [Section 91 Subsection (2) amended by No. 21 of 1996, s. 19 ] An application under this section shall – (a) be in an approved form; (b) be verified by the statutory declarations of the applicant and of such other persons as the Recorder may require; (c) be supported by proof of such matters material to the application as the Recorder may require; and (d) state the full name and last known address of the mortgagee or encumbrancee. (3) The Recorder may reject the application, or may make such requisitions as to any matter relating to the application as he thinks fit, and, at any time before granting the application, notwithstanding any direction previously given by him as to the application, reject the application if the applicant fails to comply to his satisfaction with any requisition made by him within such time as he considers to be reasonable. (4) If the Recorder does not reject the application, he shall direct that notice of the application, in such form as he directs, be advertised in such newspaper as he directs and be given to every person appearing by the Register to have any interest in the mortgage or encumbrance, and to any person named by him. (5) A notice under subsection (4) shall – (a) specify the folio of the Register or registered dealing affected by the application, and the registered number of the mortgage or encumbrance; and (b) be dated. 92. Caveat by persons claiming under mortgage, &c. (1) [Section 92 Subsection (1) amended by No. 21 of 1996, s. 19 ] Any person claiming any interest in a mortgage or encumbrance in respect of which an application under section 91 is made may, before the granting of the application, lodge a caveat in an approved form with the Recorder forbidding the granting of the application. (2) A caveat under this section shall in all respects be subject to the same provisions, and have the same effect with respect to the application against which it is lodged, as a caveat against an application to bring land under this Act. 93. Registration of order (1) If the Recorder makes an order under section 91 , he shall on making the order make such recordings on the folio of the Register or registered dealing evidencing title to the mortgaged or encumbered estate or interest as are necessary to give effect to the order, and may call in the corresponding certificate of title, grant, or duplicate registered dealing, and the duplicate mortgage or encumbrance. (2) On the making of such recordings under subsection (1) as are necessary to give effect to an order under section 91 , the mortgaged or encumbered estate or interest shall cease to be charged with any money secured by the mortgage or encumbrance. 94. Recording of satisfaction of encumbrance (1) On proof of the death of an annuitant, or the occurrence of the event or circumstance upon which, in accordance with the provisions of any registered memorandum of encumbrance, the money secured by the memorandum of encumbrance shall cease to be payable, and on proof that all arrears have been paid, the Recorder shall record on the relevant folio of the Register or registered dealing that the memorandum of encumbrance is discharged, and may call in the corresponding certificate of title, grant, or duplicate registered dealing and the duplicate encumbrance. (2) On a recording being made pursuant to subsection (1) , the encumbered estate or interest shall cease to be charged with any money secured by the encumbrance. Division 6 - Transmissions 95. Interpretation In this Division – Commonwealth Act means the Bankruptcy Act 1966 of the Commonwealth and includes that Act as amended from time to time or any Act passed in substitution for that Act; [Section 95 Amended by No. 4 of 2001, s. 8, Applied:12 Apr 2001] [Section 95 Amended by No. 4 of 2001, s. 8, Applied:12 Apr 2001] Official Receiver has the same meaning as in the Commonwealth Act . 96. Transmission on bankruptcy (1) [Section 96 Subsection (1) amended by No. 4 of 2001, s. 9, Applied:12 Apr 2001] The Official Receiver, a trustee, or any other person claiming to be entitled to registered land by virtue of the operation of the Commonwealth Act , or of anything done under that Act, may apply to the Recorder in writing to be registered as proprietor of that land. (2) On being satisfied that an applicant under subsection (1) is entitled to be registered as proprietor of the land to which the application relates, the Recorder may record on the relevant folio of the Register or registered dealing that the applicant is so registered. 97. Disclaimer or lease under Commonwealth Act (1) This section applies to a registered lease where – (a) the lessee is a bankrupt within the meaning of the Commonwealth Act ; (b) the trustee, as defined by the Commonwealth Act , has disclaimed the lease pursuant to that Act; (c) a court having jurisdiction in bankruptcy under that Act has not made an order pursuant to section 133 (9) of the Commonwealth Act vesting the lease in some person other than the lessee; and (d) no application has been made pursuant to that subsection to such a court, or any application so made has been dismissed. (2) [Section 97 Subsection (2) amended by No. 21 of 1996, s. 19 ] A lessor under a lease to which this section applies may, by notice in an approved form, served in an approved manner on a person, other than the bankrupt lessee, who is registered as proprietor of an interest in the lease and any person who, by a caveat, claims to be entitled to an estate in the lease, require that person to state within a time specified for the purpose in the notice whether the person on whom the notice is so served claims the interest of the lessee or claims an interest derived from the lease. (3) Subject to subsection (4) , the Recorder may record on the relevant folio of the Register or registered dealing that a lease to which this section applies has been surrendered by operation of law where the lessor applies for such a recording to be made, and – (a) there is no person, other than the bankrupt lessee, registered as proprietor of an estate or interest in the lease and the lease is not affected by any caveat; or (b) the lessor lodges with his application evidence that notice has been served as provided in subsection (2) upon every person, other than the bankrupt lessee, who appears from the Register to have or to claim an interest in the lease and that a person on whom notice has been so served has not, within the time specified in the notice, claimed the interest of the lessee or (otherwise than as registered proprietor of a sublease) an interest derived from the lease, and any caveat affecting the lease has lapsed or has been withdrawn. (4) Before recording a surrender of lease under subsection (3) , the Recorder shall record any sublease claimed pursuant to subsection (2) on the folio of the Register or on the registered dealing, as the case may be, evidencing the title of the lessor, and that folio or registered dealing shall, upon the sublease being so recorded, evidence the title to the reversion expectant on the sublease. (5) [Section 97 Subsection (5) amended by No. 21 of 1996, s. 19 ] Where a lease to which this section applies is subject to a registered mortgage, the mortgagee may, by notice in an approved form served in an approved manner on any person, other than the bankrupt lessee, who is registered as proprietor of an interest in the lease and any person who, by a caveat, claims to be entitled to an interest in the lease, require that person to state within a time specified for the purpose in the notice whether the person on whom the notice is so served claims the interest of the lessee or claims an interest derived from the lease. (6) Subject to subsection (7) , the Recorder may record on the relevant folio of the Register or registered dealing that a mortgage of a lease to which this section applies has been foreclosed where the mortgagee applies for such a recording to be made (the application being in respect of the whole of the land subject to the mortgage) and – (a) there is no person, other than the mortgagee and the bankrupt lessee, registered as proprietor of an estate or interest in the lease and the lease is not affected by any caveat; or (b) the mortgagee lodges with his application evidence that notice has been served as provided in subsection (5) upon every person, other than himself and the bankrupt lessee, who appears from the Register to have or to claim an interest in the lease and that a person on whom notice has been so served has not, within the time specified in the notice, claimed the interest of the lessee or (otherwise than as registered proprietor of a sublease) an interest derived from the lease, and any caveat affecting the lease has lapsed or has been withdrawn. (7) Before recording a foreclosure of mortgage under subsection (6) , the Recorder shall record on the relevant folio of the Register or registered dealing any sublease claimed pursuant to that subsection that is binding on the mortgagee and that folio or registered dealing shall upon the sublease being so recorded evidence the title to the reversion expectant on the sublease. (8) Where a lease to which this section applies is affected by a caveat, an application pursuant to subsection (3) or subsection (6) is, for the purposes of Part IX , a dealing the recording of which is prohibited by the caveat. 98. Transmission on death (old procedure) (1) [Section 98 Subsection (1) amended by No. 21 of 1996, s. 19 ] The devisee or other person claiming an estate of freehold in the land of a deceased registered proprietor, who died testate before 18th October 1935, or intestate before 1st October 1874, or a person having a power of disposition over an estate of freehold in land of a deceased testate proprietor who died before 18th October 1935 – (a) may make application in an approved form to the Recorder to be registered as proprietor of the estate; and (b) shall – (i) where the deceased proprietor dies testate, deposit with the Recorder the certificate of the death, the will, or an office copy or probate of the will of the deceased proprietor or any settlement under which the applicant claims; or (ii) where the deceased registered proprietor dies intestate, deposit with the Recorder such evidence of title as he is able to produce. (2) A person who makes application under subsection (1) shall state in the application – (a) the nature of every estate or interest held by any other person at law or in equity in the land referred to in that subsection that is within the applicant's knowledge; and (b) that he believes himself to be entitled to the estate in that land. (3) The statements made in an application referred to in subsection (1) shall be verified by the statutory declaration of the applicant. (4) The Recorder, on being satisfied that the applicant is entitled to the estate claimed in the application, shall register him as proprietor of that estate. (5) Before registering the applicant as proprietor pursuant to subsection (4) , the Recorder may, if he thinks fit, cause notice of the application to be published and given to such persons (if any) as he thinks fit, and shall in each notice appoint a time not less than one month from the completion of notice, after which he may, unless in the interval he receives a caveat forbidding him to do so, register the applicant as proprietor. (6) A caveat under subsection (5) shall be subject to the same provisions, and have the same effect with respect to the application against which it is lodged, as a caveat against an application to bring land under this Act. 99. Transmission on death to personal representative (1) [Section 99 Subsection (1) amended by No. 21 of 1996, s. 19 ] Where registered land devolved under the Deceased Persons' Estates Act 1874 or devolves under the Administration and Probate Act 1935 on the personal representative of a deceased registered proprietor, the Recorder shall, on the lodgment of – (a) an application by the personal representative in an approved form to be registered proprietor of the land; and (b) the probate, letters of administration, or other authority constituting him as personal representative of the deceased registered proprietor – make such recording on the relevant folio of the Register or registered dealing as may be necessary to register the personal representative as proprietor of the land. (2) A recording made under subsection (1) may include a statement that the person named in the recording is registered proprietor as personal representative of the deceased proprietor. 100. Registration of survivor of joint proprietors, &c. Where a person becomes entitled to an estate or interest in registered land – (a) on the death of a person registered with him as joint proprietor of that estate or interest; or (b) by the determination or defeasance, by death or the occurrence of some other event, of a registered estate or interest in land – the Recorder may, on the application of the person so entitled and proof to his satisfaction of the death or other event, as the case may require, register that person as proprietor of the estate or interest. Division 7 - Re-entry on condition broken 101. Re-entry determining fee (1) Where the grantor of registered land in fee subject to a condition has re-entered and recovered possession of the land upon condition broken, the Recorder, on proof to his satisfaction of the breach and re-entry, shall make such recording on the relevant folio of the Register as is necessary to register the grantor as proprietor of the land and on that recording being made the estate of the former registered proprietor of the land determines, and the Recorder may call in and cancel or amend the corresponding certificate of title. (2) In this section grantor includes a transferor and the successors in title of a grantor. Division 8 - Covenants running with the land 102. Covenants which run with freehold registered land [Section 102 Subsection (2) amended by No. 30 of 1995, s. 3 and Sched. 1 ] (1) Except as provided in this Division, the burden of a covenant does not run with freehold registered land. (2) [Section 102 Subsection (2) amended by No. 28 of 1994, s. 40 ] Subject to subsection (3) , the burden of a covenant runs with freehold registered land if – (a) the covenant was – (i) entered into before the land was brought under this Act or the repealed Act ; or (ii) included in a transfer which was registered before the proclaimed date; and – (iii) notice of the covenant is recorded on the folio of the Register constituting the title to the land intended to be burdened; and (iv) the land intended to be benefited by the covenant is identified in the instrument containing the covenant; (b) the covenant is set forth in a sealed plan which has taken effect under Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 ; (c) the covenant is contained in a dealing that was registered under section 27B or section 27D of the Real Property Act 1886 ; (d) the covenant is created pursuant to subsection (7) or subsection (8) ; or (e) the covenant is a covenant in gross, within the meaning of the Conveyancing and Law of Property Act 1884 . (3) A covenant which runs with freehold registered land pursuant to subsection (2) may be enforced in equity notwithstanding any provision of this Act but has no greater operation or effect by the operation of this section than it would have if the land which it is intended to burden were not registered land and the registered proprietor of the land were affected in equity by express notice of the covenant. (4) Where a transfer registered before the proclaimed date was expressed to be subject to two or more conditions including at least two of the prescribed conditions specified in subsection (5) , the parties to the transfer shall be deemed not to have intended conditions of defeasance, but shall be deemed to have intended to enter into covenants to the same effect as the conditions. (5) The following conditions are prescribed conditions for the purposes of subsection (4) : (a) that the transferor shall not be required to contribute to the cost of erecting any boundary fence between the land sold and any adjoining land belonging to the transferor; (b) that no building, other than – (i) a building for a specific use; (ii) a building of a kind approved by the transferor; or (iii) a building constructed of materials of a specific kind or materials of a kind approved by the transferor – shall be built on the land sold; (c) that no trade or business, or no trade or business of a specified kind, shall be carried on the land sold. (6) Where the Recorder is satisfied that a recording in the Register indicates the existence of – (a) a covenant which does not run with the land; or (b) conditions deemed in accordance with subsection (4) to be covenants which do not run with the land – he may cancel that recording. (7) [Section 102 Subsection (7) amended by No. 21 of 1996, s. 19 ] Where registered land is to be made subject to a covenant touching and concerning the land for the benefit of other land, whether registered land or not, and enforceable in equity by and against the assigns of the respective proprietors, a dealing in an approved form may be used and lodged for registration. (8) Where land subject to a covenant touching and concerning it and enforceable in equity against the covenantor's assigns by the covenantee's assigns is brought under this Act, a memorandum of the covenant shall be made up by the Recorder and registered as if it were a dealing made under subsection (7) . (9) [Section 102 Subsection (9) amended by No. 36 of 2012, s. 29, Applied:13 Nov 2012] Except as provided in subsection (10) , the Recorder shall register the dealing referred to in subsection (7) by recording it on the folio of the Register for the lands burdened by the covenant. (10) The Recorder may refuse to register a dealing under subsection (9) where the provisions of the dealing are wholly or in part not enforceable in equity between assigns of the parties. (11) A covenant that might have been made by a dealing under this section and has not been so made shall not be enforced in equity between assigns of the parties. (12) [Section 102 Subsection (12) amended by No. 30 of 1995, s. 3 and Sched. 1 ] Where a folio of the Register describes the land by reference to a sealed plan lodged with the Recorder under Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 , any obligations set forth in the plan that could be recorded under this section shall have effect as if embodied in an appropriate dealing recorded on the folios of the Register comprising the titles of all lands appearing by the Register to be subject to the sealed plan. (13) Where a transfer between vendor and purchaser contains a condition of defeasance the purpose of which could be achieved by means of a dealing under this section, the Recorder may refuse to register the transfer until that condition has been deleted and the appropriate dealing in accordance with this section has been lodged with the Recorder. 103. Effect of identity of parties to covenant (1) A covenant which runs with freehold registered land is not affected by the same person being the registered proprietor at any time of the lands benefited and burdened by the covenant unless the covenant is expunged from the Register as provided in subsection (2) . (2) On the application of the registered proprietor of the lands benefited and burdened by a covenant, and proof to his satisfaction that the covenant would have been extinguished but for the operation of subsection (1) , the Recorder shall expunge the covenant from the Register. (3) [Section 103 Subsection (3) substituted by No. 30 of 1995, s. 3 and Sched. 1 ] A covenant comprised in a sealed plan lodged under Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 is to be dealt with under Division 5 of that Part . 104. Discharge of covenants (1) [Section 104 Subsection (1) amended by No. 21 of 1996, s. 19 ] A covenant of a kind mentioned in paragraph (a) , paragraph (c) , or paragraph (d) of section 102 (2) may be discharged by a dealing in an approved form executed – (a) where the land to which the benefit of the covenant is annexed is registered land, by the registered proprietor of that land and any other person having a registered interest in that land; or (b) where the land to which the benefit of the covenant is annexed is not registered land, by a person entitled wholly to discharge the covenant. (2) When a dealing made under this section is lodged for registration, the Recorder shall record it on the relevant folio of the Register. (3) Where a dealing is executed under subsection (1) (b) , the Recorder shall not be concerned to investigate the title of the person executing it. 104A. Discharge of covenants in gross [Section 104A Inserted by No. 36 of 2012, s. 30, Applied:13 Nov 2012] A covenant that is a covenant in gross within the meaning of the Conveyancing and Law of Property Act 1884 may be discharged by a dealing in a form approved by the Recorder. Division 9 - Easements and profits à prendre 105. Creation of easements (1) [Section 105 Subsection (1) amended by No. 21 of 1996, s. 19 ] An easement may be granted in or over registered land for the benefit of any other land – (a) by the registered proprietor of a freehold estate in the land, by memorandum of transfer in the form approved under section 58 ; and (b) by the lessee, by memorandum of lease in the form approved under section 64 – and registered under this Act. (2) A proprietor transferring or leasing registered land may in the transfer or lease – (a) grant an easement in or over other registered land of which he is registered proprietor or lessee, for the benefit of the land transferred or the estate of the lessee under the lease; and (b) reserve an easement for the benefit of other land retained by him. (3) The Recorder, when registering a memorandum of transfer or lease which grants or reserves an easement, shall record the grant or reservation upon – (a) the folio of the Register, or the registered lease, evidencing title to the land burdened by the easement; and (b) where the land benefited by the easement is registered land, the folio of the Register or the registered lease which evidences title to the land benefited. (4) In a memorandum of mortgage or memorandum of encumbrance there may be expressed to be included as appurtenant to the land mortgaged or encumbered an easement over other registered land of which the mortgagor or encumbrancer is registered proprietor or lessee and in such a case the folio of the Register or registered lease of that other land shall be specified in the memorandum of mortgage or memorandum of encumbrance. (5) When an easement is expressed to be included in a dealing pursuant to subsection (4) , the Recorder shall when registering the memorandum of mortgage or memorandum of encumbrance record particulars of the easement upon the folio of the Register or registered lease evidencing title to the land over which the easement is expressed to be included. (6) When the memorandum of mortgage or memorandum of encumbrance in which an easement is included pursuant to subsection (4) is registered, that easement shall be deemed to be an easement appurtenant to the land mortgaged or encumbered for the purpose of enjoyment, leasing, or transfer by the mortgagee or encumbrancee, or of foreclosure, and so that upon foreclosure in favour of, or lease or transfer by, the mortgagee or encumbrancee, that easement shall, unless expressly excluded, be created by the order for foreclosure or by the registration of the lease or transfer. (7) On application in writing for that purpose, the Recorder may record in the Register any easement over or appurtenant to registered land which the Recorder is satisfied has been recognized by an order of the Supreme Court. 106. The Register as evidence of easements (1) Subject to subsection (2) , a statement in a folio of the Register to the effect that the land comprised in the folio has the benefit of an easement shall be conclusive evidence that the land has that benefit. (2) Subsection (1) shall not be construed so as to give effect as an easement to a right which is not recognized as an easement at common law. (3) An easement shall not be implied from anything appearing on a plan deposited with the Recorder after the proclaimed date. 107. Profits à prendre (1) [Section 107 Subsection (1) amended by No. 21 of 1996, s. 19 ] A profit à prendre may be granted by an instrument in an approved form, which shall indicate clearly the nature of the profit à prendre , the period for which it is to be enjoyed, and whether it is to be enjoyed – (a) in gross or as appurtenant to other land; and (b) by the grantee exclusively or by him in common with the grantor. (2) The Recorder shall register the instrument referred to in subsection (1) – (a) by recording it on the folio of the Register or the registered lease which it burdens; and (b) where it is appurtenant to registered land, by recording it on the folio of the Register or registered lease evidencing title to that land. 108. Release and extinguishment of easements and profits à prendre (1) [Section 108 Subsection (1) amended by No. 36 of 2012, s. 31, Applied:13 Nov 2012] [Section 108 Subsection (1) amended by No. 21 of 1996, s. 19 ] Subject to subsection (4) , an easement or profit à prendre which is recorded in the Register may be released wholly or partly by the person having the benefit of that easement or profit à prendre by an instrument in an approved form and registered under this Act. (2) [Section 108 Subsection (2) amended by No. 36 of 2012, s. 31, Applied:13 Nov 2012] Subject to subsection (4) , the Recorder, upon the application of a person having an estate or interest in land affected by an easement or profit à prendre , or of his own motion, may cancel the registration of the easement or profit à prendre , in whole or in part, where it appears to his satisfaction that – (a) the period of time for which it was intended to subsist has expired; (b) the event upon which it was intended to determine has occurred; or (c) it has been abandoned. (3) [Section 108 Subsection (3) substituted by No. 29 of 1997, s. 7, Applied:06 Nov 1997] [Section 108 Subsection (3) substituted by No. 36 of 2012, s. 31, Applied:13 Nov 2012] In considering whether an easement or profit à prendre has been abandoned, the Recorder, if satisfied on evidence that the easement or profit à prendre has not been used for a period of at least 20 years, is to treat that failure to use as conclusive evidence that the easement or profit à prendre has been abandoned. (4) [Section 108 Subsection (4) amended by No. 30 of 1995, s. 3 and Sched. 1 ] [Section 108 Subsection (4) substituted by No. 29 of 1997, s. 7, Applied:06 Nov 1997] This section has effect notwithstanding sections 28(14) , 40(3)(e)(ia) and 151(1)(e) . 109. Effect of unity of seisin on registered easements, &c. (1) Registered easements and profits à prendre over or for the benefit of registered land are not affected by – (a) unity of seisin of that land and of other land appearing from the Register to have the benefit or burden of the easement or profit à prendre ; or (b) identity at any time of the legal owner of a profit à prendre in gross and the registered proprietor of the land burdened by the profit à prendre – unless the easements or profits à prendre are expunged from the Register as provided in subsection (2) . (2) On the application of the registered proprietor in whom unity of seisin of the lands benefited and burdened by an easement or profit à prendre is united, or of the person who is both the legal owner of a profit à prendre in gross and the registered proprietor of the land burdened by the profit à prendre , and proof to his satisfaction that the easement or profit à prendre would have been extinguished but for the operation of subsection (1) , the Recorder shall expunge the easement or profit à prendre from the Register. (3) [Section 109 Subsection (3) substituted by No. 30 of 1995, s. 3 and Sched. 1 ] An easement or profit à prendre comprised in a sealed plan lodged under Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 is to be dealt with under Division 5 of that Part . 110. Rectification of easements, &c., in old subdivisions (1) [Section 110 Subsection (1) amended by No. 30 of 1995, s. 3 and Sched. 1 ] In this section, plan of subdivision includes – (a) a previously approved plan within the meaning of section 80 of the Local Government (Building and Miscellaneous Provisions) Act 1993 ; and (b) a plan of subdivision that does not require the approval of the corporation under that Act. (2) The Recorder may, with the consent of all persons having registered estates or interests in the land shown in a plan of subdivision comprising land which is under this Act or which he proposes to bring under this Act, make an order setting forth in respect of each lot or other piece of land shown in the plan – (a) the easements and profits à prendre to be appurtenant to the lot or other piece of land or to which it is to be subject; and (b) the benefit or burden of the covenants which are to run with the lot or other piece of land. (3) Where some but not all the lots or other pieces shown in the plan are to be affected, the Recorder may make an order referred to in subsection (2) with the consent of all persons having registered estates or interests in the lots or other pieces which are to be affected by the order. (4) The Recorder may, of his own motion or on the application of any person interested, give notice in accordance with subsection (6) that he proposes to make an order referred to in subsection (2) . (5) Without limiting subsection (4) , the Recorder may act as provided in that subsection in any case in which the plan shows the position of drainage easements but where – (a) easements have not been granted to the purchasers of lots; or (b) in the opinion of the Recorder, the easements granted by registered assurances of lots shown in the plan are not in accordance with a reasonable scheme of easements for the subdivision. (6) [Section 110 Subsection (6) amended by No. 36 of 2012, s. 32, Applied:13 Nov 2012] [Section 110 Subsection (6) amended by No. 30 of 1995, s. 3 and Sched. 1 ] The Recorder shall give notice under subsection (4) or (14) – (a) in the case of registered land which it is proposed to affect, to every person appearing by the Register to have an interest in that land; (b) in the case of land not under this Act which it is proposed to affect, to every person whom the Recorder has found by searching the register of deeds to have an interest in the land; and (c) to the council of the municipal area in which the land is situated, which shall be deemed to have an interest in the land affected – and every notice shall include a copy of the proposed order and be accompanied by a plan showing the position of the easements referred to in the proposed order, and shall specify a time (being not less than 14 days from the giving of the notice) within which written objections to the proposed order may be lodged with the Recorder. (7) After the expiration of the time limited by notice under subsection (6) , the Recorder – (a) if written objections have not been lodged with him, may make an order in terms of the proposed order; or (b) if written objections have been lodged with him, may either – (i) vary his proposed order in the light of the objections, and give notice of his new proposal in accordance with subsection (6) ; or (ii) give notice to such persons as he thinks proper that he will hear any person wishing to support or oppose the proposed order on a day to be specified in the notice, and at the conclusion of that hearing may make an order in terms of the proposed order or differing from it in the light of the objections, giving copies forthwith to all concerned. (8) The Recorder shall not give effect to an order made under subsection (7) (b) (ii) before the expiration of 30 days from the making of that order, and during that period a person affected by the order may appeal to the Supreme Court which may – (a) stay proceedings on the order wholly or in part; (b) quash or vary the order; or (c) make any order that the Recorder might have made. (9) Subject to subsection (8) and to any order of the Supreme Court made under that subsection, the Recorder may give effect to an order made under this section by – (a) registering it in the Registry of Deeds if any land affected by the order is not subject to this Act; and (b) recording the order upon the folio of the Register evidencing title to any land affected by the order. (10) On the completion of the registration or recording in accordance with subsection (9) – (a) the easements specified in the order to be in favour of the Crown or of any public or local authority constituted by or under any Act or appurtenant to a highway vest accordingly without further assurance; (b) the other easements and the profits à prendre and covenants specified in the order come into being and continue as if created by the most effectual instruments made between proper parties, and are not affected by – (i) the unity of seisin of the lands having the burden and benefit of the easement or profit à prendre ; (ii) identity at any time of the legal owner of a profit à prendre in gross and the registered proprietor of the land burdened by the profit à prendre ; or (iii) identity of the parties to the covenant – except that during that unity or identity they are in abeyance, and revive by force of this section when that unity or identity is broken or destroyed; (c) any easements or profits à prendre or covenants which are created by an instrument registered before the completion of the registration or recording in accordance with subsection (9) and which are not continued by the order, are destroyed; (d) any subsequent assurance of a block comprised in the plan to which the order relates shall, without any express mention and notwithstanding any contrary expression, assure that land together with and subject to any easements and profits à prendre which by the order exist upon or in favour of that land; (e) any obligation set forth in the order that could be recorded under section 102 shall have effect as if embodied in an appropriate dealing recorded on the folios of the Register comprising the titles of all affected lands; and (f) the Recorder shall amend any folio of the Register affected by the order and shall make the same amendments to the corresponding certificate of title when it is produced to him for any purpose, or may call in the certificate for amendment. (11) The Recorder may proceed concurrently under this section and section 142 , if in his opinion it is necessary or convenient to do so, notwithstanding that the proceedings under that section may concern a plan which is not a plan of subdivision. (12) The Recorder may make orders as to the payment of costs of the parties attending a hearing under this section, and those orders shall be filed in the Supreme Court and proceeded upon in the same manner as similar orders of a judge in chambers. (13) [Section 110 Subsection (13) inserted by No. 36 of 2012, s. 32, Applied:13 Nov 2012] The Recorder may, of his own motion or on the application of any person interested, cancel an order made under this section after it has been registered or recorded and make a fresh order. (14) [Section 110 Subsection (14) inserted by No. 36 of 2012, s. 32, Applied:13 Nov 2012] Before taking action under subsection (13) , the Recorder must give notice of the intention to cancel the order and make a fresh order in accordance with subsection (6) . (15) [Section 110 Subsection (15) inserted by No. 36 of 2012, s. 32, Applied:13 Nov 2012] If a fresh order is made under subsection (13) , that fresh order is taken to be an order made under this section. Division 10 - Recording of highways 111. Highways not to be registered as estates Where by any Act a highway is vested in a highway authority which is not the proprietor of the land lying under the highway, the highway authority shall not be registered under this Act as proprietor of the highway, and this Act shall not apply to any extension, diminution, or transfer of the estate of that authority in the highway. 112. Recording of highways (1) Where a highway exists across registered land and is not recorded on the folio of the Register evidencing title to that land or in the plan or other description of the land in that folio, the highway authority charged with the control or maintenance of the highway may obtain a recording of the highway in accordance with this section. (2) The highway authority may tender a consent to the recording of a highway to the registered proprietor of the land across which the highway exists which, if the registered proprietor signs it, operates as a deed made between the registered proprietor, the highway authority, and the Recorder, and may lodge it with the Recorder, who shall make such recording on the relevant folio of the Register, or in the plan or other description of the land in that folio, as he shall deem appropriate to show the existence of the highway. (3) [Section 112 Subsection (3) amended by No. 21 of 1996, s. 19 ] A consent under subsection (2) shall be in an approved form. (4) If the registered proprietor referred to in subsection (2) refuses to sign the consent referred to in that subsection when tendered, the highway authority may apply by originating summons to a judge in chambers for a declaration that the highway exists as shown in the consent tendered and for an order that the registered proprietor produce his grant or certificate of title to the Recorder for amendment accordingly. (5) Unless the registered proprietor referred to in subsection (2) satisfies the judge that he would have a good defence to an action to establish the existence of the whole or some part of the highway, as shown in the consent tendered, the judge shall make the declaration and order sought, but shall not award the highway authority any costs where the summons is undefended. (6) If the registered proprietor satisfies the judge in accordance with subsection (5) , the judge shall direct the trial of an issue to determine the existence of so much of the highway as is in dispute, and on the trial of that issue the Supreme Court may make an appropriate declaration and order. (7) The Supreme Court may, by consent, make an appropriate declaration in respect of the highway. (8) Except as provided in subsection (5) , costs shall be in the discretion of the Supreme Court. (9) A declaration made under this section may be lodged with the Recorder and dealt with in the same manner as a consent under subsection (2) . Division 11 - Estates tail 113. Tenancies in tail to pass fee simple Where a limitation which would before 8th December 1886 have limited to a person an estate tail, whether legal or equitable, in registered land is made on or after that day, the limitation shall be deemed to give that person an estate in fee simple (legal or equitable, as the case may be) in that land. 114. Where successive life estates are given to parent and child with estate tail to grandchild, parent and child may bar entail (1) Where under a will or settlement executed before 8th December 1886 an estate for life in registered land is given to a person, followed by an estate for life in remainder to a child of that person and ultimately or immediately by an estate tail in remainder to a grandchild of that person, that person and the child of that person may together, when that child attains the age of 18 years, bar the entail and dispose of the estate as fully and effectually as if the estate given to the child had been instead of an estate for life an estate tail similar to the estate tail given to the grandchild. (2) Subsection (1) applies to equitable and legal estates. 115. Tenant in tail under this Act entitled to deal with estate as effectually as tenant in tail under general law Subject to sections 113 and 114 , an estate tail under this Act has the same incidents as a similar estate under the general law, and the proprietor of such an estate has the same power to bar the estate tail and create an estate in fee simple absolute as against all persons whose estates are to take effect after the determination or in defeasance of the estate tail as is possessed by the owner of a corresponding estate tail in land not under this Act by virtue of the Estates Tail Act 1853 . 116. Transferee from tenant in tail may be registered for larger estate which tenant may confer A transfer or mortgage in the ordinary form by a tenant in tail under this Act having power to create an estate in fee simple shall create that estate in favour of a transferee, mortgagee, or transferee under the power of sale in the mortgage, and a transferee from a tenant in tail, or under a mortgage from a tenant in tail or a mortgagee after foreclosure shall be entitled to be registered as proprietor of the larger estate which the tenant in tail is empowered to confer, but a mortgage under this Act, if discharged, shall not bar the entail. Division 12 - . . . . . . . . [Division 12 of Part VI Repealed by No. 4 of 2001, s. 10, Applied:12 Apr 2001] 117. [Section 117 Subsection (3) amended by No. 21 of 1996, s. 19 ] [Section 117 Repealed by No. 4 of 2001, s. 10, Applied:12 Apr 2001] . . . . . . . . 118. [Section 118 Subsection (2) amended by No. 21 of 1996, s. 19 ] [Section 118 Repealed by No. 4 of 2001, s. 10, Applied:12 Apr 2001] . . . . . . . . 119. [Section 119 Subsection (1) amended by No. 30 of 1995, s. 3 and Sched. 1 ] [Section 119 Repealed by No. 4 of 2001, s. 10, Applied:12 Apr 2001] . . . . . . . . 120. [Section 120 Amended by No. 21 of 1996, s. 19 ] [Section 120 Repealed by No. 4 of 2001, s. 10, Applied:12 Apr 2001] . . . . . . . . 121. [Section 121 Repealed by No. 4 of 2001, s. 10, Applied:12 Apr 2001] . . . . . . . . 122. [Section 122 Repealed by No. 4 of 2001, s. 10, Applied:12 Apr 2001] . . . . . . . . 123. [Section 123 Repealed by No. 4 of 2001, s. 10, Applied:12 Apr 2001] . . . . . . . . 124. [Section 124 Subsection (2) amended by No. 21 of 1996, s. 19 ] [Section 124 Repealed by No. 4 of 2001, s. 10, Applied:12 Apr 2001] . . . . . . . . Division 13 - Compulsory acquisition 125. Interpretation In this Division, acquiring authority means – (a) any authority or person authorized by or under any Act or Commonwealth Act to acquire land compulsorily; and (b) where land vests in the Commonwealth pursuant to the Commonwealth of Australia Constitution Act, the Commonwealth or any authority incorporated by any Commonwealth Act in which the land is for the time being vested. 126. Registration of acquiring authority as proprietor [Section 126 Subsection (1) amended by No. 21 of 1996, s. 11 ] (1) [Section 126 Subsection (1) amended by No. 24 of 1993, s. 3 and Sched. 1 ] Notwithstanding anything in any Act, where any land vests in an acquiring authority by the operation of the Commonwealth of Australia Constitution Act or of any Act or Commonwealth Act, without transfer or conveyance to the acquiring authority, then, upon lodgment by the acquiring authority, or otherwise as required by the relevant Act, of a plan of the land, and of the notification or notice of acquisition or other instrument prescribed to be lodged by or under that Act, or, where no instrument is prescribed, upon the lodgment of an application in an approved form – (a) where the land is registered land, the Recorder shall register the acquiring authority as proprietor of the land for the estate or interest acquired in the land and may issue a certificate of title in relation to the land in the name of the acquiring authority as registered proprietor; or (b) where the land is not registered land, the Recorder shall, without any further or other application or the production or examination of any documents of title, bring the land under this Act by creating a folio of the Register for the land and may issue such certificates of title in relation to the land as the Recorder considers proper. (2) [Section 126 Subsection (2) omitted by No. 24 of 1993, s. 3 and Sched. 1 ] . . . . . . . . (3) On registering the acquiring authority as proprietor pursuant to subsection (1) (a) , the Recorder shall make such cancellations, corrections, or recordings in the Register as are necessary, and shall make the like cancellations, corrections, or recordings upon the corresponding certificates of title, grants, or duplicate registered dealings when they are next produced to him, or may call them in for that purpose. (4) Before or at the time of making compensation for the acquisition of registered land, the acquiring authority shall take possession of the certificates of title or duplicate registered dealings which are produced to it upon any claim for compensation, and shall forthwith lodge them with the Recorder for the making of such of the necessary cancellations, corrections, or recordings as have not already been made. (5) Where the Recorder brings land under this Act pursuant to subsection (1) (b) , he shall give notice that he has brought the land under this Act in the Registry of Deeds in the prescribed manner. (5A) [Section 126 Subsection (5A) inserted by No. 24 of 1993, s. 3 and Sched. 1 ] Where land vests in an acquiring authority or a person on the gazettal of a notice which amends or revokes a notice of acquisition and a plan of the land affected and a copy of that first-mentioned notice is lodged with the Recorder, the Recorder – (a) must make such cancellations, corrections or recordings in the Register as are necessary; and (b) must make the necessary cancellations, corrections and recordings on the corresponding certificates of title, grants or duplicate registered dealings when they are next produced to him or her. (5B) [Section 126 Subsection (5B) inserted by No. 24 of 1993, s. 3 and Sched. 1 ] For the purpose of complying with subsection (5A) (b) , the Recorder may call in such certificates of title, grants or duplicate dealings as he or she considers appropriate. (6) A right to compensation in respect of or in any manner arising out of the acquisition or vesting of any land shall not be prejudiced or affected by a cancellation, correction, or recording made under the authority of this section. 127. Acquiring authority to be responsible to persons injured by operation of this Division Any person who suffers any deprivation, loss, or damage by reason of – (a) the bringing of land under this Act; or (b) a cancellation, correction, or recording in the Register – pursuant to this Division shall be indemnified by the acquiring authority concerned, but a person shall not be entitled to receive or shall not receive from the Recorder or out of the assurance fund any money or compensation or consideration – (c) in respect of or in any manner arising out of the bringing of land under this Act; (d) out of any cancellation, correction, or recording in the Register; or (e) by reason that the Recorder acted under this Division in relation to what purported to be, but was not, an effective acquisition. 128. Acquiring authority not to have claim in respect of acquired land An acquiring authority shall not at any time have a claim against the Recorder or the assurance fund in respect of land of which it becomes registered as proprietor pursuant to this Division. 129. Notice to treat, or notice of intention to acquire to be given to Recorder (1) [Section 129 Subsection (1) amended by No. 24 of 1993, s. 3 and Sched. 1 ] Where it is proposed to acquire compulsorily any registered land, and where the Act under which the acquisition will be made provides that notice to treat or notice of intention to acquire the land is to be served, a copy of the notice shall be lodged with the Recorder as soon as practicable after the notice is served, accompanied by a statement specifying the folio of the Register or registered dealing evidencing title to the land to be acquired, and the Recorder shall make an appropriate recording of the notice upon that folio or dealing, and the rights under the notice shall be deemed to be an interest for the purposes of section 40 . (2) [Section 129 Subsection (2) omitted by No. 24 of 1993, s. 3 and Sched. 1 ] . . . . . . . . (3) [Section 129 Subsection (3) substituted by No. 24 of 1993, s. 3 and Sched. 1 ] Where a notice to treat or a notice of intention is withdrawn, the acquiring authority must lodge with the Recorder as soon as practicable after that withdrawal a copy of the notice of withdrawal or other document effecting that withdrawal. (4) [Section 129 Subsection (4) inserted by No. 24 of 1993, s. 3 and Sched. 1 ] The statement referred to in subsection (1) and the notice or other document referred to in subsection (3) are to be signed by – (a) the acquiring authority; or (b) [Section 129 Subsection (4) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] the clerk, within the meaning of the Land Acquisition Act 1993 , or legal practitioner of the acquiring authority if the acquiring authority is not the Crown; or (c) the Secretary of the Department responsible to the Minister for the time being administering that Act; or (d) a person authorized by the acquiring authority or that Secretary. (5) [Section 129 Subsection (5) inserted by No. 24 of 1993, s. 3 and Sched. 1 ] On receipt of a notice or other document referred to in subsection (3) , the Recorder must make such recordings in, or do such corrections to, the Register as the Recorder considers appropriate. 130. [Section 130 Repealed by No. 98 of 1986, s. 7 ] . . . . . . . . PART VII - Settled Land 131. Application of Settled Land Act 1884 to land held under this Act (1) [Section 131 Subsection (1) amended by No. 21 of 1996, s. 19 ] In the application of the Settled Land Act 1884 to settled land held under this Act, the following provisions have effect: (a) the registered proprietor or the registered proprietors shall be deemed to be the trustee or trustees of the settlement; (b) [Section 131 Subsection (1) amended by No. 4 of 2001, s. 11, Applied:12 Apr 2001] where under the Settled Land Act 1884 any power or authority is conferred upon a tenant for life, then upon the written request of the tenant for life, and upon the performance by the tenant for life of the conditions imposed by that Act upon the exercise of that power or authority by a tenant for life, the registered proprietor or registered proprietors shall exercise that power or authority; (c) where under the Settled Land Act 1884 an instrument is to be executed by a tenant for life in order to exercise any power or authority conferred on a tenant for life, that instrument shall be executed by the registered proprietor or registered proprietors, and that execution shall have the same operation as the execution of such an instrument by a tenant for life is declared to have under that Act; (d) a registered proprietor or registered proprietors executing a power or authority in accordance with the Settled Land Act 1884 upon the written request of the tenant for life, or with the sanction of the Supreme Court if, being the tenant or the tenants for life, he is himself or they are themselves the sole trustee or trustees of the settlement, shall not by reason of executing that power or authority incur any personal liability to his or their beneficiaries or to any other person; (e) the registered proprietor or registered proprietors referred to in paragraph (d) shall not, for the purpose of executing any power or authority or complying with any request referred to in that paragraph, be bound to enter into any personal covenant or contract; (f) where under the Settled Land Act 1884 it is provided that land shall be conveyed to any uses or trusts, that expression shall be taken to mean that the land shall be transferred to trustees, and shall be held by them as trustees upon the uses or trusts; (g) where under the Settled Land Act 1884 it is provided that a contract made by a tenant for life shall be binding on the settled land, that expression shall be taken also to mean that the contract shall be binding on the registered proprietor, and that he shall be bound to give effect to the contract in the same manner as if he had made it himself, subject, however, to that Act; (h) the term deed used in the Settled Land Act 1884 includes any dealing executed in pursuance of this Act; (i) notwithstanding anything contained in this section, a registered proprietor of a life estate in registered land may, in the exercise of the powers of a tenant for life under the Settled Land Act 1884 , transfer the fee simple of that land by a transfer which contains a receipt for the purchase price by the trustees of the settlement and otherwise in an approved form. (2) Nothing contained in subsection (1) shall be taken to require any person dealing with a registered proprietor of registered land to inquire whether all or any of the provisions of the Settled Land Act 1884 have been complied with in respect of the proposed dealing. (3) In this section the term registered proprietor includes any person possessed of or entitled to any charge upon land. PART VIII - Trusts 132. Trusts (1) The Recorder shall not record particulars of any trust in the Register. (2) A dealing may state that a person named in the dealing is a trustee – (a) for the purpose of expressing the consideration; (b) for the purpose of providing that the person named assumes liability only to the extent of an estate or interest of which he is a trustee; and (c) where the person named is a trustee pursuant to an Act or Commonwealth Act (other than an Act applicable to trustees generally) – but shall not disclose particulars of a trust. (3) The Recorder, in his discretion, may in a folio of the Register or certificate of title describe a registered proprietor as a trustee where – (a) the proprietor was so described in the dealing by which he became registered as a proprietor; or (b) in the Recorder's opinion it is convenient for the administration of this Act that the proprietor should be so described. (4) The describing of a person as a trustee in a dealing or in a folio of the Register or certificate of title does not affect the operation of section 41 . (5) A registered proprietor who is a trustee shall hold the estate or interest of which he is registered proprietor in trust for the persons and purposes to which it is applicable by virtue of the instrument creating the trust, but for the purpose of a dealing with the estate or interest he shall be deemed to be the absolute proprietor of the estate or interest. PART IX - Caveats Division 1 - [Division 1 of Part IX Heading inserted by No. 4 of 2001, s. 12, Applied:12 Apr 2001] Caveats against dealings 133. Caveat against dealings [Section 133 Subsection (5) amended by No. 9 of 1982, s. 7 and Sched. 10 ] (1) [Section 133 Subsection (1) amended by No. 21 of 1996, s. 19 ] Where – (a) a settlor transfers registered land to be held by the transferee as trustee; or (b) a person claims an estate or interest in registered land under an unregistered dealing, or by devolution in law or otherwise – that settlor or person may, by caveat in an approved form lodged with the Recorder, forbid the registration of any dealing affecting that land, estate, or interest. (2) [Section 133 Subsection (2) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] A caveat under this section shall state – (a) the name and address of the caveator; (b) an address for service of notices on the caveator; (c) the estate or interest claimed by the caveator; (d) the folio of the Register, or the registered dealing, affected by the caveat; and (e) where the caveat relates to part only of the land in a folio of the Register or registered dealing, such further description as may be necessary to identify the subject land – and shall be signed by the caveator or by his legal practitioner, attorney, or authorized agent. (3) If the Recorder does not refuse to register a caveat lodged pursuant to this section he shall – (a) record the caveat on the folio of the Register or registered dealing affected by the caveat; and (b) give notice of the caveat to the registered proprietor of the estate or interest affected by the caveat. (4) [Section 133 Subsection (4) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] A notice relating to a caveat lodged pursuant to this section, or to any proceedings in respect of the caveat, shall be deemed to be duly served upon the caveator if served at his address for service stated in the caveat, or at the office of the legal practitioner, attorney, or authorized agent who may have signed the caveat. (5) [Section 133 Subsection (5) amended by No. 46 of 1981, s. 6 ] A caveat under this section may be withdrawn – (a) by – (i) the caveator; (ii) [Section 133 Subsection (5) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] the caveator's legal practitioner; or (iii) an agent authorized in writing by the caveator to withdraw the caveat; (b) where a caveator is dead – (i) by his personal representative; or (ii) by the surviving caveator where the estate or interest claimed by the caveat was stated in the caveat to be held by caveators as joint tenants; (c) [Section 133 Subsection (5) amended by No. 4 of 2001, s. 13, Applied:12 Apr 2001] where the caveator is bankrupt, by the trustee, the Official Receiver (within the meaning of section 95 ), or other person in whom the estate or interest claimed in the caveat has vested pursuant to the law relating to bankruptcy; (d) [Section 133 Subsection (5) amended by No. 42 of 2001, Sched. 1, Applied:15 Jul 2001] where the caveator is a defunct company which was incorporated under the Corporations Act, by ASIC; (e) where the caveator is a friendly society which has been dissolved, by the Registrar of Friendly Societies; (f) where the caveator is a building society which has been terminated or dissolved, by the Registrar of Building Societies; (g) [Section 133 Subsection (5) amended by No. 33 of 1996, Sched. 1, Applied:01 Sep 1997] by the administrator of the estate of a person under the Guardianship and Administration Act 1995 to whom is committed the management and care of the estate or interest claimed in the caveat; or (h) [Section 133 Subsection (5) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] by the legal practitioner to a person mentioned in paragraph (b) , paragraph (c) , or paragraph (g) . (6) [Section 133 Subsection (6) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] The Recorder shall not be concerned to satisfy himself that a legal practitioner who signs a withdrawal of caveat as legal practitioner to the caveator or to a person mentioned in paragraph (b) , paragraph (c) , or paragraph (g) of subsection (5) has authority to withdraw the caveat. 134. Caveat may be lodged by judgment creditor (1) [Section 134 Subsection (1) amended by No. 21 of 1996, s. 12 ] A judgment creditor of a person registered as the proprietor of registered land may lodge a caveat in an approved form. (2) [Section 134 Subsection (2) amended by No. 21 of 1996, s. 12 ] A caveat under this section shall – (a) be accompanied by a copy of the judgment or order upon which it is founded; and (b) identify, to the Recorder's satisfaction, the judgment debtor with the registered proprietor named in the folio of the Register or registered dealing affected by the caveat. (3) The practice, procedure, and mode of dealing with a caveat under this section shall in all other respects be the same as if the judgment creditor referred to in subsection (1) claimed an estate or interest in that person's land within the meaning of section 133 . (4) At the expiration of each period of 5 years from the entry or re-entry of a caveat under this section the caveat shall lapse and cease to be of any effect unless it is re-entered as provided by this section. (5) When the time prescribed by subsection (4) expires on a day on which the office of the Recorder is closed the re-entry is effective if done on the next day on which the office is open. (6) [Section 134 Subsection (6) amended by No. 21 of 1996, s. 19 ] The Recorder shall re-enter a caveat under this section if, before it lapses, the caveator or the person for the time being entitled to enforce the judgment mentioned in the caveat so requests in an approved form and pays the prescribed fee. (7) Nothing in this section – (a) revives or restores a judgment which is extinguished or barred; or (b) affects or prejudices a judgment as between the parties to the judgment, their representatives, or those deriving as volunteers under them. (8) [Section 134 Subsection (8) inserted by No. 21 of 1996, s. 12 ] Where a judgment creditor lodges a caveat under section 48B , he or she must provide such particulars of the judgment or order on which the caveat is founded as the Recorder may require and in such manner as the Recorder may require. 135. Proceedings to remove caveat (1) [Section 135 Subsection (1) amended by No. 4 of 2001, s. 14, Applied:12 Apr 2001] Any person, other than the caveator, who claims an estate or interest in land affected by a caveat under this Act may summon the caveator to attend before the Supreme Court to show cause why the caveat should not be removed. (2) The Supreme Court, on proof that the caveator has been summoned, may make such order, either ex parte or otherwise, as it considers necessary and may determine by whom the costs of, and incidental to, the summons and the proceedings on the summons, and the entering and removal of the caveat shall be borne. 136. Lapsing of caveat on registration of dealing (1) On the lodgment for registration of a dealing the registration of which is forbidden by a caveat lodged pursuant to this Part, and on the application of the registered proprietor against whom the caveat was lodged or of a person claiming under the dealing, the Recorder shall serve on the caveator a notice of his intention to register the dealing on the expiration of the period of 28 days after the service of the notice, and shall register the dealing unless within that period – (a) an order to the contrary is made by the Supreme Court and that order or written notice of the order is served on the Recorder; or (b) the dealing is withdrawn or for any reason ceases to be in order for registration. (2) For the purposes of subsection (1) , a dealing shall not be deemed to have been lodged for registration until (except for the existence of the caveat in respect of which notice is to be given) it is in order for registration. (3) [Section 136 Subsection (3) amended by No. 46 of 1981, s. 7 ] Where, after the service of a notice of intention to register a dealing, the dealing to which the notice relates is withdrawn or for any reason becomes incapable of registration, the notice ceases to have effect and the caveat remains in full force and effect. (4) Unless an order to the contrary has been made and served on the Recorder under subsection (1) (a) , a caveat lapses and ceases to affect land at the expiration of 28 days after the service pursuant to subsection (1) of a notice of intention to register a dealing. (5) Where, after serving a notice of intention to register a dealing, the Recorder registers a dealing that does not completely dispose of the estate of the registered proprietor in the land to which the caveat relates, the caveat shall be deemed to have lapsed only to the extent necessary to permit that registration. 136A. Cancellation of caveat on application of proprietor of estate or interest [Section 136A Inserted by No. 36 of 2012, s. 33, Applied:13 Nov 2012] (1) On application by a registered proprietor against whom a caveat is lodged, the Recorder is to serve on the caveator a notice in accordance with subsection (3) . (2) An application under subsection (1) is to be in a form approved by the Recorder. (3) A notice under subsection (1) is to state that the Recorder will cancel the caveat on the expiry of 28 days after the day on which the notice is served unless – (a) an order is made by the Supreme Court extending the operation of the caveat – (i) for such further period as is specified in the order; or (ii) until the further order of that Court; and (b) that order, or an office copy of that order, is lodged with the Recorder. (4) If an order referred to in subsection (3) has not been obtained and lodged with the Recorder before the expiry of the 28-day period referred to in subsection (3) , the Recorder is to cancel the caveat on the expiry of that 28-day period. 137. No registration affecting land in respect of which caveat lodged [Section 137 Subsection (3) amended by No. 30 of 1995, s. 3 and Sched. 1 ] (1) Subject to this section, so long as a caveat forbidding the registration of a dealing remains in force, the Recorder shall not, except with the written consent of a person entitled to withdraw the caveat, record any dealing upon the folio of the Register, or the registered dealing, affected by the caveat. (2) Subsection (1) does not operate to prevent the recording of – (a) a dealing which has been lodged for registration prior to the lodging of the caveat; or (b) a dealing lodged by or on behalf of the Crown or a public or local authority – (i) pursuant to a power – (A) to resume or take land; (B) to restrict the use or alienation of land; (C) to erect works on land; (D) to charge land with the payment of money; or (E) to give notice of its intention to do one or more of the things referred to in sub-subparagraphs (A) , (B) , (C) , and (D) ; (ii) pursuant to an Act which expressly or impliedly authorizes a recording notwithstanding the existence of a caveat; or (iii) [Section 137 Subsection (2) amended by No. 10 of 2000, s. 11, Applied:28 Apr 2000] in prescribed circumstances; or (c) [Section 137 Subsection (2) amended by No. 10 of 2000, s. 11, Applied:28 Apr 2000] a scheme within the meaning of section 3 of the Strata Titles Act 1998 ; or (d) [Section 137 Subsection (2) amended by No. 10 of 2000, s. 11, Applied:28 Apr 2000] a final plan within the meaning of Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 . (3) [Section 137 Subsection (3) amended by No. 46 of 1981, s. 8 ] Except to the extent that it otherwise specifies, a caveat referred to in subsection (1) does not prevent the Recorder from recording in the Register – (a) a transfer under Division 11 of Part 9 of the Local Government Act 1993 ; (b) a writ within the meaning of section 61 ; (ba) [Section 137 Subsection (3) amended by No. 36 of 2012, s. 34, Applied:13 Nov 2012] a declaration of severance of a joint tenancy pursuant to section 63 ; (c) a dealing executed by a registered mortgagee, or a registered encumbrancee, in pursuance of a power of sale or lease contained in the mortgage or encumbrance or conferred on him by this Act; (d) a discharge of mortgage or encumbrance pursuant to section 89 , section 90 , section 93 , section 94 , or section 148 ; (e) [Section 137 Subsection (3) amended by No. 36 of 2012, s. 34, Applied:13 Nov 2012] if the caveat lapsed pursuant to section 136 so as to allow registration of a lease, mortgage or encumbrance, a subsequent dealing by the proprietor of the lease, mortgage or encumbrance (including a dealing that is an extension or variation of that lease, mortgage or encumbrance); (ea) [Section 137 Subsection (3) amended by No. 36 of 2012, s. 34, Applied:13 Nov 2012] if the caveator consented to the registration of a lease, mortgage or encumbrance, a subsequent dealing by the proprietor of the lease, mortgage or encumbrance (other than a dealing that is an extension or variation of that lease, mortgage or encumbrance); (f) an order for foreclosure under section 86 ; (g) a transmission on the death of a registered proprietor under section 98 or section 99 ; (h) the registration as proprietor of an applicant under section 100 ; (i) the discharge of a covenant pursuant to section 104 ; (j) on the folio or registered dealing constituting the title to the land benefited, a grant of easement or profit à prendre ; (k) on the folio or registered dealing constituting the title to the land burdened, a release or cancellation of easement or profit à prendre ; (l) an order under section 110 ; (m) an expungement under section 103 or section 109 ; (n) a highway under section 112 ; (o) [Section 137 Subsection (3) amended by No. 36 of 2012, s. 34, Applied:13 Nov 2012] a vesting order under section 138B , section 138D or section 138X ; (p) [Section 137 Subsection (3) amended by No. 36 of 2012, s. 34, Applied:13 Nov 2012] the registration of a person as proprietor under section 138A ; (q) a final order under section 142 ; or (r) a change in the name, or a notification of the full and correct name, of a registered proprietor. (4) Where the Recorder pursuant to subsection (2) or subsection (3) records a dealing – (a) that completely disposes of the estate of the registered proprietor in the land to which the caveat relates, the caveat lapses and ceases to have any effect; or (b) that does not completely dispose of the estate of the registered proprietor in that land, the caveat remains in full force and effect after that recording. (5) For the purpose of subsection (4) , a registration effected under section 98 or section 100 or a recording made under section 99 shall be deemed not to dispose completely of the estate of the registered proprietor whose estate is transmitted under those sections. Division 2 - [Division 2 of Part IX Heading inserted by No. 4 of 2001, s. 15, Applied:12 Apr 2001] Compensation for lodging caveat without sufficient cause 138. Compensation for lodging caveat without sufficient cause (1) A person who lodges a caveat under this Act with the Recorder without reasonable cause shall be liable to any person who may have sustained damage as a result of the caveat being lodged for such compensation as a judge, on a summons in chambers, deems just. (2) The costs of a summons referred to in subsection (1) and all proceedings in connection with the summons shall be in the discretion of the judge, and execution may issue for the amount of compensation, if any, and of costs ordered by him to be paid in such and the like manner as if the amount had been awarded in a judgment in an action in the Supreme Court. PART IXA - Orders to vest land 138A. Registration as proprietor of person entitled to land by operation of any Act [Section 138A Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] (1) In this section, Act includes an Act of the Commonwealth. (2) The Recorder, on proof to his or her satisfaction that a person other than the registered proprietor has become entitled to be registered as proprietor of registered land, either alone or jointly or in common with that registered proprietor, because – (a) the land purports to have been vested in that person, or a person through whom he or she claims, by another Act, or by reason of anything done under another Act; or (b) he or she is entitled to have that land so vested in him or her by the operation of another Act, either directly or by reason of anything done under that Act – may, of his or her own motion, or on the application in an approved form of a person in whom the land is vested or who has become so entitled, on such evidence as appears to the Recorder sufficient, and after such notice (if any) to such person as the Recorder considers proper, register the person in whom the land is vested, or who has become so entitled, as the proprietor of such estate in the land as the Recorder considers appropriate. (3) For the purposes of subsection (2) , the Recorder may make such recordings, cancellations and corrections in the Register or a plan relevant to a folio of the Register, and issue such certificates of title, as appear to him or her to be necessary or proper and may call in any certificate of title, grant or duplicate registered dealing. 138B. Recorder to carry out order of Supreme Court vesting trust estate [Section 138B Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] (1) Where a person interested in registered land appears to the Supreme Court to be a trustee of that land and an order is made by the Supreme Court, the Recorder, on application supported by an office copy of the order, must make such recording in the Register as he or she thinks necessary to register the person in whom the order purports to vest the land as proprietor of the land. (2) Unless and until a recording is made under subsection (1) , the order referred to in that subsection has no effect or operation in transferring or otherwise vesting the land. 138C. Registration of dealing by person appointed by court [Section 138C Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] Where a direction, judgment or order of a court of competent jurisdiction directs, appoints or empowers a person other than the registered proprietor to dispose of registered land, the Recorder may refuse to register a dealing executed under the direction, judgment or order unless the dealing – (a) indicates that it is executed under; and (b) is supported by an office copy of – the direction, judgment or order. 138D. Recorder may make vesting order in certain circumstances when purchaser in possession [Section 138D Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] (1) If, on application to the Recorder, it is proved to his or her satisfaction that the applicant – (a) is in possession of registered land and no claim to recover the land has been made by the registered proprietor of that land or his or her heirs, personal representatives or assigns; and (b) is entitled in equity and good conscience to be registered as proprietor of an estate in fee simple in the land in consequence of a sale of the land; and (c) is unable to obtain a transfer of the land from the registered proprietor of the land because the registered proprietor is dead or residing out of Tasmania or cannot be found or for any reason it is impracticable to obtain his or her signature within a reasonable time – the Recorder may, if in his or her opinion the case can properly be dealt with under this section rather than by an application under section 138W , make an order vesting the land in that person for an estate in fee simple. (1A) [Section 138D Subsection (1A) inserted by No. 36 of 2012, s. 35, Applied:13 Nov 2012] An order under subsection (1) may be made only with respect to the whole of the land described in a folio of the Register. (2) Where the sale referred to in subsection (1) was not made by the registered proprietor, the Recorder must not make an order under that subsection unless – (a) at least 15 years have elapsed since the sale; and (b) at least 15 years have elapsed since the last registration on the folio of the Register constituting the title to the land of a transfer, mortgage, encumbrance or lease. (3) An order made under subsection (1) vests the land in the applicant subject to registered easements and other registered interests, except that it may vest the land free from any mortgage or encumbrance which could be discharged under section 91 if evidence satisfactory to the Recorder is produced. (4) The Recorder may – (a) reject an application under subsection (1) wholly or in part; or (b) make such requisitions as to the title claimed to be acquired, or as to any other matter relating to the application, as he or she thinks fit. (5) The Recorder, if he or she does not reject an application under subsection (1) , must – (a) [Section 138D Subsection (5) amended by No. 36 of 2012, s. 35, Applied:13 Nov 2012] direct that notice be given in a form approved by the Recorder in at least one newspaper that is published, and circulating generally, in Tasmania and that is available in the locality in which the relevant land is situated; and (b) state in the notice that on the expiration of one month after the date of that notice the Recorder may make and register a vesting order in favour of the applicant. (6) The notice is to be given to every person appearing by the Register to have any estate or interest in the land, or in any mortgage or encumbrance recorded on the folio of the Register relating to that land. (7) An applicant under subsection (1) must cause a copy of the notice to be posted in a conspicuous place on the land or at such place as the Recorder may direct and to be kept so posted for not less than one month before the granting of the application. (8) The notice is to appoint a time, not less than one month from the advertisement or service of the notice at or after the expiration of which the Recorder, unless a caveat is lodged forbidding it, may make a vesting order as provided in this section. (9) At any time before making a vesting order under this section, the Recorder may, notwithstanding any direction previously given by him or her as to the application under subsection (1) , reject the application wholly or in part if the applicant fails to comply to his or her satisfaction with any requisition made or direction given by him or her. (10) On making a vesting order under this section, the Recorder – (a) must make such recordings, cancellations and corrections in the Register as he or she considers necessary to give effect to the vesting order and to register the person in whom the order vests the land as proprietor of the land; and (b) may call in any certificates of title and grants for the making of those recordings, cancellations and corrections. 138E. Caveat forbidding granting of application under section 138D [Section 138E Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] (1) A person claiming an estate or interest in the land in respect of which an application under section 138D is made may, before the Recorder makes a vesting order in respect of the application, lodge a caveat with the Recorder in an approved form forbidding the granting of the application. (2) A caveat under this section lapses unless the caveator has, within 30 days after lodgment, lodged with the Recorder a document in an approved form specifying the grounds for the caveat. (3) [Section 138E Subsection (3) substituted by No. 36 of 2012, s. 36, Applied:13 Nov 2012] The Recorder must not proceed with the application to which the caveat relates unless – (a) the caveat has been withdrawn; or (b) the caveat has lapsed; or (c) if grounds for the caveat have been lodged within the time specified in subsection (2) , the Recorder has carried out an investigation of the caveat. (4) [Section 138E Subsection (4) substituted by No. 36 of 2012, s. 36, Applied:13 Nov 2012] In investigating the caveat, the Recorder may make such investigations as the Recorder considers necessary for the proper determination of the caveat, including conducting an inquiry under section 160(2) . (4A) [Section 138E Subsection (4A) inserted by No. 36 of 2012, s. 36, Applied:13 Nov 2012] On completing the investigation of the caveat, the Recorder may grant or refuse to grant the application to which the caveat relates. (5) [Section 138E Subsection (5) amended by No. 36 of 2012, s. 36, Applied:13 Nov 2012] On the application of any person who the Supreme Court is satisfied has a proper interest in the matter, the Court may remove into the Court any proceedings before the Recorder on an application for an order under this Part. (6) A caveat under this section may be withdrawn as provided by section 133(5) and (6) but the other provisions of that section do not apply to the caveat. 138F. Restriction on renewal of caveats [Section 138F Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] (1) [Section 138F Subsection (1) substituted by No. 36 of 2012, s. 37, Applied:13 Nov 2012] Unless permitted by a Supreme Court order, a caveat that has lapsed or been withdrawn under section 138E may not be renewed and a new caveat may not be lodged by or on behalf of the same person in respect of the same estate or interest. (2) A copy of an order made under subsection (1) is to be attached to the caveat to which it refers. PART IXB - Possessory Title Division 1 - Preliminary [Division 1 Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] 138G. Interpretation (1) In this Part – dominant tenement means land that is claimed to have the benefit of rights amounting to an easement; servient tenement means land that is claimed to have the burden of rights amounting to an easement. (2) For the purposes of this Part, a person is taken to be under disability while – (a) he or she is an infant; or (b) he or she is incapable, by reason of mental illness, of managing his or her property or affairs. (3) For the purposes of, but without limiting, subsection (2)(b) , a person is presumed to be incapable, by reason of mental illness, of managing his or her property or affairs – (a) [Section 138G Subsection (3) amended by No. 69 of 2013, Sched. 1, Applied:17 Feb 2014] while he or she is subject to an assessment order or treatment order under the Mental Health Act 2013 ; or (b) while a guardianship order or an administration order in respect of his or her estate is in force under the Guardianship and Administration Act 1995 ; or (c) while the Public Trustee has under Part VII of the Public Trustee Act 1930 the powers of the administrator of his or her estate. 138H. Application to unregistered land [Section 138H Substituted by No. 36 of 2012, s. 38, Applied:13 Nov 2012] This Part applies to a dealing with land that is not registered land where that dealing with that land is not otherwise covered by this Act. Division 2 - Right to acquire easements [Division 2 Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] 138I. Abolition of common law rules (1) This Division supersedes the rules of the common law for the acquisition of easements by prescription. (2) The rule of law known as the doctrine of lost modern grant for the acquisition of easements is abolished. 138J. Acquisition of easements by possession [Section 138J Substituted by No. 36 of 2012, s. 39, Applied:13 Nov 2012] (1) A person who has exercised rights which may amount to an easement at common law for a period of not less than 15 years, or not less than 30 years if the owner of the land is a person under disability, may apply, in accordance with Division 3 , to the Recorder for an order vesting an easement in respect of those rights in the person. (2) An application is to be in a form approved by the Recorder. (3) The Recorder may make an order referred to in subsection (1) in favour of – (a) an applicant who, after giving notice under section 138K(1) , continues to exercise rights which the Recorder considers may amount to an easement; or (b) an applicant who, after giving notice under section 138K(1) , has been prevented or hindered in the exercise of rights which the Recorder considers may amount to an easement by the direct or indirect action of the owner of the servient tenement; or (c) an applicant who has exercised rights in accordance with subsection (1) which the Recorder considers may amount to an easement but, before giving notice under section 138K(1) , has been prevented or hindered in the further exercise of those rights by the direct or indirect action of the owner of the servient tenement if the applicant gives notice under section 138K(1) within 6 months after first becoming so prevented or hindered in the further exercise of those rights. Division 3 - Procedure for vesting of easements [Division 3 Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] 138K. Applicant to notify owner of servient tenement (1) [Section 138K Subsection (1) amended by No. 36 of 2012, s. 40, Applied:13 Nov 2012] Before lodging an application for an easement under this Part, the applicant must give written notice of the claim, in the approved form, to the owner of the servient tenement and produce evidence satisfactory to the Recorder that he or she has done so. (2) The owner of the land may, within 30 days after receipt of the notice, lodge with the Recorder a notice of objection in an approved form against the easement claimed. (3) If the owner does not lodge a notice of objection, the Recorder must consider the application in accordance with this Part. (4) If the owner lodges a notice of objection, the Recorder may not consider the application unless he or she is satisfied that the applicant would suffer serious hardship if the application is not granted. 138L. Requirements for application (1) [Section 138L Subsection (1) amended by No. 36 of 2012, s. 41, Applied:13 Nov 2012] In addition to the requirements of section 138K(1) , an applicant for an easement under this Part must show that – (a) during the relevant period, he or she has enjoyed the easement in the relevant land as of right; and (b) the easement has not been enjoyed by force or secretly; and (c) during the relevant period, the enjoyment of the easement has not been by virtue of a written or oral agreement made before or during that period unless the applicant can show that the relevant period commenced after any such agreement had terminated; and (d) during the relevant period, there has been no unity of seisin of the relevant dominant and servient tenements; and (e) during the relevant period, the owner of the servient tenement knew, or as a reasonable owner of land diligent in the protection of his or her interests ought to have known, of the enjoyment of the easement; and (f) the right for which the easement is claimed is not of a temporary nature; and (g) the applicant is the holder of an estate in fee simple in the dominant tenement or is under this Act or any other law entitled to such an estate as against the holder of an estate in fee simple in the servient tenement – and the applicant must produce evidence from at least one disinterested person in support of the easement claimed. (2) [Section 138L Subsection (2) amended by No. 36 of 2012, s. 41, Applied:13 Nov 2012] An application under this Division is, unless the Recorder otherwise directs, to be supported by a plan of survey, with survey notes, of the land in respect of which the easement is claimed certified as correct by a surveyor registered and certificated under the Land Surveyors Act 1909 . (3) The Recorder may – (a) reject an application under this Division wholly or in part; or (b) make such requisitions as to the easement claimed, or as to any other matter relating to the application, as he or she thinks fit. (4) At any time before the making of an order referred to in section 138J , the Recorder may reject the application, wholly or in part, if the applicant has failed within a reasonable time to comply to the Recorder's satisfaction with any requisition made by the Recorder. 138M. Tenants in common Where 2 or more applicants for an easement under this Part have interests in common, it is sufficient if one of them can show that he or she has complied with all the requirements of this Part. 138N. No easement in gross Nothing in this Part is taken to confer a right to acquire an easement in a case where there is no land capable of benefitting from the easement. 138P. Character of easement (1) An easement that is vested under this Part – (a) is to be in respect of a right that is capable of being granted as an easement under the common law or any enactment; and (b) is to be capable of existing as an easement appurtenant to the dominant tenement or an ascertainable part of the dominant tenement; and (c) is to be limited to the same character, extent and degree of use throughout the relevant period. (2) Where a person for whom an easement is vested under this Part has exercised additional rights for the period required under this Part, he or she is entitled to the grant of an additional easement in respect of those rights. 138Q. Power of Recorder to make recordings, &c. On the vesting of an easement under this Part, the Recorder – (a) must make such recordings in the Register as he or she considers necessary to give effect to the easement and its effect on the dominant tenement and the servient tenement; and (b) may call in certificates of title, grants and duplicate registered dealings for making those recordings. 138R. Abolition of claim for profit à prendre After the commencement of the Land Titles Amendment (Law Reform) Act 2001 a claim may not be made under this Part for a profit à prendre . Division 4 - Caveat by owner [Division 4 Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] 138S. Power of owner to lodge caveat (1) An owner of land may lodge a caveat in an approved form with the Recorder giving notice that a person exercising rights which may amount to an easement is doing so with the permission of the owner. (2) If the caveat is lodged before the period when an easement may be claimed under this Part and the caveat is in force under this section – (a) time does not run against the caveator or any person claiming through the caveator; and (b) time does not run in favour of the person named in the caveat exercising rights which may amount to an easement or any person claiming through any such person; and (c) the period of enjoyment of the easement before the lodgment of the caveat is to be discounted, whether or not the caveat is later withdrawn. (3) The caveat is to state – (a) the name and address of the person exercising rights which may amount to an easement; and (b) the folio of the Register of the dominant tenement; and (c) the nature and description of the easement which may be claimed. (4) The Recorder must give notice of the caveat to the person named in the caveat exercising rights which may amount to an easement. (5) A caveat under this section may be withdrawn as provided by section 133(5) and (6) . Division 5 - Title by possession [Division 5 Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] 138T. Title by possession A person who has been in possession of land owned by another person may acquire title to that land in accordance with this Division but not otherwise. 138U. Restriction on title by possession (1) For the purposes of an application to acquire title to any land by possession, any period during which council rates have been or are paid by or on behalf of the owner is to be disregarded. (2) This section does not apply to an application if the relevant council has certified in writing that it is unclear who has paid, or is paying, the relevant council rates. 138V. Requirements for title by possession [Section 138V Amended by No. 36 of 2012, s. 42, Applied:13 Nov 2012] In determining an application for title based on possession, the Recorder must consider all the circumstances of the claim, the conduct of the parties and in particular – (a) whether, during the relevant period, the applicant enjoyed possession of the land as of right; and (b) whether there is any reason to suppose that during the relevant period that enjoyment was by force or secretly or that that enjoyment was by virtue of a written or oral agreement made before or during that period unless the applicant can show that any such agreement terminated before that period; and (c) the nature and period of the possession; and (d) the improvements on the land and in particular – (i) when they were made; and (ii) by whom they were made; and (e) whether or not the land has been enclosed by the applicant; and (f) whether during the relevant period the applicant acknowledged ownership, paid rent or made any other payment in respect of the land – and the applicant must produce evidence from at least one disinterested person in support of the application. 138W. Registered proprietor to hold land on trust (1) Subject to this section, the Limitation Act 1974 applies to the title of a registered proprietor of an estate in registered land in the same manner and to the same extent as that Act applies to the title of a proprietor of land which is not registered land. (2) The estate of a registered proprietor of registered land is not extinguished by the Limitation Act 1974 , but where the estate would have been extinguished if the land had not been registered land, the registered proprietor of the estate is taken to hold that estate in trust for the person who, under that Act, would have acquired title to that estate if that land had not been registered land. (3) Nothing in subsection (2) affects the estate or interest of any other person in the land which would not have been extinguished by that person's possession if that land had not been registered land. (4) A person who claims that the registered proprietor of an estate in registered land holds that estate in trust for him or her under subsection (2) may apply to the Recorder in an approved form for an order vesting in him or her the legal estate which he or she would have acquired if the land had not been registered land. (5) The right of a person to apply under subsection (4) is not affected during the period of his or her possession of the land by – (a) the bringing of the land in respect of which that person applies under this Part or the repealed Act; or (b) the making of a vesting order in respect of the land under – (i) section 138D of this Act or section 14 of the Real Property Act 1893 ; or (ii) the Real Property (Special Vesting Orders) Act 1973 . (6) The right of a person to apply under subsection (4) is not affected – (a) by the registration of any dealing by, or the registration of the transmission of the title of, a registered proprietor of the land in respect of which that person applies; or (b) by the recertification by the Recorder in the course of the administration of this Act or the repealed Act of the estate in the land in respect of which that person applies – unless that person's possession ceased on or before 31 October 1974. (7) [Section 138W Subsection (7) amended by No. 36 of 2012, s. 43, Applied:13 Nov 2012] An application under subsection (4) is, unless the Recorder otherwise directs, to be supported by a plan of survey, with survey notes, of the land certified as correct by a surveyor registered and certificated under the Land Surveyors Act 1909 . (8) Before making an application under subsection (4) , the applicant must – (a) [Section 138W Subsection (8) amended by No. 36 of 2012, s. 43, Applied:13 Nov 2012] publish, in at least one newspaper that is published, and circulating generally, in Tasmania and that is available in the locality in which the relevant land is situated, a notice that – (i) is in a form approved by the Recorder; and (ii) states that the applicant intends to make the application; and (b) [Section 138W Subsection (8) amended by No. 36 of 2012, s. 43, Applied:13 Nov 2012] give notice of the application in a form approved by the Recorder to any person who, as endorsed on the folio of the Register relating to that land, has an interest in the land or in any mortgage or encumbrance recorded on that folio; and (c) [Section 138W Subsection (8) amended by No. 36 of 2012, s. 43, Applied:13 Nov 2012] give notice of the application in a form approved by the Recorder to any person who has an unregistered interest in the land which may have been lodged with the Recorder; and (d) [Section 138W Subsection (8) amended by No. 36 of 2012, s. 43, Applied:13 Nov 2012] cause a copy of the notice referred to in paragraph (a) to be posted in a conspicuous place on the land and to be kept so posted for not less than one month before making the application. (9) An application for title by possession is to be lodged with the Recorder not later than 2 months after the date of the last notice given under subsection (8) . (10) A notice under this section is to be in a form approved by the Recorder. (11) The Recorder may – (a) reject an application under subsection (4) wholly or in part; or (b) make such requisitions as to the estate claimed to be held in trust, or as to any other matter relating to the application, as he or she thinks fit. (12) At any time before making the vesting order, the Recorder may reject the application, wholly or in part, if the applicant fails to comply to his or her satisfaction within a reasonable time with any requisition made. 138X. Power of Recorder to make vesting order (1) Subject to section 138W , the Recorder may make an order vesting in the applicant under this Division the legal estate which the applicant would have acquired, if the land had not been registered land, free from – (a) all estates and interests recorded on the folio of the Register or registered dealing evidencing title to the land which would have been determined or extinguished by the applicant's possession of the land; and (b) any mortgage or encumbrance which could be discharged under section 91 if evidence satisfactory to the Recorder is produced; and (c) any registered easement or profit à prendre which – (i) is not an easement or profit à prendre created by a plan sealed under Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 ; or (ii) has been proved to the Recorder's satisfaction to have been abandoned – but subject to any restrictive covenant notified on that folio or registered dealing. (2) [Section 138X Subsection (2) amended by No. 36 of 2012, s. 44, Applied:13 Nov 2012] For the purposes of subsection (1) , the Recorder may treat evidence of failure to use an easement or a profit à prendre for a period of not less than 20 years as conclusive evidence that the easement or profit à prendre has been abandoned. (3) On making a vesting order under this section, the Recorder – (a) must make such recordings, cancellations and corrections in the Register as he or she considers necessary to give effect to the vesting order and to register the person in whom the order vests the land as proprietor of the land; and (b) may call in any certificates of title and grants for making those recordings, cancellations and corrections. (4) Where the registered proprietor whose registration is to be cancelled under subsection (3) is – (a) a legal owner referred to in section 13(2) of the Limitation Act 1974 ; or (b) a trustee referred to in section 13(3) of that Act – his or her right to recover the land is not extinguished, notwithstanding the registration as proprietor of the applicant under this Division, or any person deriving title under him or her otherwise than as a purchaser in good faith for value, so long as any other person has a right under section 13 of that Act to recover the land. (5) The Recorder may, if he or she thinks fit, by reason of the imperfect nature of the evidence of title or otherwise, make a vesting order under this section subject to the condition that the title vested is to be a qualified title as mentioned in Division 4 of Part III . 138Y. Avoidance of sub-minimum lots (1) In this section, sub-minimum lot means a lot that does not have the qualities of a minimum lot as provided by section 109 of the Local Government (Building and Miscellaneous Provisions) Act 1993 . (2) If the Recorder is not sure whether the granting of an application under this Division would result in the continuation or creation of a sub-minimum lot, the Recorder may require the applicant to produce a certificate from the relevant council – (a) that the application would not result in the continuation or creation of a sub-minimum lot; or (b) that the council consents to the application. (3) If the applicant fails to produce a certificate required under subsection (2) , the Recorder is not required to proceed with the application. Division 6 - Caveats against easements and title by possession [Division 6 Inserted by No. 4 of 2001, s. 16, Applied:12 Apr 2001] 138Z. Caveat forbidding granting of application under this Part (1) A person claiming an estate or interest in the land in respect of which an application under this Part is made may, before the Recorder makes a vesting order in respect of the application, lodge a caveat with the Recorder in an approved form forbidding the granting of the application. (2) The application of section 138E extends to a caveat under subsection (1) . 138ZA. Restriction on renewal of caveats (1) A caveat under section 138Z that has lapsed or been removed under section 138E may not be renewed by or on behalf of the same person in respect of the same interest unless an order to that effect is made by the Supreme Court. (2) A copy of an order made under subsection (1) is to be attached to the caveat to which it refers. PART X - Amendment of the Register 139. Correction of errors (1) Subject to subsection (2) and upon such evidence as appears to him sufficient, the Recorder may correct errors or supply omissions in the Register or in any instrument or duplicate registered dealing, and may call in any certificate of title, grant, or duplicate registered dealing for that purpose. (2) When the Recorder makes an alteration pursuant to subsection (1) – (a) he shall, except as may be otherwise prescribed, authenticate the alteration and record the date of the alteration, and preserve a record of the matter which has been altered; (b) the alteration does not prejudice or affect a right accrued from a recording made in the Register pursuant to a dealing lodged before the alteration; and (c) subject to paragraph (b) , the Register, instrument, or duplicate registered dealing shall, as so altered, have the same validity and effect as it would have had if the error or omission had not occurred. 140. Cancellation of superfluous recordings The Recorder has power to cancel in such manner as he considers proper any recording in the Register which he is satisfied does not affect or has ceased to affect the land to which the recording purports to relate, and may for that purpose call in and cancel or correct any certificate of title, grant, or duplicate registered dealing. 141. Powers of Supreme Court to direct cancellation of folio or recording in certain cases On the recovery of any land, estate, or interest, by any legal proceeding, from the person registered as proprietor of the land, the Supreme Court in any case in which that proceeding is not expressly barred by section 149 may direct the Recorder to cancel any folio of the Register, certificate of title, grant, or registered dealing, or any recording in the Register relating to that land, and to substitute a new folio, certificate of title, or recording, as the circumstances of the case may require, and the Recorder shall give effect to that order. 142. Rectification of boundaries, area or position of land [Section 142 Subsection (1) amended by No. 11 of 1990, s. 11 and Sched. 1 ] [Section 142 Subsection (4) amended by No. 30 of 1995, s. 3 and Sched. 1 ] [Section 142 Subsection (5) amended by No. 20 of 1995, s. 5 and Sched. 3 ] [Section 142 Subsection (8) amended by No. 21 of 1996, s. 13 ] [Section 142 Subsection (9) amended by No. 30 of 1995, s. 3 and Sched. 1 ] [Section 142 Substituted by No. 36 of 2012, s. 45, Applied:13 Nov 2012] (1) An interested person may apply to the Recorder for the taking of action or the making of an order under subsection (14) . (2) The application is to be – (a) in the approved form; and (b) accompanied by the prescribed fee; and (c) accompanied by such evidence in support of the application as the Recorder requires. (3) On receipt of an application, or on the Recorder's own motion, the Recorder may give notice as specified in subsections (5) and (6) if the Recorder is satisfied that the case can properly be dealt with under this section, rather than by an application under section 138W(4) , and if – (a) it appears to the Recorder that the boundary, area or position of the land described in a folio of the Register – (i) was established without the benefit of a survey or a survey that the Recorder considers sufficient; and (ii) differs from the actual boundary, area or position of the land as shown in the supporting evidence accompanying the application or, if no better evidence is available, as shown by the occupation of the land in good faith by the registered proprietor as being the land described in that folio; or (b) it appears to the Recorder that the description of land in that folio is based on erroneous or imperfect information; or (c) it appears to the Recorder that the boundary, area, position or description of the land contained in a forestry right – (i) was established without the benefit of a survey or a survey that the Recorder considers sufficient; and (ii) differs from the actual boundary, area or position of the land contained in the forestry right as shown in the supporting evidence accompanying the application or, if no better evidence is available, as shown by the use of the land in good faith by the registered proprietor as being the land contained in that forestry right; or (d) it appears to the Recorder that the boundary, area, position or description of the land contained in a forestry right is based on erroneous or imperfect information. (4) The Recorder may only act on his or her own motion if it appears to the Recorder that there is no interested person to make the application. (5) If the Recorder gives notice under subsection (3) , he or she is to give the notice to the council of the municipal area in which the land is situated and also – (a) in the case of registered land which it is proposed to affect or which may be affected, to every person appearing by the Register to have an interest in the land; and (b) in the case of land, other than registered land, which it is proposed to affect or which may be affected, to every person whom the Recorder has found by searching the Registry of Deeds to have an interest in the land; and (c) in the case of land subject to a highway which it is proposed to affect or which may be affected, to the highway authority concerned. (6) The notice is to be accompanied by – (a) in the case of notice given to a council and to a person referred to in subsection (5)(a) or (b) , a plan showing the extent to which the land is proposed to be or may be affected; and (b) in the case of notice given to a highway authority, a plan showing the extent to which the highway is proposed to be or may be affected. (7) If, after reasonable enquiry, an address for a person entitled to notice under subsection (5) cannot be ascertained, the Recorder may give the notice and relevant plan to The Public Trustee. (8) On receipt of a notice under subsection (7) , The Public Trustee may – (a) act on that person's behalf; and (b) have a lien on that person's interest for expenses incurred in so acting. (9) A person who has received a notice under subsection (5) may lodge a written objection with the Recorder within the period of not less than 21 days specified in the notice. (10) An objection must specify the grounds on which it is based. (11) If an objection has been lodged, the Recorder may conduct such investigations as he or she considers necessary for the proper determination of the matter. (12) In conducting an investigation under subsection (11) , the Recorder – (a) may hold a hearing for the purpose of receiving evidence and representations; and (b) may require a person to attend a hearing; and (c) at a hearing, may require a person – (i) to make an oath or affirmation to answer relevant questions truthfully; and (ii) to answer relevant questions; and (d) at a hearing, may require a person to produce documents; and (e) may retain documents produced at a hearing for such reasonable time as the Recorder thinks appropriate for the purposes of the investigation and make copies of those, or parts of those, documents; and (f) is to proceed as expeditiously and with as little formality and technicality as is consistent with the requirements of this Act and the proper investigation of the matter; and (g) is not bound by the rules of evidence and may gather information in any way the Recorder considers appropriate; and (h) may, subject to this Act and the rules of natural justice, determine the procedures to be followed; and (i) may enter on relevant land for the purpose of the investigation at any reasonable time after giving reasonable notice to the owner or occupier of that land. (13) A person must not, without reasonable excuse, refuse or fail to comply with a requirement made under subsection (12) . (14) If no objection has been lodged within the specified time, or on the completion of an investigation, the Recorder is to decide the matter and may do one or more of the following: (a) amend any plan, folio of the Register, certificate of title, grant or registered dealing; (b) order any person benefited by an amendment of a folio of the Register, certificate of title, grant or registered dealing to pay compensation to any person adversely affected by this section; (c) order payment of compensation out of the assurance fund; (d) order the rectification of an instrument registered in the Registry of Deeds; (e) order the execution and registration of an instrument; (f) vary, and order the registration of, an unregistered easement; (g) redefine the boundaries of a highway; (h) amend a sealed plan of subdivision under the Local Government (Building and Miscellaneous Provisions) Act 1993 if the amendment does not materially change the scheme of the subdivision; (i) determine that no further action is to be taken in respect of the boundaries, area, position or description of the relevant land in a folio of the Register or a forestry right; (j) make such order as to the costs of a person attending a hearing under subsection (12) as he or she thinks fit; (k) take any other action necessary or convenient to give effect to his or her decision. (15) The Recorder is to give a copy of his or her decision under subsection (14) to each person to whom notice has been given under subsection (5) . (16) The Recorder may refuse to proceed or to proceed further under this section – (a) if the Recorder considers that – (i) a party ought to bring an action, suit or other proceeding; or (ii) a party ought to apply for an order under section 138W(4) ; or (iii) the Recorder cannot bring the matter to a satisfactory conclusion; or (b) until a plan has been amended under Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 or an action, suit or other proceeding has been finalised. (17) A decision under subsection (14) may be registered in the Supreme Court and may be enforced, subject to subsection (18) , as if it were a judgment of that Court. (18) A decision under subsection (14) is not to be acted on for 30 days and within that period a person affected by the decision may appeal to the Supreme Court which may do any one or more of the following: (a) stay proceedings on the decision wholly or in part; (b) quash or vary the decision; (c) substitute for the decision any other decision that the Recorder was entitled to have made and do any thing that the Recorder could do under that subsection; (d) order the Recorder to amend any plan, folio of the Register, certificate of title, grant or registered dealing or do any other thing that he or she was entitled to do under that subsection. (19) The powers conferred by this section are in addition to, but are not substituted for, any powers of correction, rectification or amendment conferred by any other provision of this Act. (20) A rectification or amendment made under this section is be taken to have been made prior to the registration of the instrument that is so rectified or amended. (21) In this section – interested person includes, but is not limited to – (a) the registered proprietor, mortgagee, lessee or encumbrancee of the relevant land; and (b) the council of the municipal area in which the relevant land is situated; and (c) if the relevant land is a highway, the highway authority for that land; and (d) the Crown in right of Tasmania; and (e) any other person the Recorder considers to be an interested person. 143. Effect of certain corrections [Section 143 Amended by No. 51 of 1982, s. 12 ] [Section 143 Amended by No. 30 of 1995, s. 3 and Sched. 1 ] A correction or amendment of the Register or a registered dealing under this Act pursuant to section 9D or section 17A of the Roads and Jetties Act 1935 or Part 3 of the Local Government (Building and Miscellaneous Provisions) Act 1993 shall be deemed to have been made before the registration of any dealing that is – (a) registered on a folio of the Register or registered dealing so corrected or amended; and (b) existing at the time of the correction or amendment. PART XA - Approval of Plans [Part XA Inserted by No. 48 of 1990, s. 17 ] 143A. Recorder may specify format, &c., of certain plans [Section 143A Inserted by No. 48 of 1990, s. 17 ] (1) [Section 143A Subsection (1) amended by No. 21 of 1996, s. 14 ] A plan deposited or lodged with the Recorder in accordance with this or any other Act shall comply with the requirements of the Recorder, expressed generally or for the particular case, and the plan shall, if the Recorder so requires, be made from an actual survey and certified as correct by a surveyor registered and certified under the Land Surveyors Act 1909 . (2) [Section 143A Subsection (2) inserted by No. 21 of 1996, s. 14 ] Regulations may prescribe the manner in which a plan filed, deposited or lodged with the Recorder is to be kept. (3) [Section 143A Subsection (3) inserted by No. 21 of 1996, s. 14 ] A plan or accompanying document may be deposited or lodged with the Recorder and kept wholly or partly – (a) on paper, on microfilm or in or on such other medium as may be approved by the Recorder; or (b) in such device for storing or processing information as may be so approved. 143B. Recorder may require information, &c., in respect of plans, &c. [Section 143B Inserted by No. 48 of 1990, s. 17 ] (1) Where – (a) in accordance with this or any other Act a plan is deposited or lodged with the Recorder; and (b) the Recorder is of the opinion that the plan does not comply with the requirements of this or any other Act – the Recorder may by notice in writing require – (c) the plan or any accompanying document to be amended; or (d) additional information specified by the Recorder to be supplied – within 3 months of the receipt of the notice or within such further period as the Recorder may allow. (2) Where the Recorder requires a person to amend a plan or accompanying document or to supply additional information a prescribed fee is payable unless the Recorder is satisfied that – (a) no error was made by anyone; or (b) any error made was minor in nature. (3) If a person fails – (a) to comply with a requirement specified in a notice; or (b) to pay the prescribed fee – within 3 months of the receipt of the notice or such further period as the Recorder may allow the Recorder may reject the plan and any accompanying document. 143C. Recorder may correct errors on plans [Section 143C Inserted by No. 48 of 1990, s. 17 ] (1) [Section 143C Subsection (1) amended by No. 36 of 2012, s. 46, Applied:13 Nov 2012] The Recorder may, of the Recorder's own motion, correct an error on a plan or accompanying document deposited or lodged with the Recorder in accordance with this or any other Act. (2) The Recorder may, before correcting an error, give, to such people as the Recorder considers appropriate, at least 7 days written notice of the Recorder's intention to correct the error. (3) [Section 143C Subsection (3) substituted by No. 36 of 2012, s. 46, Applied:13 Nov 2012] A person may object to the correction proposed to be made by the Recorder before the end of the period specified in the notice given under subsection (2) . (3A) [Section 143C Subsection (3A) inserted by No. 36 of 2012, s. 46, Applied:13 Nov 2012] An objection must be in writing and state the grounds on which it is based. (4) On receipt of an objection the Recorder may – (a) decide not to make the proposed amendment; or (b) amend the plan or accompanying document in accordance with the objection; or (ba) [Section 143C Subsection (4) amended by No. 36 of 2012, s. 46, Applied:13 Nov 2012] amend the plan in accordance with the notice given under subsection (2) ; or (c) reject the plan and any accompanying document. (5) If the Recorder amends a plan without the approval of the person who deposited or lodged it the Recorder shall add to the plan a note to the effect that it has been amended by the Recorder. 143D. Recorder may require substitute plans [Section 143D Inserted by No. 48 of 1990, s. 17 ] (1) If the Recorder is of the opinion that a plan or accompanying document deposited or lodged with the Recorder in accordance with this or any other Act is, by reason of an amendment made in accordance with this Part inconvenient for subsequent use, the Recorder may by written notice require a fresh plan or accompanying document to the same effect as the original plan or accompanying document to be deposited or lodged with the Recorder within 30 days or such further period as the Recorder may allow. (2) A fresh plan or accompanying document deposited or lodged with the Recorder has effect as if it had been deposited or lodged in place of, and at the same time as, the original plan or accompanying document. (3) If a person fails to comply with a requirement specified in a notice within the time specified in that subsection the Recorder may reject the plan or accompanying document, or both such plan and document. 143E. Balance plans to be provided [Section 143E Inserted by No. 48 of 1990, s. 17 ] (1) Where a plan deposited or lodged with the Recorder in accordance with this Part relates to – (a) part of the land included in a folio in the Register; or (b) part of the land included in a title – the Recorder may refuse to accept the plan unless there is also deposited or lodged with the Recorder a plan of the remainder of the land included in that folio or title, as the case may be. (2) A reference in subsection (1) to a plan deposited or lodged with the Recorder includes a plan lodged or deposited with the Recorder by or on behalf of the Crown. 143F. Notice of rejection of plan to be given [Section 143F Inserted by No. 48 of 1990, s. 17 ] If, in accordance with this Part, the Recorder rejects a plan or any accompanying document the Recorder shall give notice accordingly and shall retain one-half of any prescribed fee paid when the plan or accompanying document was deposited or lodged with the Recorder. 143G. Giving of notice [Section 143G Inserted by No. 48 of 1990, s. 17 ] (1) Where the Recorder is required to give a written notice under this Part the notice is sufficiently given for the purposes of this Part if it is given to – (a) the person required to deposit or lodge the plan or accompanying document with the Recorder; or (b) the person who actually deposited or lodged the plan or accompanying document with the Recorder; or (c) a person who the Recorder is satisfied is authorized to receive the notice. (2) [Section 143G Subsection (2) amended by No. 98 of 2001, s. 9, Applied:01 Jan 2002] Where the Recorder gives notice under this Part in respect of a sealed plan, strata plan or a building title plan the Recorder shall serve a copy of the notice on the municipal corporation that sealed the plan. (3) [Section 143G Subsection (3) amended by No. 98 of 2001, s. 9, Applied:01 Jan 2002] [Section 143G Subsection (3) amended by No. 30 of 1995, s. 3 and Sched. 1 ] Where, in accordance with this or any other Act, a sealed plan, strata plan or a building title plan is deposited or lodged with the Recorder and – (a) the Recorder rejects the plan in accordance with this Part; or (b) the Recorder is informed that the plan has been withdrawn – the Recorder shall forward the plan to the council that sealed it so that the plan may be cancelled. (4) If a person upon whom a notice is to be served in accordance with this Part is a facsimile service subscriber or a subscriber to any electronic transmission service the notice is sufficiently served if a copy of the notice is sent via that service to that person's service number. 143H. Accompanying document defined [Section 143H Inserted by No. 48 of 1990, s. 17 ] (1) A reference in this Part to an accompanying document is a reference to any document that is required by this or any other Act to be annexed to, attached to or deposited or lodged or presented with any plan that is required to be deposited or lodged with the Recorder under this or any other Act. (2) When, in accordance with this Part, the Recorder rejects a plan the Recorder shall be taken to have rejected any accompanying document deposited or lodged with that plan. 143I. Power of Recorder to rearrange plans [Section 143I Inserted by No. 21 of 1996, s. 15 ] (1) The Recorder may rearrange parts of any plan held by him or her by creating a new plan containing the whole or part of any other plan or plans or in such other manner as may appear to the Recorder to be convenient. (2) In the exercise of his or her powers under subsection (1) , the Recorder must not create a new plan so as to permit the subdivision of land contrary to the Local Government (Building and Miscellaneous Provisions) Act 1993 . PART XI - Civil Rights and Remedies Division 1 - General 144. Proprietor if dissatisfied may summon Recorder to show cause (1) Subject to subsection (6) , if the Recorder – (a) refuses to do an act which he is required or empowered to do under this or any other Act; or (b) gives a direction or makes an order upon his own motion or upon an application while exercising his powers under this or any other Act – a person who believes himself to be aggrieved by the refusal, direction, or order may require the Recorder to state in writing the grounds for his refusal, direction, or order notwithstanding that the Recorder has acted under a discretionary power. (1A) [Section 144 Subsection (1A) inserted by No. 36 of 2012, s. 47, Applied:13 Nov 2012] A requirement under subsection (1) must be lodged with the Recorder within 3 months after the relevant refusal, direction or order is given by the Recorder, or such longer period as the Recorder allows. (2) A person referred to in subsection (1) may proceed against the Recorder by summons in the Supreme Court requiring him to justify his refusal, direction, or order, and the Court may make such order as it thinks fit. (3) All expenses attendant upon any proceedings under this section shall be borne and paid by the person referred to in subsection (2) , unless the Supreme Court certifies that there were no probable grounds for the refusal, direction, or order referred to in subsection (1) . (4) On being served with a summons referred to in subsection (2) , the Recorder shall, if the land to which his refusal, direction, or order relates – (a) is registered land, record notice of the summons on the relevant folio of the Register; or (b) is not registered land, register the summons in the Registry of Deeds. (5) When the Supreme Court makes an order pursuant to a summons under this section, the Recorder shall cancel the recording of the summons or register the order in the Registry of Deeds, as the case may require. (6) This section does not apply where the Recorder has acted pursuant to another Act that provides for an appeal to the Supreme Court. 145. Action by person claiming as beneficiary may be brought in name of trustee (1) Where a person is entitled to or interested in land as a trustee and is entitled to bring or defend any action for the recovery of registered land, that person shall be bound to allow his name to be used as a plaintiff or defendant in an action for recovery of land by a beneficiary or person claiming an estate or interest in the land. (2) Where subsection (1) applies, the person entitled or interested as a trustee is entitled to be indemnified in like manner as a trustee would before the passing of the repealed Act have been entitled to be indemnified in a similar case of his name being used in any action or proceeding referred to in subsection (1) by his cestui que trust . 146. Mortgagee, encumbrancee or lessor may obtain possession in certain cases (1) [Section 146 Subsection (1) amended by No. 20 of 2018, s. 4, Applied:15 Oct 2018] Where the term of a lease has expired or default is made in the payment of any money secured by a mortgage or an encumbrance or payable under a lease for the time specified by this Act or in the mortgage, encumbrance, or lease – (a) a mortgagee as against a mortgagor, either before or after entering into the receipt of the rents and profits of the mortgaged land or making any distress under the powers conferred by section 83 , either before or after a sale of the land is effected under the power of sale given or implied in the mortgage, and either before or after obtaining an order for foreclosure pursuant to section 86 ; (b) an encumbrancee as against an encumbrancer, either before or after entering into the receipt of the rents and profits of the encumbered land or making any distress under the powers conferred by section 83 , and either before or after any sale of the land is effected under the power of sale given or implied in his encumbrance; or (c) [Section 146 Subsection (1) amended by No. 36 of 2012, s. 48, Applied:13 Nov 2012] a lessor as against a lessee – may without any formal demand or re-entry apply to the Supreme Court for an order for possession of the premises to which the expiry of the term of the lease relates or in respect of which the default is made. (2) [Section 146 Subsection (2) omitted by No. 20 of 2018, s. 4, Applied:15 Oct 2018] . . . . . . . . (3) [Section 146 Subsection (3) amended by No. 20 of 2018, s. 4, Applied:15 Oct 2018] Service, on a lessee, mortgagor or encumbrancer, of an order under subsection (5) stands in lieu of – (a) [Section 146 Subsection (3) amended by No. 36 of 2012, s. 48, Applied:13 Nov 2012] in the case of a lessor against a lessee, a demand and re-entry; and (b) in the case of a mortgagee or encumbrancee against a mortgagor or encumbrancer, the notice required to be given in such a case by this Act. (4) [Section 146 Subsection (4) omitted by No. 20 of 2018, s. 4, Applied:15 Oct 2018] . . . . . . . . (5) [Section 146 Subsection (5) amended by No. 20 of 2018, s. 4, Applied:15 Oct 2018] If an application is made under subsection (1), then, on proof of – (a) [Section 146 Subsection (5) amended by No. 20 of 2018, s. 4, Applied:15 Oct 2018] . . . . . . . . (b) default having been made in payment of the money due under the mortgage, encumbrance, or lease for the time specified by this Act, or otherwise provided in this section before the proceedings were commenced; (c) [Section 146 Subsection (5) amended by No. 36 of 2012, s. 48, Applied:13 Nov 2012] in the case of a lessor against a lessee – (i) [Section 146 Subsection (5) amended by No. 20 of 2018, s. 4, Applied:15 Oct 2018] insufficient distress then being found to be on the premises to counteract the money due; and (ii) the plaintiff's power to enter; and (d) the money due under the mortgage, encumbrance, or lease remaining unpaid – the Supreme Court may order that possession of the premises mentioned in the application be given by the mortgagor, encumbrancer, or lessee to the applicant on or before such day, not being less than 4 weeks from the day of hearing, as the Supreme Court thinks fit to specify, unless within that period all the money due and costs are paid. (6) [Section 146 Subsection (6) amended by No. 67 of 2003, s. 28, Applied:05 Mar 2004] If an order referred to in subsection (5) is not obeyed and money due and costs are not paid, the Supreme Court, subject to subsection (6A) , shall, at the instance of the applicant, on proof of the service of that order, or that after diligent search made the party named in the order cannot be found, issue a writ authorizing and requiring the Sheriff to give possession of the premises to the applicant. (6A) [Section 146 Subsection (6A) amended by No. 45 of 2013, s. 31, Applied:01 Oct 2014] [Section 146 Subsection (6A) inserted by No. 67 of 2003, s. 28, Applied:05 Mar 2004] A writ is not to be issued under subsection (6) unless at least 60 days' written notice is given to the tenant of the affected mortgagor. (7) Every writ referred to in subsection (6) shall be dated on the day next after the last day specified by the Supreme Court in the order for the delivery of the possession of the premises, and shall continue in force for not more than 3 months from that date. (8) [Section 146 Subsection (8) amended by No. 36 of 2012, s. 48, Applied:13 Nov 2012] In the case of a lessor against a lessee, the applicant shall, from the time of the execution of a writ referred to in subsection (6) , except as otherwise provided in this Division, hold the premises discharged of the tenancy. 147. Right of mortgagee of lease not to be barred Nothing in this Act extends to bar the right of a mortgagee or encumbrancee of a lease or any part of a lease who is not in possession if that mortgagee or encumbrancee, within 6 months after the execution of the writ referred to in section 146 , pays all rent in arrears and all costs and damages sustained by the lessor and performs all the covenants and agreements which, on the part and on behalf of the first lessee, are and ought to be performed. 148. Right of mortgagor or encumbrancer tendering principal, &c., and paying same to Treasurer to obtain discharge of mortgage, &c. (1) [Section 148 Subsection (1) amended by No. 20 of 2018, s. 5, Applied:15 Oct 2018] If before the day specified in an order under section 146(5) as the day on which possession of the premises to which the order relates is to be given the person having the right to redeem any mortgaged or encumbered land to which the order relates pays to the mortgagee or encumbrancee or, in the case of the mortgagee's or encumbrancee's refusal, tenders in court and pays to the Treasurer all the principal money and interest due on the mortgage or encumbrance and costs, the money so paid to the mortgagee or encumbrancee or to the Treasurer shall be deemed and taken to be in full satisfaction and discharge of the mortgage or encumbrance. (2) The Recorder, on the receipt of the Treasurer accompanied by a certificate of the Supreme Court that the money referred to in subsection (1) has been tendered and refused, shall record on the relevant folio of the Register or registered dealing that the mortgage or encumbrance is discharged, and on that recording the mortgaged or encumbered estate or interest shall cease to be charged with any money secured by the mortgage or encumbrance. 149. Registered proprietor protected against ejectment, except in certain cases (1) An action of ejectment or other action for the recovery of registered land shall not lie or be sustained against the person registered as proprietor of the land under this Act, except in the following cases: (a) a mortgagee as against a mortgagor in default; (b) an encumbrancee as against an encumbrancer in default; (c) a lessor as against a lessee in default; (d) a person deprived of land by fraud as against the person registered as proprietor of the land through fraud, or as against a person deriving, otherwise than as a transferee bona fide for value, from or through a person so registered through fraud; (e) a person deprived of or claiming land included in a folio of the Register evidencing the title to other land, by misdescription of that other land or of its boundaries, as against the registered proprietor of that other land, not being a transferee of that other land, or deriving from or through a transferee of that other land bona fide for value; (f) the registered proprietor of land which was first brought under this Act or the repealed Act as against another registered proprietor, in a case where 2 or more folios of the Register subsist for conflicting estates in the same land. (2) In any case not referred to in subsection (1) , the production of a certified copy of the relevant folio of the Register, or, in the case of leasehold land where no folio of the Register exists for the leasehold estate, a certified copy of the lease, shall be held in every court to be an absolute bar and estoppel to any action referred to in subsection (1) against the person named in that folio as registered proprietor of the land described in that folio or the lessee. (3) A certificate signed by the Recorder that no folio of the Register exists for the leasehold estate created by a lease registered under this Act shall be received in every court as evidence of that fact. (4) For the purposes of subsection (2) , certified means certified by the Recorder or by some officer acting on his behalf. Division 2 - The assurance fund and compensation from that fund 150. The assurance fund (1) The assurance fund created for the purposes of the repealed Act is continued for the purposes of this Act. (2) All sums of money received by the Recorder under this Act as contributions to the assurance fund shall be paid by him to the Treasurer who shall invest those sums together with all interest accruing on those sums to augment the fund continued by subsection (1) . (3) [Section 150 Subsection (3) amended by No. 36 of 2012, s. 49, Applied:13 Nov 2012] If the assurance fund is at any time reduced by claims on the fund to an amount less than $2 000 000, the Governor may make regulations providing that any of the fees prescribed in Schedule 3 be increased as prescribed, the increase to be a contribution to the assurance fund, until such time as that fund is increased to such sum as may be prescribed. 151. Assurance fund not liable in certain cases (1) The assurance fund is not liable for compensation for loss, damage, or deprivation – (a) occasioned by the breach by a registered proprietor of any trust, whether express, implied, or constructive; (b) where the same land has been included in two or more grants from the Crown; (c) arising out of a matter – (i) into which the Recorder or Deputy Recorder is exonerated from inquiry; or (ii) in respect of which either of them is protected from liability – by any enactment; or (d) [Section 151 Subsection (1) amended by No. 29 of 1997, s. 8, Applied:06 Nov 1997] occasioned by the inclusion of land with other land in the same folio of the Register through misdescription of boundaries or parcels; or (e) [Section 151 Subsection (1) amended by No. 29 of 1997, s. 8, Applied:06 Nov 1997] arising from any failure of the Recorder to include an interest in a folio if the interest was not revealed in a search of title relating to the relevant period provided by section 35 of the Conveyancing and Law of Property Act 1884 . (2) Notwithstanding anything contained in subsection (1) , the assurance fund is liable for compensation where a person deprived of land in the circumstances set out in subsection (1) (d) has obtained judgment for compensation or damages against a person liable for compensation or damages under section 152 and the latter person – (a) is dead; (b) cannot be found; (c) has become bankrupt; or (d) on the issue of a writ of fieri facias or warrant of execution to enforce the judgment, has been certified by the person charged with the duty of enforcing the writ or warrant to be unable to pay the full amount of the judgment. (3) In a case to which subsection (2) applies, the assurance fund is only liable for any money that the person deprived of land has not recovered from the person against whom he has obtained judgment. (4) [Section 151 Subsection (4) inserted by No. 29 of 1997, s. 8, Applied:06 Nov 1997] Notwithstanding paragraph (e) of subsection (1) , the assurance fund is liable for compensation for loss, damage or deprivation arising from any failure of the Recorder to include an interest in a folio if the interest was not revealed in a search of title relating to the relevant period referred to in that paragraph where the land was subject to this Act when the person obtained the interest in the land and where – (a) the interest would not have come to the notice of that person if, at the time he or she acquired that interest, he or she as a prudent purchaser had inspected the land; or (b) at the time compensation is claimed – (i) the interest, if it is an easement, could not be removed by the Recorder on an application by the registered proprietor under section 108 ; or (ii) in any other case, it could not be removed by the appropriate tribunal on an application by the registered proprietor under section 84C of the Conveyancing and Law of Property Act 1884 . 152. Compensation for party deprived of land (1) Subject to section 42 , a person deprived of land or of any estate or interest in land – (a) in consequence of fraud; (b) through the bringing of that land under this Act; (c) by the registration of another person as proprietor of that land, estate, or interest; or (d) in consequence of any error, omission, or misdescription in the Register – may bring an action for the recovery of damages. (2) An action referred to in subsection (1) shall – (a) in any case in which the land has been included in 2 or more grants, be brought against such person as the Governor may appoint as nominal defendant; or (b) in any other case, subject to the provisions of subsections (3) , (4) , (5) , (6) , (7) , and (8) , be brought against the person – (i) on whose application that land was brought under this Act; (ii) on whose application the erroneous registration was made; or (iii) who acquired title to the estate or interest in question through fraud, error, omission, or misdescription. (3) Where a person is deprived of land because it is brought under this Act pursuant to Division 3 of Part III and the title registered on the bringing of the land under this Act is not a qualified title subject to a general caution, the person who is first registered as proprietor of the land shall be regarded as the person on whose application the land was brought under this Act. (4) Where a person is deprived of land by the cancellation of a caution pursuant to section 21 (6) , the person who is the registered proprietor of the land at the time the caution is cancelled shall be regarded as the person on whose application the land was brought under this Act. (5) Where a person is deprived of land by the lapsing of a caution pursuant to section 25 , that person shall be deemed to have been deprived of land through the bringing of land under this Act, and the person who is the registered proprietor at the time the caution lapses shall be regarded as the person on whose application the land was brought under this Act. (6) In every case in which the fraud, error, omission, or misdescription occurs upon a transfer for value, the transferor receiving the consideration shall be regarded as the person on whose application the certificate of title was issued to the transferee. (7) Subject to section 127 , except in the case of fraud or of error occasioned by an omission, misrepresentation, or misdescription in his application or an instrument executed by him, the person on whose application the land was brought under this Act or the erroneous registration was made, shall, on the transfer of the land in good faith for value, cease to be liable for the payment of any damages which might have been recovered from him under this section. (8) In a case where a person referred to in subsection (7) – (a) ceases to be liable for the payment of damages as provided in that subsection; (b) is dead or bankrupt; or (c) cannot be found – the damages referred to in that subsection, with costs of action, may be recovered out of the assurance fund by action against the Recorder as nominal defendant. (9) In estimating damages referred to in subsection (7) , the value of all buildings and other improvements erected or made subsequent to the deprivation shall be excluded unless they were erected or made in good faith by the claimant or by some person through whom he claims before he or that person, as the case may be, was aware of any defect in the title to the land. (10) For the purposes of this section, a person who, but for the fraud or other act of any of the persons mentioned in subsection (2) , might have been possessed of any land, estate, or interest, or have been registered proprietor of any land, estate, or interest, shall be deemed to have been deprived of the land, estate, or interest. 153. When action may lie against Recorder as nominal defendant (1) Subject to this Act, a person sustaining loss or damage – (a) through an omission, mistake, or misfeasance of the Recorder or any of his officers in the execution of their duties under this Act; or (b) [Section 153 Subsection (1) amended by No. 36 of 2012, s. 50, Applied:13 Nov 2012] by the registration of any other person as proprietor of land (except where that other person was registered as proprietor pursuant to section 138D or section 138X ) or by an error, omission, or misdescription in the Register, and – (i) who is barred by section 149 from bringing an action of ejectment or other action for the recovery of land or an estate or interest in land; or (ii) to whose claim the remedy by action for damages pursuant to section 152 is inapplicable – may bring an action against the Recorder as nominal defendant for recovery of damages. (2) In estimating damages referred to in subsection (1) , the value of buildings and other improvements erected or made subsequent to the loss or deprivation shall be excluded unless they were erected or made in good faith by the claimant or by some person through whom he claims before he or that person, as the case may be, was aware of any defect in the title to the land. 154. Date of deprivation in certain cases [Section 154 Amended by No. 36 of 2012, s. 51, Applied:13 Nov 2012] Where a person is deprived of land by the registration of another person as proprietor pursuant to a vesting order under section 138D or section 138X , the date of deprivation shall, for the purpose of calculating the damages to which he is entitled, be deemed to be – (a) [Section 154 Amended by No. 36 of 2012, s. 51, Applied:13 Nov 2012] in the case of a vesting order under section 138X , the date on which he or his predecessors in title lost possession of the land; and (b) [Section 154 Amended by No. 36 of 2012, s. 51, Applied:13 Nov 2012] in the case of a vesting order under section 138D , the date mentioned in paragraph (a) or the date of the sale pursuant to which the vesting order was made, whichever is the earlier. 155. Person sustaining loss may apply for compensation (1) A person sustaining loss or damage in a case in which he is entitled to bring an action to recover damages against the Recorder as nominal defendant may, before commencing proceedings, make application in writing to the Recorder for compensation, and that application shall be supported by statutory declaration. (2) [Section 155 Subsection (2) amended by No. 100 of 1993, s. 5 ] [Section 155 Subsection (2) substituted by No. 36 of 2012, s. 52, Applied:13 Nov 2012] If the Recorder admits the claim, or any part of the claim, and the Minister certifies the claim, or part of the claim, as so admitted – (a) in a case where the claim, or part or the claim, that is so admitted and certified is less than $10 000, the Minister may, in his or her discretion, issue a warrant to the Treasurer for payment of the amount so certified out of the assurance fund; or (b) in a case where the claim, or part of the claim, that is so admitted and certified is $10 000 or more, the Governor may, in his or her discretion, issue a warrant to the Treasurer for payment of the amount so certified out of the assurance fund. (3) [Section 155 Subsection (3) inserted by No. 36 of 2012, s. 52, Applied:13 Nov 2012] The Treasurer is to pay the amount so certified in accordance with a warrant issued under subsection (2) . 156. Notice of action In a case in which an action for recovery of damages is permitted to be brought against the Recorder as nominal defendant as provided in this Division, notice in writing of that action and of the cause of that action shall be served on the nominal defendant at least one month before the commencement of that action. 157. Results of action (1) If in an action under this Division judgment is given in favour of the nominal defendant, or if the plaintiff discontinues or is non-suited, the plaintiff shall pay all costs of defending the action, and the costs when taxed may be levied by execution in the name of the nominal defendant. (2) If in an action under this Division the plaintiff recovers final judgment against the Recorder as nominal defendant, the Supreme Court shall certify the fact of the judgment and the amount of damages and costs recovered, and the amount of the damages and costs shall be paid to the person recovering the same, and shall be charged to the account of the assurance fund. (3) [Section 157 Subsection (3) amended by No. 9 of 2003, Sched. 1, Applied:16 Apr 2003] If the balance to the credit of the assurance fund is inadequate to pay the amount specified, such sum as may be necessary for that purpose shall be paid out of the Consolidated Fund, which to the necessary extent is appropriated accordingly, and the amount so advanced shall be repaid from the assurance fund as it accrues. 158. Limitation of actions (1) An action under section 152 or section 153 shall be deemed to be an action referred to in section 4 (1) (d) of the Limitation Act 1974 . (2) [Section 158 Subsection (2) amended by No. 36 of 2012, s. 53, Applied:13 Nov 2012] The plaintiff in an action referred to in subsection (1) , at whatever time it may be brought, or the plaintiff in an action for the recovery of land, shall be non-suited in any case in which the deprivation complained of may have been occasioned through the bringing of land under this Act or the making of a vesting order under section 138D or section 138X , if it appears to the court before which the action is tried that the plaintiff, or the person through whom he claims title, had notice or was aware that application had been made to bring the land under this Act or for a vesting order under section 138D or section 138X , and had, wilfully or collusively, omitted to lodge a caveat forbidding it, or had allowed that caveat to lapse. 159. Moneys paid out of assurance fund may be recovered (1) An amount paid out of the assurance fund on account of a person shall be deemed to be a debt due by that person to the Recorder and may be recovered accordingly. (2) Where an amount has been paid out of the assurance fund on account of a person who has real or personal estate in this State and who cannot be found in this State, a court of competent jurisdiction may, upon the application of the Recorder and upon the production of a certificate signed by the Treasurer certifying that the amount has been paid in satisfaction of a judgment against the Recorder as nominal defendant, allow the Recorder to enter judgment against that person for the amount so paid out of the assurance fund together with the costs of the application. (3) A judgment referred to in subsection (2) is final, and execution may issue immediately. (4) Notwithstanding anything contained in the Limitation Act 1974 , if a person referred to in subsection (2) has not left real or personal estate in this State sufficient to satisfy the amount for which execution may have been issued under this section, the Recorder may recover that amount, or the unrecovered balance of the amount, by action against that person whenever he may be found. PART XII - General Powers, Duties, and Immunities of Recorder 160. General powers of Recorder (1) [Section 160 Subsection (1) amended by No. 43 of 1991, s. 5 and Sched. 1 ] [Section 160 Subsection (1) amended by No. 21 of 1996, s. 16 ] The Recorder may require a person who has custody, possession, or control of any instrument relating to land which is the subject of a dealing lodged with him under this or any other Act, or relating to the title to land, to produce that instrument, and he may retain an instrument, whether produced pursuant to this subsection or otherwise, until it is no longer required for action in connection with a dealing lodged with him or in connection with the bringing of land under this Act; and if that person refuses or neglects to produce that instrument he is guilty of an offence and is liable on summary conviction to a fine not exceeding 5 penalty units. (2) [Section 160 Subsection (2) amended by No. 21 of 1996, s. 16 ] The Recorder may conduct an inquiry concerning any land, title to land, or instrument affecting or relating to land which is the subject of a dealing or application lodged with him under this or any other Act; and, if an instrument which the Recorder has required under subsection (1) is withheld, or if a person summoned to attend an inquiry under this subsection fails to attend or refuses or neglects to give an explanation or information which he is required to give at the inquiry, the Recorder is not bound to proceed with the application or register the dealing under this or any other Act. (3) The Recorder may record a caveat on behalf of a person under disability (within the meaning of the Limitation Act 1974 ), or on behalf of the Crown, to prohibit the transfer or dealing with land belonging or supposed to belong to such a person or the Crown, and also to prohibit the dealing with land where it appears to him that an error has been made by misdescription of that land, or otherwise in any certificate of title or other instrument, or for the prevention of fraud or improper dealing, and sections 135 and 137 apply where the Recorder records a caveat pursuant to this subsection. (4) The Recorder may, on such evidence as appears to him to be sufficient, record in the Register any change in the name of a registered proprietor or a notification of the full and correct name of a registered proprietor if he is satisfied that that name differs from the name of that proprietor as set forth in the Register. (5) Notwithstanding anything in this Act, the Recorder may at his discretion dispense with the production to him of any instrument or document, or the duplicate of any instrument or document, or the supply of any information, or any advertisement or notice. (6) [Section 160 Subsection (6) substituted by No. 71 of 1995, s. 3 and Sched. 1 ] Section 8 and Part 3 of the Commissions of Inquiry Act 1995 apply to an inquiry or hearing that the Recorder is by this or any other Act authorized or required to make or hold as if – (a) the Recorder were a Commission established under section 4 of the Commissions of Inquiry Act 1995 ; and (b) the matter the subject of the inquiry or hearing were the matter into which that Commission had been directed to inquire under that Act. (7) [Section 160 Subsection (7) inserted by No. 4 of 2001, s. 17, Applied:12 Apr 2001] If the Recorder is satisfied that the inquiry or hearing was occasioned by frivolous or vexatious conduct by a party to the inquiry or hearing, the Recorder may order that party to pay the reasonable costs of the inquiry or hearing. (8) [Section 160 Subsection (8) inserted by No. 4 of 2001, s. 17, Applied:12 Apr 2001] An order made under subsection (7) may be enforced as if it were a judgment made by a competent court of summary jurisdiction. 161. Recorder may state case for Supreme Court (1) The Recorder may, whenever any question arises with regard to the performance of any of the duties or the exercise of any of the functions by this or any other Act conferred or imposed upon him, state a case for the opinion of the Supreme Court. (2) Where a case has been stated for the opinion of the Supreme Court in accordance with subsection (1) , the Supreme Court may give judgment on the case, and that judgment is binding on the Recorder. 162. Recorder may require map to be deposited (1) [Section 162 Subsection (1) amended by No. 36 of 2012, s. 54, Applied:13 Nov 2012] The Recorder may require the proprietor applying under section 11 to have land brought under this Act, applying under section 108 for the release or partial release of an easement or profit à prendre , or desiring to transfer or otherwise deal with land, to deposit with the Recorder a map or plan of the land complying with the requirements of the Recorder, expressed generally or for the particular case, and the map or plan shall, if the Recorder so requires, be made from an actual survey and certified as correct by a surveyor registered and certificated under the Surveyors Act 2002 . (2) If a proprietor referred to in subsection (1) neglects or refuses to comply with the Recorder's requirements, the Recorder may refuse to proceed with the bringing of the land under this Act or with the registration of the transfer or other dealing. 163. Power of Recorder to call in certificate of title, &c., in certain cases (1) Where it appears to the satisfaction of the Recorder that – (a) a certificate of title, grant, or duplicate registered dealing has been issued in error or contains a misdescription of land or of boundaries; (b) a recording has been made in error on a certificate of title, grant, or duplicate registered dealing; (c) a certificate of title, grant, or recording in the Register has been fraudulently or wrongfully obtained; (d) a certificate of title, grant, or duplicate registered dealing is fraudulently or wrongfully retained; or (e) it is necessary for him to have the certificate of title, grant, or duplicate registered dealing for the purpose of registering a dealing, or of cancelling, correcting, or otherwise dealing with the certificate, grant, or duplicate, or for the purpose of inspection in case of the loss, destruction, or obliteration of a folio of the Register or registered dealing – or the Recorder is, by this or any other Act, required or authorized to call in, or require a person to produce to him, a certificate of title, grant, or duplicate registered dealing, he may summon the person to whom that certificate, grant, or duplicate has been so issued, or by whom it has been so obtained or is retained, or who has the custody, possession, or control of it, to deliver up that certificate, grant, or duplicate for the purpose of registration, or of being cancelled, corrected, or otherwise dealt with, or inspected, as the case may require. (2) Where a person referred to in subsection (1) refuses or neglects to comply with a summons referred to in that subsection, the Recorder may apply to a judge to issue a summons for that person to appear before the Supreme Court and show cause why the certificate, grant, or duplicate referred to in that subsection should not be delivered up for the purpose of registration, or to be cancelled, corrected, or otherwise dealt with, or inspected, as mentioned in that subsection. (3) Where a person referred to in subsection (1) – (a) cannot be found within a reasonable time, so that the summons referred to in that subsection cannot be served upon him; or (b) is residing out of the State and refuses or neglects to comply with a summons referred to in that subsection – the Recorder may, if in his opinion the circumstances of the case require it, act as authorized by section 35 or section 160 (5) . (4) If a person referred to in subsection (1) , when served with a summons referred to in subsection (2) , neglects or refuses to attend before the Supreme Court at the time appointed in the summons, the Court may issue a warrant authorizing and directing the person so summoned to be arrested and brought before the Court for examination. 164. Powers of Court and Recorder (1) On the appearance before the Supreme Court of any person summoned or brought up by virtue of a warrant under section 163 , the Court may examine that person on oath, and, where the Court considers it necessary, may order that person to deliver up the certificate of title, grant, or duplicate registered dealing in accordance with section 163 , and on the refusal or neglect by that person to deliver it up pursuant to that order may commit that person to prison. (2) Where a person – (a) who has been summoned pursuant to section 163 (2) cannot be found, so that he cannot be arrested and brought before the Court for examination under section 163 (4) ; or (b) has been committed to prison – the Recorder may, if in his opinion the circumstances of the case require it, act as authorized by section 35 or section 160 (5) . 165. Protection of Recorder (1) The Recorder, in registering a dealing or in bringing land under this Act – (a) need not make any inquiry not required of; (b) is not bound by any notice that would not bind; and (c) has the same protection as if he were – a purchaser as defined in the Conveyancing and Law of Property Act 1884 . (2) Where a person registered as the personal representative of a deceased proprietor deals with land, or an estate or interest in land, which has devolved upon him under the Administration and Probate Act 1935 by way of – (a) assent; (b) mortgage; (c) lease; or (d) transfer for value to a purchaser who does not appear on the face of the transfer to be a personal representative, or trustee of the will, of the deceased proprietor, or the spouse or child of a personal representative, or trustee of the will, of a deceased proprietor – the Recorder shall not be concerned to consider, or to call for any information concerning, the reason why the assent, mortgage, lease, or transfer is made, or the terms of the will, and, whether he has notice or not of its contents, he is entitled to assume that the personal representative is acting correctly and within his powers. (3) The Recorder is not individually, nor is any person acting under his authority, liable to any action or proceeding for or in respect of any act or matter in good faith done, or omitted to be done, in the exercise or supposed exercise of the powers of this Act. 166. Payment of money received by Recorder to persons entitled under this Act (1) [Section 166 Subsection (1) amended by No. 68 of 1994, s. 3 and Sched. 1 ] Any money received by the Recorder or by the Treasurer, in trust or otherwise, on account of absentee mortgagees or other persons entitled under this Act, shall be paid into the Consolidated Fund. (2) [Section 166 Subsection (2) amended by No. 68 of 1994, s. 3 and Sched. 1 ] Any money paid into the Consolidated Fund pursuant to subsection (1) shall, on the receipt of a requisition from the Recorder and with the approval of the Treasurer, be paid to any person entitled to that money under this Act. (3) [Section 166 Subsection (3) amended by No. 68 of 1994, s. 3 and Sched. 1 ] The Consolidated Fund is, by force of this subsection, appropriated to such extent as may be necessary to give effect to subsection (2) . PART XIII - Miscellaneous 167. Jurisdiction in relation to offences Prosecutions for offences under this Act may be instituted by the Attorney-General or the Recorder and no other person. 168. Service, &c., of notices (1) A notice that is required or authorized by this Act to be given to or served on a person may be given to or served on that person – (a) by posting it as prescribed to his address for service (within the meaning of this section) or to his last-known place of abode or business; or (b) [Section 168 Subsection (1) amended by No. 4 of 2001, s. 18, Applied:12 Apr 2001] by leaving it at his address for service (within the meaning of this section) or at his last-known place of abode or business; or (c) [Section 168 Subsection (1) amended by No. 4 of 2001, s. 18, Applied:12 Apr 2001] by sending it by way of facsimile transmission to a service operated or used by the person; or (d) [Section 168 Subsection (1) amended by No. 4 of 2001, s. 18, Applied:12 Apr 2001] by any other form of transmission of messages electronically where the Recorder is satisfied that the person to be notified will receive the notice; or (e) [Section 168 Subsection (1) amended by No. 4 of 2001, s. 18, Applied:12 Apr 2001] by a method of postal service where evidence may be provided that the notice has been received by the person to be notified. (2) [Section 168 Subsection (2) amended by No. 53 of 2004, Sched. 1, Applied:16 Feb 2005] [Section 168 Subsection (2) amended by No. 102 of 2001, Sched. 2, Applied:28 Jun 2002] [Section 168 Subsection (2) amended by No. 46 of 1991, s. 4 and Sched. 2 ] The address of a person, set forth in any instrument by which that person becomes a registered proprietor or in a caveat lodged by or on behalf of that person, or in a valuation roll prepared pursuant to the Valuation of Land Act 2001 , or in an electoral roll kept pursuant to the Electoral Act 2004 , may, for the purposes of this section, be treated as his address for service. (3) On being notified in writing by a registered proprietor or a caveator of any change of the proprietor's or caveator's address, the Recorder shall alter that address as set forth in any instrument specified by the proprietor (being an instrument by which he became a registered proprietor) or in the caveat, or otherwise record the change of address as prescribed. (3A) [Section 168 Subsection (3A) inserted by No. 4 of 2001, s. 18, Applied:12 Apr 2001] Where notice is required to be given under this Act before a dealing, instrument or other document is deposited or lodged with the Recorder and the Recorder is of opinion that the notice was inaccurate or insufficient, the Recorder may require that a supplementary notice be given in accordance with this Act. (4) Notwithstanding anything in the foregoing provisions of this section, if for any special reason the Recorder thinks it desirable to do so he may direct any notice to be given or served in such manner as he may specify, either in addition to, or in substitution for, the mode of giving or serving notice prescribed in those provisions. (4A) [Section 168 Subsection (4A) inserted by No. 4 of 2001, s. 18, Applied:12 Apr 2001] Where – (a) a person is required to notify interested persons of an application under this Act; and (b) the notice is not given within the required time – the Recorder may, if it appears that it would be harsh and unconscionable to refuse the application – (c) extend the time for giving the notice; and (d) require the applicant to give further notice in such manner as the Recorder may direct; and (e) reinstate any objection or caveat lodged in respect of the application. (5) [Section 168 Subsection (5) inserted by No. 4 of 2001, s. 18, Applied:12 Apr 2001] Notwithstanding anything in this Act, if for any special reason the Recorder thinks it desirable to do so, he or she may dispense with a requirement to advertise or to give notice under this Act. (6) [Section 168 Subsection (6) inserted by No. 36 of 2012, s. 55, Applied:13 Nov 2012] If the Recorder considers it desirable in the interests of procedural fairness and the administration of this Act, he or she may require a person depositing or lodging an application, dealing, instrument or other document to do one or more of the following: (a) advertise in one or more newspapers published and circulating in Tasmania, as determined by the Recorder; (b) give notice to a person the Recorder considers to have an interest in the application, dealing, instrument or other document; (c) post notice of the application, dealing, instrument or other document on the relevant land. 169. [Section 169 Repealed by No. 21 of 1996, s. 17 ] . . . . . . . . 169A. Power of Recorder to approve forms [Section 169A Inserted by No. 21 of 1996, s. 17 ] (1) [Section 169A Subsection (1) amended by No. 9 of 2003, Sched. 1, Applied:16 Apr 2003] [Section 169A Subsection (1) amended by No. 68 of 2000, s. 62, Applied:04 Apr 2001] [Section 169A Subsection (1) substituted by No. 10 of 2000, s. 12, Applied:28 Apr 2000] The Recorder may approve forms for use under this Act, the Powers of Attorney Act 2000 , the Public Trusts Act 1882 , the Registration of Deeds Act 1935 , the Strata Titles Act 1998 and any other law which requires documents to be lodged with the Recorder. (2) An approval of a form does not have effect until 14 days after notice of the approval is given and published in accordance with subsection (3) . (3) Where the Recorder approves a form under subsection (1) – (a) the Recorder must give written notification of the approval to the Law Society of Tasmania and cause notice of the approval to be published – (i) in the publication known as the Land Titles Office Practice Book published by the Recorder and in any other publication published by the Recorder relating to the practice and procedure of the Land Titles Office; and (ii) in each daily newspaper circulating generally in Tasmania with a statement that any new or amended form is available from the Land Titles Office; and (iii) in such other manner as the Recorder thinks fit; and (b) the Recorder may supply the form bearing the seal of office used under section 6 , free of charge or at a moderate charge; and (c) the Recorder may license persons to print and sell the form bearing the seal of office used under section 6 ; and (d) any previous approval under subsection (1) of a form for the same purpose ceases to have any force or effect. (4) Where the Recorder approves a form under subsection (1) , the Recorder may register, record or grant, as the case may be, any dealing or instrument that is lodged within a period of 12 months after the approval and takes the form required immediately before the approval. (5) The Recorder may, on receipt of the prescribed fee – (a) approve a form that has been prepared by a person with the object of selling it for use by other persons; and (b) license that person to print and sell the form being the seal of office used under section 6 . (6) Subject to subsection (11) , where the Recorder approves a form under subsection (5) , any previous approval under that subsection of a form for the same purposes ceases to have any force or effect. (7) Where the Recorder approves a form under subsection (5) , the Recorder may register, record or grant, as the case may be, any dealing or instrument that is lodged within a period of 12 months after the approval and takes the form required immediately before the approval. (8) The Recorder may, on receipt of the prescribed fee – (a) approve a form under subsection (1) ; and (b) authorise a person to print the form, bearing the seal of office used under section 6 , for use by that person. (9) Subject to subsection (11) , where the Recorder approves a form under subsection (8) for use by a person, any previous approval under that subsection of a form for use by that person for the same purpose ceases to have effect. (10) Where the Recorder approves a form under subsection (8) , the Recorder may register, record or grant, as the case may be, any dealing or instrument that is lodged within the period of 12 months after the approval and takes the form required immediately before the approval. (11) A form approved under subsection (1) , (5) or (8) is to specify – (a) the full names of the parties to the dealing to which the form relates; and (b) a description of the land affected by the dealing; and (c) the nature of the transaction to be effected by the dealing – and on any such approval, the Recorder may register, record or grant, as the case may be – (d) any dealing or instrument that the Recorder is satisfied – (i) takes the form required by this Act at the time of its execution; or (ii) is in accordance with a form previously approved under this section; or (e) any dealing or instrument that contains departures, otherwise than in matters of substance, from an approved form but is sealed with the seal of office used under section 6 as if it were in an approved form. 169B. False representation as to approved forms [Section 169B Inserted by No. 21 of 1996, s. 17 ] (1) If a person falsely represents that a form has been approved for use as mentioned in section 169A , that person must indemnify any other person who suffers loss, damage or deprivation in relying on the form. (2) An indemnity under subsection (1) does not create any right to compensation from the assurance fund. 169C. Recording of common provisions [Section 169C Inserted by No. 21 of 1996, s. 17 ] (1) A person may lodge with the Recorder a memorandum in the approved form containing one or more provisions which are intended for inclusion in dealings and instruments to be lodged subsequently for registration. (2) The Recorder may retain a memorandum lodged under subsection (1) . (3) The Recorder may prepare and retain a memorandum containing any provisions which seem appropriate for inclusion in dealings and instruments to be lodged subsequently for registration. (4) A memorandum retained by the Recorder pursuant to this section is to be taken, for the purposes of section 36 , to be part of the Register. 169D. Incorporation of common provisions [Section 169D Inserted by No. 21 of 1996, s. 17 ] A dealing or instrument lodged with the Recorder may incorporate a common provision lodged with the Recorder by reference to the provision in a way sufficient to identify it clearly. 169E. Prescribed fees [Section 169E Inserted by No. 21 of 1996, s. 17 ] [Section 169E Substituted by No. 98 of 2001, s. 10, Applied:01 Jan 2002] (1) [Section 169E Subsection (1) amended by No. 35 of 2005, s. 4, Applied:15 Sep 2005] Subject to section 169EA , the fees prescribed in Schedule 3 are payable under this Act for the matters to which they respectively relate. (2) A prescribed fee – (a) is to be paid to the Recorder or an agent appointed by the Recorder; and (b) may be paid in any manner approved by the Recorder. (3) A person may, if so authorised by the Recorder or an agent appointed by the Recorder for the purpose, pay a prescribed fee after the transaction to which it relates. 169EA. Exemptions from fees [Section 169EA Inserted by No. 35 of 2005, s. 5, Applied:15 Sep 2005] (1) A fee is not payable under this Act for – (a) a dealing for the purposes of, or in accordance with – (i) an agreement, deed or other instrument referred to in section 90(1) of the Family Law Act 1975 of the Commonwealth; or (ii) an order made under the Relationships Act 2003 or a prescribed agreement; or (b) a deed or other instrument executed by a person for the purposes of, or in accordance with, an order or financial agreement made under Part VIIIA of the Family Law Act 1975 of the Commonwealth. (2) In this section – prescribed agreement means an agreement that is – (a) a personal relationship agreement or separation agreement within the meaning of the Relationships Act 2003 ; and (b) in accordance with paragraphs (b) , (c) , (d) and (e) of section 62(1) of that Act . 169F. Validation [Section 169F Inserted by No. 98 of 2001, s. 10, Applied:01 Jan 2002] No regulation that prescribed a fee for the purposes of this Act before the commencement of the Registration and Related Fees Act 2001 is to be taken as having ever been invalid by reason only of the amount of the fee so prescribed. 170. Regulations [Section 170 Substituted by No. 21 of 1996, s. 17 ] (1) The Governor may make regulations for the purposes of this Act. (2) Without limiting subsection (1) , the regulations may – (a) prescribe the manner in which dealings are to be lodged for registration and the circumstances in which the Recorder may refuse to accept dealings for lodgment; and (b) [Section 170 Subsection (2) amended by No. 66 of 2007, Sched. 1, Applied:31 Dec 2008] provide for the conduct of official searches of the Register, including provision for compensation from the assurance fund for a person suffering loss or damage arising from an error in an official search and exonerating a legal practitioner or other person in respect of loss that may arise from an error in an official search; and (c) [Section 170 Subsection (2) amended by No. 36 of 2012, s. 56, Applied:13 Nov 2012] require any approved form or other form approved by the Recorder to be in the form of, or to have the same effect as, a statutory declaration; and (d) require the substantiation by statutory declaration of all or any information given in an approved form which is not in the form of a statutory declaration; and (e) provide for the meaning to be attached to a provision specified in a particular form in a dealing; and (f) [Section 170 Subsection (2) amended by No. 98 of 2001, s. 11, Applied:01 Jan 2002] . . . . . . . . (g) [Section 170 Subsection (2) amended by No. 98 of 2001, s. 11, Applied:01 Jan 2002] . . . . . . . . (h) [Section 170 Subsection (2) amended by No. 98 of 2001, s. 11, Applied:01 Jan 2002] . . . . . . . . (i) prescribe the fees, charges and expenses to be paid by persons licensed to print and sell approved forms, whether fixed by reference to the period of the licence, the number of forms sold or to be sold, or otherwise; and (j) provide for the approval and sealing of forms for use under this Act, including fees to be paid for the approval and sealing. (3) Subsection (2) (e) does not apply to a conveyance or other deed referred to in section 75A of the Conveyancing and Law of Property Act 1884 so far as the conveyance or deed contains the short provisions specified in Schedule 6 to that Act. 170A. Combination of forms [Section 170A Inserted by No. 21 of 1996, s. 17 ] (1) [Section 170A Subsection (1) amended by No. 10 of 2017, s. 17, Applied:01 Jul 2017] [Section 170A Subsection (1) amended by No. 102 of 2001, Sched. 1, Applied:28 Jun 2002] An approved form may be combined with, or may be lodged simultaneously with, a form approved by the Recorder for the purposes of section 121 of the Local Government Act 1993 . (2) [Section 170A Subsection (2) amended by No. 10 of 2017, s. 17, Applied:01 Jul 2017] If a form under section 121 of the Local Government Act 1993 does not comply with that Act, the dealing to which it relates is taken to be not in accordance with this Act. (3) [Section 170A Subsection (3) amended by No. 10 of 2017, s. 17, Applied:01 Jul 2017] The Recorder may, of his or her own motion, correct a patent error in a form under section 121 of the Local Government Act 1993 by notation in the margin of the form and, after an error is so corrected, the dealing has the same validity as if the error had not been made. 170B. Duty of Recorder to transmit certain information [Section 170B Inserted by No. 21 of 1996, s. 17 ] [Section 170B Amended by No. 102 of 2001, Sched. 1, Applied:28 Jun 2002] [Section 170B Amended by No. 46 of 2008, s. 31, Applied:18 Nov 2008] [Section 170B Substituted by No. 10 of 2017, s. 18, Applied:01 Jul 2017] (1) The Recorder must, as soon as practicable after receiving a notice under section 121 of the Local Government Act 1993 in relation to land within a municipal area, transmit details of the notice to the general manager of the council in relation to the municipal area. (2) The Recorder must provide to the Commissioner of State Revenue – (a) the information, as specified in a notice received by the Recorder under section 121 of the Local Government Act 1993 ; and (b) the information, about the dealing to which the notice relates – that the Commissioner of State Revenue requires for the purposes of any Act related to taxation and requests the Recorder to provide to him or her. (3) The Recorder must provide to the Valuer-General – (a) the information, as specified in a notice received by the Recorder under section 121 of the Local Government Act 1993 ; and (b) the information, about the dealing to which the notice relates – that the Valuer-General requires for the purposes of the Valuation of Land Act 2001 and requests the Recorder to provide to him or her. 171. The amendments effected by this section have been incorporated into the authorised version of the appropriate Acts. 172. Transitional provision (1) [Section 172 Subsection (1) amended by No. 21 of 1996, s. 18 ] [Section 172 Subsection (1) substituted by No. 4 of 2001, s. 19, Applied:12 Apr 2001] Where an application made under Division 12 of Part VI, as in force immediately before the commencement of the Land Titles Amendment (Law Reform) Act 2001 , has not been finally dealt with before that commencement, the Recorder must, on and after that commencement, take whichever of the following courses of action he or she considers to be the more favourable to the applicant: (a) deal with the application as if that Act had not been enacted; (b) deal with the application as if it had been made under this Act after that commencement. (2) [Section 172 Subsection (2) inserted by No. 21 of 1996, s. 18 ] Where, immediately before the commencement of this subsection, a form was prescribed and in force under the regulations, that form continues to be in force until the Recorder approves another form to be used in its place under section 169A . 173. Repeal (1) The Acts specified in Schedule 2 are repealed. (2) All lands, estates, and interests which at the proclaimed date are subject to any of the Acts repealed by subsection (1) shall be subject to this Act. SCHEDULE 1 - Consequential Amendments [Schedule 1 Amended by No. 99 of 1982, s. 3 and Sched. 2 ] [Schedule 1 Amended by No. 51 of 1985, s. 4 and Sched. 2 ] Section 171 The amendments effected by this Schedule have been incorporated into the authorised version of the appropriate Acts. SCHEDULE 2 - ACTS REPEALED Section 173 Year and number of Act Short title of Act 25 Vict. No. 16 Real Property Act 1862 42 Vict. No. 9 Real Property Act 1878 50 Vict. No. 8 Real Property Act 1886 57 Vict. No. 5 Real Property Act 1893 24 Geo. V No. 26 Real Property (Commonwealth Titles) Act 1933 No. 94 of 1973 Real Property (Special Vesting Orders) Act 1973 No. 56 of 1976 Real Property Act 1976 No. 30 of 1978 Real Property (Special Vesting Orders) Act 1978 SCHEDULE 3 - Prescribed fees [Schedule 3 Inserted by No. 98 of 2001, s. 12, Applied:01 Jan 2002] Section 169E Item Matter for which fee is payable Fee $ (1) Applications, caveats and dealings 1. Lodgment of a dealing, instrument or withdrawal of caveat, request or application (other than an application made by a person for a change of name following a change in the person's family status) or making an entry or entering a memorial or notification for which a fee is not otherwise prescribed 85.50 2. Lodgment for registration of a memorandum of transfer 131.00 3. Lodgment of a caveat, discharge of mortgage or discharge of charge 106.00 4. Lodgment for registration of a memorandum granting land of the Crown 131.00 (2) Copies 5. Application or request for a copy of a single document, dealing, instrument, plan, strata plan, building title plan or diagram or part of a single document, dealing, instrument, plan, strata plan, building title plan or diagram or the field notes or survey notes of a single plan or diagram – (a) if the copy is prepared by a photocopying process, transparency process, electronic process or facsimile process, for a copy of a single folio of the Register, dealing, instrument or document or part of a single folio of the Register, dealing, instrument or document 20.00 (b) if a typed copy is requested 20.00 In addition, for each hour or part of an hour to prepare the copy 20.00 (c) in addition to any fee under paragraph (a) or (b) , if the application or request is received, or the copy is to be despatched, by post, and no reference number or an incorrect reference number is quoted 30.00 In addition, for each hour or part of an hour taken to search for the copy 20.00 (3) Certification 6. Application or request for the certification by the Recorder, Deputy Recorder or Assistant Recorder of a copy of a single document, dealing, instrument, plan or diagram or part of a single document, dealing, instrument, plan or diagram or the field notes or survey notes of a single plan or diagram, either as a machine copy or print made from a transparency 50.50 In addition, for each hour or part of an hour taken to prepare the copy for certification 30.00 (4) Notices 7. Lodgment of a priority notice or notice of withdrawal of priority notice 15.10 8. For preparing and serving notice to a caveator of intention to register a dealing under section 136 85.50 (5) Maps and plans 9. Lodgment of each map, plan or building title plan 505.00 In addition, for each parcel shown on that map, plan or building title plan 50.50 10. Lodgment of a plan prepared solely for the purpose of placing survey information on public record 50.50 11. Lodgment of an application to amend a plan 505.00 In addition, if the application involves the amendment of the Register, for each certificate of title to issue pursuant to such amendment 50.50 12. Supply of a plan for which a fee is not otherwise prescribed 505.00 In addition, for each hour or part of an hour taken to prepare the plan 50.50 (6) Sealing of instruments 13. Examination and sealing of an instrument or dealing not prepared on a form bearing the Recorder's seal 85.50 14. Lodgment of a request for the sealing of a printed form 85.50 (7) Miscellaneous 15. Application or request to search a single folio of the Register (including the face plan of the plan supporting that folio), dealing, instrument or document 20.00 16. Request to search for and supply copies of plans and field notes relevant to one specified proposed survey 30.00 In addition, for each hour or part of an hour taken to comply with the request 20.00 17. Exhibiting deeds surrendered by the applicant 30.00 18. Each requisition made by the Recorder – (a) for payment of additional fees 15.10 (b) under section 50 30.00 (c) under section 143B 30.00 19. Lodgment of requisition for statement of grounds under section 144 85.50 20. Lodgment of objection to correction of plan or accompanying document under section 143C 30.00 You are directed to information on how your personal information is protected. You are directed to a disclaimer and copyright notice governing the information provided.
https://www.legislation.tas.gov.au/view/whole/html/inforce/2019-05-27/act-1980-019
Coatings | Free Full-Text | Surface Structuring of Diamond-Like Carbon Films by Chemical Etching of Zinc Inclusions A diamond-like carbon (DLC) film with a nanostructured surface can be produced in a two-step process. At first, a metal-containing DLC film is deposited. Here, the combination of plasma source ion implantation using a hydrocarbon gas and magnetron sputtering of a zinc target was used. Next, the metal particles within the surface are dissolved by an etchant (HNO3:H2O solution in this case). Since Zn particles in the surface of Zn-DLC films have a diameter of 100–200 nm, the resulting surface structures possess the same dimensions, thus covering a range that is accessible neither by mask deposition techniques nor by etching of other metal-containing DLC films, such as Cu-DLC. The surface morphology of the etched Zn-DLC films depends on the initial metal content of the film. With a low zinc concentration of about 10 at.%, separate holes are produced within the surface. Higher zinc concentrations (40 at.% or above) lead to a surface with an intrinsic roughness. Surface Structuring of Diamond-Like Carbon Films by Chemical Etching of Zinc Inclusions by Ruriko Hatada 1 , Stefan Flege 1,* , Berthold Rimmler 1 , Christian Dietz 1 , Koumei Baba 2 1 Department of Materials Science, Technische Universität Darmstadt, 64287 Darmstadt, Germany 2 SANNO Co., Ltd., Yokohama 223-0052, Japan * Author to whom correspondence should be addressed. Coatings 2019 , 9 (2), 125; https://doi.org/10.3390/coatings9020125 Received: 31 December 2018 / Revised: 14 February 2019 / Accepted: 15 February 2019 / Published: 18 February 2019 Versions Notes Abstract : A diamond-like carbon (DLC) film with a nanostructured surface can be produced in a two-step process. At first, a metal-containing DLC film is deposited. Here, the combination of plasma source ion implantation using a hydrocarbon gas and magnetron sputtering of a zinc target was used. Next, the metal particles within the surface are dissolved by an etchant (HNO 3 :H 2 O solution in this case). Since Zn particles in the surface of Zn-DLC films have a diameter of 100–200 nm, the resulting surface structures possess the same dimensions, thus covering a range that is accessible neither by mask deposition techniques nor by etching of other metal-containing DLC films, such as Cu-DLC. The surface morphology of the etched Zn-DLC films depends on the initial metal content of the film. With a low zinc concentration of about 10 at.%, separate holes are produced within the surface. Higher zinc concentrations (40 at.% or above) lead to a surface with an intrinsic roughness. Keywords: surface morphology ; deposition ; metal ; etching ; dealloying ; nanostructures Graphical Abstract 1. Introduction Diamond-like carbon (DLC) films combine a number of advantageous properties, such as chemical inertness, low wear and friction coefficient, high hardness, corrosion resistance and biocompatibility [ 1 , 2 ]. Furthermore, DLC films tend to be very smooth. Thin DLC films deposited on a featureless substrate, for instance a commercial polished silicon wafer, can exhibit the same average roughness as the substrate [ 3 , 4 ]. On substrates with a moderate roughness, the film surface smoothens as the DLC film grows [ 5 ]. In some applications, e.g. the coating of medical implants, a higher surface roughness is desirable, however, because a rough surface promotes cell adhesion [ 6 ]. Different cell types favor specific roughness ranges, i.e. the roughness has to be optimized in this regard [ 7 ]. In tribological applications that involve liquid lubricants, surface cavities can entrap lubricant, thereby enhancing lubrication [ 8 ]. Several approaches have been utilized so far to prepare a DLC film with an inherent nanostructure. DLC deposition on an already structured surface shifts the task of structuring to the substrate. However, with mechanical and simple chemical methods it is difficult to produce a defined roughness [ 9 ]. When using a structured substrate, it has to be ensured that a homogeneous deposition can be accomplished. Thicker films will decrease the roughness, as mentioned above. Another approach is the DLC deposition on a partially masked surface. Metallic masks [ 10 , 11 ] and powder particles [ 12 ] have been used in this context to prevent localized deposition on the substrate. Especially with masks, only a coarse patterning with dimensions of several tens of µm is achievable. Another possibility is the subsequent structuring of an initially smooth DLC film. If the partial, laterally resolved removal of the film involves focused beams, e.g., one [ 13 ] or several laser beams [ 14 , 15 ] or an ion beam [ 16 ], the process is slow and costly. In summary, these techniques either produce surface structures with dimensions in the µm range or they are not suitable for the treatment of large areas. Porous carbon can be produced by various means. The techniques using high-temperature treatment of an organic precursor [ 17 , 18 ] are not suitable for every substrate, though. Bouts et al. [ 19 ] presented a concept based on the removal of copper from a copper-containing DLC film. This is the inversion of a technique described before, which dry etched Ag-DLC films with CF 4 /O 2 to reveal the embedded Ag particles [ 20 ]. Metal particles in a DLC film form clusters, with their size and distance depending on the metal content. The particle (cluster) size rarely exceeds 10 nm for a metal content of a few ten percent [ 21 ]. If the substrate contains percolated nanoparticles (as is the case for Cu concentrations above 60 at.% [ 19 ]), etching will result in sponge-like carbon thin films. Etching of non-percolated nanoparticles will lead to a roughening of the surface. The etching or dealloying technique is either limited to pore sizes of up to about 10 nm or a porous structure is produced which deteriorates film properties such as corrosion and wear resistance. The technique presented here uses larger metal clusters. For a few metals, such as silver [ 22 , 23 ], the metal particles in the surface of a metal-DLC film can be considerably larger than the 10 nm mentioned above. Thus, the holes produced by etching will be correspondingly larger. To demonstrate the feasibility of this approach, not silver- but zinc-containing DLC (Zn-DLC) films were used. With zinc, the electrical conductivity of a DLC film can be increased [ 24 , 25 ] as well as its adhesion [ 24 ]. Zinc is biocompatible [ 26 ] and biodegradable [ 27 ] and thus suitable to be used in coatings of medical implants. Additionally, when preparing Zn-DLC films by plasma source ion implantation and deposition (PSII) [ 28 ], the zinc particles within the surface of the DLC film tend to have a diameter of several ten nm, even with average Zn contents as low as 9.6 at.% [ 29 ]. 2. Materials and Methods The samples were prepared on a silicon substrate. Pieces with an edge length of 15–20 mm were cut from a commercial silicon wafer (CZ grown, single side polished, <100> orientation, P type (boron doped)) and fixed to a sample holder with 100 mm diameter by small screws. The sample holder was attached to a high voltage feedthrough in a vacuum chamber. The base pressure of the system was 3 × 10 −5 Pa. The Zn-DLC films were prepared by combining radio frequency magnetron sputtering and a PSII process. Ethylene (C 2 H 4 , 99.9%) was used as precursor and thus as carbon source. Ionization of the precursor was achieved by applying a pulsed high voltage of −10 kV (10 µs pulse length with a repetition rate of 1 kHz) to the sample holder. The Zn target (99.99%) was sputtered by argon (99.999%, flow rate of 20 sccm). The zinc content of the samples was altered by changing the C 2 H 4 flow. For the first sample, the flow was 0.75 sccm, for the second one 0.5 sccm. The pressure during the deposition was 0.7 Pa, the sputter power was 45 W, the deposition time 30 and 23 min, respectively. Before deposition, the sputter source was run for 10 min with a closed shutter using only argon as sputter gas to clean the Zn target. The distance of the sample holder to the sputter target was about 100 mm. The Zn content of the as-prepared samples was determined by X-ray photoelectron spectroscopy (XPS, Shimadzu ESCA, Tokyo, Japan), using an Mg Kα X-ray beam. Depth profiles of the samples (as prepared) were recorded using a 2 keV Ar ion beam. Additional depth profiles of the as prepared and of the etched samples were recorded by secondary ion mass spectrometry (SIMS, Cameca ims 5f, Gennevilliers, France) with a 2.5 keV O 2 + ion beam, recording positive secondary ions. The surface morphology was characterized by scanning electron microscopy (SEM, FEI Quanta 200F, Hillsboro, OR, USA, Philips XL 30 FEG, Eindhoven, The Netherlands, and Jeol JSM 6400, Tokyo, Japan, SE images) and atomic force microscopy (AFM, Asylum Research Cypher, Santa Barbara, CA, USA, tapping mode). The film thickness was determined by profilometry (Bruker Dektak Advanced XT, Karlsruhe, Germany), measuring the transition from a coated to an uncoated area of the sample. For chemical etching, the samples were immersed for 20 s into a HNO 3 :H 2 O solution (ratio 1:1), which was heated to 60 °C. Afterwards, the samples were rinsed with deionized water and dried under a stream of hot air. 3. Results The sample with a lower Zn content has 9.6 at.% Zn, 3 at.% oxygen and a film thickness of about 515 nm. It shows mostly separate particles within its surface. The Zn particles have a width of about 100–200 nm, see Figure 1 a. Some of them formed interconnected structures of about 1000 nm length. That the particles extend below the carbon surface can be seen when etching the sample. In Figure 1 b an SEM image of the etched surface is shown. The brighter structures associated with Zn have gone and, instead, holes are present, whose dimensions correlate with those of the particles in Figure 1 a. In Figure 1 b, the edges of the holes appear brighter. A small ridge, as seen in the line scan from an AFM measurement, Figure 1 c, surrounds each hole. This ridge is about 20 nm high. The hole has a width of about 95 nm on the level of the surface. It narrows with increasing depth and has a total depth of about 90 nm. In a cross-sectional SEM image, Figure 2 a, the Zn particles on the top of the film are visible. After etching, the Zn particles are removed from the surface, see the indicated voids in Figure 2 b. The film itself as seen from the side does not look porous, i.e., the etching did not affect areas further below the surface. (The film in Figure 2 b gives the impression of having a larger thickness because the film peeled off somewhat when breaking the substrate.) The lower Zn content of the surface after etching is also obvious in SIMS depth profiles of the samples, see Figure 3 (note the logarithmic scale of the y-axis). The substrate position is reached after a lower sputtering time in the profiles of the etched samples, indicating that the film thickness was reduced by the etching process. The Zn intensity at the start of the profiles of the etched samples is reduced, but it is not zero, even though in Figure 1 b all of the Zn seems to be removed from the surface. As the instrument used for depth profiling was a magnetic sector field mass spectrometer, it recorded the different elements sequentially, i.e., the first data point for Zn represents the situation after several seconds of sputtering with primary ions. Additionally, Zn is only removed in the chemical etching process where it is directly accessible by the etchant. Zn particles in the film that are very close to the surface but do not penetrate it remain in the sample. When starting to remove the surface of the sample by sputtering during the depth profiling, those Zn particles very close to the surface cause the Zn intensity at the start of the depth profile. The reduced Zn content after etching is not only found at the start of the profile but throughout the film. This is related to the influence of particles during a depth profile. The distribution of the Zn is laterally inhomogeneous, as seen in Figure 1 a. During the depth profile, it takes some time to remove the particles by sputtering during the analysis. Furthermore, due to different sputter yields and impact angles of the primary ions, a roughening of the surface during the profiling occurs. As a result, signals from different depths are collected at the same sputtering time. The sample with the higher Zn content has 38.9 at.% Zn, 6.5 at.% oxygen and a thickness of 190 nm. It shows a more network-like arrangement of intertwined Zn particles within the surface in the as-prepared state, see Figure 4 a. In Figure 4 b an image of the same sample, as prepared, is presented with a higher magnification. Just as with the sample with the lower Zn content, the Zn particles are removed from the surface by the etching process. The remaining surface consists of the nanostructured carbon skeleton and shows an inherent roughness, see Figure 4 c. Figure 4 d shows the corresponding AFM image of the etched sample. The height differences on the surface after etching amount to several ten nm, reaching 100 nm in some places. The average roughness R a of the surface is 9.2 nm. 4. Discussion The feasibility of the two-step approach, comprising the preparation of a zinc-containing DLC film and the removal of the zinc from the film surface by chemical etching, was demonstrated. A DLC film surface with a three-dimensional structure was obtained, whose dimensions are predetermined by the size and distribution of the Zn particles within the surface. Zn particles in the surface of a DLC film tend to be bigger (with a size of at least about 100 nm diameter) than those of most other metal particles (not more than 10 nm diameter) as well as bigger than the Zn particles within the film. Thus, the dimensions of the produced surface structures are, accordingly, larger. The Zn content determines the degree of interconnection of the Zn particles within the surface and thereby the resulting surface structure. Zn contents lower than 10 at.% (9.6 at.% for the sample investigated here) produce a majority of separate holes. Higher Zn contents would lead to longer or more interconnected particles, resulting in holes up to about 1 µm in length. When all “holes” are connected (at 38.9 at.% Zn and above), a rough surface results. While a large porosity of the film can be achieved by etching of a Cu-DLC film with percolated Cu particles, the resulting film is sponge-like, i.e., it is not suitable for applications that require a certain wear resistance, for instance. With the approach presented here, a continuous DLC film remains on the substrate as the etching only removes zinc particles at the surface. Even for preparation conditions that produce large Zn concentrations of nearly 40 at.% at the surface, the Zn particles are not percolated throughout the film. As a consequence, only the surface of the sample is affected by the etching. This process involves preparation techniques that are suitable for the treatment of large-scale substrates. Sputtering as well as PSII are mature techniques that can easily be scaled up. The method presented here also has some potential for three-dimensional coating of non-flat samples. While PSII is generally a suitable technique for 3D coating [ 30 ], magnetron sputtering is more of a directional technique. However, if the metal were provided in ionized form, e.g., by a vacuum arc ion source [ 31 ], those limits could be overcome. A potential drawback of the approach presented here is that the metal in the DLC film changes the properties of the whole film [ 32 ], such as its hardness. Depending on the application, this can be a disadvantage. To avoid this, at least to some degree, a possible variation could be to confine the metal to the surface region. If the metal is added only in the last stages of the deposition, most of the film still has the properties of the undoped DLC film. 5. Conclusions Nanostructured surfaces of DLC films with surface morphologies with dimensions of 100 nm and above can be produced by surface removal of zinc particles from a zinc-containing DLC film. Depending on the zinc content, two distinct surface structures can be realized: mostly separate holes in an otherwise flat surface (using zinc contents of not more than 10 at.% as otherwise more and more particles tend to interconnect), and a rough surface (if most of the surface is covered by zinc-containing particles in the as prepared state, i.e., before etching, as is the case for zinc concentrations of 38.9 at.% and above). The surface structures produced have dimensions in between those that are feasible by etching Cu-DLC films and by using masked deposition, respectively. Lower parts of the film are not influenced by the etching and a compact film (except for the holes in the surface region) remains on the substrate. 6. Patents A patent application (DE 102017121684.7) was submitted to the German patent office. Author Contributions Conceptualization, R.H. and S.F.; Validation, R.H., S.F., B.R., C.D. and K.B.; Investigation, R.H., S.F., B.R., C.D. and K.B.; Resources, K.B. and W.E.; Data Curation, S.F.; Writing—Original Draft Preparation, S.F.; Writing—Review and Editing, R.H.; Visualization, R.H., S.F., B.R., C.D. and K.B.; Supervision, W.E. Funding This research received no external funding. Acknowledgments The help of Brunhilde Thybusch and Torsten Walbert from Technische Universität Darmstadt is gratefully acknowledged. Conflicts of Interest The authors declare no conflict of interest. References Robertson, J. Diamond-like amorphous carbon. Mater. Sci. Eng. R 2002 , 37 , 129–281. [ Google Scholar ] [ CrossRef ][ Green Version ] Hauert, R. A review of modified DLC coatings for biological applications. Diamond Relat. Mater. 2003 , 12 , 583–589. [ Google Scholar ] [ CrossRef ] Peng, X.L.; Barber, Z.H.; Clyne, T.W. Surface roughness of diamond-like carbon films prepared using various techniques. Surf. Coat. Technol. 2001 , 138 , 23–32. [ Google Scholar ] [ CrossRef ] Datta, J.; Ray, N.R.; Sen, P.; Biswas, H.S.; Vogler, E.A. Structure of hydrogenated diamond like carbon by Micro-Raman spectroscopy. Mater. Lett. 2012 , 71 , 131–133. [ Google Scholar ] [ CrossRef ] Maharizi, M.; Peleg, D.; Seidman, A.; Croitoru, N. Influence of substrate and film thickness on the morphology and diamond bond formation during the growth of amorphous diamond-like carbon (DLC) films. J. Optoelectron. Adv. Mater. 1999 , 1 , 65–68. [ Google Scholar ] Ghosh, S.; Xiong, G.; Fisher, T.S.; Han, B. Guidance of cell adhesion and migration by graphitic nanopetals on carbon fibers. Mater. Lett. 2016 , 184 , 211–215. [ Google Scholar ] [ CrossRef ] Cohen, A.; Liu-Synder, P.; Storey, D.; Webster, T.J. Decreased fibroblast and increased osteoblast functions on ionic plasma deposited nanostructured Ti coatings. Nanoscale Res. Lett. 2007 , 2 , 385. [ Google Scholar ] [ CrossRef ] Gerbig, Y.B.; Ahmed, S.U.; Chetwynd, D.G.; Haefke, H. Topography-related effects on the lubrication of nanostructured hard surfaces. Tribol. Int. 2006 , 39 , 945–952. [ Google Scholar ] [ CrossRef ] Anil, S.; Anand, P.S.; Alghamdi, H.; Jansen, J.A. Dental implant surface enhancement and osseointegration. In Implant Dentistry-A Rapidly Evolving Practice ; Turkyilmaz, I., Ed.; InTech: London, UK, 2011; pp. 83–110. [ Google Scholar ] Basnyat, P.; Luster, B.; Muratore, C.; Voevodin, A.A.; Haasch, R.; Zakeri, R.; Kohli, P.; Aouadi, S.M. Surface texturing for adaptive solid lubrication. Surf. Coat. Technol. 2008 , 203 , 73–79. [ Google Scholar ] [ CrossRef ] Enomoto, T.; Sugihara, T. Improving anti-adhesive properties of cutting tool surfaces by nano-/micro-textures. CIRP Ann. 2010 , 59 , 597–600. [ Google Scholar ] [ CrossRef ] Koskinen, J.; Tapper, U.; Andersson, P.; Varjus, S.; Kolehmainen, J.; Tervakangas, S.; Buss, W. Friction reduction by texturing of DLC coatings sliding against steel under oil lubrication. Surf. Coat. Technol. 2010 , 204 , 3794–3797. [ Google Scholar ] [ CrossRef ] Chouquet, C.; Gavillet, J.; Ducros, C.; Sanchette, F. Effect of DLC surface texturing on friction and wear during lubricated sliding. Mater. Chem. Phys. 2010 , 123 , 367–371. [ Google Scholar ] [ CrossRef ] Marczak, J.; Kusinski, J.; Major, R.; Rycyk, A.; Sarzynski, A.; Strzelec, M.; Czyz, K. Laser interference patterning of diamond-like carbon layers for directed migration and growth of smooth muscle cell depositions. Opt. Appl. 2014 , 44 , 575–586. [ Google Scholar ] Czyż, K.; Marczak, J.; Major, R.; Mzyk, A.; Rycyk, A.; Sarzyński, A.; Strzelec, M. Selected laser methods for surface structuring of biocompatible diamond-like carbon layers. Diamond Relat. Mater. 2016 , 67 , 26–40. [ Google Scholar ] [ CrossRef ] McKenzie, W.; Pethica, J.; Cross, G. A direct-write, resistless hard mask for rapid nanoscale patterning of diamond. Diamond Relat. Mater. 2011 , 20 , 707–710. [ Google Scholar ] [ CrossRef ][ Green Version ] Peng, Y.; Burtovyy, R.; Yang, Y.; Urban, M.W.; Kennedy, M.S.; Kornev, K.G.; Bordia, R.; Luzinov, I. Towards scalable fabrication of ultrasmooth and porous thin carbon films. Carbon 2016 , 96 , 184–195. [ Google Scholar ] [ CrossRef ] Baena-Moncada, A.M.; Planes, G.A.; Moreno, M.S.; Barbero, C.A. A novel method to produce a hierarchical porous carbon as a conductive support of PtRu particles. Effect on CO and methanol electrooxidation. J. Power Sources 2013 , 221 , 42–48. [ Google Scholar ] [ CrossRef ] Bouts, N.; El Mel, A.A.; Angleraud, B.; Tessier, P.Y. Sponge-like carbon thin films: The dealloying concept applied to copper/carbon nanocomposite. Carbon 2015 , 83 , 250–261. [ Google Scholar ] [ CrossRef ] Tamulevičius, T.; Tamulevičienė, A.; Virganavičius, D.; Vasiliauskas, A.; Kopustinskas, V.; Meškinis, Š.; Tamulevičius, S. Structuring of DLC:Ag nanocomposite thin films employing plasma chemical etching and ion sputtering. Nucl. Instrum. Methods Phys. Res. Sect. B 2014 , 341 , 1–6. [ Google Scholar ] [ CrossRef ] Schiffmann, K.I.; Fryda, M.; Goerigk, G.; Lauer, R.; Hinze, P.; Bulack, A. Sizes and distances of metal clusters in Au-, Pt-, W- and Fe-containing diamond-like carbon hard coatings: A comparative study by small angle X-ray scattering, wide angle X-ray diffraction, transmission electron microscopy and scanning tunnelling microscopy. Thin Solid Films 1999 , 347 , 60–71. [ Google Scholar ] Cloutier, M.; Turgeon, S.; Busby, Y.; Tatoulian, M.; Pireaux, J.J.; Mantovani, D. Controlled distribution and clustering of silver in Ag-DLC nanocomposite coatings using a hybrid plasma approach. ACS Appl. Mater. Interfaces 2016 , 8 , 21020–21027. [ Google Scholar ] [ CrossRef ] [ PubMed ] Wang, L.J.; Zhang, F.; Fong, A.; Lai, K.M.; Shum, P.W.; Zhou, Z.F.; Gao, Z.F.; Fu, T. Effects of silver segregation on sputter deposited antibacterial silver-containing diamond-like carbon films. Thin Solid Films 2018 , 650 , 58–64. [ Google Scholar ] [ CrossRef ] Foong, Y.M.; Koh, A.T.T.; Lim, S.R.; Hsieh, J.; Chua, D.H.C. Materials properties of ZnO/diamond-like carbon (DLC) nanocomposite fabricated with different source of targets. Diamond Relat. Mater. 2012 , 25 , 103–110. [ Google Scholar ] [ CrossRef ] Das, A.K.; Hatada, R.; Ensinger, W.; Flege, S.; Baba, K.; Meikap, A.K. Dielectric constant, AC conductivity and impedance spectroscopy of zinc-containing diamond-like carbon film UV photodetector. J. Alloy. Compd. 2018 , 758 , 194–205. [ Google Scholar ] [ CrossRef ] Bowen, P.K.; Guillory, R.J.; Shearier, E.R.; Seitz, J.M.; Drelich, J.; Bocks, M.; Zhao, F.; Goldman, J. Metallic zinc exhibits optimal biocompatibility for bioabsorbable endovascular stents. Mater. Sci. Eng. C 2015 , 56 , 467–472. [ Google Scholar ] [ CrossRef ][ Green Version ] Seitz, J.M.; Durisin, M.; Goldman, J.; Drelich, J.W. Recent advances in biodegradable metals for medical sutures: A critical review. Adv. Healthc. Mater. 2015 , 4 , 1915–1936. [ Google Scholar ] [ CrossRef ] Conrad, J.R.; Radtke, J.L.; Dodd, R.A.; Worzala, F.J.; Tran, N.C. Plasma source ion-implantation technique for surface modification of materials. J. Appl. Phys. 1987 , 62 , 4591–4596. [ Google Scholar ] [ CrossRef ] Hatada, R.; Flege, S.; Rimmler, B.; Ensinger, W.; Baba, K. Properties of zinc-containing diamond-like carbon films prepared by plasma source ion implantation. Trans. Mater. Res. Soc. Jpn 2017 , 42 , 37–40. [ Google Scholar ] [ CrossRef ] Anders, A. Handbook of Plasma Immersion Ion Implantation and Deposition ; John Wiley & Sons: New York, NY, USA, 2000. [ Google Scholar ] Anders, A. Cathodic Arcs, Springer Series on Atomic, Optical, and Plasma Physics ; Springer: New York, NY, USA, 2008; Volume 50. [ Google Scholar ] Sánchez-López, J.C.; Fernández, A. Doping and alloying effects on DLC coatings. In Tribology of Diamond-like Carbon Films ; Springer: New York, NY, USA, 2008; pp. 311–338. [ Google Scholar ] Figure 1. Zn-diamond-like carbon (DLC) sample with about 10 at.% Zn: ( a ) scanning electron microscope (SEM) image of the sample as prepared; ( b ) SEM image of the sample after etching; ( c ) atomic force microscopy (AFM) line scan of a hole in the etched sample. Figure 2. Cross-sectional SEM images of the sample with 9.6 at.% Zn on the surface: ( a ) as prepared; ( b ) after etching. Figure 2. Cross-sectional SEM images of the sample with 9.6 at.% Zn on the surface: ( a ) as prepared; ( b ) after etching. Figure 3. Secondary ion mass spectrometry (SIMS) depth profiles of Zn-DLC samples, showing the signals 12 C, 30 Si and 64 Zn ( a ) 9.6 at.% Zn, as prepared; ( b ) 9.6 at.% Zn, etched; ( c ) 38.9 at.% Zn, as prepared; ( d ) 38.9 at.% Zn, etched. Figure 3. Secondary ion mass spectrometry (SIMS) depth profiles of Zn-DLC samples, showing the signals 12 C, 30 Si and 64 Zn ( a ) 9.6 at.% Zn, as prepared; ( b ) 9.6 at.% Zn, etched; ( c ) 38.9 at.% Zn, as prepared; ( d ) 38.9 at.% Zn, etched. Figure 4. Zn-DLC sample with 38.9 at.% Zn: ( a ) SEM image of the sample as prepared; ( b ) SEM image of the sample as prepared, with higher magnification; ( c ) SEM image of the sample after etching; ( d ) AFM image of the etched surface. Figure 4. Zn-DLC sample with 38.9 at.% Zn: ( a ) SEM image of the sample as prepared; ( b ) SEM image of the sample as prepared, with higher magnification; ( c ) SEM image of the sample after etching; ( d ) AFM image of the etched surface. MDPI and ACS Style Hatada, R.; Flege, S.; Rimmler, B.; Dietz, C.; Ensinger, W.; Baba, K. Surface Structuring of Diamond-Like Carbon Films by Chemical Etching of Zinc Inclusions. Coatings 2019, 9, 125. https://doi.org/10.3390/coatings9020125 AMA Style Hatada R, Flege S, Rimmler B, Dietz C, Ensinger W, Baba K. Surface Structuring of Diamond-Like Carbon Films by Chemical Etching of Zinc Inclusions. Coatings. 2019; 9(2):125. https://doi.org/10.3390/coatings9020125 Chicago/Turabian Style Hatada, Ruriko, Stefan Flege, Berthold Rimmler, Christian Dietz, Wolfgang Ensinger, and Koumei Baba. 2019. "Surface Structuring of Diamond-Like Carbon Films by Chemical Etching of Zinc Inclusions" Coatings9, no. 2: 125. https://doi.org/10.3390/coatings9020125
https://www.mdpi.com/2079-6412/9/2/125/xml
Israeli PM’s visit to the two sides of the Caspian Sea & lt;p& gt;& lt;strong& gt;By& amp;nbsp;Avinoam Idan& lt;/strong& gt;& lt;/p& gt; & lt;p& gt;& lt;b& gt;February 6, 2017, the CACI Analyst& lt;/b& gt;& lt;/p& gt; & lt;... Israeli PM’s visit to the two sides of the Caspian Sea Israel’s Prime Minister Binjamin Netanyahu made a landmark visit to Azerbaijan and Kazakhstan in December 2016. The Israeli Prime Minister's visit reflects Israel’s growing interest in Central Asia and the Caucasus, a region that is part of Israel's greater strategic environment. Israel's interest in Kazakhstan focuses on its trade potential, its regional and international status, and its position as a vital link in the Chinese Belt and Road Initiative. Azerbaijan's geographical location, its role as a significant energy exporter, and its security approach have been foci of the close relations that have developed between Baku and Jerusalem over the years. The Prime Minister's visit reflects the continued deepening of ties with Azerbaijan. BACKGROUND: In December, Israeli Prime Minister Benjamin Netanyahu conducted a three-day visit to Azerbaijan and Kazakhstan from December 13-15, 2016. This was the first visit by an Israeli Prime Minister to Kazakhstan and the second visit to Azerbaijan. The visit to these two countries is a direct continuation of an ongoing Israeli process to strengthen relations with Astana and Baku since their establishment as independent states. With the large bulk of Jewish immigration into Israel behind it towards the end of the 1990s, and especially after the construction of infrastructure for energy exports from the Caspian Sea in the mid-2000s, Israeli policymakers began to understand the importance of the countries bordering the Caspian Sea, while creating a distinction between Azerbaijan and Kazakhstan. Interest in Kazakhstan focused on trade and economic interests, as well as its role in convening international political fora. As for Azerbaijan, its geostrategic location, which includes a common border with Iran, as well as the existence of a large ethnic Azerbaijani community in Iran (a third of the population) made Azerbaijan especially attractive for developing relations. A heritage of coexistence and tolerance for the Jewish minority in Azerbaijan and the existence of an active community of Azerbaijani Jews in Israel facilitated strong ties between the countries, especially trade. During Netanyahu's visit to Kazakhstan, a series of agreements were signed in the fields of research and development, as well as aviation and travel. An agreement was also made to exchange teams focused on high-tech, technology and security development. The leaders of Azerbaijan viewed Israel as a successful model for a small state located in a hostile environment which manages to deal with security challenges while still thriving in all aspects of development. Israel, on its part, viewed the strengthening of ties with Azerbaijan as an opportunity to foster strong ties with a Muslim-majority country.  In addition, Azerbaijan became a major exporter of oil to Israel by way of the BTC pipeline transferring oil from the Caspian Sea to the Mediterranean Sea became operational in 2005. Approximately 40 percent of Israel's total oil imports come from Azerbaijan. Azerbaijan's desire to create a military option to regain control over its territories occupied by Armenia during the war in and around Nagorno-Karabakh has also contributed to the strengthening of relations between Azerbaijan and Israel, especially in the field of arms trade. During the PM's visit, a cooperation agreement in the field of agriculture was signed. The sides also agreed on the establishment of a joint commission to promote economic cooperation in the fields of science, technology, health, agriculture and trade. IMPLICATIONS: Prime Minister Netanyahu’s visit to Azerbaijan and Kazakhstan is an expression of Israel's growing political momentum in Central Asia and the Caucasus region. Netanyahu's visit is designed to promote Israel's relations with Kazakhstan in several aspects. Kazakhstan took the lead among the Central Asian states in both the political and economic spheres. Kazakhstan took a role in establishing CICA (Conference on Interaction and Confidence-building in Asia) as well as positions within the Shanghai Cooperation Organization and OSCE, and is since the beginning of this year also a member of the UN Security Council. Israel's interest to strengthen ties with Kazakhstan in the political sphere should therefore be viewed against the backdrop of its regional and international status. Kazakhstan has use for the technology and knowledge that Israel can offer it, and the two countries have a mutual interest in developing trade relations between them. Kazakhstan is also a major link in Central Asia for China's vision of a Belt and Road Initiative. Israel has an interest in integrating with the project in its Central Asian section as part of its deepening of  relations with China in recent years. Kazakhstan is an appropriate arena for such Israeli-Chinese cooperation to occur. Together with the security challenges and the need to combat terrorism in the region, such cooperation and use of Israeli knowledge and experience is of mutual interest to both China and Kazakhstan, and the strengthening of ties between Israel and Kazakhstan can be used to promote that trilateral  cooperation. The Israeli Prime Minister's visit to Baku marks an important milestone in the relations between Israel and Azerbaijan. The Azerbaijani President was especially forthcoming in discussing the scope of the defense export contracts signed between the two countries which come close to five billion dollars, an unprecedented statement of acknowledgment. This demonstrative show of friendship on the part of the Azerbaijani President was very different from the nature of the bilateral relations that existed before. Since the April 2016 battles between Azerbaijan and Armenia (commonly referred to as the Four Day War) and the contribution of Israeli origin arms, Israel has become extremely popular in Azerbaijan. The establishment of the Southern Gas Corridor, which provides a route for gas export from the Shah Deniz offshore field in Azerbaijan to Europe, potentially may be used  by Israel to export its own gas to Turkey and potentially  European markets, adds to the mutual interests of the countries. Azerbaijan's historical heritage of tolerance towards the Jewish community in Azerbaijan forms another significant contribution to the close relations between the two countries, as openly expressed during PM Netanyahu's current visit. CONCLUSIONS:Israel is intensifying its activity in its expanded strategic circle which includes Central Asia and the Caucasus, and Netanyahu's visit is an expression of this trend. The visit helped consolidate and strengthen the close relationship it enjoys with Azerbaijan, and promoted economic and political ties with Kazakhstan – all the while increasing its presence in an area where China has a special interest, and creating conditions for future cooperation with China in Central Asia. Close relations with Azerbaijan and Kazakhstan, two Muslim-majority countries  with no hostility toward Israel and that manage their foreign policy based on bilateral interests and a legacy of coexistence and tolerance between Islam and Judaism, helps Israel break the cycle of hostility it has with the Muslim world in the international system. This visit of the Israeli Prime Minister promoted both Israel's presence in a vital region as well as common interests shared by Israel and the two host countries, and has the potential to promote Israel's relations with other countries in the region. AUTHOR'S BIO:Dr. Avinoam Idan is a political geographer and a Senior Fellow with the Central Asia-Caucasus Institute & Silk Road Studies Program, based in Washington DC. Prior to his academic career, he served in the Israeli Embassy in Moscow during the break-up of the Soviet Union. Image source: Wikimedia Commons,accessed on February 3, 2017 Tagged under Israel Azerbaijan Kazakhstan South Caucasus Central Asia OBOR initiative Belt and Road Initiative BTC pipeline Mediterranean Sea CICA Shanghai Cooperation Organization OSCE UNSC Armenia 2016 Four Day War Nagorno Karabakh Shah Deniz gas field Binjamin Netanyahu Article Tags Afghanistan Armenia Azerbaijan Central Asia
https://www.cacianalyst.org/publications/analytical-articles/item/13427-israeli-pm%E2%80%99s-visit-to-the-two-sides-of-the-caspian-sea.html
Cahn v. Jones - California - Case Law - VLEX 888406880 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object] California Cahn v. Jones <table><tbody><tr><td> Court</td><td> California Court of Appeals</td></tr><tr><td> Writing for the Court</td><td> SHINN</td></tr><tr><td> Citation</td><td> 101 Cal.App.2d 345,225 P.2d 570</td></tr><tr><td> Decision Date</td><td> 21 December 1950</td></tr><tr><td> Parties</td><td> CAHN v. JONES. Civ. 17670.</td></tr></tbody></table> Page 570 225 P.2d 570 101 Cal.App.2d 345 CAHN v. JONES. Civ. 17670. District Court of Appeal, Second District, Division 3, California. Dec. 21, 1950. Hearing Denied Feb. 15, 1951. Sampson H. Miller, Los Angeles, for appellant. Floyd E. Pendell, El Monte, for respondent. SHINN, Presiding Justice. Plaintiff, Gertrude Cahn, appeals from a judgment of dismissal of her action against defendant, Robert S. Jones, on his motion pursuant to the provisions of section 581a of the Code of Civil Procedure. On November 26, 1945, plaintiff filed her complaint for money had and received, alleging that there was due and owing her the sum of $14,189. Summons in the action was issued the same day and an affidavit was filed for writ of attachment against certain real property in which defendant had an interest, and levy was made by the Sheriff. There was no personal service of the summons and complaint upon the defendant. Prior to October 21, 1948, the defendant made certain payments on the indebtedness in the sum of $4,897.44. On October 21, 1948, plaintiff filed an amended complaint and summons was issued on the same day. Personal service of a copy of the amended complaint together with summons was made on defendant March 3, 1949. On March 5, 1949, the defendant filed a verified answer to the amended complaint. The cause was finally set for trial on April 25, [101 Cal.App.2d 346] 1949, and on that day was continued to May 23rd. On May 17th the trial was continued by written stipulation until June 27, 1949. Prior to that time, plaintiff served on defendant and filed a notice of motion to amend the amended complaint by adding a second cause of action. This motion was heard on June 7, and granted. On June 14, 1949, defendant Page 571 demanded a bill of particulars; on June 18, defendant filed a verified answer to the amendment to the amended complaint; on June 24, plaintiff filed and served on defendant a bill of particulars; the parties then entered into an oral stipulation to continue the trial until September 30, 1949. On June 29, 1949, the defendant filed a notice of motion to dismiss the action under section 581a of the Code of Civil Procedure; the motion was granted on July 18, 1949. At the time the action was dismissed, section 581a of the Code of Civil Procedure read as follows: 'No action heretofore or hereafter commenced shall be further prosecuted, and no further proceedings shall be had therein, and all actions heretofore or hereafter commenced must be dismissed by the court in which the same shall have been commenced, on its own motion, or on motion of any party interested therein, whether named in the complaint as a party or not, unless summons shall have issued within one years, and all such actions must be in like manner dismissed, unless the summons shall be served and return thereon made within three years after the commencement of said action * * *. But all such actions may be prosecuted, if appearance has been made by the defendant or defendants, within said three years in the same manner as if summons had been issued and served; provided, that, except in actions to partition or to recover possession of, or to enforce a lien upon, or to determine conflicting claims to, real or personal property, no dismissal shall be had under this section as to any defendant because of the failure to serve summons on him during his absence from the State, or while he has secreted himself within the State to prevent the service of summons on him.* * *' Plaintiff maintains that defendant by his conduct... Tresway Aero, Inc. v. Superior Court United States United States State Supreme Court (California) August 16, 1971 ...v. Superior Court (1899) 126 Cal. 245, 247, 58 P. 450; Vrooman v. Li Po Tai (1896) 113 Cal. 302, 305, 45 P. 470; Cahn v. Jones (1950) 101 Cal.App.2d 345, 348, 225 P.2d 570). This view of section 581a was substantially altered by our ruling in Wyoming Pacific Oil Co. v. Preston (1958) 50 Cal...... National Diversified Services, Inc. v. Bernstein United States California Court of Appeals May 17, 1985 ...to allow for an additional exception to dismissal when a written stipulation to extend time was entered into. (See Cahn v. Jones (1950) 101 Cal.App.2d 345, 348, 225 P.2d 570; Stats.1949,[168 Cal.App.3d 415] ch. 744, § 89, p. 1869.) In persuasive dictum contained in the 1958 case, Wyoming Pa...... Lopa v. Superior Court United States California Court of Appeals March 24, 1975 ...not expressly stated in the statute (see, E.g., White v. Superior Court (1899) 126 Cal. 245, 247, 58 P. 450; Cahn v. Jones (1950) 101 Cal.App.2d 345, 348, 225 P.2d 570), later cases have rendered a more liberal interpretation of it. Thus, in Wyoming Pacific Oil Co. v. Preston (1958) 50 Cal....... Synanon Foundation, Inc. v. County of Marin United States California Court of Appeals July 7, 1982 ...set out by statute were not recognized. (Gonsalves v. Bank of America (1940) 16 Cal.2d 169, 172, 105 P.2d 118; Cahn v. Jones (1950) 101 Cal.App.2d 345, 348, 225 P.2d 570.) This rigid view of section 581a has given way to a viable body of judicially created exceptions to the mandatory direct...... 6 cases Tresway Aero, Inc. v. Superior Court United States United States State Supreme Court (California) August 16, 1971 ...v. Superior Court (1899) 126 Cal. 245, 247, 58 P. 450; Vrooman v. Li Po Tai (1896) 113 Cal. 302, 305, 45 P. 470; Cahn v. Jones (1950) 101 Cal.App.2d 345, 348, 225 P.2d 570). This view of section 581a was substantially altered by our ruling in Wyoming Pacific Oil Co. v. Preston (1958) 50 Cal...... National Diversified Services, Inc. v. Bernstein United States California Court of Appeals May 17, 1985 ...to allow for an additional exception to dismissal when a written stipulation to extend time was entered into. (See Cahn v. Jones (1950) 101 Cal.App.2d 345, 348, 225 P.2d 570; Stats.1949,[168 Cal.App.3d 415] ch. 744, § 89, p. 1869.) In persuasive dictum contained in the 1958 case, Wyoming Pa...... Lopa v. Superior Court United States California Court of Appeals March 24, 1975 ...not expressly stated in the statute (see, E.g., White v. Superior Court (1899) 126 Cal. 245, 247, 58 P. 450; Cahn v. Jones (1950) 101 Cal.App.2d 345, 348, 225 P.2d 570), later cases have rendered a more liberal interpretation of it. Thus, in Wyoming Pacific Oil Co. v. Preston (1958) 50 Cal....... Synanon Foundation, Inc. v. County of Marin United States California Court of Appeals July 7, 1982 ...set out by statute were not recognized. (Gonsalves v. Bank of America (1940) 16 Cal.2d 169, 172, 105 P.2d 118; Cahn v. Jones (1950) 101 Cal.App.2d 345, 348, 225 P.2d 570.) This rigid view of section 581a has given way to a viable body of judicially created exceptions to the mandatory direct......
https://case-law.vlex.com/vid/cahn-v-jones-888406880
Logical foundations of artificial intelligence | Request PDF Request PDF | On Jan 1, 1987, Michael R Genesereth and others published Logical foundations of artificial intelligence | Find, read and cite all the research you need on ResearchGate Book Logical foundations of artificial intelligence January 1987 Publisher: Morgan Kaufmann Publishers Inc. ISBN: 0934613311 Authors: <here is a image 7ac14a404796501a-abd8a0c10cf2c5e7> Michael R. Genesereth Stanford University <here is a image f2f62089ad6ff61c-d19572ff1996375a> Nils J Nilsson Nils J Nilsson <here is a image 175d1bd4b7439d95-754927124da715c1> Discover the world's research 25+ million members 160+ million publication pages 2.3+ billion citations ... The issue is well-known and faced under the name eXplainable Artificial Intelligence (XAI) [4,5], also among big players, such as The Royal Society [6], IBM [7], and DARPA [8]. The other approach [9] , based on symbolic/logic techniques, and specifically on the First-Order Logic (FOL) setting, can natively handle multi-relational representations and reproduce high-level human reasoning mechanisms. Both approaches are needed to handle the many different aspects involved in carrying out 'intelligent' behavior in the real world. ... ... Born as a philosophical discipline that deals with the nature and structure of reality, ontologies were transposed to the computational domain and given more technical definitions depending on different perspectives. Here, we will adopt the perspective of "a formal, explicit specification of a shared conceptualization" [42], where a conceptualization is "an abstract, simplified view of the world that we wish to represent for some purpose" [9] that underlies all developments in Computer Science, and especially those of Knowledge Bases. Thus, an ontology describes the kinds of entities that are of interest in a domain, their properties and relationships. ... GEAR: A General Inference Engine for Automated MultiStrategy Reasoning Article Full-text available Jan 2023 <here is a image f1cb6f03ca867af7-27911455fa3fcbb5> Stefano Ferilli The pervasive use of AI today caused an urgent need for human-compliant AI approaches and solutions that can explain their behavior and decisions in human-understandable terms, especially in critical domains, so as to enforce trustworthiness and support accountability. The symbolic/logic approach to AI supports this need because it aims at reproducing human reasoning mechanisms. While much research has been carried out on single inference strategies, an overall approach to combine them is still missing. This paper claims the need for a new overall approach that merges all the single strategies, named MultiStrategy Reasoning. Based on an analysis of research on automated inference in AI, it selects a suitable setting for this approach, reviews the most promising approaches proposed for single inference strategies, and proposes a possible combination of deduction, abduction, abstraction, induction, argumentation, uncertainty and analogy. It also introduces the GEAR (General Engine for Automated Reasoning) inference engine, that has been developed to implement this vision. ... Although it is acknowledged that the term has its origin in philosophy [12,31] it is used in a much narrower sense as "specification of a conceptualization" [31], where a conceptualization is understood as a triple of a universe of discourse with functions and relations. The universe of discourse contains the objects "hypothesized to exist" [32] , which can be properties or reified relations [32]. Where it is totally clear that "[f]or knowledgebased systems, what 'exists' is exactly that which can be represented" [31]. ... ... Although it is acknowledged that the term has its origin in philosophy [12,31] it is used in a much narrower sense as "specification of a conceptualization" [31], where a conceptualization is understood as a triple of a universe of discourse with functions and relations. The universe of discourse contains the objects "hypothesized to exist" [32], which can be properties or reified relations [32] . Where it is totally clear that "[f]or knowledgebased systems, what 'exists' is exactly that which can be represented" [31]. ... Quantum-inspired cognitive agents Article Full-text available Sep 2022 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Markus Huber-Liebl <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ronald Römer <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Günther Wirsching <here is a image 14e93c96d17c7faa-d2c7b78483460f8f> Matthias Wolff The concept of intelligent agents is—roughly speaking—based on an architecture and a set of behavioral programs that primarily serve to solve problems autonomously. Increasing the degree of autonomy and improving cognitive performance, which can be assessed using cognitive and behavioral tests, are two important research trends. The degree of autonomy can be increased using higher-level psychological modules with which needs and motives are taken into account. In our approach we integrate these modules in architecture for an embodied, enactive multi-agent system, such that distributed problem solutions can be achieved. Furthermore, after uncovering some weaknesses in the cognitive performance of traditionally designed agents, we focus on two major aspects. On the one hand, the knowledge processing of cognitive agents is based on logical formalisms, which have deficiencies in the representation and processing of incomplete or uncertain knowledge. On the other hand, in order to fully understand the performance of cognitive agents, explanations at the symbolic and subsymbolic levels are required. Both aspects can be addressed by quantum-inspired cognitive agents. To investigate this approach, we consider two tasks in the sphere of Shannon's famous mouse-maze problem: namely classifying target objects and ontology inference. First, the classification of an unknown target object in the mouse-maze, such as cheese, water, and bacon, is based on sensory data that measure characteristics such as odor, color, shape, or nature. For an intelligent agent, we need a classifier with good prediction accuracy and explanatory power on a symbolic level. Boolean logic classifiers do work on a symbolic level but are not adequate for dealing with continuous data. Therefore, we demonstrate and evaluate a quantum-logic-inspired classifier in comparison to Boolean-logic-based classifiers. Second, ontology inference is iteratively achieved by a quantum-inspired agent through maze exploration. This requires the agent to be able to manipulate its own state by performing actions and by collecting sensory data during perception. We suggest an algebraic approach where both kinds of behaviors are uniquely described by quantum operators. The agent's state space is then iteratively constructed by carrying out unitary action operators, while Hermitian perception operators act as observables on quantum eigenstates. As a result, an ontology emerges as the simultaneous solution of the respective eigenvalue equations. ... Prior work in AI, including in formal logic (Genesereth and Nilsson, 1987) , belief mainte-nance (De Kleer, 1986;Dechter and Dechter, 1988), and uncertainty (Pearl, 1986), offers models for how beliefs can be managed. Most importantly, it posits that creating a coherent set of beliefsa kind of "mental model" of the world (Johnson-Laird, 1983) -is a constructive process requiring explicit representation of beliefs, and inference about their dependencies. ... ... The idea that agents should have a belief system dates back to the earliest years of AI, e.g., Mc-Carthy (1959) envisioned representing a system's beliefs as formal propositions along with a reasoning process to identify what follows. Multiple subfields of AI have explored ways of representing and updating beliefs, including in formal logic (Genesereth and Nilsson, 1987; Moore, 1983), belief revision (De Kleer, 1986;Dechter and Dechter, 1988), and uncertainty (Pearl, 1986). Similarly, work in cognitive science has promoted mental models -coherent, constructed representations of the way the world is believed to be -as central to understanding and communication (Johnson-Laird, 1983;Gentner and Stevens, 1983;Hilton, 1996). ... BeliefBank: Adding Memory to a Pre-Trained Language Model for a Systematic Notion of Belief Conference Paper Jan 2021 <here is a image 8a07bde10fab64e4-30731c3f54e500c3> Nora Kassner Oyvind Tafjord Hinrich Schütze <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Peter Clark ... Even if all the previous definitions trend to refine what is an ontology, they all rely on the common notion of conceptualization for which no formal definition is provided. A former definition, presented in [Genesereth 1987] , was: ... ... Même si toutes les définitions précédentes tendent à affiner ce qu'est une ontologie, elles reposent toutes sur la notion commune de conceptualisation pour laquelle aucune définition formelle n'est fournie. Une ancienne définition, présentée dans [Genesereth 1987] pose. Les ontologies de domaine visent à affiner une discipline, en se concentrant sur un domaine plus restreint, comme l'ontologie SOMA [Beßler 2020] se concentrant sur la représentation des activités. ... Knowledge representation and exploitation for interactive and cognitive robots Thesis Full-text available Sep 2021 <here is a image 0ef904d335a614a0-f67c392da2df17e3> Guillaume Sarthou As robots begin to enter our daily lives, we need advanced knowledge representations and associated reasoning capabilities to enable them to understand and model their environments. Considering the presence of humans in such environments, and therefore the need to interact with them, this need comes with additional requirements. Indeed, knowledge is no longer used by the robot for the sole purpose of being able to act physically on the environment but also to communicate and share information with humans. Therefore knowledge should no longer be understandable only by the robot itself, but should also be able to be narrative-enabled. In the first part of this thesis, we present our first contribution with Ontologenius. This software allows to maintain knowledge bases in the form of ontology, to reason on them and to manage them dynamically. We start by explaining how this software is suitable for Human-Robot Interaction applications. To that end, for example to implement theory of mind abilities, it is possible to represent the robot’s knowledge base as well as an estimate of the knowledge bases of human partners. We continue with a presentation of its interfaces. This part ends with a performance analysis, demonstrating its online usability. In a second part, we present our contribution to two knowledge exploration problems around the general topic of spatial referring and the use of semantic knowledge. We start with the route description task which aims to propose a set of possible routes leading to a target destination, in the framework of a guiding task. To achieve this task, we propose an ontology allowing us to describe the topology of indoor environments and two algorithms to search for routes. The second knowledge exploration problem we tackle is the Referring Expression Generation problem. It aims at selecting the optimal set of pieces of information to communicate in order to allow a hearer to identify the referred entity in a given context. This contribution is then refined to use past activities coming from joint action between a robot and a human, in order to generate new kinds of Referring Expressions. It is also linked with a symbolic task planner to estimate the feasibility and cost of future communications. We conclude this thesis by the presentation of two cognitive architectures. The first one uses the route description contribution and the second one takes advantage of our Referring Expression Generation contribution. Both of them use Ontologenius to manage the semantic Knowledge Base. Through these two architectures, we present how our contributions enable Knowledge Base to gradually take a central role, providing knowledge to all the components of the architectures. ... Prior work in AI, including in formal logic (Genesereth and Nilsson, 1987) , belief mainte-nance (De Kleer, 1986;Dechter and Dechter, 1988), and uncertainty (Pearl, 1986), offers models for how beliefs can be managed. Most importantly, it posits that creating a coherent set of beliefsa kind of "mental model" of the world (Johnson-Laird, 1983) -is a constructive process requiring explicit representation of beliefs, and inference about their dependencies. ... ... The idea that agents should have a belief system dates back to the earliest years of AI, e.g., Mc-Carthy (1959) envisioned representing a system's beliefs as formal propositions along with a reasoning process to identify what follows. Multiple subfields of AI have explored ways of representing and updating beliefs, including in formal logic (Genesereth and Nilsson, 1987; Moore, 1983), belief revision (De Kleer, 1986;Dechter and Dechter, 1988), and uncertainty (Pearl, 1986). Similarly, work in cognitive science has promoted mental models -coherent, constructed representations of the way the world is believed to be -as central to understanding and communication (Johnson-Laird, 1983;Gentner and Stevens, 1983;Hilton, 1996). ... BeliefBank: Adding Memory to a Pre-Trained Language Model for a Systematic Notion of Belief Full-text available <here is a image 8a07bde10fab64e4-30731c3f54e500c3> Nora Kassner Oyvind Tafjord Hinrich Schütze <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Peter Clark Although pretrained language models (PTLMs) contain significant amounts of world knowledge, they can still produce inconsistent answers to questions when probed, even after specialized training. As a result, it can be hard to identify what the model actually "believes" about the world, making it susceptible to inconsistent behavior and simple errors. Our goal is to reduce these problems. Our approach is to embed a PTLM in a broader system that also includes an evolving, symbolic memory of beliefs -- a BeliefBank -- that records but then may modify the raw PTLM answers. We describe two mechanisms to improve belief consistency in the overall system. First, a reasoning component -- a weighted MaxSAT solver -- revises beliefs that significantly clash with others. Second, a feedback component issues future queries to the PTLM using known beliefs as context. We show that, in a controlled experimental setting, these two mechanisms result in more consistent beliefs in the overall system, improving both the accuracy and consistency of its answers over time. This is significant as it is a first step towards PTLM-based architectures with a systematic notion of belief, enabling them to construct a more coherent picture of the world, and improve over time without model retraining. ... Long-distance electrodynamic interactions between two small molecules have been largely studied within 11 the framework of quantum electrodynamics, since long-range forces can be detected among excited atoms 12 with similar transition frequencies 1, 2 . However, interactions beyond the Debye screening length (≃ 10Å in 13 biological systems 3 ), carried out by the molecular cognate-partners of a biochemical reaction, are not well 14 investigated. Nonetheless, experimental evidences for the existence of collective excitations of biological 15 macromolecules are available in the Raman and Far-infrared spectroscopic domains 4, 5 . ... ... Differently from other computational 56 methods, however, ABMs require to instruct the agents representing the simulated molecules with minimal 57 empirical information, letting the global behaviour of the process to result from local interactions, which 58 are generated dynamically at each step of the simulation. The system evolves due to the ability of every 59 agent to perceive and respond to the states of its environment, which is unpredictable and populated by 60 other agents; the agent's perception results in performing an appropriate action (if any) able to modify 61 the environment 13 . The agent-based approach allows both the environment and the molecules to be 62 three-dimensional (as shown in Fig. 1); molecular shapes can thus affect the diffusion processes. ... Agent-based Models for Detecting the Driving Forces of Biomolecular Interactions Preprint Full-text available Stefano Maestri <here is a image 18ec77c0502bae13-411d28f8b022ea56> Emanuela Merelli <here is a image f0a1f935fb5eccc9-e94ab0a4989d5467> Marco Pettini Agent-based modelling and simulation have been effectively applied to the study of complex biological systems, especially when composed by a large number of interacting entities. Representing biomolecules as autonomous agents allows this approach to bring out the global behaviour of biochemical processes as resulting from local molecular interactions. In this paper, we leverage the capabilities of the agent paradigm to construct an in silico replica of the glycolytic pathway of baker’s yeasts; the aim is to detect the role that long-range electrodynamic forces might have on the rate of glucose oxidation. Experimental evidences have shown that random encounters and short-range potentials might not be sufficient to explain the high efficiency of biochemical reactions in living cells. However, while the latest in vitro studies are limited by the present-day technology, agent-based simulations provide an in silico support to the outcomes hitherto obtained and shed light on behaviours not yet well understood. Our results reveal to be able to grasp properties hard to uncover through other computational methods, such as the effect of electromagnetic potentials on glycolytic oscillations. ... FIS are systems or algorithms that derive conclusions from premises (Genesereth and Nilsson, 1987) . In classical logic, the number of inference systems is limited because the implications, disjunctions, and conclusions are all uniquely defined. ... Application of neuro-fuzzy ensembles across domains: A systematic review of the two last decades (2000–2022) Article ENG APPL ARTIF INTEL <here is a image 1fe205fc1969bdb7-87a62069cfcb12cb> Hafsaa Ouifak <here is a image 292bc5365bd8ecd0-14e8564758146bd7> Ali Idri Neuro-fuzzy systems have received considerable attention from academia in the last decade. They can provide a tradeoff between the performance of artificial neural networks and the interpretability of fuzzy inference systems expressed through fuzzy rules. Single techniques do not always provide the optimal performance, especially when the results are susceptible to changes in the data or hyperparameters. Therefore, ensemble learning can be used to build a more stable and robust model. In this paper, a systematic literature review of studies evaluating neuro-fuzzy ensembles was performed to highlight the importance of ensemble learning and its role in improving the performance of neuro-fuzzy systems. Many aspects are highlighted, including publication years, sources, contribution types, application domains, single neuro-fuzzy systems, ensemble techniques, and the overall performance and interpretability. A total of forty-eight articles published from 2000 to March 2022 addressing the use of neuro-fuzzy ensembles in different engineering applications were selected and analyzed. Results show that: (i) Takagi–Sugeno–Kang neuro-fuzzy systems are the most evaluated category, especially the ANFIS single. (ii) Homogeneous ensembles, in particular boosting, are the most investigated. (iii) Logical, relational and ANFIS ensembles are outperforming. And (iv) The interpretability of neuro-fuzzy ensembles was not thoroughly investigated, but based on the number of rules, logical systems were the best. ... In den 1980er-Jahren führte man im Bereich der Forschung zu künstlicher Intelligenz sogenannte Ontologien ein als Modellierungswerkzeug, wie auch als Komponente wissensbasierter Systeme. Nach Thomas A. Gruber [8], ist eine Ontologie eine "explicit specification of ... the objects, concepts, and other entities that are assumed to exist in some area of interest and the relationships that hold among them", also eine explizite Spezifikation einer Konzeptualisierung im Sinne von [7] . ... Verwirrende Informatik III – Beschreibungen und Beschriebenes Article Full-text available <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Johannes Reich Zusammenfassung Dieser Artikel ist der dritte einer Viererreihe, die eine Diskussion über die Grundlagen der Informatik anregen soll. In ihm wird das Verhältnis von Beschreibung und Beschriebenem thematisiert. Die zu ungenaue Unterscheidung zwischen Beschreibung und Beschriebenem wird als eine wesentliche Quelle von unnötiger Unklarheit in der Informatik angesehen. In formalen Sprachen ist diese Unterscheidung die wesentliche Idee. In der natürlichen Sprache ist diese Unterscheidung ebenso wichtig, allerdings ist sie aspekthaft und kontextabhängig. Dies wird in der Informatik v.a. beim Modellkonzept relevant. Es wird der Vorschlag gemacht, sich bei der Bedeutungserteilung von Beschreibung und Beschriebenem an der mathematischen Modelltheorie zu orientieren, in der eine (konsistente) Beschreibung ein Modell beschreibt. Das Beschriebene wäre damit das, was es zu verstehen gilt, während eine Beschreibung ein Verständnis voraussetzt, also eine „Interpretation“ erfordert, um sie auf das „Beschriebene“ zu beziehen. Damit würde unser intuitives Verständnis von „Modell“ und „Beschreibung“ tatsächlich mit der mathematischen Modelltheorie präzisiert. Als Beispiele, in denen diese Unklarheiten zum Tragen kommen, werden die Model Driven Architecture (MDA) und die Ontologien diskutiert. ... NMR has become a key issue in artificial intelligence (AI) (Genesereth and Nilsson, 1987; Rich and Knight, 1991;Luger, 1993;Ginsberg, 1993;. Also, it is regarded as one of the most important problems in CAD and design studies (Coyne, 1988;Mitchell, 1990aMitchell, , 1990bGalle, 1996Galle, , 1997. ... A SYSTEM FOR NONMONOTONIC REASONING IN DESIGN Conference Paper Full-text available <here is a image 67a347e49ec6da5d-949950094c250969> Hung-Hsiang Wang Feng Tyan Lin Design process always contains nonmonotonicity, a behavior in which the previously derived conclusions could be retracted by adding new information. Such reasoning, where theorems are not incrementally increasing with adding a new axiom, is called nonmonotonic reasoning (NMR). NMR has been a serious concern in computer-aided design and artificial intelligence. Some non-monotonic logics have been developed, such as default logic, circumscription, and autoepistemic logic. However, few applications of these logics to design can be found. This paper adopts the idea of justification-based truth maintenance system (JTMS) to develop a system that supports the non-monotonic reasoning in design. We introduce a motorcycle design for a sushi shop's delivery service as one case study. The designer's reasoning is non-monotonic in terms of the whole design process, though it is monotonic in a single stage. We use C language Integrated Production System (CLIP) as the tool to develop the system, since it has a retraction function. This system allows the designer to choose or change a single design goal, add new facts or rules, and gives him a design solution as well as, if possible, a way for contradiction resolution. The future research includes further applications of assumption-based TMS and other non-monotonic logics, and studies on the relationships between design creativity and non-monotonic reasoning as well. ... For example, the definition provided by W3C as part of the Web Ontology Language (OWL) [85] describes an ontology as a set of terms in a vocabulary and their inter-relationships. Generally, an embodied agent is committed to a conceptualization regardless if the commitment is explicit (e.g., represented as knowledge graph) or implicit (e.g., represented as a set of labels for a classifier) [86] . ... Foundations of Spatial Perception for Robotics: Hierarchical Representations and Real-time Systems Preprint Full-text available Nathan Hughes <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Yun Chang Siyi Hu <here is a image 358a3e0610e3d3f4-d523b73280c7740c> Luca Carlone 3D spatial perception is the problem of building and maintaining an actionable and persistent representation of the environment in real-time using sensor data and prior knowledge. Despite the fast-paced progress in robot perception, most existing methods either build purely geometric maps (as in traditional SLAM) or flat metric-semantic maps that do not scale to large environments or large dictionaries of semantic labels. The first part of this paper is concerned with representations: we show that scalable representations for spatial perception need to be hierarchical in nature. Hierarchical representations are efficient to store, and lead to layered graphs with small treewidth, which enable provably efficient inference. We then introduce an example of hierarchical representation for indoor environments, namely a 3D scene graph, and discuss its structure and properties. The second part of the paper focuses on algorithms to incrementally construct a 3D scene graph as the robot explores the environment. Our algorithms combine 3D geometry, topology (to cluster the places into rooms), and geometric deep learning (e.g., to classify the type of rooms the robot is moving across). The third part of the paper focuses on algorithms to maintain and correct 3D scene graphs during long-term operation. We propose hierarchical descriptors for loop closure detection and describe how to correct a scene graph in response to loop closures, by solving a 3D scene graph optimization problem. We conclude the paper by combining the proposed perception algorithms into Hydra, a real-time spatial perception system that builds a 3D scene graph from visual-inertial data in real-time. We showcase Hydra's performance in photo-realistic simulations and real data collected by a Clearpath Jackal robots and a Unitree A1 robot. We release an open-source implementation of Hydra at https://github.com/MIT-SPARK/Hydra. ... According to Studer et al. [20] "an ontology is a formal, explicit specification of a shared conceptualization". A conceptualization can be understood as an "abstract simplified view of the world", as defined by Genesereth and Nilsson [21] . ... A Comprehensive Review on Ontologies for Scenario-based Testing in the Context of Autonomous Driving Preprint <here is a image 4113a9b632ef33d3-1ab0175bf17e2d61> Maximilian Zipfl Nina Koch J. Marius Zöllner The verification and validation of autonomous driving vehicles remains a major challenge due to the high complexity of autonomous driving functions. Scenario-based testing is a promising method for validating such a complex system. Ontologies can be utilized to produce test scenarios that are both meaningful and relevant. One crucial aspect of this process is selecting the appropriate method for describing the entities involved. The level of detail and specific entity classes required will vary depending on the system being tested. It is important to choose an ontology that properly reflects these needs. This paper summarizes key representative ontologies for scenario-based testing and related use cases in the field of autonomous driving. The considered ontologies are classified according to their level of detail for both static facts and dynamic aspects. Furthermore, the ontologies are evaluated based on the presence of important entity classes and the relations between them. ... It is unanimously agreed that a conceptual representation is "an abstract, simplified view of the world that we wish to represent for some purpose" [19] and is fundamentally mental in nature [20]. We adhere to an extended, spectrum-like notion 3 of conceptual representation which models concepts via a stratification across five levels viz.: ... Disentangling Domain Ontologies Preprint Full-text available In this paper, we introduce and illustrate the novel phenomenon of Conceptual Entanglement which emerges due to the representational manifoldness immanent while incrementally modelling domain ontologies step-by-step across the following five levels: perception, labelling, semantic alignment, hierarchical modelling and intensional definition. In turn, we propose Conceptual Disentanglement, a multi-level conceptual modelling strategy which enforces and explicates, via guiding principles, semantic bijections with respect to each level of conceptual entanglement (across all the above five levels) paving the way for engineering conceptually disentangled domain ontologies. We also briefly argue why state-of-the-art ontology development methodologies and approaches are insufficient with respect to our characterization. ... 220-229]. For some other 'metatheoretic' results see [5] . ... A Set of Meta-Systemetic Assumptions for Dovetailing Jaina Logic Into Jaina Metaphysics Article Full-text available This paper presents an integralist approach to Jaina logic. This is built around an analysis of the pivotal notion of antarvyāpti in Jaina logic. It is shown in this connection why antarvyāpti needs to be considered the ‘Core Perspective/Problem’ of Jaina logic. Next, it is shown how all the salient features of Jaina logic (as viewed from its language-oriented perspective and the epistemic perspective respectively) stand intimately related to the so-called core perspective. In the remaining sections of the paper topics like relationship of the core perspective i) to various non-standard systems of logic [DL, FL, NMR etc.,], ii) to the four pillars and to the eight MPC’s of Jaina philosophy, iii) to some bluntly unimaginative ways of looking at Jaina logic [e.g., Ducko-Rabbitism], iv) to the scheme of classification of propositions in Jaina logic, v) to the resulting conceptual economies related to methodology, and especially to a unified theory of Hetvābhāsa and, finally, vi) to a re-assessment of Frege-Husserl discord in the light of the significance of Jñānātmakatā vs Vākyātmakatā in Jaina logic, etc., have been discussed. ... The minimal system syntax of temporal logic introduces temporal operators that have the property of being defined in terms of others Note the link between temporal logic and modal logic in terms of their operators. Modal logic studies the reasoning that involves the use of expressions "necessarily" and "possibly" [24] . ... The Influence of Temporal Logic on Finite Automata Article <here is a image 398fdc7a81bee061-47bf6a37e8d3e10e> Ahmad Mohammed Sinjari ... The framework for first order logic may be unsuitable for certain situations which require complete knowledge about the world. In this case inference will be non-monotonic, meaning that additional knowledge can invalidate previous conclusions [64] [65] . Many knowledge modeling constructs are related to CWA and cannot be expressed in first- ... An Overview of Web Intelligence Article Full-text available أ.د. محمد أديب غنيمي أ.د. محمد أديب غنيمي . This paper gives an overview of Web intelligence which will enable the current Web to reach the Wisdom level by containing Distributed, Integrated, and Active knowledge. In this case it will be capable of performing tasks like problem solving and questionanswering. In addition, it will be capable of processing and understanding natural languages. Web intelligence draws results from a number of disciplines like: Artificial intelligence, Information technology. Mathematics and Physics, Psychology and Linguistics. The paper covers the following topics: Web evolution and architecture, Topics related to Web intelligence, The Deep Web, Semantic computing and the Semantic Web, The Wisdom Web, Precisiated Natural Language. ... These models are of interest to us in this paper because an expert is certainly an intelligent agent. Fig. 3 shows a formal model of a goal-driven, utility-based learning/evolving intelligent agent [21, 26] . ... The Expertise Level Preprint Full-text available <here is a image c3bbf8f4ccece590-1296e91482a9d466> Ron Fulbright Computers are quickly gaining on us. Artificial systems are now exceeding the performance of human experts in several domains. However, we do not yet have a deep definition of expertise. This paper examines the nature of expertise and presents an abstract knowledge-level and skill-level description of expertise. A new level lying above the Knowledge Level, called the Expertise Level, is introduced to describe the skills of an expert without having to worry about details of the knowledge required. The Model of Expertise is introduced combining the knowledge-level and expertise-level descriptions. Application of the model to the fields of cognitive architectures and human cognitive augmentation is demonstrated and several famous intelligent systems are analyzed with the model. ... Cette définition repose sur deux concepts essentiels : -conceptualisation. Selon (Genesereth et Nilsson, 1987) , une conceptualisation est « une vision abstraite et simplifiée du monde que nous souhaitons représenter afin d'atteindre un but bien précis ». Gruber (Gruber, 1993;Gruber, 1995) s'est référé à cette notion pour présenter la notion de conceptualisation. ... Une approche d’aide à la décision pour la réponse à une crise Thesis Full-text available <here is a image 050d231fd315bee1-90eb309a4327056c> Walid Bannour Depuis la nuit des temps, l’Homme a toujours été victime des désastres, que ce soit naturels ou causés par lui-même. En effet, ces catastrophes inévitables engendrent souvent des pertes économiques et sociales importantes. La réponse aux situations de crise demeure, jusqu’à nos jours, une tâche complexe et cruciale et représente un défi majeur pour l’Homme en général et pour les preneurs de décisions d’urgence en particulier. Assister ces derniers à la réponse aux crises par la mise en oeuvre d’approches d’aide à la décision est un challenge à relever. L’objectif de cette thèse est de proposer une approche d’aide à la décision pour la réponse à une crise. Particulièrement, le but de cette approche est de générer un plan de réponse d’urgence adaptable à une situation de crise courante. L’approche proposée est basée sur un couplage entre les ontologies et le Raisonnement à Partir de Cas (RàPC). Concernant les ontologies, elles ont servi, entre autres, à la représentation des connaissances liées à la réponse aux crises. Quant au RàPC, qui est une méthodologie de raisonnement par analogie et d’apprentissage issue de l’intelligence artificielle, il a permis la capitalisation des connaissances issues des retours d’expériences des situations antérieures de réponse aux crises. L’intérêt de l’approche proposée réside, non seulement dans l’assistance des gestionnaires de crise dans leur tâche de génération d’une solution de réponse d’urgence, mais aussi dans l’amélioration du cycle de raisonnement. ... De Groot established the importance of perception in expertise in that an expert perceives the most important aspects of a situation faster than novices [45]. Formally, experts are goal-driven intelligent agents where set of goals, G, and a set of utility values, U, drive the expert's perceiving, reasoning and acting over time [23] [24]. Intelligent agents perceive a subset, T, of possible states, S, of the environment and perform actions from set of actions, A, to effect changes on the environment. ... Synthetic Expertise Preprint Full-text available <here is a image c3bbf8f4ccece590-1296e91482a9d466> Ron Fulbright We will soon be surrounded by artificial systems capable of cognitive performance rivaling or exceeding a human expert in specific domains of discourse. However, these cogs need not be capable of full general artificial intelligence nor able to function in a stand-alone manner. Instead, cogs and humans will work together in collaboration each compensating for the weaknesses of the other and together achieve synthetic expertise as an ensemble. This paper reviews the nature of expertise, the Expertise Level to describe the skills required of an expert, and knowledge stores required by an expert. By collaboration, cogs augment human cognitive ability in a human/cog ensemble. This paper introduces six Levels of Cognitive Augmentation to describe the balance of cognitive processing in the human/cog ensemble. Because these cogs will be available to the mass market via common devices and inexpensive applications, they will lead to the Democratization of Expertise and a new cognitive systems era promising to change how we live, work, and play. The future will belong to those best able to communicate, coordinate, and collaborate with cognitive systems. ... Step 5) Define Relationships between Neighboring Viewpoints: Next, the authors defined the relationships between M[x] and M[x-1] viewpoints where x∈ (1, 2, 3). With Guizzardi's work (Fig. 3), authors observed that the semantic triangle's Knowledge (K) vertex is comprised of 1) conceptualization knowledge and 2) mental model knowledge [57,66, 71] . Where conceptualization knowledge is used to-contemplate or compose mental models of reality, a mental model is an instance-of conceptualization knowledge. ... A Method for Structuring Complex Clinical Knowledge and its Representational Formalisms to Support Composite Knowledge Interoperability in Healthcare Article Full-text available <here is a image a68991a30b85288e-717a613d06a0b5b6> Robert Lario <here is a image 8319a842cf2791b0-9cf52d80a446e048> Blackford Middleton Introduction The use and interoperability of clinical knowledge starts with the quality of the formalism utilized to express medical expertise. However, a crucial challenge is that existing formalisms are often suboptimal, lacking the fidelity to represent complex knowledge thoroughly and concisely. Often this leads to difficulties when seeking to unambiguously capture, share, and implement the knowledge for care improvement in clinical information systems used by providers and patients. Objectives To provide a systematic method to address some of the complexities of knowledge composition and interoperability related to standards-based representational formalisms of medical knowledge. Methods Several cross-industry (Healthcare, Linguistics, System Engineering, Standards Development, and Knowledge Engineering) frameworks were synthesized into a proposed reference knowledge framework. The framework utilizes IEEE 42010, the MetaObject Facility, the Semantic Triangle, an Ontology Framework, and the Domain and Comprehensibility Appropriateness criteria. The steps taken were: 1) identify foundational cross-industry frameworks, 2) select architecture description method, 3) define life cycle viewpoints, 4) define representation and knowledge viewpoints, 5) define relationships between neighboring viewpoints, and 6) establish characteristic definitions of the relationships between components. System engineering principles applied included separation of concerns, cohesion, and loose coupling. Results A “Multilayer Metamodel for Representation and Knowledge“ (M*R/K) reference framework was defined. It provides a standard vocabulary for organizing and articulating medical knowledge curation perspectives, concepts, and relationships across the artifacts created during the life cycle of language creation, authoring medical knowledge, and knowledge implementation in clinical information systems such as electronic health records (EHR). Conclusion M*R/K provides a systematic means to address some of the complexities of knowledge composition and interoperability related to medical knowledge representations used in diverse standards. The framework may be used to guide the development, assessment, and coordinated use of knowledge representation formalisms. M*R/K could promote the alignment and aggregated use of distinct domain-specific languages in composite knowledge artifacts such as clinical practice guidelines (CPGs). ... On the other hand, the information required for this deduction, that was gained during the initial ad lib condition of Experiment 1 without apparent overt manifestation, appears to have the characteristics of declarative knowledge. It is worth noting in this connection that in computer science and artificial intelligence, the meaning and status of the distinction between declarative and procedural information is still controversial: some authors argue that it is basic (Genesereth & Nilsson, 1987) , while others note that it tends to evanesce when the computational processes are examined closely (Wegner, 1968;Winston, 1977). ... Animal Cognition in Relation to Farm Animal Welfare: The Need for a Different Approach Article Jan 1998 Int J Comp Psychol Lloyd Fell ... The quote above, originally appeared in [40] , was also referred by Gruber in his seminal paper on computational ontologies [41]. Hence, the objective of a conceptualization is the identification and modelling of the entities and relationships between them to provide a description of a given application domain, with respect to a defined purpose. ... An Ontology-based approach for Modelling and Querying Alzheimer’s Disease Data Preprint Full-text available Jun 2022 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Francesco Taglino <here is a image 30ee85582bcf63a8-d8a36659cdd641d1> Fabio Cumbo Giulia Antognoli <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Paola Bertolazzi Background: The recent advances in biotechnology and computer science have led to an ever-increasing availability of public biomedical data distributed in large databases worldwide. However, these data collections are far from being “big” enough and “standardized” so to be integrated, making impossible to fully exploit latest machine learning technologies for the analysis of data themselves. Hence, facing this huge flow of biomedical data is a challenging task for researchers and clinicians due to their complexity and high heterogeneity. An effective strategy to address this issue could be the building of a formal conceptual model, which in general allows the design of semantic tools to collect and explore data for a given pathology. This is the case of neurodegenerative diseases and the Alzheimer Disease (AD), in particular. The last years have witnessed the creation of specialized data collections such as the one maintained by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which contains the largest number of biomedical concepts in the field of AD. For this class of diseases Big Data and Deep Learning give hope for the discovery of new biomarkers for early diagnosis. Hence, a new way must be undertaken of collecting and managing biomedical data. Results: We developed a detailed ontology for clinical multidimensional datasets from the ADNI repository in order to simplify the data access, to obtain new diagnostic knowledge about Alzheimer’s disease and ease the task of harmonization. Conclusions: The semantic data base, populated by ADNI data will suggest new queries allowing machine learning techniques to be applied to any possible combination of data set. The conceptual model could be adopted by any center, so giving rise to new databases that, if made public available, will simplify data integration and multi center data collection projects. ... Such a distinction has its roots in discrete control theory (Ramadge and Wonham 1989), and has lately been adopted in Verification for dealing with synthesis from temporal specifications (Piterman, Pnueli, and Sa'ar 2006). Also, this distinction has been explicitly made in some AI work on reasoning about actions and on agents, e.g., (Lespérance, De Giacomo, and Ozgovde 2008; Genesereth and Nilsson 1987; Wooldridge 2009). Formally, such a distinction allows for separately quantifying over both environment's and controller's moves. ... Two-Player Game Structures for Generalized Planning and Agent Composition Article Jul 2010 <here is a image 1a4840943b5f8b82-df5b99c825e0f600> Giuseppe De Giacomo <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Paolo Felli Fabio Patrizi <here is a image 40b5fa3ca4b0b596-8b07edfd889cbed5> Sebastian Sardina In this paper, we review a series of agent behavior synthesis problems under full observability and nondeterminism (partial controllability), ranging from conditional planning, to recently introduced agent planning programs, and to sophisticated forms of agent behavior compositions, and show that all of them can be solved by model checking two-player game structures. These structures are akin to transition systems/Kripke structures, usually adopted in model checking, except that they distinguish (and hence allow to separately quantify) between the actions/moves of two antagonistic players. We show that using them we can implement solvers for several agent behavior synthesis problems. ... We call this property the induction principle for common knowledge. It has been argued by some that this would make common knowledge too strong [95,69], and logics in which this does not hold have been developed, such as that by Genesereth and Nilsson [58] , used in modal extensions of logic programming in the 90s [13,12], in which common knowledge is seen as knowledge of a 'fictitious knower' or 'any fool'. ... Lightweight approaches to reasoning about knowledge and belief Thesis Oct 2021 Elise Perrotin-Boithias In this thesis we study a lightweight framework in which to model knowledge and beliefs and the evolution thereof in multiagent systems. The standard logic used for this is very expressive, but this comes at a high cost in terms of computational efficiency. We here propose a framework which captures more than other existing approaches while remaining cost-effective. In particular, we show its applicability to epistemic planning: given an initial situation and some possible actions, can we find a way to reach our desired goal? This might mean knowing who to ask in order to learn something, making sure we aren't seen when reading someone else's mail, or preventing someone from overhearing our secrets. We also discuss possible extensions to logics of belief, and the relations between our framework and other related approaches. ... An example of an answer that comes from a 3WD technique could be the functional version of the well-known Closed World Assumption (CWA) from Nonmonotonous Reasoning in AI (cf. [21] ). ... Concept learning consistency under three-way decision paradigm Article Full-text available May 2022 <here is a image c5de14383373de17-fba0e2b35bb30c6f> Gonzalo A. Aranda-Corral <here is a image 4238e42f6698deb4-2945036339ea8b0f> Joaquín Borrego-Díaz <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Juan Galán-Páez Concept Mining is one of the main challenges both in Cognitive Computing and in Machine Learning. The ongoing improvement of solutions to address this issue raises the need to analyze whether the consistency of the learning process is preserved. This paper addresses a particular problem, namely, how the concept mining capability changes under the reconsideration of the hypothesis class. The issue will be raised from the point of view of the so-called Three-Way Decision (3WD) paradigm. The paradigm provides a sound framework to reconsider decision-making processes, including those assisted by Machine Learning. Thus, the paper aims to analyze the influence of 3WD techniques in the Concept Learning Process itself. For this purpose, we introduce new versions of the Vapnik-Chervonenkis dimension. Likewise, to illustrate how the formal approach can be instantiated in a particular model, the case of concept learning in (Fuzzy) Formal Concept Analysis is considered. ... 1. Kemp et al. (2007) and Mustafa Ersen et al. (2017) provide comprehensive review articles about challenges and approaches to autonomous robot manipulation in human environments. 2. Excellent textbooks on the logic-based approach to building intelligent systems include Genesereth and Nilsson (1987) ; Reiter (2001); Davis (1990). ... Knowledge Representation and Reasoning Chapter Full-text available May 2022 Michael Beetz The current state of the art in cognitive robotics, covering the challenges of building AI-powered intelligent robots inspired by natural cognitive systems. A novel approach to building AI-powered intelligent robots takes inspiration from the way natural cognitive systems—in humans, animals, and biological systems—develop intelligence by exploiting the full power of interactions between body and brain, the physical and social environment in which they live, and phylogenetic, developmental, and learning dynamics. This volume reports on the current state of the art in cognitive robotics, offering the first comprehensive coverage of building robots inspired by natural cognitive systems. Contributors first provide a systematic definition of cognitive robotics and a history of developments in the field. They describe in detail five main approaches: developmental, neuro, evolutionary, swarm, and soft robotics. They go on to consider methodologies and concepts, treating topics that include commonly used cognitive robotics platforms and robot simulators, biomimetic skin as an example of a hardware-based approach, machine-learning methods, and cognitive architecture. Finally, they cover the behavioral and cognitive capabilities of a variety of models, experiments, and applications, looking at issues that range from intrinsic motivation and perception to robot consciousness. Cognitive Robotics is aimed at an interdisciplinary audience, balancing technical details and examples for the computational reader with theoretical and experimental findings for the empirical scientist. ... We specify a tropistic ( [32] , Section 13.1) Linked Data agent AGENT k as an active component ... stigLD: Stigmergic Coordination in Linked Systems Article Full-text available Mar 2022 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> René Schubotz <here is a image 1bfd7da5a787b650-401223fa0140a44c> Torsten Spieldenner <here is a image 77a7307c856b9509-104348fc3cdb44a8> Melvin Chelli While current Semantic Web technologies are well-suited for data publication and integration, the design and deployment of dynamic, autonomous and long-lived multi-agent systems (MAS) on the Web is still in its infancy. Following the vision of hypermedia MAS and Linked Systems, we propose to use a value-passing fragment of Milner’s Calculus to formally specify the generic hypermedia-driven behaviour of Linked Data agents and the Web as their embedding environment. We are specifically interested in agent coordination mechanisms based on stigmergic principles. When considering transient marker-based stigmergy, we identify the necessity of generating server-side effects during the handling of safe and idempotent agent-initiated resource requests. This design choice is oftentimes contested with an imprecise interpretation of HTTP semantics, or with rejecting environments as first-class abstractions in MAS. Based on our observations, we present a domain model and a SPARQL function library facilitating the design and implementation of stigmergic coordination between Linked Data agents on the Web. We demonstrate the efficacy our of modelling approach in a Make-to-Order fulfilment scenario involving transient stigmergy and negative feedback as well as by solving a problem instance from the (time constrained) Trucks World domain as presented in the fifth International Planning Competition. ... We specify a tropistic ( [32] , Section 13.1) Linked Data agent AGENT k as an active component ... stigLD: Stigmergic Coordination of Linked Data Agents Chapter Full-text available Jan 2022 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> René Schubotz <here is a image 1bfd7da5a787b650-401223fa0140a44c> Torsten Spieldenner <here is a image 77a7307c856b9509-104348fc3cdb44a8> Melvin Chelli While current Semantic Web technologies are well-suited for data publication and integration, the design and deployment of dynamic, autonomous and long-lived multi-agent systems (MAS) on the Web is still in its infancy. Following the vision of hypermedia MAS and Linked Systems, we propose to use a value-passing fragment of Milner’s Calculus to formally specify the generic hypermedia-driven behaviour of Linked Data agents and the Web as their embedding environment. We are specifically interested in agent coordination mechanisms based on stigmergic principles. When considering transient marker-based stigmergy, we identify the necessity of generating server-side effects during the handling of safe and idempotent agent-initiated resource requests. This design choice is oftentimes contested with an imprecise interpretation of HTTP semantics, or with rejecting environments as first-class abstractions in MAS. Based on our observations, we present a domain model and a SPARQL function library facilitating the design and implementation of stigmergic coordination between Linked Data agents on the Web. We demonstrate the efficacy our modeling approach in a Make-to-Order fulfilment scenario involving transient stigmergy and negative feedback.KeywordsLinked DataSemantic WebMulti-agent systemsStigmergyNature inspired algorithmRDFSPARQL ... Per represents the perception of the environment from the agent's point of view. An agent observes the environment (see), selects the appropriate action (action), and acts (do) on the environment itself 9 . ... Agent-based models for detecting the driving forces of biomolecular interactions Agent-based modelling and simulation have been effectively applied to the study of complex biological systems, especially when composed of many interacting entities. Representing biomolecules as autonomous agents allows this approach to bring out the global behaviour of biochemical processes as resulting from local molecular interactions. In this paper, we leverage the capabilities of the agent paradigm to construct an in silico replica of the glycolytic pathway; the aim is to detect the role that long-range electrodynamic forces might have on the rate of glucose oxidation. Experimental evidences have shown that random encounters and short-range potentials might not be sufficient to explain the high efficiency of biochemical reactions in living cells. However, while the latest in vitro studies are limited by present-day technology, agent-based simulations provide an in silico support to the outcomes hitherto obtained and shed light on behaviours not yet well understood. Our results grasp properties hard to uncover through other computational methods, such as the effect of electromagnetic potentials on glycolytic oscillations. ... A formula consists of literals connected by logical connectives (i.e., ∨ and ∧). A first-order knowledge base (KB) is a set of sentences or formulas in first-order logic [19] . A ∧ B ⇒ C is an example of an implication formula. ... Sequential Prediction with Logic Constraints for Surgical Robotic Activity Recognition ... Modern exponents often emphasize the sentential structures studied by formal logic. Many AI researchers, including Genesereth and Nilsson (1987) and McCarthy and Hayes (1969), pursue a 'logicist' agenda that treats the predicate calculus, or a suitably supplemented variant of it, as the primary, paradigmatic, or even exclusive medium of thought. ... What Proto-logic Could not be Inspired by Bermúdez’s notion of proto-logic, I would like to fathom what the true proto-logic could be like. But this will be approached only in a negative way of figuring out what it could not be. I shall argue that it could not be purely deductive by exploiting the recent researches in logic of maps. This will allow us to reorient the search for proto-logic, starting with animal abduction. I will also suggest that proto-logic won’t get off the ground without proto-geometry. These negative results will shed some lights on some further conceptual and historical issues around the language of thought hypothesis to arrive at the true proto-logic. ... De Groot established how experts perceive the most important aspects of a situation faster than novices [8]. Formally, experts are goal-driven intelligent agents where a set of goals, G, and a set of utility values, U, drive the expert's perceiving, reasoning and act cycles over time [15, 29]. Intelligent agents perceive a subset, T, of possible states, S, of the environment and perform actions from set of actions, A, to effect changes on the environment. ... A Synthetic Elderly Companion Named Lois Described is a synthetic elderly companion named Lois, short for Loved One’s Information System, able to tend to an elder’s needs, monitor overall well-being and progress, detect decline and signs of further medical problems, and in general, ‘be there’ for an elder. Lois is a cognitive system comprised of computer displays, cameras, speakers, microphones, and various sensors placed throughout the home facilitating both non-invasive monitoring and highly interactive collaboration. Lois maintains a set of models enabling the recognition of events and changes of condition as well as the compiling of a historical record for later use by medical personnel and family members. Since Lois lives with the elder over an extended period of time Lois becomes tailored specifically to the elder learning their schedule, likes, dislikes, and tendencies. By working with the elder, the elder’s family members, and medical personnel, Lois is at the center of a synthetic elderly caregiver ensemble capable of performance superior to any human caregiver. ... Artificial Intelligence (AI) is an intelligence mechanism for machines which enables them to imitate human intelligence and mimic their behavior to a certain extent or better (Charniak 1985, Genesereth and Nilsson 2012) . AI was developed keeping in mind to solve complex real-world problems through an approximation of human decision-making capabilities and perform tasks in ever more humane ways (Russell and Norvig 2002). ... Revisiting the Machine Learning Algorithms and Applications in Engineering and Computer Science Introduction to Metareasoning Robots have limited computational resources, often due to size, weight, and power (SWaP) constraints, and these resources must perform the reasoning and computation tasks for sensor management, image processing, mapping, planning, control, collaboration, and communications. In this dynamic environment, as the robot executes different reasoning tasks that compete for resources, the constraints on processors, memory, communication bandwidth, and power can interact in unpredictable ways to degrade the robot’s performance. To avoid this problem, the robot needs a way to monitor and control its reasoning processes. An intelligent robot can use metareasoning (reasoning about reasoning) to improve its reasoning and decision-making processes by adapting them in response to changes in the environment or the system. This makes it safer and more resilient as well. This chapter introduces some key concepts related to robots and autonomous systems. It then discusses why metareasoning is needed and the benefits of metareasoning, which is a branch of artificial intelligence (AI). It presents a list of key sources that one should read for more information about metareasoning. Finally, it discusses the systems engineering approach that informs the structure and contents of this book. Logic-Based Modeling of Cognition The Cambridge Handbook of Computational Cognitive Sciences is a comprehensive reference for this rapidly developing and highly interdisciplinary field. Written with both newcomers and experts in mind, it provides an accessible introduction of paradigms, methodologies, approaches, and models, with ample detail and illustrated by examples. It should appeal to researchers and students working within the computational cognitive sciences, as well as those working in adjacent fields including philosophy, psychology, linguistics, anthropology, education, neuroscience, artificial intelligence, computer science, and more. MLN4KB: an efficient Markov logic network engine for large-scale knowledge bases and structured logic rules Zastosowania sztucznej inteligencji w obsłudze klientów sklepów internetowych branży mody In this work, the author presents various definitions of artificial intelligence, describing its essence, genesis, and evolution over the years. In addition, it introduces the use of applied areas of artificial intelligence in business, including marketing activities of enterprises. The work also contains a description of the specificity of the use of artificial intelligence in the fashion industry, considering the characteristics of this industry. The scope of the use of artificial intelligence by the managers of fashion brands is considered, together with examples of the tools used. The third, last part of the work includes an analysis of case studies of three operators of online stores of fashion industry brands: MODIVO, Zalando, ASOS - the characteristics of these brands, identification of tools used to serve e-consumers using technologies based on artificial intelligence, the impact of these tools on the multi-channel strategy and the benefits for e-consumers resulting from their use, as well as forms of communication regarding the topic of artificial intelligence usage coming from companies itself. Specification of the Fundamental Concepts in the Ontology of Processes; Event, Process, Activity Cross‐Cultural Commonalities in Religiosity by Measurement Invariance In this study, we attempted to determine the cross‐cultural commonalities in religiosity between the U.S. and Japan by measurement invariance. While both countries share many common values and similar social systems, some differences exist in religion. We collected religious propositions/concepts typical in most religions in the two countries. Then, using a mind map tool and database, we prepared 100 mutually exclusive and collectively exhaustive religious belief items that do not employ the terminologies of any specific religion. U.S. and Japanese research companies administered the survey via the internet. By differential item functioning (DIF) analysis, we found 23 common items, and five remarkably specific items showing opposing patterns. By multiple‐group confirmatory factor analysis, we found that the two countries share the same structure of religiosity, consisting of three correlated factors: “Supernaturalism,” “Psychological Benefits of Religion,” and “New Age Spirituality.” The factor “New Age spirituality” connects the other two factors. Could artificial intelligence revolutionize the development of nanovectors for gene therapy and mRNA vaccines? Gene therapy enables the introduction of nucleic acids like DNA and RNA into host cells, and is expected to revolutionize the treatment of a wide range of diseases. This growth has been further accelerated by the discovery of CRISPR/Cas technology, which allows accurate genomic editing in a broad range of cells and organisms in vitro and in vivo . Despite many advances in gene delivery and the development of various viral and non-viral gene delivery vectors, the lack of highly efficient non-viral systems with low cellular toxicity remains a challenge. The application of cutting-edge technologies such as artificial intelligence (AI) has great potential to find new paradigms to solve this issue. Herein, we review AI and its major subfields including machine learning (ML), neural networks (NNs), expert systems, deep learning (DL), computer vision and robotics. We discuss the potential of AI-based models and algorithms in the design of targeted gene delivery vehicles capable of crossing extracellular and intracellular barriers by viral mimicry strategies. We finally discuss the role of AI in improving the function of CRISPR/Cas systems, developing novel nanobots, and mRNA vaccine carriers. BİLİŞİM ALANI LİSANSÜSTÜ ÖĞRENCİLERİNİN YAPAY ZEKÂ KONUSUNDAKİ GÖRÜŞLERİ Defining Artificial Intelligence The dream of the intelligent machine is the vision of creating something that does not depend on having people preprogram its problem‐solving behaviour. Put another way, artificial intelligence (AI) should not seek to merely solve problems but should rather seek to solve the problem of how to solve problems. This chapter seeks to provide a focused explication of particular methods that indeed allow machines to improve themselves by learning from experience and to explain the fundamental theoretical and practical considerations of applying them to problems of machine learning. To begin this explication, the discussion first goes back to the Turing Test. The acceptance of the Turing Test focused attention on mimicking human behaviour. A human may be described as an intelligent problem‐solving machine. The idea of constructing an artificial brain or neural network has been proposed many times. Contributions to the process at Risk Assessment of Groundwater Contamination: A Fuzzy-Probabilistic Model Proposal│Contribuições ao Processo de Avaliação de Riscos de Contaminação das Águas Subterrâneas: Proposta Fuzzy-Probabilística ALGORITMOS E CÁLCULO NUMÉRICO Neste capítulo, você vai aprender os conceitos fundamentais sobre o tema da lógica de predicados, de fundamental importância para desenvolver uma solução algorítmica para determinado problema, possibilitando, assim, sua implementação posterior por meio de uma adequada linguagem de programação. Nesse sentido, inicialmente será definida a lógica dos predicados, momento em que serão apresentados a simbologia a ser utilizada, as fórmulas, os quan�tificadores e os enunciados. Em um segundo momento, será trabalhado o tema da lógica dos conjuntos por meio dos diagramas de Venn para a representação dos enunciados. Por fim, haverá um estudo comparando os predicados e a lógica proposicional, quando serão apresentados exemplos de aplicações. Ao final deste capítulo , você terá aprendido os fundamentos da lógica de predicados, o que lhe auxiliará no desenvolvimento de seus futuros algoritmos e implementações computacionais A Visual Graphs Transformative Deductive System with Applications to Analytics, Spatial Navigation, planning, and Haptic Neurocognitive AI A novel graphical reasoning with abstract models diagrams, on a visual virtual tree-based functional deductive system called Morph Gentzen were developed since 1997 is briefly presented. Context abstractions with categorical linguistics, agent languages, and Meta-Contextual Reasoning are newer areas encompassed since the Morph Gentzen computing logic by this author since 1997. Reflecting on what was accomplished over the years, this brief is a glimpse on the techniques that bring forth computable AI world knowledge representable with generic model diagrams, characterized with a minimal family of Skolem functions applied on multiagent graph transformations. The functions may correspond to objects defining shapes and depicting pictures. A Unifying Framework for Agency in Hypermedia Environments One of the emerging trends in engineering multi-agent systems (MASs) is to use the Web as an environment. On the Web, hypermedia is the guiding principle of agent perception and action. Web standards allows agents to have a single uniform interface to their environment, be it real or simulated. Most recent proposals for hypermedia MASs tend, however, to introduce a coupling between agents or between agents and their environment.This paper introduces a framework based on Semantic Web technologies to formalize interactions between agents and a hypermedia environment. Semantic Web technologies and, more specifically Web ontologies, guarantee interoperability on the Web and maximize uncoupling between components. We show how existing ontologies can be used to make existing MAS prototypes fit our framework.Our framework formalizes the guiding principle of agent-environment interactions in hypermedia, state transfer, with respect to a reference formalism originally introduced by Genesereth and Nilsson. We also show the equivalence between the two in the paper, under certain conditions.KeywordsSemantic WebLinked DataHypermediaMulti-agent system Prédiction de l’évolution d’un système complexe dans un contexte non déterministe : architecture basée sur le couplage SMA / RàPC et la clusterisation. La gestion des risques liés aux actions et aux conditions des différents éléments qui composent un bloc opératoire est une préoccupation majeure lors d'une intervention chirurgicale. La prédiction d’événement indésirables graves associés aux soins (EIGS), et l’analyse de leur survenue sont des enjeux majeurs. Dans cet objectif, nous proposons une architecture qui couple un système multi-agents (SMA) avec un raisonnement à partir de cas (RàPC). Le SMA capable de produire un grand nombre de situations où les agents interagissent entre eux créent des phénomènes émergents et donc un possible nouvel EIGS. Le couplage du système multi-agents avec un raisonnement à partir de cas, enrichit la base de connaissances du modèle, et répond à notre recherche d’approche de résolution de problèmes par analogie à partir d’expériences passées. Au-delà de la détermination d’EIGS nous avons intégré des outils d’aide à la décision. Les deux premiers Algorithmes (similVar et similVar+) que nous avons conçus et comparés à d’autres méthodes sont orientés sur classification des données. Ils consistent à clusteriser les données dans le but d’établir ensuite des corrélations entre les comportements des agents. Deux autres Algorithmes (liaisAttrib et predictPath) sont quant eux respectivement dédiés à la détermination de corrélations entre des données clusterisées et à la prédictivité de l’évolution du système. Les résultats encourageants montrent l’efficacité de notre approche dans la capacité à produire, à analyser et à prédire la survenue d’EIGS dans un contexte non déterministe où évoluent des entités hétérogènes. Brain and Behavior: Blending of Human and Artificial Minds Toward Stress Recognition and Intervention in Organizational Well‐Being Stress attracts significant attention in the era of Artificial Intelligence (AI). Stress has become a part of every human and its consequences are severe if left untouched. The chapter pens down the impressions of AI as an enabler of human‐technology interaction through various facilitators like sensor technology and wearable devices with physiological and psychological signals. Stress at workplace is a phenomenon that can neither be avoided nor be ignored but can be condensed to a great extent. In this chapter, attempt is made to explore all possible AI‐powered stress recognition techniques and effective stress management interventions toward organizational well‐being. The chapter is purely descriptive in nature following a qualitative approach. The intention of the study is to carry systematic literature review on AI‐powered stress recognition and stress management interventions and its role in mental and physical well‐being of employees. AI‐powered devices and app are developed to manage stress, depression, and anxiety, even to prevent suicidal risk. After extensive literature review, it has been concluded that AI plays a positive and an impactful role in real time, and accurate stress recognition and interventions through chatbot, virtual therapist, biofeedback systems, wearable devices with sensor technology, and smart phone apps are effective in reducing the stress at workplace. MAS agents development for mining industry
https://www.researchgate.net/publication/319393908_Logical_foundations_of_artificial_intelligence
Jekkannu Sami Iyer v. Muthukumara Ramaswami Chettiar Major | Madras High Court | Judgment | Law | CaseMine Get free access to the complete judgment in Jekkannu Sami Iyer v. Muthukumara Ramaswami Chettiar Major on CaseMine. Jekkannu Sami Iyer v. Muthukumara Ramaswami Chettiar Major Madras High Court Oct 4, 1922 Jekkannu Sami Iyer v. Muthukumara Ramaswami Chettiar Major Case Information CITATION CODES citation codes CASE NO. Appeal Against Appellate Order No. 7 of 1922. ATTORNEY(S) Mr. M. S. Venkatarama Aiyar for the Appellant. Mr. A. C. Sampath Aiyangar for the Respondent. JUDGES Spencer Venkatasubba Rao, JJ. ACTS Sect. 101 of the Transfer of Property Act 129, 130, 133 and 135 of the Contract Act 128 and 134 of the Indian Contract Act Sect. 128 of the Contract Act TRANSFER OF PROPERTY ACT Sect. 128, Contract Act, Sect. 134 Contract Act, Indian Contract Act Smart Summary Jekkannu Sami Iyer v. Muthukumara Ramaswami Chettiar Major Spencer, J. — This appeal raises a question as to the liability of a surety when his principal's debt has been extinguished by an act which causes the merger of the estates of the debtor and the creditor. As the facts have been set out in my learned brother's judgment, I will not recapitulate them. Ordinarily the liability of a surety is co-extensive with that of the principal debtor, unless it is otherwise provided for. There is no provision to the contrary in the security bond executed on January, 16th 1917, by the appellant and his mother. Therein they declared that they would stand as sureties and make themselves responsible for the amount of Rs. 225 that might be found due to the plaintiffs (from the defendants). An illustration of the effect ofSect. 128 of the Contract Actoccurs inShek Suleman v. Shivram Bhikaji(1), where it was observed that if an amount recoverable by a plaintiff from a defendant debtor is diminished in appeal, the surety's engagement, being one of indemnity, would diminish in like proportion. So if the sum recoverable became zero owing to the decree being reversed, the surety's liability would also be reduced to nothing. The present is not a case of continuing guarantee or of time being given to the principal debtor, or of the terms of any contract between the creditor and the debtor being varied. Therefore the references by the respondents' vakil to Sects.129, 130, 133 and 135 of the Contract Actand toSubroya Chetty…(Plaintiff) v. Ragammall…(First Defendant) .*(2) are not to the point. Nor is there any question of the remedy against the principal debtor becoming barred by limitation or being kept alive by payment, as to which it was held inBrajendra Kishore Roy Chowdhury v. Hindustan Co-Operative Insurance Society, Ld.*, thatSect. 128, Contract Act,would not prevent the liabilities of the principal and the debtor being distinct in matters of limitation, and inJambu Ramaswamy Bhagavathar v. Sundararaja ChettithatSect. 134 Contract Act,would not help the surety. The main question to be decided in this case is whether the 1st defendant's debt became extinguished in consequence of the merger of his estate with the estate of the plaintiffs (respondents). If that question is answered in the affirmative, it will follow from Sects.128 and 134 of the Indian Contract Actthat the respondents cannot proceed to recover anything on account of mesne profits from the appellant who stood as surety for the 1st defendant. In other words the question is whether the legal consequence of the creditor's act in taking over the 1st defendant's estate was to discharge the principal debtor. The principle of merger has been described inBanarsi Das v. Maharani Kuar(3), as a union in the same person of the character of debtor and creditor and its origin has been traced to the confusio of Roman Law. InKudhai v. Sheo Dayal(4) it has been further explained by Mahmood, J., who observes at p. 575 that a man cannot be his own creditor, or the mortgagee of his own rights. Lord Halsbury in Vol. 13 of his Laws of England, p. 146 state:— “At law, when a less estate was vested in the same person as a greater estate without any intermediate estate between them, the less estate merged in the greater and was extinguished, without regard to the intention of the parties concerned. Equity is not guided by the rules of law as to merger, and so the question whether merger takes place depends upon the intention, actual or presumed, of the person in whom the interests became united”. So as I observed in my judgment inChidambaram Pillai v. Meenakshi Ammal(5), the question of merger is one of intention, and in the case of a limited owner the presumption is against a merger.Sect. 101 of the Transfer of Property Actwhich creates a statutory merger has no application to the present case of a personal decree obtained against the 1st defendant for future mesne profits at the rate of Rs. 75 per annum. But the principle of merger exists independently of statute, and theTransfer of Property Acthas been treated as codifying the law that already existed prior to its enactment. InKudhai v. Sheo Dayalthe principle is stated to apply whenever rights devolve either by inheritance or are acquired under a valid transfer if the result of such devolution or acquisition is that the estates of the judgment-creditor and the judgment-debtor or of the mortgagee and the mortgagor become united in whole or in part in the person of a single’ individual. From the intention of the parties in the present case it might be held that there was no merger when the 2nd defendant Kagammal succeeded to the estate of her deceased son 1st defendant, as the former was a limited owner and the decree remained executable against the 1st defendant's estate under Sect. 50, Civil Procedure Code. But when she surrendered the whole estate to the plaintiffs as being the nearest reversioner reserving for herself nothing but a right of maintenance under Ex. II, it cannot be supposed that these reversioners intended to keep alive a debt owed by that estate to themselves, a debt of which no mention is made in Ex. II. They took over among others the properties which were pledged by the 1st defendant's guardian as security for reimbursement of the sureties in the event of their having to pay the 1st defendant's decree debt for mesne profits. What they must be deemed to have got in succession by 1st defendant's untimely death and his mother's release-deed was the balance of his estate after wiping out his debt to them. Respondent's vakil attempted to support the lower Appellate Court's judgment by several other arguments. He contended that the rules as to creditors, and debtors would not apply to this case, as the bond was executed under Sect. 145, Civil Procedure Code in favour of the Court in the form given in Appendix H, No. 13. He maintained that this procedure made the Court the creditor and prevented the surety from pleading discharge under Sects. 133 or 135 of the Contract Act on account of any variance of the terms or any composition between the creditor and the debtor. It is impossible to conceive how the execution of the surety bond in favour of the District Munsif converted that officer into a creditor in respect of the decree debt. Sect. 145 has been enacted for the purpose of expeditious enforcement of liabilities against sureties, in order to avoid the cumbrous procedure of assigning the bond to a decree-holder and his instituting a separate suit upon it. The surety can put forward in those proceedings any defence that is open to him, and for the purpose of appealing against any order that is made against him he is expressly declared to be deemed to be a party within the meaning of Sect. 47. Though the security bond may be executed in favour of the Court, the Court holds it for the benefit of the decree-holder. No doubt it was held inRamanathan Pillai v. M. Doraiswami Ayyangarthat if the surety wants to get the bond cancelled, he must proceed by regular suit, but it was admitted that he might become a party to execution proceedings, when an application was made for an order against him. This case is not an authority for the startling proposition now advanced that in proceedings under Sect. 145 a surety is precluded from raising any defence. Then it was argued that the incidents connected with the merger of estates would not attach where the decree-holders obtain the 1st defendant's estate long after delivery of their share of property and some time after the estate vested in 1st defendant under a release-deed or conveyance, and not by the mere operation of Hindu Law. But it is the surrender of the widow of her life estate by means of a deed that brings the Hindu Law into operation and it is immaterial when the surrender took place. Lastly, stress was laid on the fact that the arrears accrued during the life time of 1st defendant and gave rise to a personal liability against him which had not been extinguished. On the death of a judgment-debtor, however, execution can only, under Sect. 50, Civil Procedure Code, be taken out against his property in the hands of his legal representative. This judgment-debtor's property is now in the hands of the decree-holders. When it is apparent that they can now do nothing but take out execution against themselves, the argument ends in a reductio ad absurdum. The appeal is allowed with costs here and in the lower appellate Court, and the District Munsifs order dismissing 1st and 2nd respondent's petition is restored. Venkatasubba Rao, J.—This appeal raises the question whether the plaintiffs are entitled to execute the decree under Sect. 145, Civil Procedure Code, against the surety, who is the appellant before us. The District Munsif held that the plaintiffs were not entitled but the Subordinate Judge reversed the decision of the District Munsif. The facts may be briefly stated. The plaintiffs brought the action for partition of certain properties and for possession of their share. A decree was passed which inter alia directed the 1st defendant to pay the plaintiffs mesne profits at the rate of Rs. 75 per annum from the date of the plaint. An appeal was filed to the District Court, and it was dismissed. A second appeal was preferred to the High Court and stay of execution was ordered of the decree on the condition that security was furnished in respect of the mesne profits decreed. A security bond was then executed by the surety—appellant—who undertook to be liable to the extent of Rs. 225 on account of the said profits. The Second Appeal was also ultimately dismissed. It is alleged by the plaintiffs that a sum of Rs. 203-12-0 is due to them on account of mesne profits from the date of the plaint till the date of the delivery of the immoveable property decreed to them. The execution petition is in respect of that sum. The 1st defendant died after the sum now claimed by the plaintiffs accrued due and the 2nd defendant the mother of the 1st defendant took possession of all the properties of the latter claiming to be his heir under the Hindu Law. The plaintiffs asserted a title to the said properties against the 2nd defendant on the ground that their father and the 1st defendant who were stepbrothers divided their properties under a partition award and that according to the terms of that award the plaintiffs were entitled to succeed to the 1st defendant's properties. It may be noted that apart from any question of any special rule of succession, the 2nd defendant the mother of the 1st defendant would under the Hindu Law inherit his properties. It is said that this special rule of succession was recognised and given effect to in the Second Appeal to which reference has been made, though I must confess this point is by no means clear to my mind and it is unnecessary to pursue this further, for, as a matter of fact, the 2nd defendant as stated above took possession of all the properties of the 1st defendant without at first recognising the title of the plaintiffs, but she subsequently surrendered the entire estate to the plaintiffs, who on the date of the execution application were in possession of it. It is not denied that the plaintiffs alone have come into possession of all the properties of the deceased 1st defendant and that the said properties far exceeded in value the sum now claimed in the execution petition. The District Munsif as well as the Subordinate Judge assumes that the plaintiffs succeeded to the properties of the 1st defendant as his heir, but the correct view would seem to be that the plaintiffs acquired the said properties by transfer from the 2nd defendant who is the heir of the 1st defendant. The plaintiffs seek to recover the amount from the surety and the District Munsif dismissed the application on the ground that the debt was extinguished by reason of the fact that the qualities of debtor and creditor became united in the same person viz., the plaintiffs and that the extinction of the principal obligation put an end to that of the surety. The Subordinate Judge disagreeing with the District Munsif held that the plaintiffs were entitled to recover the amount. It seems to me that the Subordinate Judge was clearly wrong. It is not denied that the plaintiffs became the legal representatives of the 1st defendant. Nor is it denied that the properties taken possession of by the plaintiffs were worth considerably more than the amount claimed by the plaintiffs in execution. Under Sect. 50, Civil Procedure Code, where a judgment-debtor dies before the decree has been fully satisfied, the holder of the decree may apply to execute it against the legal representatives of the deceased judgment-debtor. The section further provides that where the decree is executed against such legal representative he shall be liable only to the extent of the property of the deceased which has come to his hands and has not been duly disposed of. Now what has happened? The plaintiffs became the legal representatives of their debtor, and they were therefore entitled to execute the decree against themselves to the extent of his property which had come to their hands and the plaintiffs must accordingly be deemed to have obtained satisfaction of their decree. The circumstance that the plaintiffs did not actually take out execution against themselves and recover the sum in execution is immaterial and I am therefore satisfied that the principal obligation was in this case extinguished. The debt due by the judgment-debtor having become extinguished, are the plaintiffs entitled to proceed against the surety? They are not. To my mind the question does not admit of any doubt. Cunningham and Shephard in theirIndian Contract Actquote the following passage from Pothier on Obligations when dealing with Sect. 134: “It results from the definition of a surety's engagement, as being accessory to a principal obligation, that the extinction of the principal obligation, necessarily induces that of the surety, it being the nature of an accessory obligation that it cannot exist without its principal.” The learned commentators add: “The rule may also be put upon the less technical ground that, if the release of the surety did not follow from that of the debtor, the latter's release would be purely illusory, because the consequence would be that the surety on being compelled to pay, would immediately turn round on the debtor.” I find it impossible to hold that the creditor can proceed against the surety although the debt has been recovered. It has been argued on behalf of the plaintiffs that this rule which accords with common sense is not applicable to surety bonds executed as in this case in favour of the Court. Though this extraordinary contention was repeatedly urged by the plaintiffs' vakil no authority was cited in support of it and I have no hesitation in rejecting it as utterly untenable. It may be remarked that there is an additional circumstance which renders this argument palpably unsound. In consideration of his having executed the bond in question, the surety obtained from the 1st defendant a mortgage in respect of a property belonging to the latter, with a view to recoup himself out of that property in the event of his being compelled to pay the decree amount on the judgment-debtor making the default. That property has passed to the plaintiffs and is in their possession along with the other properties of the judgment-debtor. If the surety is compelled to pay the amount he can immediately claim it from the principal debtor. In this instance the surety's position is even stronger. He can, on paying the amount, proceed against the property in the hands of the plaintiffs themselves and get a refund of the sum in virtue of the express contract between him and the judgment-debtor. Another argument which has been advanced on behalf of the plaintiffs is this: That when an application is made against a surety under Sect. 145, he is precluded from raising a defence on the score of the decree having become satisfied and that he must pay up the amount and then sue the plaintiffs again for the recovery of it. There is no warrant for this position and the argument must be rejected. It has been further urged on behalf of the plaintiffs that the properties having been originally taken by the 2nd defendant from whom only the plaintiffs obtained them, the principal obligation was not extinguished. I have dealt with this point above and I cannot accept the argument. The appeal must therefore be allowed with costs in this and in the lower appellate Court. K. V. S.Appeal allowed..
https://www.casemine.com/judgement/in/56e10d9f607dba3896614276
Zip code 39769 Mississippi Healthcare data and hospitals 39735 and 39759 Zip code 39769 Mississippi Healthcare industry data and local research 39735 and 39759 ZIP code 39769 Health Insurance Charts This section of charts shows ZIP code 39769 Mississippi healthcare data based on the most recent 2022 data from the Census Bureau which was released in November of 2022 and tracks healthcare in the United States. Figure 1 shows the percentage of people who acquired some form of health coverage insurance during open enrollment. 39769 depicts it has a With Coverage of 87.7% which is the second smallest as measured by health insurance coverage of all the other zip codes in the area. The zip code with the highest health insurance coverage in the area is 39735 which shows an insured of 91.6% (only about 4.4% larger). The next chart ( Figure 2 ) shows the change in the percent of people covered from 2020 to 2021 (latest year available) in the percentage of people in the greater ZIP code 39769 area who had some form of health insurance coverage. ZIP code 39769 depicts it has a Change in Coverage of -9.5% which is the smallest in terms of change in health insurance coverage of all the other zip codes in the local area. The zip code with the highest change in health insurance coverage in the area is 39752 which shows a change in insured of 13.0% (37.9% larger). Figure 3 the relative proportions of different types of health insurance coverage benefits are shown (broken down by major categories of public versus private.) Not public insurance includes affordable care act/Obamacare, Medicare, and Medicaid. ZIP code 39769 has one of the largest proportions of private health insurance at 42.6% of the total and is ranked #3. Only #2 39339 (48.1%), and #1 39772 (54.9%) are larger. Second, it has one of the largest proportions of public health insurance at 12.3% of the total and is ranked #2. The only larger zip code being 39339 with 12.8%. Figure 4 shows the proportion of ZIP code 39769 Mississippi residents who are covered by more than one health insurance carrier. This occurs when, for instance a person might have Medicare as well as a private health plan. ZIP code 39769 has one of the largest proportions of people with one health care insurance policy at 23% of the total and is ranked #2. The only larger zip code being 39339 with 23%. Second, it has one of the largest proportions of people with two or more types of health insurance at 12% of the total and is ranked #2. The only larger zip code being 39339 with 13%. The next chart shows a more detailed view of the types of health insurance held by people in the area including employer provided, direct purchased, Medicare, and public healthcare options (e.g. Medicaid.) Figure 5 , has the smallest proportion of direct-purchase health insurance at 3% of the total. Second, it has the smallest proportion of medicare at 8% of the total. Third, it has the largest proportion of medicaid or public coverage at 23% of the total and is ranked #1. The next two charts show the percentage of men and women with coverage. First, Figure 6 shows men and it has a With Healthcare Coverage-Men of 86% which is less than most other zip codes in the greater region. The zip code with the highest men with health care insurance coverage in the area is 39750 which depicts an insurance coverage of 93% (7.8% larger). In the next chart women are shown for the percentage that are covered by health insurance. Figure 7 shows it has a With Healthcare Coverage-Women of 90% which is less than most other zip codes in the metro area. The zip code with the highest women with health care insurance coverage in the area is 39735 which shows an insurance coverage of 94% (only about 4.4% larger). The next two charts show the percentage of people who do not have health care insurance. Both charts show the data broken out by household income with Figure 8 showing the percent covered by income group. ZIP code 39769 depicts it has the hightest change in the percentage of people not covered with insurance of 35.6% for the over $100k group. Figure 9 shows the change in the percentage of people who have no insurance from 2020 to 2021. ZIP code 39769 depicts it has the hightest change in the percentage of people not covered with insurance of 243.4% for the over $100k-change category. The next chart shows the percentage of children (17 years of age and younger) who do not have health insurance. In Figure 11 , it has a Children without Health Insurance of 3.6% which is less than most other zip codes in the local area. The zip code with the highest children without health insurance in the area is 39752 which depicts a children without insurance of 15.3% (approximately 4.2 times bigger). ZIP code 39769 Area Hospital Info Charts Figure 14 shows a listing of hospitals in the area which provide a variety of health services/treatment including: primary care, urgent care, hospice, ICU, orthopedic, family medicine, clinic, home health care and other health coverage to the community. Data from Medicare and Medicaid Services (CMS) and not the Mississippi Department of Health. Some of the Area Hospital Info are: Winston Medical Center & Swingbed, Och Regional Medical Center, Webster General Hospital/Swing Bed, Clay County Medical Center, and Kilmichael Hospital. In Figure 15 , the number of patients discharged from each hospital is shown. Looking at Discharges for Area Hospital Info we find that Baptist Mem Hosp/Golden Triangle Inc ranks the largest with a value of 3,377 discharges. The next largest values are for: Clay County Medical Center (1,155), Och Regional Medical Center (1,055), Webster General Hospital/Swing Bed (931), and Winston Medical Center & Swingbed (481). The difference between the highest value (Baptist Mem Hosp/Golden Triangle Inc) and the next highest (Clay County Medical Center) is that the discharges is about approximately 2.9 times bigger. The next Figure 16 shows the average level of illness of an average patient treated at each hospital using the Medicare Case Mix Index (CMI). This indicator is considered an important healthcare industry metric for a hospital and shows the average severity level of procedures performed by a physician at the location. Looking at CMI for Area Hospital Info we find that Baptist Mem Hosp/Golden Triangle Inc ranks the largest with a value of 1.36 cmi. The next largest values are for: Och Regional Medical Center (1.25), Clay County Medical Center (1.06), Webster General Hospital/Swing Bed (0.99), and Winston Medical Center & Swingbed (0.98). The difference between the highest value (Baptist Mem Hosp/Golden Triangle Inc) and the next highest (Och Regional Medical Center) is that the cmi is about 9.4% larger. ZIP code 39769 Patient Experience Charts The next set of charts are based on a national survey of patient experience in hospitals and covers a range of caregiver staff (doctor, primary care, medical assistant, behavioral health, pain management, and other provider.) These metrics provide overall and important quality of care metrics for the hospitals in the community and how comfortable your child or loved ones will be at the facility. Figure 17 shows the percent of patients surveyed who said their hospital room and bathroom were always clean. Looking at Room and bathroom Always clean for Patient Experience we find that Kilmichael Hospital ranks the largest with a value of 91.0% room and bathroom always clean. The next largest values are for: Webster General Hospital/Swing Bed (88.0%), Och Regional Medical Center (83.0%), Clay County Medical Center (81.0%), and Winston Medical Center & Swingbed (80.0%). The difference between the highest value (Kilmichael Hospital) and the next highest (Webster General Hospital/Swing Bed) is that the room and bathroom always clean is about only about 3.4% larger. Figure 18 shows the percent of patient residents surveyed who said the area around the hospital room was always quiet. Looking at Always quiet at night for Patient Experience we find that Kilmichael Hospital ranks the largest with a value of 85.0% always quiet at night. The next largest values are for: Winston Medical Center & Swingbed (79.0%), Montfort Jones Memorial Hospital (79.0%), Och Regional Medical Center (77.0%), and Baptist Mem Hosp/Golden Triangle Inc (76.0%). The difference between the highest value (Kilmichael Hospital) and the next highest (Winston Medical Center & Swingbed) is that the always quiet at night is about 7.6% larger. In Figure 19 , the percent of patients who said that they always received help when they need it. Looking at Always received help when needed for Patient Experience we find that Kilmichael Hospital ranks the largest with a value of 96.0% always received help when needed. The next largest values are for: Winston Medical Center & Swingbed (82.0%), Montfort Jones Memorial Hospital (80.0%), Clay County Medical Center (75.0%), and Och Regional Medical Center (74.0%). The difference between the highest value (Kilmichael Hospital) and the next highest (Winston Medical Center & Swingbed) is that the always received help when needed is about 17.1% larger. Figure 20 provides a pain management analysis using the percent of patient residents who reported that their pain was always well controlled for all the hospitals in the community. Looking at Pain Always Well Controlled for Patient Experience we find that Kilmichael Hospital ranks the largest with a value of 96.0% pain always well controlled. The next largest values are for: Webster General Hospital/Swing Bed (79.0%), Winston Medical Center & Swingbed (78.0%), Och Regional Medical Center (76.0%), and Clay County Medical Center (74.0%). The difference between the highest value (Kilmichael Hospital) and the next highest (Webster General Hospital/Swing Bed) is that the pain always well controlled is about 21.5% larger. The next chart, Figure 21 , is the percent of patients who said that the nurses always communicated well with them. Looking at Nurses Always Communicated Well for Patient Experience we find that Kilmichael Hospital ranks the largest with a value of 97.0% nurses always communicated well. The next largest values are for: Webster General Hospital/Swing Bed (87.0%), Och Regional Medical Center (86.0%), Clay County Medical Center (85.0%), and Winston Medical Center & Swingbed (83.0%). The difference between the highest value (Kilmichael Hospital) and the next highest (Webster General Hospital/Swing Bed) is that the nurses always communicated well is about 11.5% larger. Figure 22 , shows the percent of patients who said that the doctors always communicated well with them. Looking at Doctors Always Communicated Well for Patient Experience we find that Kilmichael Hospital ranks the largest with a value of 98.0% doctors always communicated well. The next largest values are for: Webster General Hospital/Swing Bed (95.0%), Winston Medical Center & Swingbed (92.0%), Clay County Medical Center (90.0%), and Och Regional Medical Center (89.0%). The difference between the highest value (Kilmichael Hospital) and the next highest (Webster General Hospital/Swing Bed) is that the doctors always communicated well is about only about 3.2% larger. In Figure 23 , each hospital in the community is rated based on a scale from 1 to 10 (where 10 is the best) and provides a high level metric of favorable wellness from treatment. Looking at Hospital Rating for Patient Experience we find that Kilmichael Hospital ranks the largest with a value of 89.0% hospital rating. The next largest values are for: Webster General Hospital/Swing Bed (79.0%), Och Regional Medical Center (76.0%), Clay County Medical Center (72.0%), and Baptist Mem Hosp/Golden Triangle Inc (70.0%). The difference between the highest value (Kilmichael Hospital) and the next highest (Webster General Hospital/Swing Bed) is that the hospital rating is about 12.7% larger. The final chart ( Figure 24 ) provides comparative data for ZIP code 39769 community hospitals looking at overall patient experience. This section specifically shows the percent of patients who would definitely recommend this adult specialty hospital to other people in the community. Looking at Would Recommend Hospital for Patient Experience we find that Kilmichael Hospital ranks the largest with a value of 93.0% would recommend hospital. The next largest values are for: Och Regional Medical Center (75.0%), Webster General Hospital/Swing Bed (75.0%), Clay County Medical Center (69.0%), and Baptist Mem Hosp/Golden Triangle Inc (66.0%). The difference between the highest value (Kilmichael Hospital) and the next highest (Och Regional Medical Center) is that the would recommend hospital is about 24.0% larger. Zip code 39769, Mississippi Healthcare Data Demographics Housing Economy Education Figure 1: Percent of People with Health Insurance Figure 2: Change in People with Health Coverage (2019 to 2020) 0% 50% 100% 39339 39769 Mississippi 39752 Columbus-West Point 39772 39759 39750 United States 39735 Place With Coverage 39339 87.2% 39769 87.7% Mississippi 87.9% 39752 87.9% Columbus-West Point 88.3% 39772 90.5% 39759 90.9% 39750 91% United States 91.2% 39735 91.6% ... -20% 0% 20% 39769 39339 39750 Columbus-West Point 39735 Mississippi United States 39759 39772 39752 Place Change in Coverage 39769 -9.5% 39339 -7.8% 39750 -5.3% Columbus-West Point -2.2% 39735 -1.1% Mississippi -0.1% United States -0% 39759 0% 39772 5% 39752 13% ... Figure 3: Type of Health Insurance Figure 4: Amount of Health Insurance Coverage Private he… Public heal… No health i… 39769 0% 50% 100% Place Private health insurance Public health insurance No health insurance 39769 57.3% 42.6% 12.3% No health in… One Coverage T… 1/3 0% 100% 200% 39769 39735 39759 39339 39752 39772 39750 United States Mississippi Columbus-West Point Place One Coverage Type Two Coverage Types No Healthcare Coverage 39769 64% 23% 12% 39735 72% 19% 8% 39759 77% 14% 9% 39339 64% 24% 13% 39752 74% 14% 12% 39772 73% 18% 10% 39750 75% 16% 9% United States 75% 17% 9% Mississippi 70% 18% 12% Columbus-West Point 73% 15% 12% No Healthcare Co… Figure 5: Detailed Types of Health Insurance Coverage in 39769, MS Employer-Based He… Direct-Purchase He… Medicare Medicaid or Public… No Coverage 39769 39735 39759 39339 39752 39772 39750 United States Mississippi Columbus-West Point 0% 50% 100% 150% Place Employer-Based Health Insurance Direct-Purchase Health Insurance Medicare Medicaid or Public Coverage No Coverage 39769 65% 16% 3% 8% 23% 39735 60% 12% 13% 14% 12% 39759 64% 17% 4% 9% 11% 39339 47% 13% 11% 15% 20% 39752 56% 14% 11% 10% 14% 39772 43% 23% 8% 26% 19% 39750 64% 9% 6% 11% 16% United States 63% 11% 4% 15% 12% Mississippi 58% 11% 7% 14% 18% Columbus-West Point 57% 10% 6% 13% 18% Medicaid or Public C… Figure 6: Men with Health Insurance Coverage Figure 7: Women with Health Insurance Coverage 0% 50% 100% 39752 39339 39769 Mississippi Columbus-West Point 39772 39735 39759 United States 39750 Place With Healthcare Coverage-Men 39752 85% 39339 86% 39769 86% Mississippi 87% Columbus-West Point 87% 39772 89% 39735 89% 39759 90% United States 90% 39750 93% ... 0% 50% 100% 39339 Mississippi Columbus-West Point 39750 39769 39752 39772 39759 United States 39735 Place With Healthcare Coverage-Women 39339 88% Mississippi 89% Columbus-West Point 89% 39750 90% 39769 90% 39752 91% 39772 92% 39759 92% United States 92% 39735 94% ... Figure 8: Percent of People with No Insurance by Income Group Figure 9: Change in Percent of People with No Insurance from 2019 to 2020 Under $25k $25k to $… 1/3 39769 0% 20% 40% Place Under $25k $25k to $50k $50k to $75k $75k to $100k Over $100k 39769 9.5% 10% 8.2% 0% 35.6% $75k to $1… Under… $25k t… 1/3 0 2 4 39769 Place Under $25k-change $25k to $50k-change $50k to $75k-change $75k to $100k-change Over $100k-change 39769 225.7% 237.6% 0% 0% 243.4% $75k to… Figure 10: People without Health Insurance Coverage by Race White Black Hispanic Asian Native American 39769 39735 39759 39339 39752 39772 39750 United States Mississippi Columbus-West Point 0% 50% 100% 150% Place White Black Hispanic Asian Native American 39769 100% 0% 0% 0% 0% 39735 83% 17% 0% 0% 0% 39759 30% 49% 9% 8% 6% 39339 36% 59% 2% 0% 3% 39752 95% 5% 0% 0% 0% 39772 30% 70% 0% 0% 0% 39750 71% 27% 2% 0% 0% United States 50% 12% 32% 4% 2% Mississippi 49% 42% 8% 1% 1% Columbus-West Point 37% 61% 2% 0% 0% Native American Figure 11: Children without Health Insurance Figure 12: Advertisement 0% 10% 20% 39769 Columbus-West Point 39735 United States Mississippi 39759 39339 39752 Place Children without Health Insurance 39769 3.6% Columbus-West Point 4.2% 39735 4.5% United States 5.3% Mississippi 5.5% 39759 6.4% 39339 7.6% 39752 15.3% ... Figure 13: Insurance Coverage Broken Down by Age and Detailed Type Insurance All Under 18 18 to 64 65+ Direct Purchase 20.8% 20.2% 16.3% 30.9% Employer Paid 47.3% 34.7% 65.4% 23.1% Medicare 25.2% 0% 3% 98.7% Military 1.3% 0% 0.6% 4.2% No Insurance 12.3% 3.6% 22.7% 0% Public 20.5% 54.1% 7.7% 11.1% Two or More Types 23.4% 12.7% 15.6% 51.1% Figure 14: Hospitals in the 39769, MS Area and Key Information Hospital Name City Hospital Type Hospital Ownership Emergency Services Winston Medical Center & Swingbed Louisville Acute Care Hospitals Government - Local Yes Webster General Hospital/Swing Bed Eupora Acute Care Hospitals Voluntary non-profit - Other Yes Och Regional Medical Center Starkville Acute Care Hospitals Government - Local Yes Montfort Jones Memorial Hospital Kosciusko Critical Access Hospitals Voluntary non-profit - Other Yes Kilmichael Hospital Kilmichael Acute Care Hospitals Government - Local No Clay County Medical Center West Point Acute Care Hospitals Voluntary non-profit - Private Yes Baptist Mem Hosp/Golden Triangle Inc Columbus Acute Care Hospitals Voluntary non-profit - Private Yes Figure 15: Patients Discharged Figure 16: Level of Illness Measured by Case Mix Index 0 2,000 4,000 Kilmichael Hospital Winston Medical Center & Swingbed Webster General Hospital/Swing Bed Och Regional Medical Center Clay County Medical Center Baptist Mem Hosp/Golden Triangle Inc Hospital Name Discharges Kilmichael Hospital 248 Winston Medical Center & Swingbed 481 Webster General Hospital/Swing Bed 931 Och Regional Medical Center 1,055 Clay County Medical Center 1,155 Baptist Mem Hosp/Golden Triangle Inc 3,377 Triangle Inc 0 1 2 Kilmichael Hospital Winston Medical Center & Swingbed Webster General Hospital/Swing Bed Clay County Medical Center Och Regional Medical Center Baptist Mem Hosp/Golden Triangle Inc Hospital Name CMI Kilmichael Hospital 0.87 Winston Medical Center & Swingbed 0.98 Webster General Hospital/Swing Bed 0.99 Clay County Medical Center 1.06 Och Regional Medical Center 1.25 Baptist Mem Hosp/Golden Triangle Inc 1.36 Triangle Inc Figure 17: Patients Room and Bathroom Always clean Figure 18: Patients Room Always Quiet at Night 0% 50% 100% Baptist Mem Hosp/Golden Triangle Inc Montfort Jones Memorial Hospital Winston Medical Center & Swingbed Clay County Medical Center Och Regional Medical Center Webster General Hospital/Swing Bed Kilmichael Hospital Hospital Name Room and bathroom Always clean Baptist Mem Hosp/Golden Triangle Inc 73% Montfort Jones Memorial Hospital 74% Winston Medical Center & Swingbed 80% Clay County Medical Center 81% Och Regional Medical Center 83% Webster General Hospital/Swing Bed 88% Kilmichael Hospital 91% Hospital/Swing Bed 0% 50% 100% Webster General Hospital/Swing Bed Clay County Medical Center Baptist Mem Hosp/Golden Triangle Inc Och Regional Medical Center Winston Medical Center & Swingbed Montfort Jones Memorial Hospital Kilmichael Hospital Hospital Name Always quiet at night Webster General Hospital/Swing Bed 71% Clay County Medical Center 74% Baptist Mem Hosp/Golden Triangle Inc 76% Och Regional Medical Center 77% Winston Medical Center & Swingbed 79% Montfort Jones Memorial Hospital 79% Kilmichael Hospital 85% Hospital Figure 19: Patients Always Received Help When Needed Figure 20: Patients Pain Always Well Controlled 0% 50% 100% Baptist Mem Hosp/Golden Triangle Inc Webster General Hospital/Swing Bed Och Regional Medical Center Clay County Medical Center Montfort Jones Memorial Hospital Winston Medical Center & Swingbed Kilmichael Hospital Hospital Name Always received help when needed Baptist Mem Hosp/Golden Triangle Inc 64% Webster General Hospital/Swing Bed 68% Och Regional Medical Center 74% Clay County Medical Center 75% Montfort Jones Memorial Hospital 80% Winston Medical Center & Swingbed 82% Kilmichael Hospital 96% Swingbed 0% 50% 100% Montfort Jones Memorial Hospital Baptist Mem Hosp/Golden Triangle Inc Clay County Medical Center Och Regional Medical Center Winston Medical Center & Swingbed Webster General Hospital/Swing Bed Kilmichael Hospital Hospital Name Pain Always Well Controlled Montfort Jones Memorial Hospital 69% Baptist Mem Hosp/Golden Triangle Inc 73% Clay County Medical Center 74% Och Regional Medical Center 76% Winston Medical Center & Swingbed 78% Webster General Hospital/Swing Bed 79% Kilmichael Hospital 96% Hospital/Swing Bed Figure 21: Nurses Always Communicated Well Figure 22: Doctors Always Communicated Well 0% 50% 100% Baptist Mem Hosp/Golden Triangle Inc Montfort Jones Memorial Hospital Winston Medical Center & Swingbed Clay County Medical Center Och Regional Medical Center Webster General Hospital/Swing Bed Kilmichael Hospital Hospital Name Nurses Always Communicated Well Baptist Mem Hosp/Golden Triangle Inc 80% Montfort Jones Memorial Hospital 81% Winston Medical Center & Swingbed 83% Clay County Medical Center 85% Och Regional Medical Center 86% Webster General Hospital/Swing Bed 87% Kilmichael Hospital 97% Hospital/Swing Bed 0% 50% 100% Baptist Mem Hosp/Golden Triangle Inc Montfort Jones Memorial Hospital Och Regional Medical Center Clay County Medical Center Winston Medical Center & Swingbed Webster General Hospital/Swing Bed Kilmichael Hospital Hospital Name Doctors Always Communicated Well Baptist Mem Hosp/Golden Triangle Inc 84% Montfort Jones Memorial Hospital 84% Och Regional Medical Center 89% Clay County Medical Center 90% Winston Medical Center & Swingbed 92% Webster General Hospital/Swing Bed 95% Kilmichael Hospital 98% Hospital/Swing Bed Figure 23: Overall Hospital Rating of 9 or 10 by Patients Figure 24: Would Definitely Recommend Hospital 0% 50% 100% Winston Medical Center & Swingbed Montfort Jones Memorial Hospital Baptist Mem Hosp/Golden Triangle Inc Clay County Medical Center Och Regional Medical Center Webster General Hospital/Swing Bed Kilmichael Hospital Hospital Name Hospital Rating Winston Medical Center & Swingbed 60% Montfort Jones Memorial Hospital 68% Baptist Mem Hosp/Golden Triangle Inc 70% Clay County Medical Center 72% Och Regional Medical Center 76% Webster General Hospital/Swing Bed 79% Kilmichael Hospital 89% Hospital/Swing Bed 0% 50% 100% Winston Medical Center & Swingbed Montfort Jones Memorial Hospital Baptist Mem Hosp/Golden Triangle Inc Clay County Medical Center Och Regional Medical Center Webster General Hospital/Swing Bed Kilmichael Hospital Hospital Name Would Recommend Hospital Winston Medical Center & Swingbed 59% Montfort Jones Memorial Hospital 61% Baptist Mem Hosp/Golden Triangle Inc 66% Clay County Medical Center 69% Och Regional Medical Center 75% Webster General Hospital/Swing Bed 75% Kilmichael Hospital 93% Hospital/Swing Bed Cities marked with an asterisk ("*") should resemble a city or town but do not have their own government (i.e. Mayor, City Council, etc.) These places should be recognizable by the local community but their boundaries have no legal status. Technically these include both Census Designated Places (CDP) and Census County Divisions (CCD) which are defined by the Census Bureau along with local authorities. (For more information, see: Census Designated Place or "CDP") and Census County Division "CCD".) For comparison purposes, the US national average and the state average value are provided. Additionally, the "Combined Statistical Area" or CSA is shown that is closest to the city, county, or zip code shown. A CSA is a large grouping of adjacent metropolitan areas that identified by the Census Bureau based on social and economic ties. (See: Combined Statistical Area ) Data sources - Mouse over icon in upper right corner of each chart for information.
https://www.towncharts.com/Mississippi/Healthcare/39769-Zipcode-MS-Healthcare-data.html
Text - H.R.4097 - 113th Congress (2013-2014): Salmon Solutions and Planning Act | Congress.gov | Library of Congress Text for H.R.4097 - 113th Congress (2013-2014): Salmon Solutions and Planning Act H.R.4097 - Salmon Solutions and Planning Act 113th Congress (2013-2014) Bill Sponsor: Rep. McDermott, Jim [D-WA-7] (Introduced 02/26/2014) Committees: House - Transportation and Infrastructure; Natural Resources; Energy and Commerce Latest Action: House - 02/28/2014 Referred to the Subcommittee on Energy and Power.  ( All Actions ) Tracker: TipThis bill has the status IntroducedHere are the steps for Status of Legislation: Introduced Array ( [actionDate] => 2014-02-26 [displayText] => Introduced in House [externalActionCode] => 1000 [description] => Introduced [chamberOfAction] => House ) Subject — Policy Area: Text: H.R.4097 — 113th Congress (2013-2014) All Information (Except Text) 113th CONGRESS 2d Session H. R. 4097 To ensure that proper information gathering and planning are undertaken to secure the preservation and recovery of the salmon and steelhead of the Columbia River Basin in a manner that protects and enhances local communities, ensures effective expenditure of Federal resources, and maintains reasonably priced, reliable power, to direct the Secretary of Commerce to seek scientific analysis of Federal efforts to restore salmon and steelhead listed under the Endangered Species Act of 1973, and for other purposes. IN THE HOUSE OF REPRESENTATIVES February 26, 2014 Mr. McDermottintroduced the following bill; which was referred to the Committee on Transportation and Infrastructure, and in addition to the Committees on Natural Resources and Energy and Commerce, for a period to be subsequently determined by the Speaker, in each case for consideration of such provisions as fall within the jurisdiction of the committee concerned A BILL To ensure that proper information gathering and planning are undertaken to secure the preservation and recovery of the salmon and steelhead of the Columbia River Basin in a manner that protects and enhances local communities, ensures effective expenditure of Federal resources, and maintains reasonably priced, reliable power, to direct the Secretary of Commerce to seek scientific analysis of Federal efforts to restore salmon and steelhead listed under the Endangered Species Act of 1973, and for other purposes. Be it enacted by the Senate and House of Representatives of the United States of America in Congress assembled, SECTION 1. Short title . This Act may be cited as the “Salmon Solutions and Planning Act”. SEC. 2. Findings and purposes . (a) Findings.—Congress finds and declares the following: (1) Thirteen salmon and steelhead species in the Columbia and Snake River Basin are listed for protection under the Endangered Species Act of 1973 (16 U.S.C. 1531 et seq.) as a consequence of various factors, including the construction and operation of hydroelectric projects, harvest management practices, habitat degradation, altered in-stream flow regimes, and unsound hatchery practices. (2) The original range of Snake River salmon included not only their existing habitat, but also habitat in the upper Columbia River and the upper Snake River Basins, including southern Idaho, southeast Oregon, and northern Nevada. (3) Since the construction of 4 Federal dams on the lower Snake River in Washington, all salmon and steelhead populations in the Snake River are either already extinct or listed as an endangered or threatened species under the Endangered Species Act of 1973. (4) Without action, climate change and rising water temperatures will continue to have detrimental effects on many North American coldwater fish species, including salmon and steelhead populations. Due to their high-elevation spawning grounds, Snake River salmon are key to maintaining and rebuilding those salmon populations threatened by rising water temperatures throughout the Columbia River Basin. (5) Salmon and steelhead populations have major economic, ecological, educational, recreational, scientific, cultural, and spiritual significance to the Nation and its people. Even at their current depressed population levels, these salmon and steelhead populations generate hundreds of millions of dollars in direct and indirect benefits for communities in Alaska, Washington, Oregon, Idaho, and California; restoring these populations is estimated to generate billions of dollars in additional revenue for these States. (6) The United States has signed treaties with Indian tribes in Washington, Oregon, Montana, and Idaho and with the Government of Canada, creating legally enforceable treaty obligations to restore salmon populations to sustainable and harvestable levels. (7) The Federal Government, the Bonneville Power Administration, and United States ratepayers in the Pacific Northwest have spent more than $11,000,000,000 on salmon recovery efforts in the Columbia and Snake River Basin to date. (8) A federally funded group of State, tribal, Federal, and independent scientists found that removing the 4 lower Snake River dams in Washington is the surest way to protect and recover these salmon and steelhead populations. Similar conclusions have been reached by the Army Corps of Engineers and the Department of Commerce. (9) Significant sediment buildup behind the Lower Granite Dam poses a flood risk to the city of Lewiston, Idaho. A study by the Army Corps of Engineers found that nearly $2,000,000,000 worth of buildings and infrastructure face a growing threat of major damage from levee breaching. The same Corps study estimates that the costs of river-dredging and levee-raising needed to protect this area could cost taxpayers hundreds of millions of dollars. (10) A Federal court has found that all 4 lower Snake River dams violate water quality standards under the Federal Water Pollution Control Act (33 U.S.C. 1251 et seq.). (11) The removal of the 4 lower Snake River dams would open up more than 100 miles of free-flowing river ways to inland Northwest communities and provide needed resources for more effective and efficient freight transportation systems. (12) In the event the 4 lower Snake River dams are removed, their electricity generation, freight shipping, and water supply benefits must be replaced through other means in order to protect affected communities, farms, and the regional energy supply system; the dams' energy benefits should be replaced with cost-effective, clean renewable sources that focus on energy efficiency and conservation. (13) Studies have found that the Northwest has ample additional existing and potential clean renewable energy sources to replace the renewable electricity produced by the 4 lower Snake River dams in an environmentally sound and cost effective manner. (14) By completing the planning and evaluation required under this Act, the Northwest and the Nation will be better prepared to efficiently manage salmon recovery and ensure prompt implementation of Federal salmon recovery actions needed to protect and restore wild Columbia and Snake River salmon and steelhead. (b) Purposes.—The purpose of this Act are— (1) to ensure the protection and recovery of wild Columbia and Snake River salmon and steelhead to self-sustaining, harvestable levels, while providing for reliable, reasonably priced, clean renewable energy in the Northwest, a reliable and affordable freight transportation system, an economically sustainable salmon recovery program; and (2) to maximize the economic benefits of removal of the 4 lower Snake River dams while mitigating for its impacts. SEC. 3. Scientific analysis of Federal salmon recovery actions . (a) In general.—Not later than 30 days after the date of enactment of this Act, the Secretary of Commerce shall enter into an agreement with the National Academy of Sciences providing for a scientific analysis of Federal salmon recovery actions. (b) Review of Snake River dam removal and other actions.—Pursuant to the agreement under subsection (a), the National Academy of Sciences shall review, at minimum— (1) the impact, if any, that removal of the 4 lower Snake River dams would have on recovery of salmon and steelhead populations; and (2) any additional actions that may be necessary to achieve recovery of salmon and steelhead populations. (c) Report.—Pursuant to the agreement under subsection (a), the National Academy of Sciences shall submit, not later than 10 months after the date of enactment of this Act, a report on the results of the scientific analysis conducted under the agreement— (1) to the Secretary of the Army for consideration in developing the updated feasibility study under section 8; (2) to the Secretaries of Commerce, Transportation, Energy, and the Interior and the Administrator of the Environmental Protection Agency; and (3) to Congress. SEC. 4. Study of rail, highway, and barge improvements . (a) In general.—The Secretary of Transportation shall conduct a peer-reviewed study of the rail, highway, and Columbia River barge infrastructure improvements that would be necessary to ensure a cost-effective and efficient transportation system for agricultural and other shippers who— (1) currently use barge transportation between Lewiston, Idaho, and the confluence of the Snake and Columbia Rivers; and (2) would be unable to do so if the 4 lower Snake River dams were removed. (b) Review of potential cost increases.—In carrying out subsection (a), the Secretary of Transportation shall review, at a minimum— (1) increases, if any, in shipping costs that would result if the 4 lower Snake River dams were removed; and (2) options for addressing any such increases so as to minimize the potential impact on shippers. (c) Input of interested parties.—In carrying out subsection (a), the Secretary of Transportation shall incorporate— (1) input and feedback from— (A) farmers and other shippers; (B) the Washington, Idaho, and Oregon State departments of transportation; and (C) other relevant stakeholders in the agricultural, business, and public interest communities; and (2) any suggestions or decisions arrived at through consensus deliberations of the same or similar participants. (d) Report.—Not later than 12 months after the date of enactment of this Act, the Secretary of Transportation shall transmit a report on the results of the study— (1) to the Secretary of the Army for consideration in developing the updated feasibility study under section 8; and (2) to Congress. SEC. 5. Study of energy replacement . (a) In general.—The Secretary of Energy, in consultation with the Council on Environmental Quality, shall conduct a peer-reviewed study of the energy replacement options that exist to replace the power currently generated by the 4 lower Snake River dams in the event the dams are removed. (b) Review of potential clean renewable energy resources and certain projects.—In carrying out subsection (a), the Secretary of Energy shall review— (1) existing, planned, and potential clean renewable energy resources; and (2) energy efficiency, energy conservation, and combined heat and power projects. (c) Report.—Not later than 12 months after the date of enactment of this Act, the Secretary of Energy shall transmit a report on the results of the study— (1) to the Secretary of the Army for consideration in developing the updated feasibility study under section 8; and (2) to Congress. SEC. 6. Study of lower Snake River riverfront revitalization . (a) In general.—The Secretary of the Army, in consultation with relevant State and local governments and interested parties, shall conduct a study of— (1) the riverfront revitalization and restoration opportunities that would exist in the event of the removal of the 4 lower Snake River dams; and (2) the costs that would be incurred to implement such revitalization and restoration measures. (b) Riverfront revitalization.—In carrying out subsection (a), the Secretary of the Army shall focus on riverfront revitalization for Lewiston, Idaho, and Clarkston, Washington, but may include a review of other impacted communities along the 140 miles of the lower Snake River. (c) Peer review.—The study shall be subject to peer review generally in accordance with section 2034 of the Water Resources Development Act of 2007 (33 U.S.C. 2343) to determine the accuracy of the preferred engineering options and costs determined by the Secretary. (d) Report.—Not later than 12 months after the date of enactment of this Act, the Secretary shall transmit to Congress a report on the results of the study, including the Secretary’s determinations concerning engineering options and costs. SEC. 7. Study of irrigation protections . (a) In general.—The Secretary of the Interior, acting through the Bureau of Reclamation, shall conduct a peer-reviewed study of the options and costs regarding any modifications to affected irrigation systems, cooling systems, and private wells that would be needed if the 4 lower Snake River dams were removed. (b) Report.—Not later than 12 months after the date of enactment of this Act, the Secretary of the Interior shall transmit a report on the study— (1) to the Secretary of the Army for consideration in developing the updated feasibility study under section 8; and (2) to Congress. SEC. 8. Authorization and study of salmon recovery . (a) Dam removal authorization.—Congress hereby determines that the Secretary of the Army may remove the 4 lower Snake River dams. (b) Review and Update of Feasibility Study.—The Secretary of the Army, in consultation with the Secretary of Commerce, the Secretary of the Interior, and the Administrator of the Environmental Protection Agency, shall re-evaluate and update the U.S. Army Corps of Engineers' Final Lower Snake River Juvenile Salmon Migration Feasibility Report/Environmental Impact Statement (February 2002) pursuant to new information. (c) Considerations.—The updated feasibility study shall— (1) take into consideration the results of the studies and analyses carried out under this Act; and (2) incorporate and address, at a minimum— (A) current and expected future climate change impacts on Columbia and Snake River salmon and steelhead populations and their habitat; (B) replacement of the 4 lower Snake River dams’ average energy output (not nameplate capacity) with clean renewable energy resources, including energy efficiency and conservation; (C) options for keeping currently irrigated acreage intact and under irrigation in a dam removal scenario; (D) costs associated with Lower Granite Dam reservoir sediment/flood risk mitigation in a non-dam-removal scenario; (E) Passive Use Values associated with both dam removal and non-dam-removal scenarios; and (F) alternate methods for removing the 4 lower Snake River dams in addition to the method analyzed in the 2002 environmental impact statement, including full dam removal and removing or notching the dams’ concrete portions. (d) Completion; report; peer review.—The Secretary of the Army shall— (1) complete the re-evaluation and update and submit a report thereon to Congress within 24 months after the date of enactment of this Act; (2) include in the report a determination of engineering options and costs; and (3) submit the results of the re-evaluation and update (including such determination of engineering options and costs) to peer review generally in accordance with section 2034 of the Water Resources Development Act of 2007 (33 U.S.C. 2343) to determine the accuracy of the preferred engineering options and costs. SEC. 9. Definitions . In this Act, the following definitions apply: (1) CLEAN RENEWABLE ENERGY RESOURCES.—The term “clean renewable energy resources” means— (A) incremental electricity produced as the result of efficiency improvements to existing hydroelectric generation projects, including in irrigation pipes and canals, where the additional generation in either case does not result in new water diversions or impoundments; (B) wind; (C) solar energy; (D) geothermal energy; (E) landfill gas; (F) wave, ocean, or tidal power; (G) gas from sewage treatment facilities; (H) biomass energy (as defined in section 932(a) of the Energy Policy Act of 2005 (42 U.S.C. 16232(a))), excluding energy derived from— (i) pulping liquor from paper production; or (ii) forest materials from old growth forests; or (I) any combination of the energy resources described in this paragraph. (2) FEDERAL SALMON RECOVERY ACTIONS.—The term “Federal salmon recovery actions” means Federal actions required to protect, recover, and restore salmon and steelhead in the Columbia and Snake River basin that are listed under section 4(c) of the Endangered Species Act of 1973 (16 U.S.C. 1533(c)). The term shall not be construed as just those actions needed to avoid jeopardy of these salmon and steelhead populations under the Endangered Species Act of 1973 (16 U.S.C. 1531 et seq.). (3) 4 LOWER SNAKE RIVER DAMS.—The term “4 lower Snake River dams” means the following dams on the Snake River, Washington: (A) The Ice Harbor dam. (B) The Lower Monumental dam. (C) The Little Goose dam. (D) The Lower Granite dam. (4) PEER-REVIEWED STUDY.—The term “peer-reviewed study” means, unless otherwise specified, a study subject to peer review in accordance with the guidelines issued by the Director of the Office of Management and Budget under section 515 of the Treasury and General Government Appropriations Act, 2001 (as enacted into law byPublic Law 106–554; 114 Stat. 2763A–153). (5) SALMON AND STEELHEAD POPULATIONS.—The term “salmon and steelhead populations” means the evolutionarily significant units of salmon and steelhead in the Columbia and Snake River basin that are listed under section 4(c) of the Endangered Species Act of 1973 (16 U.S.C. 1533(c)).
https://www.congress.gov/bill/113th-congress/house-bill/4097/text
Cureus | Buttoned Shut: Management of Complete Unilateral Nasal Obstruction Secondary to Button Battery Injury | Article Pediatric button battery ingestion is known to cause potentially devastating injuries to the aerodigestive tract. Placement of a button battery in the nasal passages and subsequent damage it may cause poses a unique management problem as it may involve bony and membranous scarring, aesthetic irregularities, and long-term nasal obstruction. We present a case of a child with complete stenosis of the right nasal vestibule after a button battery injury. With a multidisciplinary surgical approach between an otolaryngologist and a plastic surgeon, the nasal airway patency was restored via a series of dilations and stents. The patient now has a patent right nasal airway that measures equal in diameter to the contralateral side. We conclude that in the case of a child with a button battery in the nose, repair of stenosis may be approached similarly to a case of unilateral choanal atresia, including dilations and stents. Buttoned Shut: Management of Complete Unilateral Nasal Obstruction Secondary to Button Battery Injury Abstract Pediatric button battery ingestion is known to cause potentially devastating injuries to the aerodigestive tract. Placement of a button battery in the nasal passages and subsequent damage it may cause poses a unique management problem as it may involve bony and membranous scarring, aesthetic irregularities, and long-term nasal obstruction. We present a case of a child with complete stenosis of the right nasal vestibule after a button battery injury. With a multidisciplinary surgical approach between an otolaryngologist and a plastic surgeon, the nasal airway patency was restored via a series of dilations and stents. The patient now has a patent right nasal airway that measures equal in diameter to the contralateral side. We conclude that in the case of a child with a button battery in the nose, repair of stenosis may be approached similarly to a case of unilateral choanal atresia, including dilations and stents. Introduction Button batteries can cause long-term and potentially devastating injuries to the aerodigestive tract[1]. Management of these injuries includes identification and intervention as early as possible, either medically or surgically[2]. Placing a button battery in the nasal passage may have long-term consequences such as nasal stenosis, septal perforation, and structural deformities such as a saddle nose, which may be difficult to manage[3]. We present a case of a child who presented for care after a button battery injury was sustained to the right nasal vestibule. Case Presentation Figure 1: Photograph of the patient demonstrating right-sided saddle nose deformity. Figure 2: Photograph demonstrating complete obstruction of the right nasal cavity on anterior rhinoscopy. It was recommended that he undergo adenotonsillectomy with the concurrent repair of right nasal vestibular obstruction and the family was in agreement. He was referred to the plastic surgery department for further evaluation and reconstructive planning. Ultimately, the repair was deferred until the child was 10 years of age due to the fact that repair would require prolonged use of a nasal stent, which is often difficult for young children to tolerate and may jeopardize outcomes. Additionally, there were extenuating social circumstances for this particular child (he and his family moved overseas and back several times) and age 10 was the earliest appropriate opportunity for intervention. In the interim from our first evaluation until surgical repair, the patient was able to tolerate breathing through the left nasal passage and the mouth only. The patient was taken to the operating room with the otolaryngology and plastic surgery teams. Adenotonsillectomy was performed at the start of the case with no complications. Endoscopy with a zero-degree endoscope was performed and revealed a complete obstruction of the right choana with fibrotic and bony components. Additionally noted was a septal perforation, which was likely caused by the initial button battery injury. The right nasal passage repair began with a three-limb incision into the mucosa covering the osseous components of the scar. Three mucosal flaps were elevated and the bony scar was removed using an osteotome and cutting rongeur. To prevent exposure of raw areas and to decrease the risk of re-scarring, the three flaps of mucosa were carefully laid in place in the newly reconstructed airway and sutured with 5-0 chromic. A silicone 14-French stent was shortened and sutured to the septum with a 3-0 nylon stitch (Figure 3). Figure 3: Intraoperative photograph of nasal stent fashioned from 24 French nasal airway being sutured into place. The child returned for a follow-up examination in the clinic on postoperative day six and was found to be doing well with no discomfort caused by the stent. One month postoperatively, the child reported being able to breathe well through the right naris with complete resolution of his snoring and improvement in overall quality of sleep. Approximately one and a half months after the initial surgery, the patient was brought back to the operating room for nasal endoscopy and stent upsizing. The nasal airway was noted to be patent but not equal in diameter to the contralateral side. There were mucosal adhesions present that were sharply released inferiorly. A long nasal speculum was used to further dilate the airway. A 24-French silastic tube was then easily inserted into the airway and sutured to the membranous septum with a 3-0 nylon stitch. He was evaluated in the clinic two months after the stent upsize and the surgical site was noted to be healing well. He was breathing easily from his bilateral nasal passages and continued to be unbothered by the presence of the stent. He underwent repeat endoscopic evaluation one month afterward (four months after the first surgery) at which time it was demonstrated that the right nasal passage was equivalent in diameter to the left, both easily permitting a 24 French nasal airway. This was sutured into place on the right and remained in place as a stent. This stent was left in place for approximately four months, at which time it was removed in the office and the child began a part-time home stenting regimen. For one month, the patient placed the stent in the nose at night and removed it in the morning but the patient's caregiver noted it was more difficult to replace after a few weeks. They attempted to keep the stent in place at all times but the patient experienced issues at school with bullying from other children regarding the stent. The current regimen consists of replacing the stent during all waking hours that the child is not at school, which has worked well for them. It has now been almost a year since surgical intervention first began and the plan is to continue the home stenting regimen. The patient’s saddle nose deformity does not cause the child any cosmetic concerns and there are no plans for surgical repair at this time, although the patient may elect for this in the future. Discussion This case is an example of the long-lasting damage that button battery burns can inflict on the tissues of the aerodigestive tract. This is significant due to the increase in recent years of button battery-related emergency room visits[4]. A 2012 retrospective single-institution study demonstrated that over a 20-year period, 10.2% of all battery-related visits were due to nasal insertion[5]. This was the second most common chief complaint behind ingestion, which comprised 76.6% of these visits. Nasal insertion can present unique diagnostic challenges, especially if the foreign body is not suspected based on the initial history given to a clinician. They can remain in place for days before causing outward signs of a problem, often presenting with foul nasal discharge, pain, or swelling of the area. The most important step in managing button batteries in the nose is to remove the battery as soon as possible. Septal perforation may occur in as little as three hours and inferior turbinate necrosis has occurred within 24 hours of button battery insertion[6,7]. Further management strategies primarily consist of addressing mucosal scarring as early as possible with topical treatments such as nasal saline and honey; however, by the time of ideal intervention, this patient had already developed significant osseous and fibrotic scarring[2]. In this case, due to delayed ability to provide care, the patient developed bony stenosis of the right nasal passage as well as a saddle nose deformity due to a nasal septal perforation sustained at the same time. The bony stenosis component in this case required a management approach similar to that of unilateral choanal atresia with revisions, destruction of bony scarring, and long-term stenting required in much the same way. Our unique case is an example of a button battery injury to the nasal cavity that was not able to be immediately addressed, therefore creating a more complex surgical problem. Conclusions Button battery ingestion is generally caught early enough to intervene and prevent further damage. In this particular case, the ingestion was caught early, but the surgical intervention was delayed. This was partly by intention and partially due to social circumstances; however, an ideal outcome was achieved. Unfortunately, the delay allowed osseous scar formation that mandated an approach similar to choanal atresia repair. In that same vein, repeated scar lysis and stenting have proven to be successful in this patient. Delaying surgical intervention has been advantageous in that the patient is mature enough to tolerate intermittent stenting at home to maintain the equal diameter of the bilateral nares. In conclusion, there were both drawbacks and benefits to delaying surgical repair but ultimately there was a good end result for this patient. References Leinwand K, Brumbaugh DE, Kramer RE: Button battery ingestion in children: a paradigm for management of severe pediatric foreign body ingestions . Gastrointest Endosc Clin N Am. 2016, 26:99-118. 10.1016/j.giec.2015.08.003 Sethia R, Gibbs H, Jacobs IN, Reilly JS, Rhoades K, Jatana KR: Current management of button battery injuries . Laryngoscope Investig Otolaryngol. 2021, 6:549-63. 10.1002/lio2.535 Bakshi SS, Coumare VN, Priya M, Kumar S: Long-term complications of button batteries in the nose . J Emerg Med. 2016, 50:485-7. 10.1016/j.jemermed.2015.10.041 Zipursky AR, Ratnapalan S: Button battery ingestions in children . CMAJ. 2021, 193:E1498. 10.1503/cmaj.210572 reconstructive surgery
https://www.cureus.com/articles/146536-buttoned-shut-management-of-complete-unilateral-nasal-obstruction-secondary-to-button-battery-injury
UNIPROT:Q8TAT5 - FACTA Search Gene/Protein Disease Symptom Drug Enzyme Compound Pivot Concepts: Target Concepts: Query: UNIPROT:Q8TAT5 ( NEIL3 ) 71 Previous studies have found a link between a low DNA repair capacity (DRC) level and increased risk for breast cancer (BC). A recent study by Matta et al. 2012 showed that women with BC have an average reduction of 60% in DRC compared to controls ( P < 0.001). Using the same group of Hispanic women, we selected a subgroup of cases (n=35) and controls (n=2) who donated their tumors and normal tissue for performing molecular studies in order to 1) compare the expression of DNA repair genes in breast tissue between BC cases and controls without this disease, 2) assess the correlation between gene expression and DRC levels, 3) examine whether DRC levels are associated with tumor DNA repair gene expression profiling when women were stratified according to their hormone receptor status. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. Gene expression levels were measured in tumors by means of DNA microarray analysis. Twenty-one DNA repair genes were found to be differentially and significantly expressed in women with BC. Those candidate genes were CHEK2, EME1 (MMS4L), ERCC3 (XPB), FANCM, H2AFX ( H2AX ), HMGB1, HUS1, MBD4, NEIL3 , PCNA, RAD1, RAD23B, RAD51, RAD54B, RDM1 (RAD52B), SHFM1 (DSS1), TP1, UBE2N ( UBC13 ) and XRCC5 (Ku80) . Most DNA repair genes (n=18 or 82%) were overexpressed, ranging from 3.76-fold ( RDM1 ) to 1.47-fold ( XRCC5 ). Only 4 genes (18%) were underexpressed, ranging from 62% ( SAPCD1 ) to 25% ( RAD23B ). Statistically significant positive correlations between DRC level and gene expression were found for the RAD51, FANCB and FANCA genes. We discuss the clinical and translational significance of these findings. Our results support the usefulness of studying DNA repair as a measure of BC risk. This study also provides a list of candidate DNA repair genes that might be associated with dysregulation of DNA repair in breast cancer. ... PMID:Differential expression of DNA repair genes in Hispanic women with breast cancer. 2530 43 Ochratoxin A (OTA) is reported to induce nephrotoxicity and immunotoxicity in animals and humans. However, the underlying mechanism and the effects of OTA on DNA damage have not been reported until now. The present study aims to investigate OTA-induced cytotoxicity and DNA damage and the underlying mechanism in PK15 cells and PAMs. The results showed that OTA at 2.0-8.0 µg/mL for 24 h induced cytotoxicity and DNA damage in PK15 cells and PAMs as demonstrated by decreasing cell viabilities and mRNA levels of DNA repair genes (OGG1, NEIL1 and NEIL3 ), increasing LDH release, Annexin V staining cells, apoptotic nuclei and the accumulation of γ- H2AX foci. OTA at 2.0-8.0 µg/mL increased DNMT1 and SOCS3 mRNA expressions about 2-4 fold in PK15 cells or 1.3-2 fold in PAMs. OTA at 2.0-8.0 µg/mL increased DNMT1, SOCS3, JAK2 and STAT3 protein expressions in PK15 cells or PAMs. DNMT inhibitor (5-Aza-2-dc), promoted SOCS3 expression, inhibited JAK2 and STAT3 expression, alleviated cytotoxicity, apoptosis and DNA damage induced by OTA at 4.0 µg/mL in PK15 cells. While, in PAMs, 5-Aza-2-dc had no effects on SOCS3 expression induced by OTA at 4.0 µg/mL, but inhibited JAK2 and STAT3 expression, and alleviated cytotoxicity, apoptosis and DNA damage induced by OTA. JAK inhibitor (AG490) or STAT3-siRNA alleviated OTA-induced cytotoxicity and DNA damage in PK15 cells or PAMs. Taken together, nephrotoxicity instead of immunotoxicity of OTA is induced by targeting SOCS3 through DNMT1-mediated JAK2/STAT3 signaling pathway. These results provide a scientific and new explanation of the underlying mechanism of OTA-induced nephrotoxicity and immunotoxicity. ... PMID:Nephrotoxicity instead of immunotoxicity of OTA is induced through DNMT1-dependent activation of JAK2/STAT3 signaling pathway by targeting SOCS3. 3092 67
http://www.nactem.ac.uk/facta/cgi-bin/facta3.cgi?query=UNIPROT%3AQ8TAT5%7C111111%7C0%7C0%7C71448%7C0%7C10
CARLINI v. PARAMOUNT PICT | No. 21-55213. | 20220302104 | Leagle.com NOT FOR PUBLICATION MEMORANDUM Joe Carlini appeals the district court s dismissal of his copyright infringement action...20220302104 CARLINI v. PARAMOUNT PICTURES CORPORATION No. 21-55213. View Case Cited Cases JOE GREGORY CARLINI, an individual, Plaintiff-Appellant, v. PARAMOUNT PICTURES CORPORATION, a Delaware corporation; WILL PACKER PRODUCTIONS, INC., a California corporation; BLACK ENTERTAINMENT TELEVISION, a district of Columbia limited liability corporation; TINA GORDON CHISM, an individual; PETER HYUCK, an individual; ALEX GREGORY, an individual; JAS WATERS, an individual; WILL PACKER, an individual; JAMES LOPEZ, an individual; DOES, 1 through 100, inclusive, Defendants-Appellees. United States Court of Appeals, Ninth Circuit. https://leagle.com/images/logo.png Argued and Submitted February 17, 2022 — Pasadena, California. United States Court of Appeals, Ninth Circuit. NOT FOR PUBLICATION MEMORANDUM * Joe Carlini appeals the district court's dismissal of his copyright infringement action against Paramount Pictures Corporation. Carlini claims Paramount's movie What Men Want ("WMW")infringed Carlini's copyright in What the F is He Thinking,an unpublished screenplay that Carlini co-authored. We review de novo the district court's granting of a motion to dismiss under Federal Rule of Civil Procedure 12(b)(6), construing the allegations in the complaint in favor of the plaintiff. Nguyen v. Endologix, Inc.,962 F.3d 405, 413 (9th Cir. 2020). We have jurisdiction under 28 U.S.C. § 1291, and we affirm. To allege copyright infringement, Carlini must sufficiently allege unlawful appropriation and copying. Skidmore v. Led Zeppelin,952 F.3d 1051, 1064 (9th Cir. 2020) (en banc). Unlawful appropriation requires a plaintiff to allege that there are " substantialsimilarities" between the two works. Id."Copying" may be shown with "direct evidence of copying" or "by showing that the defendant had access to the plaintiff's work." Id.The district court correctly concluded that Carlini failed to allege unlawful appropriation. 1 First,Carlini did not sufficiently allege that the two works were substantially similar. To assess substantial similarity, we apply the extrinsic test. See id.Under that test, "[a] court must take care to inquire only whether the protectible elements, standing alone,are substantially similar." Cavalier v. Random House, Inc.,297 F.3d 815, 822 (9th Cir. 2002) (quotations omitted). "Scenes-a-faire, or situations and incidents that flow necessarily or naturally from a basic plot premise, cannot sustain a finding of infringement." Id.at 823. The extrinsic test "is objective in nature" and "focuses on articulable similarities between the plot, themes, dialogue, mood, setting, pace, characters, and sequence of events in the two works." Funky Films, Inc. v. Time Warner Entm't Co.,462 F.3d 1072, 1077 (9th Cir. 2006) (quotations omitted), overruled on other ground by Skidmore,952 F.3d at 1067-69. After a careful review of the two works, we conclude they are not substantially similar as a matter of law. Most notably, the plots of each work are not substantially similar. Both works follow a woman who gains the ability to hear men's thoughts, but the plots diverge substantially from there: WMWfocuses primarily on the protagonist navigating career struggles, whereas Carlini's screenplay focuses on two people in relationships with the wrong person. See Benay v. Warner Bros. Entm't, Inc.,607 F.3d 620, 625 (9th Cir. 2010) (finding a lack of substantial similarity when, "[t]hough the Screenplay and the Film share the same basic plot premise, a closer inspection reveals that they tell very different stories"), overruled on other grounds by Skidmore,952 F.3d at 1067-69. Although Carlini points to superficial similarities in how the main characters gain their mind-reading powers, the events play out in materially different ways in each work. Other features of the plot that Carlini focuses on are unprotectable scenes à faireassociated with a story about hearing the private thoughts of other persons. See Cavalier,297 F.3d at 822. Carlini's list of 16 different "events" also fails plausibly to allege substantial similarity based on the sequence of events in both works. Although it is appropriate to "rel[y] on such lists of similarities . . . for illustrative purposes," this court is "particularly cautious where . . . the list emphasizes random similarities scattered throughout the works." Litchfield v. Spielberg,736 F.2d 1352, 1356 (9th Cir. 1984) (quotations omitted). Carlini advances that kind of list. In this case, any similarities in sequencing are commonplace or, given the plot premise, unremarkable. They do not "belie[] any claim of literary accident." Metcalf v. Bochco,294 F.3d 1069, 1074 (9th Cir. 2002) (quotations omitted), overruled on other grounds by Skidmore,952 F.3d at 1067-69. Other features of the two works likewise belie Carlini's allegations that the works are substantially similar. The female protagonists are not similar: one is a junior high school teacher in her mid-20s, and the other is a high-powered, career-obsessed, sports agent trying to succeed at a firm dominated by men. The protagonists' male love interests share generic characteristics commonly found in romantic comedies. See Rice v. Fox Broad. Co.,330 F.3d 1170, 1176 (9th Cir. 2003) ("[W]hile there may exist similarities between the . . . `characters,' any shared attributes . . . are generic and common[.]"), overruled on other grounds by Skidmore,952 F.3d at 1067-69. And while TJ and Brandon have some similarities as the gay best friends of the protagonists, they are otherwise quite different. TJ, described as "energetic, very colorful and flamboyant," has no work relationship with the protagonist, and acts as her best friend throughout the story. In contrast, Brandon is portrayed as a reserved and career-oriented assistant whom the protagonist treats poorly for most of the film. Other aspects of the works, such as themes, settings, dialogue, and mood and pace are not substantially similar either, or else are unprotectable scenes à faireof a romantic comedy. And the isolated lines of dialogue that Carlini relies on do not demonstrate substantial similarity because "extended similarity of dialogue [is] needed to support a claim of substantial similarity." Olson v. National Broad. Co., Inc.,855 F.2d 1446, 1450 (9th Cir. 1988). AFFIRMED. FootNotes ** The Honorable Robert S. Lasnik, United States District Judge for the Western District of Washington, sitting by designation. * This disposition is not appropriate for publication and is not precedent except as provided by Ninth Circuit Rule 36-3. 1. Because Carlini fails plausibly to allege that the two works are substantially similar, we do not reach whether Carlini adequately pleaded access.
https://www.leagle.com/decision/infco20220302104
Foods | Free Full-Text | Rheological and Antimicrobial Properties of Chitosan and Quinoa Protein Filmogenic Suspensions with Thyme and Rosemary Essential Oils Food packaging faces the negative impact of synthetic materials on the environment, and edible coatings offer one alternative from filmogenic suspensions (FS). In this work, an active edible FS based on chitosan (C) and quinoa protein (QP) cross-linked with transglutaminase was produced. Thyme (T) and rosemary (R) essential oils (EOs) were incorporated as antimicrobial agents. Particle size, Z potential, and rheological parameters were evaluated. The antimicrobial activity against Micrococcus luteus (NCIB 8166) and Salmonella sp. (Lignieres 1900) was monitored using atomic force microscopy and image analysis. Results indicate that EOs incorporation into C:QP suspensions did not affect the Z potential, ranging from & minus;46.69 & plusmn; 3.19 mV to & minus;46.21 & plusmn; 3.83 mV. However, the polydispersity index increased from 0.51 & plusmn; 0.07 to 0.80 & plusmn; 0.04 in suspensions with EO. The minimum inhibitory concentration of active suspensions against Salmonella sp. was 0.5% (v/v) for thyme and 1% (v/v) for rosemary. Entropy and fractal dimension of the images were used to confirm the antimicrobial effect of EOs, which modified the surface roughness. Rheological and Antimicrobial Properties of Chitosan and Quinoa Protein Filmogenic Suspensions with Thyme and Rosemary Essential Oils by Monserrat Escamilla-García 1 , Raquel A. Ríos-Romo 1 , Armando Melgarejo-Mancilla 1 , Mayra Díaz-Ramírez 2 , Hilda M. Hernández-Hernández 3 , Aldo Amaro-Reyes 1 , Prospero Di Pierro 4 and Carlos Regalado-González 1,* 1 Department of Food Research and Postgraduate Studies, Faculty of Chemistry, Autonomous University of Querétaro, C.U., Cerro de las Campanas S/N, Col. Las Campanas, Querétaro 76010, Mexico 2 Department of Food Science, Division of Biological Sciences and Health, Autonomous Metropolitan University, Lerma Unit, Avenida de las Garzas N°. 10, El Panteón, Lerma de Villada 52005, Mexico 3 CONACyT-Center for Research Technological Assistance and Design of the State of Jalisco, A.C. (CIATEJ), Av. Normalistas 800, Volinas de la Normal, Guadalajara 44270, Jalisco, Mexico 4 Department of Chemical Sciences, University of Naples “Federico II”, 80126 Naples, Italy * Author to whom correspondence should be addressed. Foods 2020 , 9 (11), 1616; https://doi.org/10.3390/foods9111616 Received: 7 October 2020 / Revised: 28 October 2020 / Accepted: 4 November 2020 / Published: 6 November 2020 Abstract : Food packaging faces the negative impact of synthetic materials on the environment, and edible coatings offer one alternative from filmogenic suspensions (FS). In this work, an active edible FS based on chitosan (C) and quinoa protein (QP) cross-linked with transglutaminase was produced. Thyme (T) and rosemary (R) essential oils (EOs) were incorporated as antimicrobial agents. Particle size, Z potential, and rheological parameters were evaluated. The antimicrobial activity against Micrococcus luteus (NCIB 8166) and Salmonella sp. (Lignieres 1900) was monitored using atomic force microscopy and image analysis. Results indicate that EOs incorporation into C:QP suspensions did not affect the Z potential, ranging from −46.69 ± 3.19 mV to −46.21 ± 3.83 mV. However, the polydispersity index increased from 0.51 ± 0.07 to 0.80 ± 0.04 in suspensions with EO. The minimum inhibitory concentration of active suspensions against Salmonella sp. was 0.5% ( v / v ) for thyme and 1% ( v / v ) for rosemary. Entropy and fractal dimension of the images were used to confirm the antimicrobial effect of EOs, which modified the surface roughness. Keywords: filmogenic suspension ; Salmonella ; thyme ; rosemary Graphical Abstract 1. Introduction Numerous factors affect the original quality of food products [ 1 ], and up to date, many synthetic food packaging materials are used due to their good mechanical and barrier properties, but they show long biodegradation processes [ 2 ]. Besides providing food protection from the environment, active packaging may also protect from foodborne illness outbreaks [ 3 , 4 ]. Biopolymers are commonly used to produce coatings, such as polysaccharides (starch, chitosan, cellulose), proteins (animal or vegetable), and also lipids (waxes, fatty acids), or a mixture of them [ 4 ]. These materials act as barriers against the transport of gases and water vapor, leading to longer shelf life, keeping the organoleptic properties of foods. Protection from spoilage and pathogenic microorganisms may be achieved by incorporating antimicrobial compounds [ 5 ]. Coatings made from filmogenic suspensions (FS) of polysaccharides are primarily designed to be an efficient oxygen barrier due to their well-ordered hydrogen-bonded network. However, they provide a deficient moisture barrier due to their hydrophilic nature. Polysaccharide coatings are colorless, show good appearance, and alone or in combination with other biopolymers may be used to extend the shelf life of fruits, vegetables, seafood, or meat products by significantly reducing dehydration, surface darkening, and rancidity [ 6 ]. Chitosan (C) is the second most abundant polysaccharide in nature, comprising two units β-(1-4)-2-acetamido- d -glucose, and β-(1-4)-2-amino- d -glucose [ 7 ]. Chitosan is described in terms of deacetylation extent and average molecular weight. This compound’s importance relies on antimicrobial properties, together with its cationic nature and film-forming properties [ 8 ]. Chitosan-based coatings show extremely low oxygen permeability, low relative humidity, and high water vapor permeability [ 9 ]. Chitosan exhibits bacteriostatic and fungistatic properties, and thus, can be used for active packaging, producing films of good mechanical properties, high permeability to CO 2 , and low to O 2 [ 10 ]. FS of proteins may produce coatings by their denaturation using heat, solvents, or pH changes, followed by association of peptide chains through new intermolecular interactions [ 7 ]. The polymeric interactions produce coatings with a rigid protein network, less flexible, and less permeable to gases and vapors. Therefore, protein-based films or coatings are considered highly effective oxygen barriers, even at high relative humidity [ 11 ]. There are limited reports on FS of quinoa protein ( Chenopodium quinoa Willd; QP), despite being able to produce edible coatings that combined with chitosan showed enhanced mechanical properties [ 12 ]; while the addition of small amounts of plasticizers to this mixture results in improved water vapor permeability [ 13 ]. Different antimicrobial agents have been added to edible coatings to avoid microbial contamination in food [ 14 ]. Essential oils are aromatic compounds of natural origin, with a broad spectrum of biological activities [ 15 ], and many exert strong antibacterial, antiviral and antifungal activities, leading to wide applications in food and beverage products [ 16 ]. Thyme ( Thymus vulgaris ) (T) essential oil (EO) has been used as a flavor ingredient in a wide variety of foods, beverages, and confectionery. It has been labeled as Generally Recognized as Safe (GRAS) food additive by the Food and Drug Administration (FDA) of the USA [ 17 ]. The antimicrobial activity is mainly due to thymol and carvacrol, which are also found in other EOs. Its antioxidant properties have been used to combat reactive oxygen species and prevent oxidation of food [ 18 ]. This oil has demonstrated antifungal activity against Aspergillus , Penicillium , Ulocladium , Cladosporium , Trichoderma , Rhizopus , and Chaetomium [ 19 ]. Thyme spectrum against pathogenic bacteria includes Listeria monocytogenes , Pseudomonas aeruginosa , Staphylococcus aureus , and Salmonella sp. [ 20 , 21 ]. Rosemary ( Rosmarinus officinalis L. Labiadas) is a long-lasting aromatic perennial herb, and its oil has been used in food preservation [ 22 ]. Rosemary EO contains monoterpenes such as 1,8-cineole, α-pinene, camphor, and camphene, which give antioxidant, antimicrobial, and anticancer effects [ 23 ]. Its effect has been analyzed against Gram-positive ( S. aureus and Bacillus subtilis ) and Gram-negative ( Escherichia coli , Salmonella enteritidis , and Klebsiella pneumoniae ) strains. However, it has shown greater activity against Gram-positive bacteria [ 24 ]. This EO has been studied as an active agent in cellulose acetate films or chitosan coatings for food preservation [ 25 ]. In this work, we demonstrate the antimicrobial effect of rosemary and thyme EOs incorporated into QP:C filmogenic suspensions on Salmonella sp.’s surface microstructure, which has been reported as the second largest responsible for food outbreaks in the USA [ 26 ]. Few reports perform texture image analysis from atomic force micrographs to determine image texture, fractal dimension, and roughness, to visualize the antimicrobial effect of the active FS against this pathogen. This has not been previously reported for these active filmogenic suspensions. Here we show the effect of the FS containing R and T EOs on microbial population reduction using conventional methodology, which is compared with high resolution visualization of their mechanisms of action at cell surface level by atomic force microscopy, which to our knowledge has not been previously reported. The present work’s objective was to develop and characterize a filmogenic suspension based on chitosan and quinoa protein cross-linked with transglutaminase, with antimicrobial effect by incorporation of rosemary and thyme essential oils. 2. Materials and Methods 2.1. Supplies Chitosan (Cat. No. 417963, Sigma-Aldrich, St. Louis, MO, USA), Peruvian commercial quinoa (Hanseatik), rosemary (R) EO (Drogueria Cosmopolita, Ciudad de México, Mexico), thyme (T) EO (Drogueria Cosmopolita, CDMX, Mexico), sorbitol (Cat. No. W302902, Sigma Aldrich), microbial transglutaminase (TG) derived from Streptoverticillium sp., with 92 IU/g (Activa WM, Ajinomoto, France). Salmonella sp. and Micrococcus luteus NCIB 8166 were obtained from the Department of Food Research and Postgraduate Studies of the Autonomous University of Querétaro, Querétaro, México. Tryptic soy broth (TSB) was purchased from BD Difco (Franklin Lakes, NJ, USA). 2.2. Methods 2.2.1. Quinoa Protein Extraction The quinoa seeds were ground to about 200 µm using a coffee grinder (Krups Model GX410011, Solingen, Germany). The flour was defatted by three extractions with ethanol (70% v / v ) in the ratio 1:10 w / v (flour:solvent) under constant stirring for 2 h and 25 °C [ 27 , 28 ]. The defatted flour was suspended in distilled water (10%, w / v ) adjusting to pH 11 with 1 N NaOH, and stirred for 1 h at room temperature (25 °C). Then, the samples were centrifuged at 3200× g , at 10 °C for 30 min. The supernatant was adjusted to pH 4.5 and stirred for 30 min, followed by centrifugation as before. The precipitate was re-suspended in distilled water at a 5:95 ratio (precipitate: water, w / v ) and neutralized with 2 N NaOH, followed by oven drying at 50 °C (ED, Binder, Tuttlingen, Germany). The protein isolates were ground for 2 min using the coffee grinder and passed through a No. 9 mesh (Tyler standard) of 200 μm pore opening [ 12 ]. 2.2.2. Quinoa Protein-Chitosan Filmogenic Suspension The quinoa protein (QP) FS (2% w / v ) was adjusted to pH 11, with constant stirring for 1 h. On the other hand, a 2% ( w / v ) chitosan solution was prepared in 0.5 M HCl, according to Escamilla [ 12 ]. The solutions were then mixed in 1:10 ratio (C:QP), sorbitol was added in a 1:1 weight ratio (C:sorbitol), and adjusted to pH 11. Then, the mixture was homogenized by a high speed mixer (IKA T25-Ultra-Turrax, Wilmington, USA) at 21,500 rpm for 3 min, followed by sonication for 10 min at 150 W, and 20 kHz (SONOPULS, HD3200, Bandelin GmbH, Berlin, Germany) [ 29 ]. 2.2.3. Crosslinking with Transglutaminase The C:QP FS ( Section 2.2.2 ) before homogenization was adjusted to pH 9 and added with 1.4% ( v / v ) of TG solution (10% w / v ), stirred for 1 h, followed by pH adjustment to 11. After cross-linking, the FS was homogenized by a high-speed mixer (IKA T25-Ultra-Turrax) at 21,500 rpm for 3 min, followed by sonication for 10 min at 150 W and 20 kHz (SONOPULS, HD3200). 2.2.4. Minimum Inhibitory Concentration The minimum inhibitory concentration (MIC) of the EOs was evaluated against Salmonella sp., and Micrococcus luteus , adjusted to an optical density of 0.08 (10 6 CFU/mL) at 600 nm. Salmonella sp. was chosen due to its highly frequent presence in foodborne outbreaks, being lethal in many cases. Micrococcus luteus is not a severe pathogenic bacterium, but for many years it has been used as a model system for bacterial cell wall study due to low peptidoglycan cross-linking (about 25%) [ 30 , 31 ]. M. luteus sensitivity to cell wall disruption was the reason to choose this microorganism as Gram-positive model. EOs at six different concentrations (0%, 0.5%, 0.7%, 1.0%, 1.5%, and 2.0%, v / v ), and Tween 80 at constant concentration of 0.5% ( v / v ), were added to the TSB culture media. Absorbance readings were recorded every h, and the MIC was considered as the lowest concentration tested that inhibited microbial growth. 2.2.5. Active Filmogenic Suspension The 1:10 C:QP FS ( Section 2.2.2 ) was cross-linked with TG ( Section 2.2.3 ), and then the active FS was produced by adding the EOs at the previously found MIC and Tween 80 at 0.5% ( v / v ). The active FS was homogenized by a high-speed mixer (IKA T25-Ultra-Turrax) at 21,500 rpm for 3 min, followed by sonication for 10 min at 150 W, and 20 kHz (SONOPULS, HD3200) [ 32 ] 2.2.6. Kinetic Parameters of Tested Microorganisms The effect of the active FS on Salmonella sp. and M. luteus was evaluated by measuring the kinetic parameters, which was associated with the antimicrobial effect. The tested microorganisms were grown in the QP and C biopolymers, C:QP FS, and the FS added with EOs (C:QP:T and C:QP:R). The parameters determined were doubling time (T d ) and specific growth rate (μ) following the Monod model [ 33 ], using the GraphPad Prism 5.0 software (San Diego, CA, USA), showing the active FS effect on microbial growth. 2.2.7. Antimicrobial Activity of Active Filmogenic Suspension Salmonella sp. was activated in TSB broth for 24 h at 37 °C, whereas the same media was used to activate M. luteus for 48 h at 30 °C. Then, the FS of C:QP; and FS with EOs (C:QP-R; C:QP-T) were inoculated with each microbial culture to reach 10 6 CFU/mL. The antimicrobial activity was determined by evaluating the microbial population after 2, 4, 8, 12, 24, and 48 h, using the pour plate method in TSB agar, and incubating as above mentioned. 2.2.8. Filmogenic Suspension Characterization Particle Size The mean particle diameter of FS was determined with a Zetasizer Nano-ZS laser diffractometer (Malvern Instruments, Worcestershire, UK) at 633 nm and 25 °C, equipped with a backscatter detector [ 34 ]. Z Potential Z potential (mV) was determined by phase analysis light scattering (PALS) with a Zetasizer Nano-ZS laser diffractometer (Malvern Instruments, Worcestershire, UK), which determines electrical charge at interface of droplets dispersed in aqueous phase [ 34 ]. Rheological Properties of Emulsion A rheometer equipped with concentric cylinder geometry (Discovery Hybrid Rheometer TA Instruments, New Castle, DE, USA), was used to determine the rheological properties of the FS at 25 °C. Temperature equilibration and particles settling were allowed for 5 min before steady-state flow measurements were carried out, using a shear rate range of 0 to 100 s −1 . Shear stress, shear rate, and apparent viscosity were evaluated using the TRIOS 4 software (TA instruments); the experimental flow curves were fitted to the Casson model (Equation (1)): γ 1 / 2 (1) where σ is shear stress (Pa), σ 0 is the elastic limit (Pa), γ is the shear rate (s −1 ) and η is apparent viscosity of the fluid [ 35 ]. 2.2.9. Antimicrobial Evaluation of Filmogenic Suspension Sample Preparation Samples were prepared according to Mathelié–Guinlet [ 36 ] with some modifications. The bacteria were activated for 5 h, at 37 °C, to reach the log phase. Then, 5 µL (10 6 UFC/mL) of each tested microorganism were inoculated into 2 mL of the FS (control) and 2 mL of FS containing T and R EOs at the previously determined MIC. All mixtures were incubated for 5 h, at 37 °C. An aliquot of 100 µL of each treatment was deposited on glass slides of 26 × 76 mm and 1.1 ± 0.1 mm thick and allowed to dry for 2 h at room temperature in a laminar flow cabinet. Cell adhesion was enhanced by previously adding a layer of 100 µL of FS without EOs to the glass slides and allowed to dry at room temperature. Cells Topography This determination was carried out using an atomic force microscope (AFM; Multimode V, Veeco, Plainview, NY, USA) in contact mode to avoid any damage to the samples. The images were obtained at a scanning speed from 0.5 to 1.0 Hz, with a resolution of 512 × 512 pixels and at different areas (50 μm × 50 μm; 2.5 μm × 2.5 μm; 0.5 μm × 0.5 μm) [ 36 ]. Texture Image Analysis Texture image analysis was conducted following Arzate–Vazquez [ 37 ] and was applied to quantitatively characterize the microbial surface microstructure treated with the FS C:QP with and without EOs. Three characteristics were selected: entropy, fractal dimension, and roughness. All images obtained by atomic force microscopy (AFM) were converted to grayscale images. Subsequently, the gray level co-occurrence matrix (GLCM) and differential box count (SDBC) algorithms were applied to obtain the texture characteristics from grayscale images, both included in the Image J 1.52 software (NIH, Bethesda, MD, USA). GLCM is a second-order statistical algorithm that compares two neighboring pixels at once and compiles the frequency with which different gray levels can be found within a restricted area. In this algorithm, three variables are considered: the number of gray levels (0–255), the distance of the pixels (d), and the offset angle (θ). The image texture (entropy) was analyzed by studying the spatial dependence of pixel values represented by a co-occurrence matrix Gd, θ, with the input Gd, θ (i, j), which represents the frequency whereby a pixel with intensity i is adjacent to a pixel with intensity j, separated in direction θ. These parameters were measured at a distance d equal to 1 and an angle equal to 0 °, using Equation (2). Entropy = − ∑ i j ( G d , θ ( i , j ) log ( G d , θ ( i , j ) ) ) (2) The fractal texture was evaluated using the power law scale to obtain its fractal dimension (FD) using the SDBC algorithm based on the surface intensity graph. It is generated from 2D grayscale images by plotting pixel coordinates (x, y) versus their gray level in the z-axis. FD was estimated from the slope of the plot log (number of boxes) vs. log (box size) (Equation (3)), where “N” is the number of boxes and “r” is the length of the box size FD = log ( N ) log ( 1 / r ) (3) The FD is an object property that shows how much of the space that contains it is occupied and can acquire continuous values in the space of real numbers between 0 and 3. FD tries to measure the extent that a 2D object fills the 3D space, or a one-dimension object resembles a 2D surface allowing the description of the geometry of many natural structures that appear to have great complexity but having the same geometric regularity. According to fractal geometry, the line has FD greater than zero, but less than 1, the FD of a dot is 0, the plane FD is between 1 and 2, whereas that of the cube is between 2 and 3. FD is directly related to the extent of surface roughness (Rq) (Equation (4)), which was obtained following the protocol of Escamilla–García [ 12 ]. Rq is the standard deviation of Zi values indicating roughness (nm); Zi is the difference in the height of i relative to the average height, and N is the number of points in the image. R q = ∑ Zi 2 N (4) 2.2.10. Statistical Analysis All tests were performed in triplicate, and data were evaluated by one-way analysis of variance using GraphPad Prism 5.0 software (GraphPad Software, San Diego, CA, USA). Significant differences were determined by Dunnett’s test, with a significance level of p < 0.01. Data are presented as the mean ± standard deviation. 3. Results and Discussion 3.1. Antimicrobial Activity The antimicrobial activity of R and T free EOs against M. luteus (Gram-positive) and Salmonella sp. (Gram-negative) showed a MIC for both microorganisms of 0.5% ( v / v ) and 1.0% ( v / v ) of T and R EOs, respectively ( Figure 1 ). The EOs were added to the FS of C:QP using these concentrations. The doubling time (T d ) of M. luteus and Salmonella sp. is shown in Figure 2 . For M. luteus , the C:QP FS exhibited the lowest T d value (5.25 ± 0.11 h), but not significantly different from the QP solution ( Figure 2 a). Solutions of C and FS with added EOs were significantly different from the C:QP FS, with the highest T d obtained by the C:QP:T (44.54 ± 1.10 h), which was 1.77 times the T d of the C:QP:R FS. The T d value showed by the C solution was lower than those presented by the C:QP:T and C:QP:R FS ( Figure 2 a), indicating stronger antimicrobial activity of FS added with EOs, than the C solution. Salmonella sp. ( Figure 2 b) was significantly inhibited in the presence of EOs, especially with C:QP:R (81.40 ± 7.01 h), which increased about 3.6 times the T d of C:QP:T (22.47 ± 1.27 h), while the inhibition shown by QP, C, and C:QP FS was significantly lower. The μ value for M. luteus decreased in the presence of the FS C:QP:T and C:QP:R ( Figure 3 a). The C:QP:T FS presented the lowest μ value (5.55 ± 0.07 h −1 ), indicating higher antimicrobial activity of C:QP:T than that of C:QP:R, whereas the highest microbial growth was shown by the C:QP FS (μ = 13.2 ± 0.26 h −1 ) ( Figure 3 a). All FS resulted in significantly different Salmonella sp. specific growth rate ( Figure 3 b). Both EOs in the FS showed high Salmonella sp. inhibition, but the FS containing R EO showed the highest (μ = 0.085 ± 0.001 h −1 ). The FS producing the least inhibition was C:QP (μ = 0.111 ± 0.001 h −1 ). Although FS added with T EO showed antimicrobial activity against both bacteria, the effect was greater against M. luteus , which is reflected in a doubling time about twice of that showed for Salmonella sp. (T d = 22.47 ± 1.27 h) ( Figure 3 ). Hosseini [ 38 ] reported that T EO had greater activity against Gram-positive than Gram-negative bacteria due to their thick layer of peptidoglycan (90–95%) and the presence of an outer lipopolysaccharide membrane [ 39 ]. The outer membrane has also been associated with higher antimicrobial activity of the combination of C and EOs because it restricts hydrophobic compounds [ 21 ]. However, the effectiveness of EOs in the presence of C depends on their composition, structure, and functional groups. The C:QP:R FS showed strong Salmonella sp. inhibition, with T d = 81.04 ± 7.01 h, value 3.23 times greater than that of M. luteus . The FS C:QP did not exhibit inhibition against M. luteus , but FS with EOs exerted an antimicrobial effect ( Figure 4 a). There was 2 log population reduction exerted by FS containing either T or R EOs after 4 h of contact time, whereas after 24 h, the reduction increased to 3 log cycles. In contrast, Salmonella sp. population was reduced by the FS containing either R or T EOs about 1 log cycle after 2 h, whereas the maximum reduction of 3 log cycles was achieved after 48 h ( Figure 4 b). As expected, higher inhibition was observed against the Gram-positive bacterium M. luteus . 3.2. Filmogenic Suspension Characterization 3.2.1. Stability The stability of FS was evaluated by particle size, Z potential, and polydispersity index (IPD). Z potential values were evaluated initially and after 10 d of storage ( Table 1 ), giving values in the range −46.21 to −54.13 mV. After 10 d of storage, the emulsion C:QP:R significantly increased its z potential, whereas all FS showed increased values, although not significant. Absolute values of Z-potential greater than 30 mV indicate high emulsions stability [ 40 ], and thus, all the emulsions are stable. This effect may be associated with the presence of the non-ionic surfactant (Tween 80), which permitted a balance of what is known as hydrophilic-lipophilic numbness, allowing the maintenance of stable emulsions, even during storage [ 41 ]. The negative charge of the Z potential was attributed to the alkaline pH used to produce the emulsions. Despite chitosan positive charges, aqueous FS at pH > 6 promotes a higher number of deprotonated species followed by aggregation due to hydrogen bonds formation involving the neutralized NH 2 groups of the chitosan chains [ 40 ]. In addition, a study has shown that Tween can favor negative electrical charges, which are attributed to the presence of anionic impurities [ 42 ]. The stability of FS may be enhanced by the resulting protein network, which, through hydrophilic and hydrophobic groups, allows both water and oil interactions, preventing the FS from collapsing [ 43 ]. From the results obtained, the particle size presented two main populations for each sample. It was observed that the population is representing agglomerated particles comprised most of the FS ( Table 2 ). The FS with added EOs showed significantly increased particle size, especially considering the more abundant large particles (597.56 ± 37.59 nm to 677.02 ± 35.08 nm) as compared to FS without EOs. However, there was no significant difference among the smaller particles (97.55 ± 10.79 nm to 153.58 ± 13.76 nm). On the other hand, the addition of EOs generated a significant increase in the polydispersity index (PDI). PDI is the ratio of weight average to number average molecular weight, and values close to zero indicate highly monodisperse (homogeneous) FS, while values > 0.7 indicate a broad particle size distribution [ 44 ]. The results in Table 2 show PDI values between 0.5 and 0.80, suggesting that the produced FS are heterogeneous, while EOs addition caused greater heterogeneity. Quinoa protein is soluble at pH 11, where it has greater solubility and water absorption capacity. It also contains high amounts of sulfur amino acids, threonine, and tryptophan, although experiencing small protein denaturation [ 45 ]. FS were prepared using this pH, which favored the formation of aggregates, which was reflected in suspensions exhibiting two different particle sizes ( Table 2 ). The C:QP FS revealed one population of particle sizes close to 600 nm, which may correspond to protein aggregates resulting from the formation of hydrogen bonds within the QP and with C, together with hydrophobic interactions and covalent disulfide bonds that are formed in the protein under these conditions [ 46 ]. Disulfide bond formation is favored by the presence of TG and by heat processing of the FS, leading to the formation of agglomerates [ 46 ]. The particle size of the FS (597.56 ± 37.59 nm) increased in the presence of EOs, which was attributed to the increase in hydrophobic interactions among drops of individual EOs [ 47 ]. 3.2.2. Rheology The FS rheology was successfully fitted to the Casson model (R 2′ = 0.995–0.998), without significant differences ( Table 3 ). The C:PQ-R FS showed the lowest elastic limit but was not significantly different from the other emulsions. Similarly, the calculated apparent viscosity of the different FS was not significantly different. Non-Newtonian fluids that behave as elastic solids and show shear-thinning behavior can be fitted with the Casson’s rheological model, which shows infinite viscosity at zero shear rate [ 48 ]. The FS made with C:PQ-R showed the highest apparent viscosity (3.04 ± 0.002 × 10 −3 Pa.s), which according to Dapueto [ 49 ], can be related to the formation of significant amounts of protein aggregates, associated with the increased particle sizes in the presence of EOs. Proteins, like surfactants, form monolayers in aqueous solutions that can have high elastic properties behaving like sticky droplets [ 43 ], whose interactions with the EOs promote elasticity reduction. The apparent viscosity of FS decreased when applying higher shear rates ( Figure 5 a). However, when reaching a speed of approximately 20 s −1 , as the shear rate increased, there were few changes in apparent viscosity. Figure 5 b shows a directly proportional relationship between stress and shear rate for the FS. However, for both properties, the evaluated FS were not significantly different. 3.2.3. Antimicrobial Evaluation of Filmogenic Suspension by Atomic Force Microscopy Figure 6 shows M. luteus topography for the control and FS with EOs. M. luteus revealed a coccus morphology when growing in the FS without EOs ( Figure 6 a). However, in the presence of the R EO ( Figure 6 b) and T EO ( Figure 6 c), M. luteus lost its characteristic spherical structure, suggesting an antimicrobial effect. The T EO showed a greater antimicrobial effect on M. luteus by causing massive destruction of its structure. Meanwhile, the effect of R EO was milder because some cells retained their spherical shape, suggesting partial inhibition, as shown in Figure 1 . Salmonella sp. is characterized by presenting the bacillus shape ( Figure 7 a). The R EO ( Figure 7 b) and T EO ( Figure 7 c) exerted an antimicrobial effect on this microorganism by damaging the cell surface. The EOs showed antimicrobial activity against the tested microorganisms ( Figure 1 ), and when incorporated into the FS, they modified the growth kinetic parameters ( Figure 2 and Figure 3 ), exerting antimicrobial effect ( Figure 4 b), which was visualized by using AFM. The control treatments exhibited rough and heterogeneous surfaces consisting of agglomerated matter with a structure that coincided with the morphologies of M. luteus and Salmonella sp. The spherical shape of M. luteus showed dimensions of 0.5–3.5 µm ( Figure 6 a), whereas Salmonella sp. revealed a short bar geometry ( Figure 7 a) [ 50 , 51 ]. However, when adding EOs, these shapes were lost, which was attributed to damage to the cell wall and cytoplasmic membrane with loss of structural integrity, as confirmed by the population reduction ( Figure 4 ). This effect might include the disruption of the proton motive force, inhibition of substrate oxidation, and disruption of DNA synthesis [ 52 ]. The hydrophobicity of essential oils enables the separation of lipids present in the cell membrane of bacteria, altering their structure, making them more permeable, and causing cell lysis [ 53 ]. 3.2.4. Image Analysis Entropy (E) is a measure of the heterogeneity of the images, and to quantitatively evaluate the images obtained by AFM; the grayscale co-occurrence matrix algorithm was used. In addition, the fractal dimension (FD), also known as fractal texture through the Differential Box Count (SDBC) algorithm, is a parameter related to the irregularity of the surface. There are no reports about the E and FD calculated from image analysis evaluation to confirm the antimicrobial effect of T and R EOs on the two microorganisms used in this work, as shown in Figure 4 . From Figure 8 a, it is observed that the entropy of the samples of C:QP did not significantly change in the FS, incorporating the EOs when Salmonella sp. was inoculated. The lowest entropy was observed for M. luteus in T EO suspensions ( Figure 8 a), suggesting a more homogeneous image relative to the control, which was attributed to the effect of microbial growth inhibition, which correlates well with the antimicrobial activity shown in Figure 4 a. The fractal dimension ( Figure 8 b) decreased when EOs were added, and this phenomenon was observed in the roughness value ( Figure 8 c), except for Salmonella sp. in the presence of T EO, which may be associated with cell lysis caused by the EOs. According to our results, the FD decreased in the presence of EOs. Fractal dimension is a mathematical concept in which a set of multiple scales exhibits the same repeating pattern on each scale, which can be transferred to texture analysis. This parameter is correlated with roughness; the larger the FD, the rougher the texture [ 53 ]. The addition of EOs to the C:QP FS generally produced smoother surfaces, and thus, the roughness reduction was attributed to cell lysis promoted by the EOs. The characteristic structures of M. luteus and Salmonella sp. provided high FD and entropy, considering it as the randomness or degree of disorder showed by the image; whereas the roughness was high for M. luteus, but lower for Salmonella sp. The entropy is higher when all elements of the co-occurrence matrix are equal and smaller when the elements are different [ 54 ]; thus, more homogeneous surfaces are probably the result of the antimicrobial effect of EOs. 4. Conclusions Essential oils imparted antimicrobial activity on M. luteus and Salmonella sp., at concentrations of 0.5% ( v / v ) and 1% (v / v ) for thyme and rosemary EOs, respectively. When EOs were incorporated into the FS, thyme EO showed a greater inhibitory effect on Salmonella sp. and M. luteus than rosemary EO. The FS of C:QP with and without EOs were stable but heterogeneous dispersions. EOs addition significantly increased the particle size distribution, showing two major populations. Casson’s rheological model was successfully fitted to the non-Newtonian fluids (FS with and without EOs), that behave like an elastic solid. Formation of protein aggregates allowed greater interaction between protein and aqueous phase, which increased the apparent viscosity of the C:QP-R FS, compared to the control. AFM permitted the evaluation of the characteristic structures of M. luteus and Salmonella sp. and confirmed the antimicrobial activity of the EOs, which was also monitored by significant changes in their kinetic parameters. Image analysis of FS containing T and R EOs showed that entropy, roughness, and FD changes might correlate with the generation of more homogeneous surfaces and with the antimicrobial effect. The properties of the active FS may be of use as an alternative coating material for food preservation. Author Contributions Resources and funding acquisition, C.R.-G.; writing—original draft preparation, M.E.-G.; investigation, R.A.R.-R.; visualization, A.M.-M. and H.M.H.-H.; methodology M.D.-R.; writing—review and editing A.A.-R.; validation P.D.P. All authors have read and agreed to the published version of the manuscript. Funding This research was funded by “UAQ, grant number FOPER-2019-00633” and “MAECI, grant number CUP:E68D18000130001”. Acknowledgments The authors are grateful to the “Centro de Nanociencias y Micro y Nanotecnologías” of IPN (CNMN) and “Escuela Nacional de Ciencias Biológicas” of IPN for providing the facilities for this research work and for technical assistance. Conflicts of Interest The authors declare no conflict of interest. References Valde, F.D.; Banos, S.B.; Valdes, D.F.; Ramirez, A.O.; García, P.A.; Falcón, R.A. Películas y recubrimientos comestibles: Una alternativa favorable en la conservación poscosecha de frutas y hortalizas. Rev. Cien. Tec. Agros. 2015 , 24 , 52–57. [ Google Scholar ] Guerreiro, T.M.; De Oliveira, D.N.; Melo, C.F.O.R.; Lima, E.D.O.; Catharino, R.R. Migration from plastic packaging into meat. Food Res. Int. 2018 , 109 , 320–324. [ Google Scholar ] [ CrossRef ] [ PubMed ] Majid, I.; Nayik, G.A.; Dar, S.M.; Nanda, V. Novel food packaging technologies: Innovations and future prospective. J. Saudi Soc. Agric. Sci. 2018 , 17 , 454–462. [ Google Scholar ] [ CrossRef ][ Green Version ] Ahmed, I.; Lin, H.; Zou, L.; Brody, A.L.; Li, Z.; Qazi, I.M.; Pavase, T.R.; Lv, L. A comprehensive review on the application of active packaging technologies to muscle foods. Food Control 2017 , 82 , 163–178. [ Google Scholar ] [ CrossRef ] Escamilla-García, M.; Calderón-Domínguez, G.; Chanona-Pérez, J.; Mendoza-Madrigal, A.G.; Di Pierro, P.; García-Almendárez, B.E.; Amaro-Reyes, A.; Regalado-González, C. Physical, structural, barrier, and antifungal characterization of chitosan–zein edible films with added essential oils. Int. J. Mol. Sci. 2017 , 18 , 2370. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Thakur, R.; Pristijono, P.; Bowyer, M.; Singh, S.P.; Scarlett, C.J.; Stathopoulos, C.E.; Vuong, Q.V. A starch edible surface coating delays banana fruit ripening. LWT 2019 , 100 , 341–347. [ Google Scholar ] [ CrossRef ][ Green Version ] Dehghani, S.; Hosseini, S.V.; Regenstein, J.M. Edible films and coatings in seafood preservation: A review. Food Chem. 2018 , 240 , 505–513. [ Google Scholar ] [ CrossRef ] [ PubMed ] Elsabee, M.Z.; Abdou, E.S. Chitosan based edible films and coatings: A review. Mater. Sci. Eng. C 2013 , 33 , 1819–1841. [ Google Scholar ] [ CrossRef ] Jost, V.; Kobsik, K.; Schmid, M.; Noller, K. Influence of plasticiser on the barrier, mechanical and grease resistance properties of alginate cast films. Carbohydr. Polym. 2014 , 110 , 309–319. [ Google Scholar ] [ CrossRef ] Ma, Z.; Garrido-Maestu, A.; Jeong, K.C. Application, mode of action, and in vivo activity of chitosan and its micro- and nanoparticles as antimicrobial agents: A review. Carbohydr. Polym. 2017 , 176 , 257–265. [ Google Scholar ] [ CrossRef ] Enujiugha, V.N.; Oyinloye, A.M. Protein-Lipid Interactions and the Formation of Edible Films and Coatings. In Encyclopedia of Food Chemistry ; Elsevier BV: Amsterdam, The Netherlands, 2019; pp. 478–482. [ Google Scholar ] Escamilla-García, M.; Delgado-Sánchez, L.F.; Ríos-Romo, R.A.; García-Almendárez, B.E.; Calderón-Domínguez, G.; Méndez-Méndez, J.V.; Amaro-Reyes, A.; Di Pierro, P.; Regalado-González, C. Effect of transglutaminase cross-linking in protein isolates from a mixture of two quinoa varieties with chitosan on the physicochemical properties of edible films. Coatings 2019 , 9 , 736. [ Google Scholar ] [ CrossRef ][ Green Version ] Caro, N.; Medina, E.; Díaz-Dosque, M.; López, L.; Abugoch, L.; Tapia, C. Novel active packaging based on films of chitosan and chitosan/quinoa protein printed with chitosan-tripolyphosphate-thymol nanoparticles via thermal ink-jet printing. Food Hydrocoll. 2016 , 52 , 520–532. [ Google Scholar ] [ CrossRef ] Musumeci, T.; Puglisi, G. 10. Antimicrobial agents. In Drug-Biomembrane Interaction Studies ; Pignatello, R., Ed.; Woodhead Publishing Series in Biomedicine; Woodhead Publishing: Sawston, UK; Cambridge, UK, 2013; pp. 305–333. ISBN 978-1-907568-05-3. [ Google Scholar ] El Asbahani, A.; Miladi, K.; Badri, W.; Sala, M.; Addi, E.H.A.; Casabianca, H.; El Mousadik, A.; Hartmann, D.; Jilale, A.; Renaud, F.N.R.; et al. Essential oils: From extraction to encapsulation. Int. J. Pharm. 2015 , 483 , 220–243. [ Google Scholar ] [ CrossRef ] [ PubMed ] Donsì, F.; Ferrari, G. Essential oil nanoemulsions as antimicrobial agents in food. J. Biotechnol. 2016 , 233 , 106–120. [ Google Scholar ] [ CrossRef ] Benjemaa, M.; Neves, M.A.; Falleh, H.; Isoda, H.; Ksouri, R.; Nakajima, M. Nanoencapsulation of Thymus capitatus essential oil: Formulation process, physical stability characterization and antibacterial efficiency monitoring. Ind. Crop. Prod. 2018 , 113 , 414–421. [ Google Scholar ] [ CrossRef ] Gonçalves, N.D.; Pena, F.D.L.; Sartoratto, A.; Derlamelina, C.; Duarte, M.C.T.; Antunes, A.E.C.; Prata, A.S. Encapsulated thyme ( Thymus vulgaris ) essential oil used as a natural preservative in bakery product. Food Res. Int. 2017 , 96 , 154–160. [ Google Scholar ] [ CrossRef ] Grande-Tovar, C.D.; Chaves-Lopez, C.; Serio, A.; Rossi, C.; Paparella, A. Chitosan coatings enriched with essential oils: Effects on fungi involved in fruit decay and mechanisms of action. Trends Food Sci. Technol. 2018 , 78 , 61–71. [ Google Scholar ] [ CrossRef ] Sadekuzzaman, M.; Mizan, F.R.; Kim, H.-S.; Yang, S.; Ha, S.-D. Activity of thyme and tea tree essential oils against selected foodborne pathogens in biofilms on abiotic surfaces. LWT 2018 , 89 , 134–139. [ Google Scholar ] [ CrossRef ] Yuan, G.; Chen, X.; Li, D. Chitosan films and coatings containing essential oils: The antioxidant and antimicrobial activity, and application in food systems. Food Res. Int. 2016 , 89 , 117–128. [ Google Scholar ] [ CrossRef ] Turasan, H.; Sahin, S.; Sumnu, G. Encapsulation of rosemary essential oil. LWT 2015 , 64 , 112–119. [ Google Scholar ] [ CrossRef ] Rizzo, V.; Amoroso, L.; Licciardello, F.; Mazzaglia, A.; Muratore, G.; Restuccia, C.; Lombardo, S.; Pandino, G.; Strano, M.G.; Mauromicale, G. The effect of sous vide packaging with rosemary essential oil on storage quality of fresh-cut potato. LWT 2018 , 94 , 111–118. [ Google Scholar ] [ CrossRef ] Okoh, O.; Sadimenko, A.; Afolayan, A.J. Comparative evaluation of the antibacterial activities of the essential oils of Rosmarinus officinalis L. obtained by hydrodistillation and solvent free microwave extraction methods. Food Chem. 2010 , 120 , 308–312. [ Google Scholar ] [ CrossRef ] Souza, V.G.; Pires, J.R.A.; Vieira, É.T.; Coelhoso, I.M.; Duarte, M.P.; Fernando, A.L. Activity of chitosan-montmorillonite bionanocomposites incorporated with rosemary essential oil: From in vitro assays to application in fresh poultry meat. Food Hydrocoll. 2019 , 89 , 241–252. [ Google Scholar ] [ CrossRef ] Tack, D.M.; Ray, L.; Griffin, P.M.; Cieslak, P.R.; Dunn, J.; Rissman, T.; Jervis, R.; Lathrop, S.; Muse, A.; Duwell, M.; et al. Preliminary incidence and trends of infections with pathogens transmitted commonly through food—Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2016–2019. MMWR Morb. Mortal. Wkly. Rep. 2020 , 69 , 509–514. [ Google Scholar ] [ CrossRef ] [ PubMed ] Elsohaimy, S.; Refaay, T.; Zaytoun, M. Physicochemical and functional properties of quinoa protein isolate. Ann. Agric. Sci. 2015 , 60 , 297–305. [ Google Scholar ] [ CrossRef ][ Green Version ] Ruiz, G.A.; Xiao, W.; Van Boekel, M.; Minor, M.; Stieger, M. Effect of extraction pH on heat-induced aggregation, gelation and microstructure of protein isolate from quinoa ( Chenopodium quinoa Willd). Food Chem. 2016 , 209 , 203–210. [ Google Scholar ] [ CrossRef ] Giosafatto, C.; Fusco, A.; Al-Asmar, A.; Mariniello, L. Microbial transglutaminase as a tool to improve the features of hydrocolloid-based bioplastics. Int. J. Mol. Sci. 2020 , 21 , 3656. [ Google Scholar ] [ CrossRef ] E Jensen, S.; Campbell, J.N. Peptidoglycan biosynthesis in Micrococcus luteus (sodonensis): Transglycosidase and phosphodiesterase activities in membrane preparations. J. Bacteriol. 1976 , 127 , 309–318. [ Google Scholar ] [ CrossRef ][ Green Version ] Deng, L.; Alexander, A.A.; Lei, S.; Anderson, J.S. The cell wall teichuronic acid synthetase (TUAS) is an enzyme complex located in the cytoplasmic membrane of Micrococcus luteus . Biochem. Res. Int. 2010 , 2010 , 1–8. [ Google Scholar ] [ CrossRef ][ Green Version ] Di Pierro, P.; Marquez, G.R.; Mariniello, L.; Sorrentino, A.; Villalonga, R.; Porta, R. Effect of transglutaminase on the mechanical and barrier properties of whey protein/pectin films prepared at complexation pH. J. Agric. Food Chem. 2013 , 61 , 4593–4598. [ Google Scholar ] [ CrossRef ] Olivares-Marin, I.K.; González-Hernádez, J.C.; Regalado-González, C.; Madrigal-Pérez, L.A. Saccharomyces cerevisiae exponential growth kinetics in batch culture to analyze respiratory and fermentative metabolism. Available online: https://pubmed.ncbi.nlm.nih.gov/30320748/ (accessed on 15 September 2020). Arredondo-Ochoa, T.; García-Almendárez, B.E.; Escamilla-García, M.; Martín-Belloso, O.; Rossi-Márquez, G.; Medina-Torres, L.; Regalado-González, C. Physicochemical and antimicrobial characterization of beeswax–starch food-grade nanoemulsions incorporating natural antimicrobials. Int. J. Mol. Sci. 2017 , 18 , 2712. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Zhao, X.; Liu, F.; Ma, C.; Yuan, F.; Gao, Y. Effect of carrier oils on the physicochemical properties of orange oil beverage emulsions. Food Res. Int. 2015 , 74 , 260–268. [ Google Scholar ] [ CrossRef ] Mathelié-Guinlet, M.; Grauby-Heywang, C.; Martin, A.; Février, H.; Moroté, F.; Vilquin, A.; Béven, L.; Delville, M.-H.; Cohen-Bouhacina, T. Detrimental impact of silica nanoparticles on the nanomechanical properties of Escherichia coli , studied by AFM. J. Colloid Interface Sci. 2018 , 529 , 53–64. [ Google Scholar ] [ CrossRef ][ Green Version ] Arzate-Vázquez, I.; Chanona-Pérez, J.; Calderón-Domínguez, G.; Térres-Rojas, E.; Garibay-Febles, V.; Martínez-Rivas, A.; Gutierrez-López, G.F. Microstructural characterization of chitosan and alginate films by microscopy techniques and texture image analysis. Carbohydr. Polym. 2012 , 87 , 289–299. [ Google Scholar ] [ CrossRef ] Hosseini, M.; Razavi, S.; Mousavi, M. Antimicrobial, physical and mechanical properties of chitosan-based films incorporated with thyme, clove and cinnamon essential oils. J. Food Process. Preserv. 2009 , 33 , 727–743. [ Google Scholar ] [ CrossRef ] Khorshidian, N.; Yousefi, M.; Khanniri, E.; Mortazavian, A.M. Potential application of essential oils as antimicrobial preservatives in cheese. Innov. Food Sci. Emerg. Technol. 2018 , 45 , 62–72. [ Google Scholar ] [ CrossRef ] Roy, J.C.; Salaün, F.; Giraud, S.; Ferri, A.; Guan, J. Surface behavior and bulk properties of aqueous chitosan and type-B gelatin solutions for effective emulsion formulation. Carbohydr. Polym. 2017 , 173 , 202–214. [ Google Scholar ] [ CrossRef ] Hong, I.K.; Kim, S.I.; Lee, S.B. Effects of HLB value on oil-in-water emulsions: Droplet size, rheological behavior, zeta-potential, and creaming index. J. Ind. Eng. Chem. 2018 , 67 , 123–131. [ Google Scholar ] [ CrossRef ] Guerra-Rosas, M.I.; Morales-Castro, J.; Ochoa-Martínez, L.A.; Salvia-Trujillo, L.; Martín-Belloso, O. Long-term stability of food-grade nanoemulsions from high methoxyl pectin containing essential oils. Food Hydrocoll. 2016 , 52 , 438–446. [ Google Scholar ] [ CrossRef ] Hoffmann, H.; Reger, M. Emulsions with unique properties from proteins as emulsifiers. Adv. Colloid Interface Sci. 2014 , 205 , 94–104. [ Google Scholar ] [ CrossRef ] [ PubMed ] Danaei, M.; Dehghankhold, M.; Ataei, S.; Davarani, F.H.; Javanmard, R.; Dokhani, A.; Khorasani, S.; Mozafari, M.R. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018 , 10 , 57. [ Google Scholar ] [ CrossRef ][ Green Version ] Dakhili, S.; Abdolalizadeh, L.; Hosseini, S.M.; Shojaee-Aliabadi, S.; Mirmoghtadaie, L. Quinoa protein: Composition, structure and functional properties. Food Chem. 2019 , 299 , 125161. [ Google Scholar ] [ CrossRef ] Wu, X.; Liu, Y.; Liu, A.; Wang, W. Improved thermal-stability and mechanical properties of type I collagen by cross-linking with casein, keratin and soy protein isolate using transglutaminase. Int. J. Biol. Macromol. 2017 , 98 , 292–301. [ Google Scholar ] [ CrossRef ] Yang, M.; Liu, F.; Tang, C.-H. Properties and microstructure of transglutaminase-set soy protein-stabilized emulsion gels. Food Res. Int. 2013 , 52 , 409–418. [ Google Scholar ] [ CrossRef ] Animasaun, I.; Adebile, E.; Fagbade, A. Casson fluid flow with variable thermo-physical property along exponentially stretching sheet with suction and exponentially decaying internal heat generation using the homotopy analysis method. J. Niger. Math. Soc. 2016 , 35 , 1–17. [ Google Scholar ] [ CrossRef ][ Green Version ] Dapueto, N.; Troncoso, E.; Mella, C.; Zúñiga, R. The effect of denaturation degree of protein on the microstructure, rheology and physical stability of oil-in-water (O/W) emulsions stabilized by whey protein isolate. J. Food Eng. 2019 , 263 , 253–261. [ Google Scholar ] [ CrossRef ] Hafedh, H.; Fethi, B.A.; Mejdi, S.; Emira, N.; Amina, B. Effect of Mentha longifolia L. ssp longifolia essential oil on the morphology of four pathogenic bacteria visualized by atomic force microscopy. Afr. J. Microbiol. Res. 2010 , 4 , 1122–1127. [ Google Scholar ] [ CrossRef ] Liu, Y.; Mollaeian, K.; Ren, J. Finite element modeling of living cells for AFM indentation-based biomechanical characterization. Micron 2019 , 116 , 108–115. [ Google Scholar ] [ CrossRef ] Zengin, H.; Baysal, A.H. Antibacterial and antioxidant activity of essential oil terpenes against pathogenic and spoilage-forming bacteria and cell structure-activity relationships evaluated by SEM microscopy. Molecules 2014 , 19 , 17773–17798. [ Google Scholar ] [ CrossRef ][ Green Version ] Di Cataldo, S.; Ficarra, E. Mining textural knowledge in biological images: Applications, methods and trends. Comput. Struct. Biotechnol. J. 2017 , 15 , 56–67. [ Google Scholar ] [ CrossRef ][ Green Version ] Reis, M.M.; Van Beers, R.; Al-Sarayreh, M.; Shorten, P.; Yan, W.Q.; Saeys, W.; Klette, R.; Craigie, C. Chemometrics and hyperspectral imaging applied to assessment of chemical, textural and structural characteristics of meat. Meat Sci. 2018 , 144 , 100–109. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Figure 1. Free essential oils antimicrobial effect on ( a ) Micrococcus luteus ; ( b ) Salmonella sp. Figure 1. Free essential oils antimicrobial effect on ( a ) Micrococcus luteus ; ( b ) Salmonella sp. Figure 2. Effect of biopolymers alone, combined, and incorporated with EOs on doubling time of ( a ) Micrococcus luteus ; ( b ) Salmonella sp. T d : doubling time; QP: quinoa protein; C: chitosan; T: thyme essential oil 0.5% ( v / v ); R: rosemary essential oil 1% ( v / v ). Data are presented as the mean ± standard deviation. a–d Indicate significant difference ( p < 0.001). Figure 2. Effect of biopolymers alone, combined, and incorporated with EOs on doubling time of ( a ) Micrococcus luteus ; ( b ) Salmonella sp. T d : doubling time; QP: quinoa protein; C: chitosan; T: thyme essential oil 0.5% ( v / v ); R: rosemary essential oil 1% ( v / v ). Data are presented as the mean ± standard deviation. a–d Indicate significant difference ( p < 0.001). Figure 3. Effect of biopolymers alone, combined, and incorporated with EOs on the specific growth rate of ( a ) Micrococcus luteus ; ( b ) Salmonella sp. μ: specific growth rate; QP: quinoa protein; C: chitosan; T: thyme essential oil 0.5% ( v / v ); R: rosemary essential oil 1% ( v / v ). Data are presented as the mean ± standard deviation. a–e Indicate significant difference ( p < 0.01). Figure 3. Effect of biopolymers alone, combined, and incorporated with EOs on the specific growth rate of ( a ) Micrococcus luteus ; ( b ) Salmonella sp. μ: specific growth rate; QP: quinoa protein; C: chitosan; T: thyme essential oil 0.5% ( v / v ); R: rosemary essential oil 1% ( v / v ). Data are presented as the mean ± standard deviation. a–e Indicate significant difference ( p < 0.01). Figure 4. Antimicrobial activity of filmogenic suspensions with and without thyme and rosemary essential oils. ( a ) Micrococcus luteus , ( b ) Salmonella sp. Figure 4. Antimicrobial activity of filmogenic suspensions with and without thyme and rosemary essential oils. ( a ) Micrococcus luteus , ( b ) Salmonella sp. Figure 5. Rheology of filmogenic suspensions C:QP, C:QP:T, and C:QP:R. ( a ) Apparent viscosity vs. shear rate; ( b ) Stress vs. shear rate. QP: quinoa protein; C: chitosan; T: essential oil of thyme; A: rosemary essential oil. Data are presented as the mean ± standard deviation. Figure 5. Rheology of filmogenic suspensions C:QP, C:QP:T, and C:QP:R. ( a ) Apparent viscosity vs. shear rate; ( b ) Stress vs. shear rate. QP: quinoa protein; C: chitosan; T: essential oil of thyme; A: rosemary essential oil. Data are presented as the mean ± standard deviation. Figure 6. Visualization by AFM of the antimicrobial effect on Micrococcus luteus of EOs incorporated into the filmogenic suspension. ( a ) Control, ( b ) Rosemary essential oil, ( c ) Thyme essential oil. Figure 6. Visualization by AFM of the antimicrobial effect on Micrococcus luteus of EOs incorporated into the filmogenic suspension. ( a ) Control, ( b ) Rosemary essential oil, ( c ) Thyme essential oil. Figure 7. Visualization by AFM of the antimicrobial effect on Salmonella sp. of EOs incorporated into the filmogenic suspension. ( a ) Control, ( b ) Rosemary essential oil, ( c ) Thyme essential oil. Figure 7. Visualization by AFM of the antimicrobial effect on Salmonella sp. of EOs incorporated into the filmogenic suspension. ( a ) Control, ( b ) Rosemary essential oil, ( c ) Thyme essential oil. Figure 8. Atomic force micrographs image analysis on the effect of filmogenic suspensions with and without essential oils of Salmonella sp. and M. luteus. ( a ) Entropy (u.a: arbitrary units), ( b ) fractal dimension, and ( c ) roughness. Figure 8. Atomic force micrographs image analysis on the effect of filmogenic suspensions with and without essential oils of Salmonella sp. and M. luteus. ( a ) Entropy (u.a: arbitrary units), ( b ) fractal dimension, and ( c ) roughness. Table 1. Z potential of filmogenic suspensions. Table 1. Z potential of filmogenic suspensions. Z Potential (mV) Sample Day 0 Day 10 C:QP −47.69 ± 3.19 ab −50.60 ± 4.04 ab C:QP:T −46.86 ± 4.38 ab −52.01 ± 4.04 ab C:QP:R −46.21 ± 3.83 a −54.13 ± 4.73 b QP: Quinoa protein; C: Chitosan; T: thyme essential oil, R: rosemary essential oil. Mean values in the same column showing the same lowercase letter are not significantly different ( p < 0.01). Table 2. Particle size and polydispersity index of filmogenic suspensions. Table 2. Particle size and polydispersity index of filmogenic suspensions. Sample Particle Size (nm) Particle Size Intensity (%) PDI C:QP 597.56 ± 37.59 a 89.41 ± 2.66 a 0.51 ± 0.07 a 97.55 ± 10.79 b 7.28 ± 0.49 b C:QP:T 677.02 ± 50.34 c 73.35 ± 4.16 c 0.80 ± 0.04 b 153.58 ± 13.76 b 22.04 ± 2.60 d C:QP:R 672.98 ± 35.08 c 79.79 ± 3.74 e 0.79 ± 0.05 b 120.93 ± 20.96 b 16.17 ± 3.04 d QP: Quinoa protein; C: Chitosan; T: thyme essential oil, R: rosemary essential oil. Mean values in the same column showing the same lowercase letter are not significantly different ( p < 0.01). Table 3. Rheological properties of filmogenic suspensions. Table 3. Rheological properties of filmogenic suspensions. Sample σ o (×10 3 Pa) η (×10 3 Pa.s) R 2 PQ:C 11.23 ± 1.42 a 2.82 ± 0.15 a 0.997 C:PQ–T 11.51 ± 0.50 a 2.80 ± 0.02 ab 0.995 C:PQ–R 9.96 ± 0.24 a 3.04 ± 0.002 ac 0.998 σ o : Elastic limit; η: Apparent viscosity; QP: Quinoa protein; C: Chitosan; T: thyme essential oil, R: rosemary essential oil. Mean values in the same column showing the same lowercase letter are not significantly different ( p < 0.01). © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/ ). Share and Cite MDPI and ACS Style Escamilla-García, M.; Ríos-Romo, R.A.; Melgarejo-Mancilla, A.; Díaz-Ramírez, M.; Hernández-Hernández, H.M.; Amaro-Reyes, A.; Pierro, P.D.; Regalado-González, C. Rheological and Antimicrobial Properties of Chitosan and Quinoa Protein Filmogenic Suspensions with Thyme and Rosemary Essential Oils. Foods 2020, 9, 1616. https://doi.org/10.3390/foods9111616 AMA Style Escamilla-García M, Ríos-Romo RA, Melgarejo-Mancilla A, Díaz-Ramírez M, Hernández-Hernández HM, Amaro-Reyes A, Pierro PD, Regalado-González C. Rheological and Antimicrobial Properties of Chitosan and Quinoa Protein Filmogenic Suspensions with Thyme and Rosemary Essential Oils. Foods. 2020; 9(11):1616. https://doi.org/10.3390/foods9111616 Chicago/Turabian Style Escamilla-García, Monserrat, Raquel A. Ríos-Romo, Armando Melgarejo-Mancilla, Mayra Díaz-Ramírez, Hilda M. Hernández-Hernández, Aldo Amaro-Reyes, Prospero Di Pierro, and Carlos Regalado-González. 2020. "Rheological and Antimicrobial Properties of Chitosan and Quinoa Protein Filmogenic Suspensions with Thyme and Rosemary Essential Oils" Foods9, no. 11: 1616. https://doi.org/10.3390/foods9111616 Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here . Article Metrics
https://www.mdpi.com/2304-8158/9/11/1616/xml
1 Chronicles 2 (RSV) - The sons of Onam: Shammai 1 Chronicles 2 - The sons of Onam: Sham'mai and Jada. The sons of Sham'mai: Nadab and Abi'shur. Prev Chapter Help Quick Nav Advanced Options Next Chapter Copy Options Cite Share Print 1 Chronicles 2 :: Revised Standard Version (RSV) Strong's Red Letter Verse Paragraph Audio Bibles KJV (Narrated) NKJV (Narrated) NKJV (Dramatized) NLT (Dramatized) NIV (Narrated) NIV (Dramatized) ESV (Narrated) NASB95 (Narrated) RVR60 (Español) NAV (Arabic) Genealogy: Twelve Sons of Jacob (Israel) ( Gen 35:23–26 ; 46:8–25 ) Tools 1Ch 2:1 ¶ 1Ch 2:1 - These are the sons of Israel: Reuben, Simeon, Levi, Judah, Is'sachar, Zeb'ulun, Tools 1Ch 2:2 1Ch 2:2 - Dan, Joseph, Benjamin, Naph'tali, Gad, and Asher. ( Rth 4:18–22 ; Mat 1:2–6 ; Luk 3:31–33 ) Tools 1Ch 2:3 1Ch 2:3 - The sons of Judah: Er, Onan, and Shelah; these three Bath-shu'a the Canaanitess bore to him. Now Er, Judah's first-born, was wicked in the sight of the LORD, and he slew him. Tools 1Ch 2:4 1Ch 2:4 - His daughter-in-law Tamar also bore him Perez and Zerah. Judah had five sons in all. Tools 1Ch 2:5 ¶ 1Ch 2:5 - The sons of Perez: Hezron and Hamul. Tools 1Ch 2:6 1Ch 2:6 - The sons of Zerah: Zimri, Ethan, Heman, Calcol, and Dara, five in all. Tools 1Ch 2:7 1Ch 2:7 - The sons of Carmi: Achar, the troubler of Israel, who transgressed in the matter of the devoted thing; Tools 1Ch 2:8 1Ch 2:8 - and Ethan's son was Azari'ah. Genealogy of David Tools 1Ch 2:9 ¶ 1Ch 2:9 - The sons of Hezron, that were born to him: Jerah'meel, Ram, and Chelu'bai. Tools 1Ch 2:10 1Ch 2:10 - Ram was the father of Ammin'adab, and Ammin'adab was the father of Nahshon, prince of the sons of Judah. Tools 1Ch 2:11 1Ch 2:11 - Nahshon was the father of Salma, Salma of Bo'az, Tools 1Ch 2:12 1Ch 2:12 - Bo'az of Obed, Obed of Jesse. Tools 1Ch 2:13 1Ch 2:13 - Jesse was the father of Eli'ab his first-born, Abin'adab the second, Shim'ea the third, Tools 1Ch 2:14 1Ch 2:14 - Nethan'el the fourth, Raddai the fifth, Tools 1Ch 2:15 1Ch 2:15 - Ozem the sixth, David the seventh; Tools 1Ch 2:16 1Ch 2:16 - and their sisters were Zeru'iah and Ab'igail. The sons of Zeru'iah: Abi'shai, Jo'ab, and As'ahel, three. Tools 1Ch 2:17 1Ch 2:17 - Ab'igail bore Ama'sa, and the father of Ama'sa was Jether the Ish'maelite. Tools 1Ch 2:18 ¶ 1Ch 2:18 - Caleb the son of Hezron had children by his wife Azu'bah, and by Jer'ioth; and these were her sons: Jesher, Shobab, and Ardon. Tools 1Ch 2:19 1Ch 2:19 - When Azu'bah died, Caleb married Ephrath, who bore him Hur. Tools 1Ch 2:20 1Ch 2:20 - Hur was the father of Uri, and Uri was the father of Bez'alel. Tools 1Ch 2:21 ¶ 1Ch 2:21 - Afterward Hezron went in to the daughter of Machir the father of Gilead, whom he married when he was sixty years old; and she bore him Segub; Tools 1Ch 2:22 1Ch 2:22 - and Segub was the father of Ja'ir, who had twenty-three cities in the land of Gilead. Tools 1Ch 2:23 1Ch 2:23 - But Geshur and Aram took from them Havvoth-ja'ir, Kenath and its villages, sixty towns. All these were descendants of Machir, the father of Gilead. Tools 1Ch 2:24 1Ch 2:24 - After the death of Hezron, Caleb went in to Eph'rathah, the wife of Hezron his father, and she bore him Ashhur, the father of Teko'a. Tools 1Ch 2:25 ¶ 1Ch 2:25 - The sons of Jerah'meel, the first-born of Hezron: Ram, his first-born, Bunah, Oren, Ozem, and Ahi'jah. Tools 1Ch 2:26 1Ch 2:26 - Jerah'meel also had another wife, whose name was At'arah; she was the mother of Onam. Tools 1Ch 2:27 1Ch 2:27 - The sons of Ram, the first-born of Jerah'meel: Ma'az, Jamin, and Eker. Tools 1Ch 2:28 1Ch 2:28 - The sons of Onam: Sham'mai and Jada. The sons of Sham'mai: Nadab and Abi'shur. Tools 1Ch 2:29 1Ch 2:29 - The name of Abi'shur's wife was Ab'ihail, and she bore him Ahban and Molid. Tools 1Ch 2:30 1Ch 2:30 - The sons of Nadab: Seled and Ap'pa-im; and Seled died childless. Tools 1Ch 2:31 1Ch 2:31 - The sons of Ap'pa-im: Ishi. The sons of Ishi: Sheshan. The sons of Sheshan: Ahlai. Tools 1Ch 2:32 1Ch 2:32 - The sons of Jada, Sham'mai's brother: Jether and Jonathan; and Jether died childless. Tools 1Ch 2:33 1Ch 2:33 - The sons of Jonathan: Peleth and Zaza. These were the descendants of Jerah'meel. Tools 1Ch 2:34 1Ch 2:34 - Now Sheshan had no sons, only daughters; but Sheshan had an Egyptian slave, whose name was Jarha. Tools 1Ch 2:35 1Ch 2:35 - So Sheshan gave his daughter in marriage to Jarha his slave; and she bore him Attai. Tools 1Ch 2:36 1Ch 2:36 - Attai was the father of Nathan and Nathan of Zabad. Tools 1Ch 2:37 1Ch 2:37 - Zabad was the father of Ephlal, and Ephlal of Obed. Tools 1Ch 2:38 1Ch 2:38 - Obed was the father of Jehu, and Jehu of Azari'ah. Tools 1Ch 2:39 1Ch 2:39 - Azari'ah was the father of Helez, and Helez of Ele-a'sah. Tools 1Ch 2:40 1Ch 2:40 - Ele-a'sah was the father of Sismai, and Sismai of Shallum. Tools 1Ch 2:41 1Ch 2:41 - Shallum was the father of Jekami'ah, and Jekami'ah of Eli'shama. Tools 1Ch 2:42 ¶ 1Ch 2:42 - The sons of Caleb the brother of Jerah'meel: Mare'shah his first-born, who was the father of Ziph. The sons of Mare'shah: Hebron. Tools 1Ch 2:43 1Ch 2:43 - The sons of Hebron: Korah, Tap'puah, Rekem, and Shema. Tools 1Ch 2:44 1Ch 2:44 - Shema was the father of Raham, the father of Jor'ke-am; and Rekem was the father of Sham'mai. Tools 1Ch 2:45 1Ch 2:45 - The son of Sham'mai: Ma'on; and Ma'on was the father of Bethzur. Tools 1Ch 2:46 1Ch 2:46 - Ephah also, Caleb's concubine, bore Haran, Moza, and Gazez; and Haran was the father of Gazez. Tools 1Ch 2:47 1Ch 2:47 - The sons of Jah'dai: Regem, Jotham, Geshan, Pelet, Ephah, and Sha'aph. Tools 1Ch 2:48 1Ch 2:48 - Ma'acah, Caleb's concubine, bore Sheber and Tir'hanah. Tools 1Ch 2:49 1Ch 2:49 - She also bore Sha'aph the father of Madman'nah, Sheva the father of Machbe'nah and the father of Gib'e-a; and the daughter of Caleb was Achsah. Tools 1Ch 2:50 1Ch 2:50 - These were the descendants of Caleb. The sons of Hur the first-born of Eph'rathah: Shobal the father of Kir'iath-je'arim, Tools 1Ch 2:51 1Ch 2:51 - Salma, the father of Bethelem, and Hareph the father of Beth-gader. Tools 1Ch 2:52 1Ch 2:52 - Shobal the father of Kir'iath-je'arim had other sons: Haro'eh, half of the Menu'hoth. Tools 1Ch 2:53 1Ch 2:53 - And the families of Kir'iath-je'arim: the Ithrites, the Puthites, the Shu'mathites, and the Mish'ra-ites; from these came the Zo'rathites and the Esh'taolites. Tools 1Ch 2:54 1Ch 2:54 - The sons of Salma: Bethlehem, the Netoph'athites, At'roth-beth-jo'ab, and half of the Man'aha'thites, the Zorites. Tools 1Ch 2:55 1Ch 2:55 - The families also of the scribes that dwelt at Jabez: the Ti'rathites, the Shim'e-athites, and the Su'cathites. These are the Ken'ites who came from Hammath, the father of the house of Rechab. Interlinear Bibles Cross-Refs Commentaries Dictionaries Misc Interlinear Bibles Cross-References Commentaries Dictionaries Misc Close Tools ← Prior Chapter Next Chapter → ← Prior Book Next Book → Back to Top Downloaded from the Oxford Text Archive and used with permission. The following header is required to be posted: Source: Transcribed from: The Holy Bible: Revised Standard Version containing the Old and New Testaments, translated from the original tongues: being the version set forth A.D. 1611, revised A.D. 1881-1885 and A.D. 1901: compared with the most ancient authorities and revised A.D. 1946-52. — 2nd ed. of New Testament A.D. 1971. There should be enough in the rest of the description to identify the text. Language: English Availability: Freely available for non-commercial use provided that this header is included in its entirety with any copy distributed. Pericope
https://www.blueletterbible.org/rsv/1ch/2/28/s_340028
Speckled sussexes with allergies? | BackYard Chickens - Learn How to Raise Chickens Help please. I have 5 speckled sussex, about 6 weeks old. They came from Cackle originally but I bought them some the person who ordered them. All their... Thread starter monkeemakr Start date Jul 26, 2011 1 2 Next 1 of 2 Go to page Go Next Last ••• More options Who Replied? Date sort Score sort Jul 26, 2011 #1 monkeemakr Chirping 8 Years Jun 28, 2011 216 1 89 Swansea, SC Help please. I have 5 speckled sussex, about 6 weeks old. They came from Cackle originally but I bought them some the person who ordered them. All their birds looked good and healthy, clean surroundings and the chicks looked good. I noticed on the way home, one was kind of tired looking but didn't look really unusual for the stress of an hour long drive. When we got home, they were all running around like normal. the next day I noticed that the one that had been tired seemed a little listless and usually stayed away from the others, but was eating and drinking fine. We have been in 100+ heat here in SC so I kept a close eye and put a fan on them in case it was the heat getting to her. Now 3 of them seem to have sneezes and a little bit of swelling around the eyes, just like humans do when they have allergies. I use wheat straw for bedding and put down agri-lime and DE beneath it, with a little DE in a spot for dust baths. I'm hoping this is just allergies and not some respiratory problem. When I got them, they were in something like a playpen on a grass lawn. I thought at first when I saw one sneeze that they were trying to crow. I hate to put them on anitbiotics if I don't have to, but don't want to risk an outbreak of disease, or losing my sweet speckles. Thanks. Reply Jul 26, 2011 #2 Judy Crowing Premium Feather Member 10 Years Feb 5, 2009 34,024 624 448 South Georgia Most respiratory diseases in chickens are viral so antibiotics will not affect them, they only prevent secondary infection. Reply Jul 26, 2011 Thread starter #3 monkeemakr Chirping 8 Years Jun 28, 2011 216 1 89 Swansea, SC Thanks ddawn. Any suggestions on dealing with the viral or just making them more comfortable? Reply Jul 26, 2011 #4 Daisy668 Chirping 8 Years Jul 25, 2011 134 0 79 It may be a allergic reaction. Do you know what feed they were on before you got them? If its an allergic reaction to the feed you may want to find out the feed they had before and keep them on that. Hope they get better. Daisy. xx Reply Jul 26, 2011 Thread starter #5 monkeemakr Chirping 8 Years Jun 28, 2011 216 1 89 Swansea, SC Hi Daisy, They were on the same food from the same local milling company that I use. I am kind of wondering if maybe my son (who did the last DE and lime treatment) may have gotten some dust in their lungs and eyes now. I'm hoping it's not some of the respiratory diseases I've read about. Scary stuff that. One thing for sure, I have been giving serious consideration to closing my flock except for hatching eggs, and this definitely urges that on! Reply Jul 26, 2011 #6 Daisy668 Chirping 8 Years Jul 25, 2011 134 0 79 Hi, If its that they got dust in their eyes maybe try washing them down and checking their eyes for bits in them. If it was respiratory disease it would have spreaded to all of them quite quickly so i think your safe their. Its a shame Don't give up on them but its quite exciting hatching eggs so i see your point... Hope this helps. Daisy. xx Last edited: Jul 26, 2011 Reply Jul 26, 2011 #7 crazyhen Crowing 11 Years Aug 26, 2008 3,196 105 264 mtns of ,NC. If you find it is not an allergy look up a med called Denaguard. If it is MS a viral disease it can be transferred through the eggs. Good luck with your flock. Gloria Jean Reply Jul 26, 2011 Thread starter #8 monkeemakr Chirping 8 Years Jun 28, 2011 216 1 89 Swansea, SC Thanks Daisy, that's encouraging. I have about 50 other birds in my flock, not counting the ducks and turkeys, so that's encouraging. Thank goodness we put the speckleds in pen by themselves when we got them, just to be on the safe side. So far, none of the other chickens have shown any sign of anything wrong. And I will check out that Denagard. Have you used it before? Reply Jul 26, 2011 #9 crazyhen Crowing 11 Years Aug 26, 2008 3,196 105 264 mtns of ,NC. I have been using it as a preventative since I lost my flock last yr to MS. It was insiduous. My hens had tested clear of disease three months before and then the sneezing and clear drainage started. I lost one hen quickly and then the others seem to get over it. Then we had cold weather and it started up again. I had the vet ck them and it was MS. He said I could keep the hens but I would have to have a closed flock. Thats for eggs and hens. I would not catch the disease through meat or eggs. I could not watch then weaken one by one and die so I had the flock culled. It about killed me. I cleaned and repaired the coops and wire. Cleaned out the runs. Used clorox and then vikron-S to finish the job. I put in new sand in the run. Where I did not put sand I limed , tilled and planted alfalfa and clover. someone told me about Denagard. I looked it up. I use 8cc per gal of water for three days every two to three wks as a preventative. If I had the virus again I would use more. It seems that ms is very prevalent. Good luck with your flock. If they over it they would be carriers for life. Have a vet check one while they are sick. You really need to know what is going on with these. It is catching to other birds. Gloria Jean Reply Jul 26, 2011 Thread starter #10 monkeemakr Chirping 8 Years Jun 28, 2011 216 1 89 Swansea, SC Thanks Gloria Jean. I'm going to order that stuff whether they have it or not, sounds like it's worth its weight in gold just as a preventative. I'm trying now to find a vet around Columbia SC that knows something about chickens. The good news is that my son says he did get a lot of DE on them when he dusted, but want to make sure. Told him from now on, dust the pen when they're not in it! Reply 1 2 Next 1 of 2 Go to page Go Next Last Smilies Bold Text color Font size 9 10 12 15 18 22 26 Font family Arial Book Antiqua Courier New Georgia Tahoma Times New Roman Trebuchet MS Verdana Italic List Ordered list Unordered list Indent Outdent Alignment Align left Align center Align right Justify text More options… Insert image Quote Insert link Media More options… Drafts Save draft Delete draft More options… Preview Strike-through Underline Inline spoiler Paragraph format Normal Heading 1 Heading 2 Heading 3 Inline code Insert GIF Gallery embed AMS: Article | Page | Series embed Insert horizontal line Insert table Spoiler Code Undo Toggle BB code Remove formatting Write your reply...
https://www.backyardchickens.com/threads/speckled-sussexes-with-allergies.546682/
2.7401 14/247-14:17:02.590 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-14:18:33.594 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-14:21:32.598 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1478 0.4508 1122 2.7377 14/247-14:23:02.598 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-14:24:32.602 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-14:32:02.617 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1478 0.4508 1123 2.7401 14/247-14:33:32.625 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-14:33:33.625 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-14:44:02.648 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-14:48:33.660 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF 1479 0.4511 1122 2.7377 14/247-14:56:02.676 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF 1479 0.4511 1123 2.7401 14/247-15:03:32.691 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF 1479 0.4511 1122 2.7377 14/247-15:03:33.699 ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-15:14:02.715 ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-15:15:32.719 ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-15:18:32.727 ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-15:18:33.730 ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-15:24:32.742 ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-15:33:32.762 ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1478 0.4508 1123 2.7401 14/247-15:33:33.766 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1478 0.4508 1123 2.7401 14/247-15:35:02.766 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-15:39:32.773 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1124 2.7426 14/247-15:42:32.785 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-15:45:32.789 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1124 2.7426 14/247-15:47:02.793 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-15:48:33.797 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-15:51:32.801 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-16:03:33.836 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-16:08:02.836 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-16:18:33.867 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-16:32:02.895 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-16:33:33.902 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-16:38:02.910 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-16:48:33.938 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-16:51:32.941 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-17:02:02.965 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-17:03:33.973 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF 1479 0.4511 1121 2.7352 14/247-17:05:02.973 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF 1479 0.4511 1122 2.7377 14/247-17:11:02.984 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF 1479 0.4511 1121 2.7352 14/247-17:18:34.004 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-17:33:34.043 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-17:38:03.043 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-17:48:34.078 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-17:57:33.094 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-18:03:34.109 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-18:05:03.113 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1124 2.7426 14/247-18:17:03.141 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-18:18:34.145 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-18:24:33.156 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-18:33:34.184 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-18:35:03.180 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-18:48:34.215 ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-18:50:03.215 ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-18:53:03.223 ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-18:57:33.230 ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1124 2.7426 14/247-19:03:33.246 ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-19:03:34.250 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1123 2.7401 14/247-19:08:03.254 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-19:18:34.285 ON ON ON ON ON OFF OFF OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1122 2.7377 14/247-19:24:33.297 ON ON ON ON ON OFF OFF OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-19:33:34.320 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1479 0.4511 1121 2.7352 14/247-19:41:03.332 ON ON ON OFF ON ON ON OFF ON OFF
https://lasp.colorado.edu/maven/sdc/public/data/sites/site-20170421T223151/anc/eng/sasm1/sci_anc_sasm114_246_248.drf
Connecting Climate Change and Health Equity in Public Health Agencies | ASTHO Connecting Climate Change and Health Equity in Public Health Agencies This episode focuses on the Washington State Department of Health’s (WA DOH) approach to understanding and addressing climate and equity concerns. Guests discuss the need to continuously make connections between climate change and public health, the role of community engagement and partnerships in advancing these efforts, the use of existing networks to reach at-risk populations, and how to stay grounded in the public health messaging on climate change. WA DOH discusses some of its recent initiatives for engaging environmental justice communities, shares its approach for training and coordinating resiliency planning, and highlights ways the department raises awareness of the climate’s impact on health. Show Notes Guests Umair Shah, MD, MPH, Secretary of Health, Washington State Department of Health Rad Cunningham, MPH, MPA, Senior Epidemiologist, Washington State Department of Health Resources WA DOH Climate and Health webpage WA State Environmental Justice Task Force Final Report ASTHO Report : Climate Change and Environmental Justice: A Snapshot of Jurisdiction Activities Transcript ROBERT JOHNSON:This is Public Health Review. I'm Robert Johnson. UMAIR SHAH:There is so much work to be done. Let's not get stuck in the left-right dynamic, the political piece where—ultimately, we know public health is political, but we've got to be able to rise above that. RAD CUNNINGHAM:There's going to be a pretty massive change in what the public health community is going to be able to do on climate change because of these new opportunities coming up. JOHNSON:Welcome to Public Health Review, a podcast brought to you by the Association of State and Territorial Health Officials. With each episode, we examine what health departments are doing to tackle the most pressing public health issues facing our states and territories. Today: climate change hurts some communities more than others. Its impacts are felt the most in places where people already suffer from hardships that can derail their attempts to get and stay healthy. Across the country, public health leaders are looking for ways to demonstrate the connections between increasingly common natural disasters and the public health of their communities. Rad Cunningham is an epidemiologist at the Washington State Department of Health. He's along later to tell us how his department is working to make those connections across all of its programs. But first, we hear from Washington's Secretary of Health, Dr. Umair Shah, about the importance of this work and the need to forge ahead through the politics that can often dampen progress. SHAH:I'll say, first and foremost, that climate change threatens everybody's health, but it seems to accentuate that impact on certain groups more than others. And that may be those who have less resources to cope and adapt to a changing environment or climate, or maybe people that have less income, people that may be disproportionately impacted by pollution or hazards that are in the environment. So, when we bring environmental social justice movement together, we oftentimes are really trying to connect not just what's happening in policy and theory, but to communities that are impacted. JOHNSON:Given the connections, what have you decided to do about it in Washington State? SHAH:Yeah, so you know, whether it goes back to the wildfire smoke or the 2021 heat dome, where we had, unfortunately, 150+ individuals with heat-related deaths and hundreds of hospitalizations, whether it's flooding—whatever the calamity that we've had, our real goal is to, one, make sure that we give the connection of climate and health, to remind everybody that the climate is changing, right. And articulating that change is, I think, the first step is that we've got to continue to remind everybody that it is happening. And so, when you have an event like a hurricane in the Gulf Coast, or you've got a winter storm, or you've got some extreme drought, that these are not disconnected events. This is exactly what you will start to see with the changing climate—you're going to start to see extreme weather events. And, again, people need to make the connection. What I always love to say is that we've spent a lot of time collecting the dots, it's important for us to spend as much time connecting those dots so people can understand what is happening around them. And then it's important for us to invest. And it's really about what are the sustainable things that we can do by investing in real environmental-friendly policies. We've already done a lot of that. So, there's a lot of broad support outside even public health. We're just talking about the state itself, the governor and all the state agencies saying, "We are going to do everything we can to take on climate change." But then, within the Department of Health, it's things like making sure that as part of our work with health equity or anti-racism, environmental justice, that that conversation continues to happen at a federal level, at a state level, at a local community level. And what's unique about Washington is that we're also able to bring the investments to staff members, to people. So, we've actually hired people to be able to work through some of these issues. We put investments in the very programs on environmental health and the programs around climate change. So, it's really about communicating, it's listening, it's the messaging. But I think the most important thing is to create the space for our staff members, and even our partners, to be able to come together and say, "There is something, there is a problem, and we've got to work on it." JOHNSON:What about the team implementing these ideas? Did any of them require new training? SHAH:Well, yeah. I mean, it depends on who they are, right? So, if you've gotten newer people that maybe haven't been in the space, and you do, you may need to actually train them. And what we have been doing is to work towards recruiting people. So, one of the things that you and I have talked about previously is that our cornerstone values at the department are equity, innovation, engagement. So, when we have three cornerstone values and equity is the first value, it is not surprising that, when we're hiring people, we want to make sure that we're hiring people who understand that equity is important to us as an agency. And we want people to recognize the importance of innovation, we want people to recognize the importance of engaging partners and community members as well as each other. So, all of that comes together. Newer people may have some of that environmental and that health equity training, and that's great; but we also want to make sure that we continue to provide our staff members the tools so that they can be ready for this changing system that all of us in public health are really a part of. JOHNSON:So, are you tracking every climate event and then doing some kind of overlay with other issues where you've identified health equity concerns? How are you doing this? SHAH:Yeah, it's a combination of looking at what the assets and resources are across the state and then trying to map it into where we're projecting—for example, future heating degree days, cooling degree days—and trying to put those projections, from a climate standpoint, onto where the assets are. Or where there may not be assets, right, where you're missing something. And then, working with other agencies, whether it's at the state level or local level, and say, "Here's where the maps are. Here's where the visualization is. Here's where we are seeing either opportunities or gaps." And we've got to work together on trying to, you know, try to fill those gaps. JOHNSON:We can't forget about partnerships. How do those figure into this equation? SHAH:Well, yeah, absolutely. You know, I'd be remiss if I didn't mention our local health departments, our local public health. As you know, I spent the vast majority of my career in public health in a local health department. And you know, it happens on the ground, it happens in local communities. And so, we have to absolutely work with our local health departments in making sure that we're moving forward with our work. I do want to just make one quick comment about community because, ultimately, we've got to also make sure that our work is visible to our community members. And that means not just people who are representing community, but also the end user, the end community member. And so, that means oftentimes community-rooted organizations. And so, we're really making sure that we're taking an active role in how do we involve community with listening sessions, and really working around what does climate really truly mean to your health and wellbeing, for your family. And that's the kind of thing that people really—it resonates with them, but also it helps them really understand what's happening around our environment, and how that may impact their community. JOHNSON:Some of your colleagues can outwardly make this connection, others maybe politically are not able to do that. What is your advice to everyone listening about how to approach connecting climate change and health equity? SHAH:Yeah, I think we have to stay focused on public health, and we have to stay focused on what the science shows us, the data show us. I think we have to also remind ourselves that no matter what the environment is, whether it's a more blue environment, a more red environment, maybe an environment where we may have less receptivity for the words even, "climate change" or "the impact of climate on health," that we have to engage people. That may be our policymakers, that may be partners on the ground, and maybe each other. But ultimately, there is so much work to be done. Let's not get stuck in the left-right dynamic, the political piece where—ultimately, we know public health is political, but we've got to be able to rise above that. And so remember, Robert, I was in a different state. You know, I came from a place where there are different ways of looking at the world and looking at the nomenclature of climate change or climate and health. And yet, even there, we were able to do so much. Anybody in public health cannot just say, "Look, I can't do anything here." There's something you can always do. There's always something. Whether it's recycling, or whether you're, you know, going to try to talk about the business interest or the financial reasons that we're doing certain things, whether we're turning off our lights, whether we're doing certain things to catch water and making sure that we're reusing that water—there's so many green-friendly and environmentally-friendly, sound things that we can do ourselves as public health agencies, and public health leaders, and articulate that to our communities. So, I think no matter where you are—whether east, west, south, north, whether it's, you know, communities that oftentimes may not be thinking about this—I will say the one thing is that all of us have been impacted by climate and its impact on health. JOHNSON:Rad Cunningham manages the climate change and health section at the Washington State Department of Health. He says there's no doubting the disproportionate effects of climate change on people already facing a mountain of daily challenges. CUNNINGHAM:So, when I'm trying to talk about that, I just want to make sure that people understand that the people who are getting impacted first and worst by environmental conditions in general—those environmental conditions are just being exacerbated by climate change, so those same environmental justice communities are often the ones that are being impacted first and worse by climate change. And climate change is unique risk. So, it's not going to be exactly the same. But you know, there are, you know, where the flooding is a risk, where wildfire smoke is a persistent problem, you know, where there's not a lot of resilience to extreme heat—those are areas where we think people are really the most vulnerable. And we want to, you know, access those areas' person. Same with our homeless population. So, we have a homelessness coordinator now with DOH, and we've been coordinating with that person, just making sure that those populations are—you know, it's hard to reach them, it's hard to get services to them—we want to make sure that we think about that group when we're planning all of our rest of our programming. JOHNSON:Thinking about planning, how do you integrate health equity into your climate policies there in Washington? CUNNINGHAM:Yeah, so, I think the most important piece of integrating health equity in the climate policy is community engagement. So, reaching out to communities and listening to what they say. And sometimes that's really open ended. Because if you really want to let them drive these, you know, how we do climate resilience, you've got to go to them with an open mind, and not with a plan that's 90% done, right. So, we want to make sure we get to those communities, you know, engage those communities through partnerships. So, one thing we've heard through a partner we work with, which is Front and Centered, which is a—Front and Centered, they've called themselves a grass tops organization, where they, you know, they're connected with a lot of the grassroots organizations, but they sort of, you know, engage with all of them. And when they talk to us, sometimes they say, "Department of Health, we need to have this conversation and you can't be there, because it's going to change the discussion in the room." And so sometimes, you know, we need to partner just to be able to listen, or be able to create a space where we can listen appropriately to the concerns of the communities. And then, we need to demonstrate that we are listening and responding to that. And that's how we start building trust. And so, that's kind of the approach we're starting to take. But that's a long-term approach. And so, we're a relatively young program, and we're building the foundation for doing that well, but it takes some time. JOHNSON:Who do you partner with in all of this? Is it mostly organizations that are interested in equity and environmental justice, or do you broaden that out a little bit and work with organizations that maybe don't have those terms in their names? CUNNINGHAM:That's a good question. So, one of the things we've worked on is this climate health adaptation initiative, and that's a group that we bring together—various state agencies and federal agencies. So, EPA attended those meetings, so does the Federal Reserve Bank of San Francisco, Health and Human Services. And what we're trying to do in that group—and those groups, you know, they all care about environmental justice, but it's not in their name—but we are trying to work together to figure out what are the resources we can provide as state and federal governments to these local communities so that, by the time we go to the communities, we're not just asking them, "Hey, what are your concerns?" But we're saying, "Hey, what are your concerns, and here are the resources we have for you right now." Like, here's what we can do, and making sure that we're not, you know, performing an extractive process to say that we did community engagement, but like earnestly engaging with communities in a way that's going to benefit them and let them drive the climate resilience work. JOHNSON:What are some of the challenges that you've encountered or identified to date? CUNNINGHAM:So, I think a great example, I think—as you know, we worked with Pierce County, and we, you know, pulled together these climate partners in Pierce County. And, you know, Pierce County, there's a county climate resilience plan, the city of Tacoma has a climate resilience plan, and there's a sustainability plan. We had all the partners in the room, but nobody had read all three plans, so that coordination piece was really missing. So I was like, "If nobody in this call has read it, then nobody's read that whole set." And so, getting that coordination piece is really critical. And it's one of the roles I think public health is uniquely able to play, making sure we have that coordination piece. So, in a lot of what we're trying to do is build our coordination capacity. So, we have our climate justice coordinator and a climate change coordinator, and they are full up with that coordination work. So, we're looking to try and expand the staff and capacity we have there to make sure we have someone who's read all those plans, that can kind of coordinate work in an area like Pierce County, or maybe facilitate Pierce County getting somebody who can do that coordination of work. So, that's one major challenge. Another one is climate change is so interdisciplinary. So, you know, there are people who work on, you know, permafrost and wildfire smoke and air quality and water quality, and, you know, extreme heat, you know, emergency response, vector-borne disease—it gets really hard to kind of pull all that together. And when you pull people together from that many different facets, the work can kind of go slow. So, I think that high-level coordination is needed to kind of bring all these groups together to move that stuff forward. JOHNSON:Are the teams in your department already dialed in, or have you had to train them about the connections between climate change and equity? CUNNINGHAM:Yeah, I think both of those are areas where lots of people never undergo. Like, I'm personally still working on training myself on, you know, making sure I understand the equity implications of climate change. And, you know, I'm in a climate change general club, and in our staff meetings, every other staff meeting, we discuss racial justice and equity resources. So, we're learning ourselves. But we also are taking on that role of trying to educate others in the agency around it. So, we have other parts of the agency, they're working in climate sensitive areas, you know, like our office of drinking water, our shellfish protection program, emergency management response. We want to make sure that we're talking with those groups, and they're building their capacity too, so it's kind of something we're working on all together as an agency. And so, there's a lot of cross training going on. But it's also just bringing new staff on. So, I hired an epidemiologist recently who's starting tomorrow, actually, which is really exciting. And she's a great epidemiologist, and has worked in infectious disease for a bunch of years, but we're gonna have to train her on climate change. And there aren't a lot of people when you put out hiring notices who come in with a lot of climate change and public health experience at the same time. So, you gotta hire the climate change person and teach them public health, or hire the public health person and teach them climate change. And so, one of the reasons I like the office and just the agency I work in is that our director says, you know, the values are that we care about each other and we're always learning. And I think this climate change is a perfect place to be if you were in an environment like that, because both of those things are necessary. JOHNSON:What about lessons learned? Do you have any that you can offer right now? CUNNINGHAM:Yeah, this one is a little tongue in cheek, but I think it actually can be helpful for some areas, which is, I've got a two-step process for starting a climate section for free. And the first one is you identify some people in your agency that are working on climate-sensitive risks—air quality, wildfire, smoke, flooding, drought—and then pull them over into a section and name them the climate health section. So, you know, part of that is just naming the work. And so that's one recommendation I have is that, you know. In 2021, over 200 medical journals signed an op ed where they called the failure to act on climate change is the biggest threat to public health. So, if we're not resourcing that risk as a public health community, we're contributing to that risk that those academic journals are calling out. So, I think it's really important to start addressing climate change head on and not sort of like a little bit from emergency management and a little bit from environmental justice and kind of walking around the issue, but really setting up a program and starting to get it going. JOHNSON:As we close the conversation and the podcast, tell me what is the best argument, in your view, for doing a program like the one you have there in Washington State? CUNNINGHAM:You know, I think when you're talking about like climate and environmental justice, the things we need to change in order to address climate change are, you know, our transportation systems and our public health systems and our environmental health capacity issues. We need to change all those things anyway to address the history of racist, you know, public health and planning policies. And so, we have a chance to not only address those historical inequities, but respond to the greatest public health challenge of our generation at the same time. And that's a challenge, you know, that I would like to see public health really rise up to. I think we can be the champions and the conveners of this climate health space. And you know, the studies all show that the public health messaging, the health connection and climate change is the one that speaks to people, especially people who aren't already all bought in on climate change. So, we can really be the messengers on that adaptation that we need to do and sort of on that piece where you get to address some of the historic inequities that public health has been either directly or indirectly involved in. JOHNSON:Thank you for listening to Public Health Review. By the way, did you hear the slight thumping behind some of Rad's comments near the end of his interview? Those were Washington's finest squirrels playing on the roof of Rad's office. No doubt they're concerned about the climate, too. We were glad to have them join the show. If you like what we're doing here, maybe take a minute to send the episode to your colleagues on social media. And if you have comments or questions, we'd like to hear from you. Email us at [email protected]. That address again, P-R at A-S-T-H-O dot org. You can also follow us using the Follow button on your favorite podcast player. This show is a production of the Association of State and Territorial Health Officials. For Public Health Review, I'm Robert Johnson. Be well.
https://www.astho.org/communications/podcast/connecting-climate-change-health-equity-public-health-agencies/?_t_hit.id=Brightfind_CMS_Pages_DetailPage%2F_2f70ada5-2c70-4934-8a55-e49a1bbda9c0_en&_t_hit.pos=5&_t_tags=language%3Aen%2Csiteid%3A9e70eb08-8aab-4b4a-a62a-52bd8c432544
Doctors in Ariadaha, Kolkata - Book Appointment Online, View Fees, and Contact Number Find doctors in Ariadaha, Kolkata. Book top doctor's appointment online. View fees, address, phone number, user feedback, reviews and appointment timings. Doctors in Ariadaha Filters used: Ariadaha Dr. Mainak Sanyal Kolkata-based Dr. Mainak Sanyal is a well-known doctor specialising in General Physician. With 5 years of experience, He has been associated with various prestigious hospitals and clinics. Dr. Mainak Sanyal is known for excellence in Health Checkup (General), Fever Treatment. Please see the profile page for a comprehensive list of Dr. Mainak Sanyal's expertise. Edu Care Clinic - #139, Santoshpur Avenue, Landmark: Near UCO Bank., Landmark: Santoshpur Kolkata Clinic fee: ₹150.0 Mr. Dipan Chakraborty Kolkata-based Mr. Dipan Chakraborty is a well-known doctor specialising in Ophthalmology. Having worked with several hospitals, Mr. Dipan Chakraborty has 5 years of relevant experience. Mr. Dipan Chakraborty is a specialist in Gastroenteritis Treatment, Eye Ceck Up, Power Determination. Please view the profile for a complete list of Mr. Dipan Chakraborty's expertise. Mahavir Opticals - #514/2, Diamond Harbour Road, Vidya Sagar Bipony Market, 1st Floor, Beside Behala Corporation, Kolkata- 700034., Landmark: Behala Kolkata Clinic fee: ₹150.0 View Doctor Profile Ms. Pritha Banik Kolkata-based Ms. Pritha Banik is a well-known doctor specialising in Psychology. With 9 years of experience, Ms. Pritha Banik has been associated with various prestigious hospitals and clinics. Ms. Pritha Banik is an expert in Anger Management, Loss of Interest, Grief Counselling, Behaviour &amp; Thought Problems, Adolescent Medicine, Anxiety Disorders Treatment. Please view the profile for a complete list of Ms. Pritha Banik's expertise. Psychologist Pritha - Chamber No-1, Mordecai Lane, Surenbag Colony, Chatakol; Landmark - Near Kishore Sangha Club / Big Pond, Landmark: Dumdum Kolkata Clinic fee: ₹400.0 Dr. Azhar Ali Dr. Azhar Ali is a well-known doctor based in Kolkata who specialises in General Physician. Having worked with several hospitals, Dr. Azhar Ali has 7 years of relevant experience. Preventive Medicine, Fever Treatment, Health Checkup (General) are Dr. Azhar Ali’s speciality. Dr. Azhar Ali's profile page has the full list of expertise. Shri Shyam Pharmacy - #168/A, Muktaram Babu street, Bidhan Sarani, Landmark: Near Marble Place., Landmark: Bidhan Sarani Kolkata Clinic fee: ₹100.0 Dr. Pratiroop Ganguly Dr. Pratiroop Ganguly is a well-known doctor based in Kolkata who specialises in Ophthalmology. Dr. Pratiroop Ganguly has more than 1 years of experience. Please see Dr. Pratiroop Ganguly's profile for the complete list. Dr. S.C Basak Dr. S.C Basak is a renowned doctor in Kolkata. Dr. S.C Basak specialises in Dentistry. Dr. S.C Basak has been a practicing doctor for over 47 years. Dr. S.C Basak is an expert in Teeth Whitening, Tooth Extraction, Dental Fillings, Impaction / Impacted Tooth Extraction, Scaling / Polishing. Dr. S.C Basak's profile page has the full list of expertise. DR. BASAK&#039;S DENTAL CLINIC - #522/C, D H Road, Behala, Kolkata 700034, Landmark: Opposite New Shitala Mandir., Landmark: Behala Kolkata Dr. Shradha S Agarwala (PhD) Dr. Shradha S Agarwala (PhD) is a renowned doctor in Kolkata. Dr. Shradha S Agarwala (PhD) specialises in Dietician. Dr. Shradha S Agarwala (PhD) has been a practicing doctor for over 5 years. Diet Counselling, High Cholesterol Diet Counselling, Infant &amp; Child nutrition, Thyroid Diet Counseling, Coaching for Weight Loss, Renal (Kidney) Diet Counselling are Dr. Shradha S Agarwala (PhD)’s speciality. Dr. Shradha S Agarwala (PhD)'s profile page has the full list of expertise. Health Quotient - 298A, Bagmari Road, Landmark: Shree Lokenath Temple Manicktala Kolkata Clinic fee: ₹1000.0 Dr. Ravi Singh Dr. Ravi Singh is a renowned doctor in Kolkata. Dr. Ravi Singh specialises in General Surgery. Dr. Ravi Singh has been a practicing doctor for over 2 years. Please see Dr. Ravi Singh's profile for the complete list. Dr. Arijit Das Dr. Arijit Das is a well-known doctor based in Kolkata who specialises in Other. With 1 years of experience, Dr. Arijit Das has been associated with various prestigious hospitals and clinics. Dr. Arijit Das's profile page has the full list of expertise. Dr. Kathakali Chatterjee Dr. Kathakali Chatterjee is an esteemed doctor practising Psychiatry in Kolkata. Dr. Kathakali Chatterjee has over 3 years of experience practising medicine in various hospitals and clinics. Please view the profile for a complete list of Dr. Kathakali Chatterjee's expertise. Dr. Chhaya Shaw Kolkata-based Dr. Chhaya Shaw is a well-known doctor specialising in Homeopathy. Dr. Chhaya Shaw has more than 2 years of experience. Please view the profile for a complete list of Dr. Chhaya Shaw's expertise. Dr. Sohail Anwar Dr. Sohail Anwar is an esteemed doctor practising Dentistry in Kolkata. He has over 9 years of experience practising medicine in various hospitals and clinics. Dr. Sohail Anwar is a specialist in Cast Partial Denture, Impaction / Impacted Tooth Extraction, Acrylic Partial Denture, BPS Dentures Fixing, Crowns and Bridges Fixing, Artificial Teeth. Please see the profile page for a comprehensive list of Dr. Sohail Anwar's expertise. Advance Dental Care - #98, Collin Street, Elliot Road, Landmark: Near Kalanga Masjid., Landmark: Elliot Road Kolkata Clinic fee: ₹200.0 Ms. Shreshtha Dhar Ms. Shreshtha Dhar is an esteemed doctor practising Psychology in Kolkata. Ms. Shreshtha Dhar has been a practicing doctor for over 4 years. Child Psychology, Psychotherapy for Couples, Psychotherapy Adult, Individual psychotherapy are Ms. Shreshtha Dhar’s speciality. Please see Ms. Shreshtha Dhar's profile for the complete list. K.F. Clinic - 7B, Fern Place, Landmark: Opp Dena Bank Gariahat Kolkata Clinic fee: ₹800.0 Dr. Avijit Bhowmick (PT) Dr. Avijit Bhowmick (PT) is a well-known Physiotherapist in Kolkata. Dr. Avijit Bhowmick (PT) has been a practicing doctor for over 6 years. Dr. Avijit Bhowmick (PT) is known for excellence in Cryotherapy/Cold Therapy, Strengthening Excercise, Physiotherapy for Sports Injury Rehabilitation, Electrical Stimulation, Joint Mobilization, Range Of Motion Excercise. Please see Dr. Avijit Bhowmick (PT)'s profile for the complete list. Lakshmi Physiotherapy Clinic - #238, Sreenagar Main Road, Gitanjali Apartment, Garia Station, Kolkata- 700094, Landmark- Near SBI ATM., Landmark: Garia Kolkata Clinic fee: ₹150.0 Ms. Priyangee Lahiry Ms. Priyangee Lahiry is an esteemed doctor practising Dietician in Kolkata. She has over 9 years of experience practising medicine in various hospitals and clinics. Please see Ms. Priyangee Lahiry's profile for the complete list. N G Medicare Diagnostic Centre - 123A, Landmark: Near Triangular Park Rash Behari Avenue Kolkata Clinic fee: ₹350.0 Ms. Vaishali Shah Ms. Vaishali Shah is an esteemed doctor practising Dietician in Kolkata. She has over 6 years of experience practising medicine in various hospitals and clinics. Ms. Vaishali Shah specialises in Weight Loss Treatment, health related issues, fitness. Please view the profile for a complete list of Ms. Vaishali Shah's expertise. Gurupadma Wellbeing Centre - 8,Dr Sarat banerjee road, Landmark: Above Meera Saree Shop Southern Avenue Kolkata Clinic fee: ₹1200.0 Ms. Annesha Das Ms. Annesha Das is a well-known doctor based in Kolkata who specialises in Ophthalmology. She has been a practicing doctor for over 7 years. Gastroenteritis Treatment, Eye Checkup - General are Ms. Annesha Das’s speciality. A full list of Ms. Annesha Das's expertise can be found on the profile page. Eye Zone - #201/1, NSC Bose Road, Kolkata 700047, Landark: Opposite Reliance Digital, Landmark: Bansdroni Kolkata Clinic fee: ₹150.0 Dr. Arindam Bain Kolkata-based Dr. Arindam Bain is a well-known doctor specialising in Dentistry. Having worked with several hospitals, Dr. Arindam Bain has 2 years of relevant experience. Please view the profile for a complete list of Dr. Arindam Bain's expertise. Abinash Dental Clinic - Rabindra Sarani, Nimta, Near Dhalai Karkhana Bus Stop, Landmark: Durganagar Kolkata Clinic fee: ₹150.0 Dr. Arnab Bera Dr. Arnab Bera is a renowned doctor in Kolkata. He specialises in Pulmonology. He has more than 3 years of experience. Dr. Arnab Bera's profile page has the full list of expertise. Nidaan Clinic - 202, Jessore Road, Shyam Lake Gardens, Landmark: Near Barat Bus Stop Lake Town Kolkata Clinic fee: ₹500.0 Dr. Priyanka Kar Dr. Priyanka Kar is a well-known Dentistry in Kolkata. Having worked with several hospitals, She has 1 years of relevant experience. Dr. Priyanka Kar's profile page has the full list of expertise. Rabindra Dental Clinic - 27/4, Rabindra Sarani, Nimta, Landmark: Kolkata Airport Kolkata Clinic fee: ₹200.0 Dr. Suparna Das (PT) Dr. Suparna Das (PT) is a well-known doctor based in Kolkata who specialises in Physiotherapist. With 3 years of experience, Dr. Suparna Das (PT) has been associated with various prestigious hospitals and clinics. Physiotherapy Rehab, Back Pain Physiotherapy, Home Care Physiotherapy, Knee Pain Physiotherapy are Dr. Suparna Das (PT)’s speciality. Dr. Suparna Das (PT)'s profile page has the full list of expertise. Bright Healthcare &amp; Wellness Private Limited - 9/5, Biren Roy Road (East), Landmark: Behala Chowrasta Behala Kolkata Clinic fee: ₹400.0 Dr. Sudip Kumar Ghosh Dr. Sudip Kumar Ghosh is a renowned doctor in Kolkata. Dr. Sudip Kumar Ghosh specialises in General Surgery. Having worked with several hospitals, Dr. Sudip Kumar Ghosh has 3 years of relevant experience. Please see the profile page for a comprehensive list of Dr. Sudip Kumar Ghosh's expertise. Sparsh Diagnostic Centre - 231/1 NSC Bose Road, Landmark : Near Usha Gate Bus Stop, Kolkata, Landmark: Near Usha Gate Bus Stop Bansdroni Kolkata Clinic fee: ₹350.0 Dr. Soumik Kolay (PT) Dr. Soumik Kolay (PT) is a renowned doctor in Kolkata. Dr. Soumik Kolay (PT) specialises in Physiotherapist. Having worked with several hospitals, Dr. Soumik Kolay (PT) has 11 years of relevant experience. Please view the profile for a complete list of Dr. Soumik Kolay (PT)'s expertise. Portea Home Healthcare - Sco 30, Top Floor, Phase 10, Landmark: SAS Nagar Mohali Clinic fee: ₹500.0 Dr. Dilip Biswas Dr. Dilip Biswas is an esteemed doctor practising General Physician in Kolkata. Dr. Dilip Biswas has over 11 years of experience practising medicine in various hospitals and clinics. Please view the profile for a complete list of Dr. Dilip Biswas's expertise. 15 million myUpchar subscribers
https://www.myupchar.com/en/doctors/kolkata/ariadaha?page=49
Human Rights Reports: Custom Report Excerpts - United States Department of State Custom Report Excerpts: Venezuela Bureau of Democracy, Human Rights, and Labor Venezuela Executive Summary Venezuela is formally a multiparty, constitutional republic, but for more than a decade, political power has been concentrated in a single party with an increasingly authoritarian executive exercising significant control over the legislative, judicial, citizen, and electoral branches of government. Nicolas Maduro won the presidency in 2013 by a 1.5-percent margin amid allegations of pre- and post-election fraud, including government interference, the use of state resources by the ruling party, and voter manipulation. The opposition won in a landslide control of the National Assembly in the December 2015 legislative elections, but the executive branch exercised extensive influence over the judiciary to secure favorable decisions from the Supreme Tribunal of Justice that undermined the National Assembly’s autonomy, ignored the separation of powers, and enabled the president to govern through a series of emergency decrees. The ruling United Socialist Party (PSUV) subsequently thwarted opposition efforts to recall the President under terms laid out by the constitution, and gubernatorial elections slated for December 2016 were summarily postponed. Civilian authorities maintained effective, though politicized, control over the security forces. Principal human rights abuses reported during the year included systematic, politicized use of the judiciary to undermine legislative branch action, and intimidate and selectively prosecute critics; indiscriminate police action against civilians leading to widespread arbitrary detentions, unlawful deprivation of life, and torture; and government curtailment of freedom of expression and of the press. The government arrested and imprisoned opposition figures and showed little respect for judicial independence or generally did not permit judges to act according to the law without fear of retaliation. At times the government blocked media outlets and harassed and intimidated privately owned television stations, other media outlets, and journalists throughout the year using threats, fines, property seizures, arrests, criminal investigations, and prosecutions. Nongovernmental organizations (NGOs), the media, and government agencies reported extrajudicial killings by police and security forces; torture and other cruel, inhuman, or degrading treatment; harsh and life-threatening prison conditions and lack of due process rights that contributed to widespread violence, riots, injuries, and deaths in prisons; inadequate juvenile detention centers; corruption and impunity in the police; arbitrary arrests and detentions; abuse of political prisoners; interference with privacy rights; lack of government respect for freedom of assembly; lack of protection for Colombian migrants; corruption at all levels of government; threats against domestic NGOs; violence against women; employment discrimination based on political preference; and restrictions on workers’ right of association. The government sometimes took steps to punish lower-ranking government officials who committed abuses, but there were few investigations or prosecutions of senior government officials. Impunity remained a serious concern in the security forces. Section 1. Respect for the Integrity of the Person, Including Freedom from: a. Arbitrary Deprivation of Life and other Unlawful or Politically Motivated Killings Although the government did not release statistics on extrajudicial killings, NGOs reported that national, state, and municipal police entities, as well as the armed forces and government-supported paramilitary groups, known as “colectivos,” carried out such killings during the year. There was also no official information available on the number of public officials prosecuted or sentenced to prison for involvement in extrajudicial killings, which, in the case of killings committed by police, were often classified as “resistance to authority.” The NGO Committee for the Families of Victims of February-March 1989 (COFAVIC) continued to report there was no publicly accessible national registry of reported cases of extrajudicial killings. COFAVIC reported that in 2015 there were 1,396 alleged extrajudicial killings committed by members of security forces, a 37-percent increase over 2014. The national police Scientific, Penal, and Criminal Investigative Corps (CICPC) reportedly committed 30 percent of the acts, with others committed by regional and municipal police. According to NGOs, prosecutors occasionally brought cases against such perpetrators, but prosecutions often resulted in light sentences, and convictions often were overturned on appeal. COFAVIC reported cases in all 23 states and the national capital district of what it defined as extrajudicial killings committed by elements within local and state police forces. COFAVIC reported these elements systematically and arbitrarily detained and killed individuals (mainly young men from lower social classes) without any recourse to proper investigation by the government. The government continued its nationwide anticrime strategy begun in 2015, the Operation for the Liberation and Protection of the People (OLP), characterized by large-scale raids conducted by hundreds of government security agents in neighborhoods allegedly harboring criminals. These operations often resulted in the deaths of suspected criminals. The NGO Venezuela Program for Education/Action on Human Rights (PROVEA) reported that 245 persons were killed during OLP security exercises in 2015. The government continued to prosecute individuals connected with the 1989 killings in Caracas known as the “Caracazo,” in which the Public Ministry estimated 331 individuals died, and the 1988 El Amparo massacre, in which government security forces allegedly killed 14 persons. On November 27, the state prosecutor stated the government would charge 11 members of the military for responsibility in the death of 12 civilians following a security raid in October in the coastal state of Miranda. The Defense Ministry declared that it condemned the deaths, as did the National Assembly in a rare, unanimous resolution. b. Disappearance There were no substantiated reports of politically motivated disappearances. c. Torture and Other Cruel, Inhuman, or Degrading Treatment or Punishment Although the constitution states no person shall be subjected to cruel, inhuman, or degrading punishment, there were credible reports security forces tortured and abused detainees. There were no reports of any government officials being charged under the law that states an agent or public official who inflicts pain or suffering–whether physical or mental–on another individual to obtain information or a confession, or seeks to punish an individual for an act the individual has committed, may be imprisoned for a maximum of 25 years, dismissed from office, and barred from holding public office for a maximum of 25 years. Prison and detention center officials who commit torture may face a maximum of five years in prison and a maximum fine of 53.5 million bolivars (BsF) ($5.3 million at the official rate, or $80,666 at the secondary Dicom exchange rate as of December 1). The law also includes mechanisms for reparations to victims and their families and creates a special National Commission for Torture Prevention composed of several government ministries. The Office of the Human Rights Ombudsman and the Public Ministry did not publish statistics regarding allegations of torture by police during the year. Several NGOs detailed cases of widespread torture and “cruel, inhumane, and degrading treatment.” The Venezuelan NGO Foro Penal documented more than 138 cases of torture in the country between February 2014 and May 2015. Foro Penal maintained that hundreds of cases were not reported to government institutions because of victims’ fear of reprisal. NGOs detailed reports from detainees whom authorities allegedly sexually abused, threatened with death, and forced to spend hours on their knees in detention centers. Human rights groups reported that the government continued to influence the prosecutor general and the public defender to conduct investigations selectively and subjectively. No data was available on investigations, prosecutions, or convictions in cases of alleged torture. Press and NGO reports of beatings and humiliating treatment of suspects during arrests were common and involved various law enforcement agencies and the military. Torture and other cruel, inhuman, or degrading treatment or punishment of prisoners were reported during the year. Two common methods of cruel treatment were the denial of medical care by prison authorities and the remanding of prisoners to long periods in solitary confinement. In the case of opposition leader Leopoldo Lopez, family members stated that prison authorities held him in solitary confinement for much of his imprisonment, subjected him to strip searches multiple times daily, denied him visitation rights, and occasionally deprived him of reading and writing material. Prison officials also subjected visiting family members to humiliating strip searches. The NGO Foro Penal reported multiple instances of political prisoners denied adequate medical treatment while in government custody. Foro Penal noted instances where detainees were transferred to a medical facility, where instead of receiving treatment, they were interrogated by security officials. Prison and Detention Center Conditions Most prison conditions were harsh and life threatening due to insufficient numbers of staff, who were also poorly trained and allegedly corrupt; weak security; deteriorating infrastructure; severe overcrowding; lack of adequate medical care; and shortages of food and potable water. Armed gangs effectively controlled some prisons in which they were incarcerated. Physical Conditions : The Ministry of Penitentiary Services reported there were 50,791 inmates in the country’s 58 prisons and penitentiaries and an estimated of 33,000 inmates in police station jails. According to the NGO Venezuelan Observatory for Prisons (OVP), the capacity for penitentiaries was 22,459 inmates, and for police station jails, the capacity was for 5,000 inmates. Overcrowding was 126 percent for penitentiaries and 560 percent for police station jails on average, although the OVP noted that in some jails the overcrowding ranged from 800 to 1,200 percent. According to OVP reports, records for detainees were not properly maintained and often featured incomplete information. Official figures taken from the Penitentiary Services Ministry’s 2015 annual report estimated 31,503 pretrial detainees and 17,374 convicted prisoners were held in the same facilities. Authorities assigned another 265 individuals to work detachment programs and held 522 individuals in police station facilities not fit to serve as detention centers. Women (2,629 inmates) and men (48,162 inmates) generally were held in separate prison facilities. There was only one penitentiary exclusively for women, and female prisoners in other detention centers were held in annexes or separate women’s departments in otherwise male-only prisons. Security forces and law enforcement authorities often held minors together with adults, even though separate facilities existed. Because institutions were filled to capacity, hundreds of children accused of infractions were confined in juvenile detention centers where they were reportedly crowded into small, unsanitary cells. The CICPC and police station jails and detention centers also were overcrowded, causing many police station offices to be converted into makeshift prison cells. Prisoners reportedly took turns sleeping on floors and office chairs, and sanitation facilities were inadequate or nonexistent. In the temporary detention facility in the downtown Caracas Zona 7 police station, a reported 700 detainees awaiting transport to prisons were held in a facility built for 70. On January 21, Mayor Ramon Muchacho of the Caracas municipality of Chacao declared that Chacao Police Department detention centers were operating at 300 percent of capacity, and temporary facilities were being used for long-term detention due to the lack of space in national penitentiaries. Muchacho highlighted that temporary detention centers lacked the infrastructure and security conditions to handle long-term imprisonment, and that overcrowding limited the fundamental rights for prisoners to receive visitors and legal counsel. The National Guard and the Ministry of Interior, Justice, and Peace have responsibility for prisons’ exterior and interior security, respectively. The government failed to provide adequate prison security. The OVP estimated a staffing gap of 90 percent for prison security personnel, with only one guard for every 100 inmates, instead of one every 10 as recommended by international standards. The OVP reported 309 prisoner deaths and 1,709 serious injuries in 2014. Most deaths and injuries resulted from prisoner-on-prisoner violence, riots, fires, and generally unsanitary and unsafe conditions. On August 3, seven prisoners at Alayon prison in Maracay died and approximately 60 individuals, three of them police officers, were severely injured when subjects riding motorcycles threw five grenades into the facility. The media reported that after the incident an undetermined number of inmates escaped from the prison. During the year numerous prison riots resulted in inmate deaths and injuries. On January 11, 50 inmates took 40 persons hostage, including prison guards and staff and visiting family members, in Coro Penitentiary while protesting against food shortages and inadequate health care. The riot lasted for 55 hours and led to 11 injuries, 10 of them prison guards. On August 10, gangs rioted at the San Felix police station jail, leaving two inmates dead and 11 injured. Gang-related violence and alleged extortion by guards and inmates was fueled by trafficking in arms and drugs. NGOs, human rights lawyers, and the press frequently claimed prison gang leaders, rather than government authorities, controlled the penitentiaries and were able to lead organized crime networks based outside the prison system. On July 15, a new law came into effect limiting cellphone and internet availability inside prisons to prevent inmates from using the technology to engage in criminal activity. The law was not implemented, however; inmates threatened a “full-scale war” if the government limited their ability to communicate. The NGO A Window to Liberty (UVL) reported that authorities asked family members to provide nonperishable foods to prisoners at police station jails and the Fenix, Rodeo I, Rodeo II, Rodeo III, Yare III, and National Institute of Feminine Orientation penitentiaries due to inadequate provisioning of food by the prison administration. Lack of potable and running water in the 26 de Julio penitentiary led to gastrointestinal and skin diseases for large portions of the inmate population and prison staff. The government restricted information regarding deaths in prisons from tuberculosis, HIV/AIDS, and other diseases, or lack of medical care. A study by the NGO Solidarity Action found prison rules regarding the classification of inmates resulted in the isolation of those with HIV/AIDS in “inadequate spaces without food and medical attention.” The OVP reported a generalized lack of medical care, drugs, equipment, and physicians for prisoners, and reportedly inmates often received the same pills regardless of their symptoms. The OVP reported that due to inadequate nutrition plans and lack of potable water, stomach illnesses were common among inmates. According to the OVP, pregnant women lacked adequate facilities for their medical attention. Administration : The government’s recordkeeping on prisoners was inadequate. Prison authorities did not maintain accurate counts of inmates. According to press reports, the most recent accurate daily counts at the General Penitentiary of Venezuela and the La Planta Penitentiary occurred in 2009 and 2010, respectively. The National Assembly released a report in May evaluating the use of funds by Minister Varela, noting that the Prisons Ministry had built only two new penitentiaries of 24 planned since 2012. In addition, the ministry’s 2015 annual report indicated that the budget for prisons, managed by the National Penitentiaries Fund (FONEP), had been reduced by 86 percent from 2013 to 2015. The Ministry of Penitentiary Services did not respond to any of the requests it received from the OVP, UVL, other human rights organizations, inmates, or families regarding inmates or investigations of the harsh conditions that led to hunger strikes or violent uprisings. Prisoners and detainees generally had access to visitors, but in some cases prison officials harassed or abused visitors. Prison officials imposed significant restrictions on visits to political prisoners. The family of imprisoned opposition leader Leopoldo Lopez denounced mistreatment by prison guards when attempting to visit him in the Ramo Verde Military Prison, including being subjected to strip searches on both entry and exit from the facility. Independent Monitoring : Human rights observers continued to experience lengthy delays and restrictions in accessing prisons and detention centers. Requests by the International Committee of the Red Cross (ICRC) to visit penitentiary centers and interview inmates in confidentiality have been rejected since 2013. More than 300 lay members from the Venezuelan Episcopal Conference of the Roman Catholic Church volunteered in 40 prisons. Although prohibited from formally entering prisons, Catholic laity visited prisoners on family visitation days. Improvements : In February the Ministry of Penitentiary Services announced closure of the San Antonio Prison in Nueva Esparta after a series of videos were released on social media showing inmates firing weapons to commemorate the death of prison gang leader “El Conejo,” who was killed on January 24. Authorities moved 1,828 prisoners to other government penitentiaries. The ministry implemented educational programs for inmates, although reports from an NGO claimed enrollment was low. d. Arbitrary Arrest or Detention The constitution prohibits the arrest or detention of an individual without a judicial order and provides for the accused to remain free while being tried, but individual judges and prosecutors often disregarded these provisions. While NGOs such as Foro Penal, COFAVIC, the Institute for Press and Society (IPYS), Public Space, and PROVEA noted at least 2,000 open cases of arbitrary detentions, authorities rarely granted them formal platforms to present their petitions. Multiple individuals, including American citizens, were arbitrarily detained for extended periods without criminal charges. In the weeks before a planned opposition rally on September 1, the government initiated a series of arbitrary detentions targeting opposition activists. On August 29, security forces arrested former student leader Yon Goicoechea for allegedly carrying explosives. Authorities held Goicoechea incommunicado for almost three days, and as of December 22, he remained in custody on politically motivated charges. On September 3, independent journalist Braulio Jatar, a dual Venezuelan-Chilean citizen, was detained by Venezuelan authorities after reporting on an impromptu protest against President Maduro in Villa Rosa, Margarita Island. Jatar was charged with money laundering by a Venezuelan court, and as of December 22, he remained in the custody of the Bolivarian National Intelligence Service (SEBIN). On September 19, SEBIN agents arrested Marco Trejo, Cesar Cuellar, and James Mathison without a warrant for producing a short video denouncing military repression. The government alleged the individuals committed a military offense because the video featured actors in military uniforms and charged the three under the military’s code of conduct. ROLE OF THE POLICE AND SECURITY APPARATUS The Bolivarian National Guard (GNB)–a branch of the military that reports to both the Ministry of Defense and the Ministry of Interior, Justice, and Peace–is responsible for maintaining public order, guarding the exterior of key government installations and prisons, conducting counternarcotics operations, monitoring borders, and providing law enforcement in remote areas. The Ministry of Interior, Justice, and Peace controls the CICPC, which conducts most criminal investigations, and SEBIN, which collects intelligence within the country and is responsible for investigating cases of corruption, subversion, and arms trafficking while maintaining its own detention facilities separate from those of the Ministry of Penitentiary Services. Police include municipal, state, and national police forces. Mayors and governors oversee municipal and state police forces. The Bolivarian National Police (PNB) reports to the Ministry of Interior, Justice, and Peace and had a reported 14,500 officers. According to its website, the PNB largely focused on policing Caracas’ Libertador municipality; patrolling Caracas-area highways, railways, and metro system; and protecting diplomatic missions; the PNB maintained a minimal presence in seven of the country’s 23 states. Corruption, inadequate police training and equipment, and insufficient central government funding, particularly for police forces in states and municipalities governed by opposition officials, reduced the effectiveness of the security forces. There were continued reports of police abuse and involvement in crime, including illegal and arbitrary detentions, extrajudicial killings, kidnappings, and the excessive use of force. Impunity remained a serious problem in the security forces. The Public Ministry is responsible for initiating judicial investigations of security force abuses. The Office of Fundamental Rights in the Public Ministry is responsible for investigating cases involving crimes committed by public officials, particularly security officials. According to the Public Ministry’s annual report for 2015, the Office of Fundamental Rights cited 13,911 specific actions taken to “process claims” against police authorities for human rights abuses and charged 959 with violations. The Office of the Human Rights Ombudsman did not provide information regarding human rights violations committed by police and military personnel, nor did the Attorney General’s Office release data. State and municipal governments also investigated their respective police forces. By law, national, state, and municipal police forces have a police corps disciplinary council, which takes action against security officials who commit abuses. The National Assembly also may investigate security force abuses. During the year the government at both the local and national levels took few actions to sanction officers involved in abuses. According to the NGO Network of Support for Justice and Peace, the lack of sufficient prosecutors made it difficult to prosecute police and military officials allegedly involved in human rights abuses. In addition, NGOs reported the following problems contributed to an ineffective judicial system: long procedural delays, poor court administration and organization, lack of transparency in investigations, and impunity of government officials. The National Experimental University for Security (UNES), tasked with professionalizing law enforcement training for the PNB and other state and municipal personnel, had centers in Caracas and five other cities. UNES requires human rights training as part of the curriculum for all new officers joining the PNB, state, and municipal police forces. Members of the PNB and state and municipal police also enrolled for continuing education and higher-learning opportunities as part of the Special Plan of Police Professionalization at UNES. Societal violence remained high and continued to increase. The Public Ministry reported 19,453 homicides in 2015, a rate of 63.5 per 100,000 residents. The NGO Venezuelan Observatory of Violence estimated the rate to be higher, with 27,875 homicides, a rate of 90 per 100,000 residents. Criminal kidnappings for ransom were widespread in both urban centers and rural areas. Kidnappings included both “express kidnappings,” in which victims were held for several hours and then released, and traditional kidnappings. The Public Ministry reported 793 cases of kidnapping or extortion in 2015. NGOs and police noted many victims did not report kidnappings to police or other authorities due to fear of retribution or lack of confidence in the police and that the actual occurrence was likely far higher. ARREST PROCEDURES AND TREATMENT OF DETAINEES While a warrant is required for an arrest, detention is permitted without an arrest warrant when an individual is caught in the act of committing a crime or to secure a suspect or witness during an investigation. Police often detained individuals without a warrant. The law mandates that detainees be brought before a prosecutor within 12 hours and before a judge within 48 hours to determine the legality of the detention; the law also requires detainees be informed promptly of the charges against them. Authorities routinely ignored these requirements. Although there is a functioning system of bail, it is not available for certain crimes. Bail also may be denied if a person is apprehended in the act of committing a crime or if a judge determines there is a danger the accused may flee or impede the investigation. The law allows detainees access to counsel and family members, but that requirement was often not met, particularly for political prisoners. The constitution also provides any detained individual the right to immediate communication with family members and lawyers who, in turn, have the right to know a detainee’s whereabouts. A person accused of a crime may not be detained for longer than the possible minimum sentence for that crime or for longer than two years, whichever is shorter, except in certain circumstances, such as when the defendant is responsible for the delay in the proceedings. Arbitrary Arrest : Foro Penal reported 5,853 cases of arbitrary detention between February 2014 and June 2016. Persons so detained claimed security personnel subjected them to inhuman and degrading treatment and in some cases torture. Pretrial Detention : Pretrial detention was a serious problem. According to the OVP, approximately 79 percent of the prison population was in pretrial detention. According to the Supreme Court of Justice (TSJ), only 17 percent of trials concluded or reached sentencing. The NGO Citizen Observatory of the Penal Justice System attributed trial delays to the shortage of prosecutors and penal judges (4.7 penal judges per 100,000 inhabitants in 2010). The Public Ministry’s 2015 annual report stated it had 346 prosecutors specializing in common crimes who processed more than 556,613 cases during the year. Cases were often deferred or suspended when pertinent parties, such as the prosecutor, public defender, or judge, were absent. An automated scheduling calendar in use since 2013, which selected dates based on the availability of all pertinent parties and prohibited judges from scheduling more than 10 hearings per day, did not reduce the backlog. In some instances judges scheduled hearings six months from the start of the case. According to the Public Ministry’s 2015 annual report, the ministry pressed charges in 9.7 percent of the 556,000 cases involving common crimes. The ministry reported the closure of the remainder of the complaints but did not indicate final outcomes. Prisoners reported to NGOs that a lack of transportation and disorganization in the prison system reduced their access to the courts and contributed to trial delays. On April 11, the Supreme Court ruled unconstitutional an amnesty law the National Assembly passed in March, which would have provided a framework to release political prisoners. Detainee’s Ability to Challenge Lawfulness of Detention before a Court : Individuals under detention may legally challenge grounds for their detention, but the processes were often delayed or tabled, and hearings were postponed, stretching trials for years. On many occasions the right to be judged in liberty for some offenders was not granted, and detainees were not allowed to consult with an attorney or to have access to their case records in order to challenge the detention. There are credible accounts that some detainees were placed on probation or under house arrest indefinitely and thus prevented from challenging their status by the threat of being sent back to detention. e. Denial of Fair Public Trial While the constitution provides for an independent judiciary, there was significant evidence the judiciary lacked independence. There were credible allegations of corruption and political influence throughout the judiciary. According to reports from the International Commission of Jurists (ICJ), between 66 and 80 percent of all judges had provisional appointments, and the TSJ Judicial Committee could remove them from office at will. Provisional and temporary judges, who legally have the same rights and authorities as permanent judges, allegedly were subject to political influence from the Ministry of Interior, Justice, and Peace and the attorney general to make progovernment determinations. The ICJ reported a lack of transparency and stability in the assignments of district attorneys to cases and the lack of technical criteria to assign district attorneys to criminal investigations. These deficiencies hindered the possibility of bringing offenders to justice and resulted in a 90-percent rate of impunity for common crimes and a higher percentage of impunity for human rights violation cases. TRIAL PROCEDURES Defendants are to be considered innocent until proven guilty. The law requires that detainees be informed promptly of the charges against them, and the requirement was generally respected, although in high-profile cases the charges were often dubious, according to international human rights organizations. The law provides for open, public, and fair trials with oral proceedings for all individuals. Defendants have the right to consult with an attorney. Public defenders are provided for indigent defendants, but there continued to be a shortage of such attorneys. Defendants are not provided free interpretation as necessary from the moment charged through all appeals. According to the Office of the Human Rights Ombudsman, there were approximately 1,500 public defenders. COFAVIC and Foro Penal noted that the government pressured defendants in trials related to the 2014 student protests into utilizing public defenders instead of private defense attorneys with the promise of receiving more-favorable sentences. Additionally, several NGOs provided pro bono counsel to defendants. While defendants and their attorneys have the right to access government-held evidence, access often was not allowed; in some instances, particularly in politically motivated cases, the court or prosecution did not allow defendants or their attorneys to access such information. Defendants may request no fewer than 30 days and no more than 45 days to prepare their defense. Defendants have the right to question adverse witnesses and present their own witnesses. By law defendants may not be compelled to testify or confess guilt. Defendants and plaintiffs have the right of appeal. The law extends these rights to all defendants. Trial delays were common. Trials “in absentia” are permitted in certain circumstances, although opponents of them claimed the constitution prohibits such trials. The law also states a trial may proceed in the absence of the defense attorney, with a public defender that the court designates. The law gives judges the discretion to hold trials behind closed doors if a public trial could “disturb the normal development of the trial.” At the September 28 hearing of Judge Maria Lourdes Afiuni, witnesses refused to appear for the prosecution. The legal situation of Afiuni, accused of corruption and abuse of authority for her 2009 decision to conditionally release on limits, remained unresolved. Afiuni continued to be subject to protective measures in place since her release to house arrest in 2011 that mandate she may not leave the country, talk to the media, or use social media, although the law states that such measures may not last more than two years. The law mandates municipal courts to handle “less serious” crimes, i.e., those carrying maximum penalties of imprisonment for less than eight years. Municipal courts may levy penalties that include three to eight months of community service. Besides diverting some “less serious” crimes to the municipal courts, this diversion also permits individuals accused of “lesser crimes” to ask the courts to suspend their trials conditionally in exchange for their admission of responsibility, commitment to provide restitution “in a material or symbolic form,” community service, and any other condition imposed by the court. The law provides that trials for military personnel charged with human rights abuses after 1999 be held in civilian rather than military courts. In addition, under the Organic Code of Military Justice, an individual may be tried in the military justice system for “insulting, offending, or disparaging the national armed forces or any related entities.” NGOs expressed concern with the government’s practice of trying civilians under the military justice system for protests and other actions not under military jurisdiction. POLITICAL PRISONERS AND DETAINEES The government used the judiciary to intimidate and selectively prosecute individuals critical of government policies or actions. The NGO Foro Penal reported that more than 100 political prisoners remained incarcerated as of November. An additional 1,998 individuals were subject to either restricted movement or precautionary measures. In late August security forces detained numerous political activists in the days preceding antiregime demonstration on September 1. In some cases political prisoners were held in SEBIN installations or the Ramo Verde military prison without an explanation of why they were not being held in traditional facilities. Authorities have denied the ICRC access to these prisoners since 2013. On June 19, National Guardsmen arrested opposition party (Voluntad Popular) activists Gabriel San Miguel and others at a highway checkpoint in Cojedes State. The men were carrying pro-opposition pamphlets and approximately $3,000 worth of local currency and were traveling to help collect signatures as part of the recall referendum petition drive. SEBIN held the two men in solitary confinement and reportedly interrogated them without legal counsel present. Cojedes Governor Erika Farias accused them of carrying money “to pay mercenaries of destabilization” and blamed them for lootings at local supermarkets. On June 22, authorities charged them with “inciting violence” and money laundering, which could carry a prison sentence of more than 15 years. Authorities released San Miguel, a Spanish-Venezuelan dual national, on September 9 and dropped all charges; the other person, a U.S.-Venezuelan dual national, was released October 18. Metropolitan Caracas Mayor Antonio Ledezma, arrested in February 2015, remained under house arrest while awaiting trial for alleged participation in a conspiracy to topple the government. On August 12, a Caracas appeals court upheld the September 2015 conviction of Popular Will (Voluntad Popular) party leader and former Caracas Chacao municipality mayor Leopoldo Lopez on four counts of public incitement, damage to property, fire damage, and association for conspiracy, in a trial that began in 2014. Lopez continued serving a maximum sentence of 13 years and nine months in prison in Ramo Verde Military Prison, where he was held in solitary confinement. The court also denied the appeals of codefendants Christian Holdack and Marco Coello. During the appeal proceedings, as during the previous trial, court officials refused defense lawyers’ requests to allow the media to cover the proceedings and denied admission to international observers. On August 27, SEBIN agents transferred former San Cristobal mayor Daniel Ceballos from house arrest back to prison, alleging that he had been planning to engage in “destabilizing acts” during a September 1 political demonstration. Authorities had remanded Ceballos to house arrest in August 2015. He continued to await trial on charges of civil rebellion dating to 2014 protests, charges that carry a maximum sentence of 25 years. CIVIL JUDICIAL PROCEDURES AND REMEDIES While there are separate civil courts that permit citizens to bring lawsuits seeking damages, there are no procedures for individuals or organizations to seek civil remedies for human rights violations. f. Arbitrary or Unlawful Interference with Privacy, Family, Home, or Correspondence The constitution provides for the inviolability of the home and personal privacy, but the government generally did not respect these prohibitions. In some cases government authorities infringed on citizens’ privacy rights by searching homes without judicial or other appropriate authorization, seizing property without due process, or interfering in personal communications. Beginning in August 2015, President Maduro declared 60-day “states of exception” in 23 municipalities bordering Colombia in Zulia, Tachira, Apure, and Amazonas states, thereby suspending the constitutional requirement for authorities to obtain a court order prior to entering a private residence or violating the secrecy of a person’s private communications, among other constitutional rights. These states of exception continued throughout the year. Section 2. Respect for Civil Liberties, Including: a. Freedom of Speech and Press The law provides for freedom of speech and press, but the combination of laws and regulations governing libel and media content, as well as legal harassment and physical intimidation of individuals and the media, resulted in significant repression of these freedoms. National and international groups, such as the Inter-American Commission on Human Rights (IACHR), the UN Human Rights Committee, Freedom House, the Inter American Press Association, Reporters without Borders, and the Committee to Protect Journalists, condemned or expressed concern over government efforts throughout the year to restrict press freedom and create a climate of fear and self-censorship. Freedom of Speech and Expression : The law makes insulting the president punishable by six to 30 months in prison without bail, with lesser penalties for insulting lower-ranking officials. Comments exposing another person to public contempt or hatred are punishable by prison sentences of one to three years and fines. PSUV officials threatened violence against opposition figures and supporters, in particular leading up to the opposition’s September 1 march. Press and Media Freedoms : The law provides that inaccurate reporting that disturbs the public peace is punishable by prison terms of two to five years. The requirement that the media disseminate only “true” information was undefined and open to politically motivated interpretation. The Office of the UN High Commissioner for Human Rights (OHCHR) issued a statement in August expressing serious concern over the continuing erosion of media freedom. The law prohibits all media from disseminating messages that incite or promote hate or intolerance for religious, political, gender-related, racial, or xenophobic reasons; incite, promote, or condone criminal acts; constitute war propaganda; foment anxiety in the population or affect public order; do not recognize legitimate government authorities; incite homicide; or incite or promote disobedience to the established legal order. Penalties range from fines to the revocation of licenses. Despite such laws, President Maduro and the ruling PSUV used the nearly 600 government-owned or-controlled media outlets to insult and intimidate the political opposition throughout the year. Maduro regularly referred to Miranda state governor Henrique Capriles using homosexual slurs on live television, while PSUV First Vice President Diosdado Cabello used his weekly television program to bully journalists and media outlets. The law declares telecommunications a “public interest service,” thereby giving the government greater authority to regulate the content and structure of the radio, television, and audiovisual production sectors. The law provides that the government may suspend or revoke licenses when it judges such actions necessary in the interests of the nation, public order, or security. The law empowers the government to impose heavy fines and cancel broadcasts for violations of its norms; the National Telecommunications Commission (CONATEL) oversees the law’s application. The government introduced legal actions against high-profile independent media outlets Tal Cual, El Nacional, El Nuevo Pais, La Patilla, and Globovision. The government’s economic policies made it difficult for newspapers to access foreign currency, preventing many newspapers from purchasing critical supplies and equipment necessary for day-to-day business operations. Items that must be imported included ink, printing plates, camera equipment, and especially newsprint. As the government prevented newspapers from purchasing foreign currency, media companies were forced to buy newsprint from the government-run Alfredo Maneiro Editorial Complex, the only company allowed by the government to import it. Consequently, nearly every newspaper in the country reduced pages and news content in an attempt to conserve paper. On March 16, El Carabobenostopped printing daily newspapers after 82 years in operation, the latest nongovernment-owned media outlet to cease production due to lack of access to dollars to purchase newsprint from the government. The NGO Public Space reported 144 cases of violations of freedom of expression between January and June, defined as the “obstruction, impediment, or criminalization of the search, receipt, and distribution of information by the media,” noting an increasing trend. The most common violations were aggressions against journalists and censorship. State-owned and state-influenced media provided almost continuous progovernment programming. In addition private and public radio and television stations were required to transmit mandatory nationwide broadcasts throughout the year. According to the online tracking program Citizens Monitoring, run by the civil society network Legislative Monitor, between January and September the government implemented more than 100 hours of national “cadenas” featuring President Maduro, interrupting regular broadcasts. Both Maduro and other ruling-party officials utilized mandatory broadcast time to campaign for progovernment candidates. Opposition candidates generally did not have access to media broadcast time. The law requires practicing journalists to have journalism degrees and be members of the National College of Journalists, and it prescribes jail terms of three to six months for those practicing the profession illegally. These requirements are waived for foreigners and opinion columnists. Violence and Harassment : Senior national and state government leaders continued to harass and intimidate privately owned and opposition-oriented television stations, media outlets, and journalists by using threats, property seizures, administrative and criminal investigations, and prosecutions. Government officials, including the president, used government-controlled media outlets to accuse private media owners, directors, and reporters of fomenting antigovernment destabilization campaigns and coup attempts. IPYS reported 12 assaults on media offices from January to August. In two separate incidents in August, unidentified assailants threw feces at El Nacional’s Caracas headquarters and shot bullets at the offices of Diario de los Andesin Trujillo. According to statistics taken from an El Carabobenospecial report, 34 percent of journalists claimed to have been harassed by government officials. IPYS recorded at least 17 cases of journalists arbitrarily detained from January to August. On September 3, SEBIN agents detained Reporte Confidencialeditor and Chilean-Venezuelan dual national Braulio Jatar for disseminating video of residents of Villa Rosa, Nueva Esparta, banging pots and pans in protest during President Maduro’s visit to their community. Authorities charged Jatar with money laundering and using the proceeds to finance terrorism against the Maduro administration. As of December 22, Jatar remained in state custody. Government officials also harassed foreign journalists working within the country. On August 31, immigration officials detained and deported a Miami Heraldjournalist despite having permitted him entry into the country the day before to cover planned opposition protests. Reporters from The Washington Post, ABC, Al-Jazeera, Le Monde, National Public Radio, and Colombia’s Caracol Radio and TV were also expelled or denied entry upon arrival in the country during the year. Censorship or Content Restrictions : In its 2015 report, IPYS noted the government’s preference for using legal proceedings, financial sanctions, and administrative actions against unfavorable news outlets instead of incurring the political cost of shutting down them down outright. Members of the independent media stated they regularly engaged in self-censorship due to fear of government reprisals. This resulted in many journalists posting articles to their personal blogs and websites instead of publishing them in traditional media. The NGO Public Space reported that in 2015 there were 47 cases involving censorship. The government also exercised control over content through licensing and broadcasting requirements. CONATEL acted selectively on applications from private radio and television broadcasters for renewal of their broadcast frequencies. According to Nelson Belfort, former president of the Venezuelan Radio Chamber, and NGO reports, approximately 2,000 radio stations were in “illegal” status throughout the country due to CONATEL having not renewed licenses for most radio stations since 2007. The government controlled a large portion of the country’s businesses and paid for advertising only with government-owned or government-friendly media. Libel/Slander Laws : Government officials engaged in reprisals against individuals who publicly expressed criticism of the president or government policy. On April 11, a judge sentenced David Natera, editor of independent newspaper Correo del Caroni , to four years in prison for criminal defamation due to his newspaper’s investigation of corruption at a state-run mining company in Bolivar State. Natera remained free pending appeal but was prohibited from leaving the country and required to appear before court officials every 30 days. In addition, the judge fined Natera BsF 201,249 ($20,124, or $30.34 at the Dicom exchange rate as of December 1) and ordered the newspaper not to publish stories about the case. Correo del Caroni also faced civil penalties stemming from the defamation case, which could result in the confiscation of its office and printing press, according to a statement released by the NGO Public Space. National Security : The law allows the government to suspend or revoke licenses when it determines such actions to be necessary in the interests of public order or security. The government exercised control over the press through the public entity known as the Strategic Center for Security and Protection of the Homeland (CESPPA), established in 2013, which is similar to the government entity Center for National Situational Studies (CESNA), established in 2010. CESNA and CESPPA have similar mandates and are responsible for “compiling, processing, analyzing, and classifying” both government-released and other public information with the objective of “protecting the interests and objectives of the state.” On May 13, Maduro declared the “state of exception,” citing a continuing economic emergency, and granted himself the power to restrict rights guaranteed in the constitution. The 60-day emergency decree allowed the president to block any action he deemed could “undermine national security” or could “obstruct the continuity of the implementation of economic measures for the urgent reactivation of the national economy.” According to Human Rights Watch, the “state of exception” negatively affected the right to freedom of association and expression. On September 23, the TSJ renewed President Maduro’s decree of a “state of exception.” Nongovernmental Impact : Widespread violence in the country made it difficult to determine whether attacks on journalists resulted from common criminal activity or whether criminals or others targeted members of the media. INTERNET FREEDOM The executive branch exercised broad control over the internet through the state-run CONATEL. Free Access reported that CONATEL supported monitoring of private communications and persecution of internet users who expressed dissenting opinions online. According to media reports, users of social networks accused CONATEL of monitoring their online activity and passing identifying information to intelligence agencies, such as SEBIN. According to Free Access, CONATEL provided information to SEBIN, including internet protocol addresses, which assisted authorities in locating the users. Free Access cited arrests of Twitter users during the 2014 protests. The law puts the burden of filtering prohibited electronic messages on service providers, and it allows CONATEL to order service providers to block access to websites that violate these norms and sanctions them with fines for distributing prohibited messages. CONATEL’s director William Castillo repeatedly declared in press statements that the government did not actively block websites. Castillo stated CONATEL’s role was to enforce the law and prevent dissemination of illegal information or material unsuitable for children and adolescents. Nevertheless, the government continued to block internet sites that post dollar- and euro-to-bolivar currency exchange rates differing from the government’s official rate. Government-owned internet service provider CANTV facilitated blockages. The government used Twitter hashtags to attain “trending” status for official propaganda and employed hundreds of employees to manage and disseminate official government accounts. At least 65 official government accounts used Twitter to promote the ruling PSUV party. Intelligence agencies, which lacked independent oversight, conducted surveillance for political purposes. Courts relied on evidence obtained from anonymous “patriotas cooperantes” (cooperating patriots) to persecute perceived opponents of the government, and senior government officials used personal information gathered by cooperating patriots to intimidate government critics and human rights defenders. CONATEL reported 53 percent of the population used the internet during the year and estimated that 16.2 million citizens connected to the internet five to seven days per week. ACADEMIC FREEDOM AND CULTURAL EVENTS There were some government restrictions on academic freedom and cultural events. University leaders and students alleged the government retaliated against opposition-oriented autonomous universities by providing government subsidies significantly below the annual inflation rate to those universities. Autonomous universities, which receive partial funding from the government, received considerably less than the total budgets they requested. Furthermore, budgetary allocations were based on figures not adequately adjusted for inflation and covered expenses only through March. On May 18, progovernment gangs attacked student protesters at the University of the Andes (ULA) in Merida and set fire to the medical school after students took refuge inside. On June 14, President Maduro instructed the Education Ministry to implement a new high school curriculum in 127 schools nationwide for the 2016-17 school year. Teachers’ associations criticized the new standards as being a form of political indoctrination, noting the replacement of key subjects such as history and geography with “homeland and civic duties” courses. b. Freedom of Peaceful Assembly and Association FREEDOM OF ASSEMBLY The constitution provides for freedom of assembly, but the government significantly restricted it. The Law on Political Parties, Public Gatherings, and Manifestations and the Organic Law for Police Service and National Bolivarian Police Corps regulate the right to assembly. Human rights groups continued to criticize such laws that enable the government to charge protesters with serious crimes for participating in peaceful demonstrations. Ambiguous language in the laws also allowed the government to criminalize organizations that were critical of the government. Protests and marches require government authorization in advance and are forbidden within designated “security zones.” The opposition held large peaceful protests in September and October. As part of the “states of exception” in place throughout the year in municipalities bordering Colombia and imposed via the “Economic Emergency Decree,” the government ordered the suspension of the constitutional right to meet publicly or privately without obtaining permission in advance, as well as the right to demonstrate peacefully and without weapons. Security agencies did not routinely provide sufficient protection for protesters in public rallies or to political leaders sponsoring them. NGOs and political activists cited a widespread fear of repression due to the militarization of the country and the increasing activities of progovernment gangs, (“colectivos,”) against demonstrations. The government continued repressing protesters and their leaders. On September 3, authorities briefly detained 30 individuals on Margarita Island for heckling President Maduro, after scores of inhabitants protested food shortages by banging pots and pans. FREEDOM OF ASSOCIATION The constitution provides for freedom of association and freedom from political discrimination, but the government did not respect these rights. Although professional and academic associations generally operated without interference, a number of associations complained the National Electoral Council (CNE), which is responsible for convoking all elections and establishing electoral dates and procedures, and the Supreme Court repeatedly interfered with their attempts to hold internal elections. On July 26, Jorge Rodriguez, the mayor of Libertador municipality in Caracas and PSUV party leader, called on the CNE to dissolve the Democratic Unity Roundtable (MUD) opposition coalition due to alleged fraud committed during its campaign to organize a recall referendum. The president’s May 13 “state of exception” decree called upon the Foreign Ministry to suspend international funding to NGOs when “it is presumed” that funding is used with “political purposes or for destabilization.” Human Rights Watch pointed out that in a country where authorities routinely accused human rights defenders of destabilizing democracy, this order could effectively shut down or dramatically scale back the operations of NGOs that rely on foreign funding to work independently. As of December 1, there were no reports of the government implementing the threats contained in this decree. c. Freedom of Religion d. Freedom of Movement, Internally Displaced Persons, Protection of Refugees, and Stateless Persons The constitution provides for freedom of internal movement, foreign travel, emigration, and repatriation; however, the government did not respect these rights. Abuse of Migrants, Refugees, and Stateless Persons : Beginning in August 2015 and continuing during the year, the government implemented OLP security measures and increased the presence of security forces in Tachira State on the Colombian border. Authorities deported more than 1,700 Colombians in early stages of operations, and at least 22,000 more left the country due to fear of security abuses or deportation, according to the UN Office for the Coordination of Humanitarian Affairs. According to Colombia’s Ombudsman’s Office, which investigated 700 cases of deportations, none of the interviewed deportees received a hearing in order to challenge their removal. Many deportees claimed to have had legal permits to live in Venezuela. More than 400 of the Colombians who returned to Colombia had either requested asylum or been granted refugee status by Venezuela, according to the Global Protection Cluster in Colombia. With the refugee status determination process centralized at the National Refugee Commission (CONARE) headquarters in Caracas, asylum seekers waited as long as three years to obtain a final decision. During this period they had to continue renewing their documentation every three months to stay in the country and avoid arrest and deportation. While travelling to the commission, particularly vulnerable groups, such as women with young children, the elderly, and persons with disabilities, faced increased protection risks, such as arrest and deportation, extortion, exploitation, and sexual abuse by authorities at checkpoints and other locations. In addition to arbitrary deportations, Colombians expelled from the country complained of abuses by security forces. The IACHR reported that many deported Colombians alleged Venezuelan security forces used excessive force to evict them from their homes, which were subsequently destroyed, and that security agents subjected them to physical abuse and forceful separation from their families. While no official statistics were available, a women’s shelter reported recurring problems with gender-based violence and trafficking of refugee women. The government generally cooperated with the Office of the UN High Commissioner for Refugees (UNHCR) and other humanitarian organizations in providing protection and assistance to refugees, asylum seekers, and other persons of concern. In-country Movement : Following the declaration of a localized “state of exception” in August 2015, the government suspended transit through the national territory, including across international borders, and closed the border with Colombia. In August 2016 the countries negotiated an agreement to reopen the border gradually. The government deployed thousands of security forces to restrict access to Caracas in the days leading up a major opposition-organized rally on September 1. Citing public safety, the government also routinely shut down public transportation networks on days and in areas where the opposition attempted to hold political rallies. PROTECTION OF REFUGEES Access to Asylum : According to UNHCR, 98 percent of asylum seekers came from Colombia. UNHCR estimated there were approximately 167,000 Colombian citizens in need of international protection in the country. Most of the Colombians had not accessed procedures for refugee status determination, due to the inefficiency of the process. UNHCR reported only 6,843 persons legally recognized as refugees. The influx of individuals seeking international protection continued through the different border areas until August 2015, when the government began closing key border crossings between Tachira and Zulia states and Colombia as part of the “states of exception” and the OLP. The vast majority of such persons remained without any protection. On January 12, the Office of the Human Rights Ombudsman and UNHCR signed an agreement to guarantee refugees’ human rights. The agreement aimed to expand the presence of regional ombudsman offices in the border regions. On May 27, CONARE and UNHCR launched a joint program to better assist refugees’ needs. The program was designed to provide for a more complete registry of refugees, including victims of human trafficking. Access to Basic Services : Colombian asylum seekers without legal residency permits had limited access to the job market, education, and health systems. The lack of documentation created significant challenges to achieving sufficient protection and long-term integration. Section 3. Freedom to Participate in the Political Process The 1999 constitution, the country’s twenty-sixth since independence, provides citizens the ability to change their government through free and fair elections, but government interference, electoral irregularities, and manipulation of voters restricted the exercise of this right. In January government agencies harassed or fired workers following the December 2015 legislative elections. In June the CNE made available online a database of identifying citizens who had signed a petition requesting a recall referendum against President Maduro. PSUV politicians later used the database to fire or engage in employment discrimination against public employees and to withhold subsidized food benefits under the newly created Local Committees for Supply and Production program. Elections and Political Participation Recent Elections : On December 6, 2015, nationwide legislative elections took place largely peacefully, and the government initially accepted the results. Opposition candidates won 112 seats in the 167-seat National Assembly, while ruling-party PSUV candidates took 55 seats, despite a process that heavily favored the ruling party. The government rejected international election observation by the Organization of American States but permitted an “accompaniment” mission by the Union of South American Nations. Domestic observers reported voting machine failures, ruling-party tents illegally close to the entrance of the polls, improper use of public resources (e.g., state oil company vehicles with campaign slogans and government buses transporting supporters to vote), and press intimidation. In response to losing control of the legislative branch of government for the first time since 1999, the PSUV mobilized to appoint to the Supreme Court 13 new justices and 21 new alternates loyal to the PSUV. On December 30, 2015, this newly reconstituted TSJ blocked one ruling party deputy-elect and three opposition deputies-elect from Amazonas State from taking office, based on allegations of electoral fraud, a decision that deprived the opposition of its two-thirds super-majority in the legislature. On July 28, the National Assembly, ignoring the TSJ’s decision, swore in the three affected opposition deputies-elect for the second time. The TSJ subsequently ruled that the National Assembly was in contempt and all of its actions and future actions were invalid. In accordance with agreements from the dialogue talks, on November 15, the three opposition deputies from Amazonas State submitted their resignations to Congress. The government subsequently called for new elections in Amazonas State for late December, but the TSJ’s contempt ruling against the National Assembly stood. On October 20, the CNE suspended a nationwide, constitutionally based recall referendum process against President Maduro; the CNE referred to allegations of fraud in brought by government supporters before several state-level criminal courts. The CNE also declined to organize constitutionally mandated elections in December for the country’s 23 governorships. Political Parties and Political Participation : Opposition political parties operated in a restrictive atmosphere characterized by intimidation, the threat of prosecution or administrative sanction on questionable charges, and very limited mainstream media access. On September 2, after a series of partisan decisions favoring the ruling PSUV, the TSJ annulled all actions taken by the opposition-dominated National Assembly because of its failure to comply with previous TSJ rulings. Some political organizations reported their main activists and leaders were victims of harassment and violence by the government and progovernment groups. Participation of Women and Minorities : No laws limit the participation of women and members of minorities in the political process. A 2015 regulation requires political parties to put forth gender-balanced slates of candidates for legislative elections. Women held 24 of the 167 seats in the legislature and nine of the more than 30 cabinet-level positions. Section 4. Corruption and Lack of Transparency in Government The law provides criminal penalties for corruption by government officials, but the government did not implement the law effectively. Some government officials explicitly acknowledged impunity for corruption as a major problem. The government frequently investigated and prosecuted its political opponents on corruption charges to harass, intimidate, or imprison them. The Public Ministry cited numerous examples of investigations, stemming largely from improprieties in the distribution and sale of price-controlled items and in government currency allocations. Corruption : The government continued a campaign to combat corruption through fast-track authority and executive powers, but critics contended the government’s efforts focused only on low- to mid-level public officials while targeting high-level opposition politicians. The campaign included enforcement against smuggling of goods carried out by private citizens as part of what the government calls the fight against the “economic war” waged by the political opposition and foreign governments. According to the NGO Transparency Venezuela, weak government institutions and a lack of transparency allowed public officials at all levels to participate in corrupt activity with impunity. The National Assembly conducted its own corruption investigations, including against Rafael Ramirez, former head of PDVSA and current Venezuela Permanent Representative to the United Nations. Although well- publicized, these activities yielded no results. On August 17, a court sentenced two executives of the state-owned airline Conviasa to four and one-half years in prison for their involvement in an overpricing scheme. Corruption was a major problem in all police forces, whose members were generally poorly paid and minimally trained. There was no information publicly available about the number of cases involving police and military officials during the year, although the Public Ministry publicized several individual cases against police officers for soliciting bribes and other corrupt activities. In a June 14 report, Transparency Venezuela criticized the widespread practice of nepotism in the government and cited the example of Controller General Manuel Gallindo, who employed at least 13 close family members in his office. Financial Disclosure : The law requires public officials, as well as all directors and members of the boards of private companies, to submit sworn financial disclosure statements. By law the Public Ministry and competent criminal courts may require such statements from any other persons when circumstantial evidence arises during an investigation. In 2015 (the most recent data available) the Public Ministry cited 19,562 complaints or grievances of corruption, leading to charges against 4,119 individuals. Public Access to Information : Although the law provides for public access to government information, human rights groups reported the government routinely ignored this requirement. The law requires a government agency to respond to a petition within 20 days of filing. The agency must also notify the applicant within five days of any missing information needed to process the request. Government agencies are subject to sanctions if they do not respond to a request. If the agency rejects the petition, an individual may file another petition or appeal to a higher level within the government agency. The agency must respond to the appeal within 15 days. The Pro Access Coalition, composed of NGOs advocating for the right to access public information, released a study in 2013 noting the government ignored 94 percent of citizen petitions for information, a trend cited as continuing during the year. Section 5. Governmental Attitude Regarding International and Nongovernmental Investigation of Alleged Violations of Human Rights A variety of independent domestic and international human rights groups generally operated with some government restrictions. Major domestic human rights NGOs conducted investigations and published their findings on human rights cases. Government officials generally were not cooperative or responsive to their requests. Some domestic NGOs reported government threats and harassment against their leaders, staff, and organizations, in addition to government raids and detentions, but were able to publish dozens of reports during the year. NGOs played a significant role in informing citizens and the international community about alleged violations and key human rights cases. NGOs asserted the government created a dangerous atmosphere for them to operate. PSUV First Vice President Diosdado Cabello used his weekly talk show to intimidate members of NGOs, including Public Space, PROVEA, and Foro Penal. Several organizations, such as the OVP, PROVEA, Foro Penal, and Citizen Control, reported threats to their staff, conducted electronically or sometimes in person. Human rights organizations claimed they were subject to frequent internet hacking attacks and attempts to violate their e-mail privacy. The law prohibits domestic NGOs from receiving funds from abroad if they have a “political intent”–defined as those that “promote, disseminate, inform, or defend the full exercise of the political rights of citizens”–or that seek to “defend political rights.” The government threatened NGOs with criminal investigations for allegedly illegally accepting foreign funds. Various government officials accused human rights organizations on national television and media of breaking the law by receiving funding from international donors. For violations, the law stipulates monetary penalties, a potential five- to eight-year disqualification from running for political office, or both. The law defines political organizations as those involved in promoting citizen participation, exercising control over public offices, and promoting candidates for public office. Although there was no formal application or enforcement of the law, it created a climate of fear among human rights NGOs and a hesitancy to seek international assistance. In addition to the restrictions placed on fund raising, domestic NGOs also faced regulatory limitations on their ability to perform their missions. The law includes provisions eliminating the right of human rights NGOs to represent victims of human rights abuses in legal proceedings. The law provides that only the public defender and private individuals may file complaints in court or represent victims of alleged human rights abuses committed by public employees or members of the security forces. The United Nations or Other International Bodies : The government was generally hostile toward international human rights bodies and continued to refuse to permit a visit by the IACHR, which had not visited the country since 2002. The government withdrew from the Inter-American Convention on Human Rights in 2013, but the IACHR continues to receive complaints from citizens and civil society. The government also refused to grant access to the OHCHR to investigate the human rights situation. The IACHR, UNHRC, and other human rights bodies criticized the government’s handling of human rights issues during the year, including a September 29 joint statement by 30 countries at the 33rd session of the UN Human Rights Council. Government Human Rights Bodies : In its May report, the Global Alliance of Human Rights Institutions, an international organization of national human rights institutions, recommended downgrading the country’s status and cited the Office of the Human Rights Ombudsman, also called the Public Defender, for its failure to respond impartially to cases of human rights abuses in 2014. On February 27, President Maduro approved the national Human Rights Plan for 2016-19. Several NGOs criticized the plan, saying that it was produced without consultation. Throughout the year the government gave the plan minimal attention. The National Assembly’s subcommission on human rights played an insignificant role in human rights debates. Section 7. Worker Rights a. Freedom of Association and the Right to Collective Bargaining The law provides that all private- and public-sector workers (except armed forces members) have the right to form and join unions of their choice, and it provides for collective bargaining and the right to strike. The law, however, places several restrictions on these rights, and in practice, the government deployed a variety of mechanisms to undercut the rights of independent workers and unions. Minimum membership requirements for unions differ based on the type of union. Forming a company union requires a minimum of 20 workers; forming a professional, industrial, or sectoral union in one jurisdiction requires 40 workers in the same field; and forming a regional or national union requires 150 workers. Ten persons may form an employees association, a parallel type of representation the government endorses and openly supports. The law prohibits “any act of discrimination or interference contrary to the exercise” of workers’ right to unionize. The law requires that all unions must provide the Ministry of Labor a membership roster that includes the full name, home address, telephone number, and national identification number for each union member. The ministry reviews the registration and determines whether the union fulfilled all requirements. Unions must submit their registration by December 31 of the year the union forms; if not received by the ministry or if the ministry considers the registration unsatisfactory, the union is denied the ability legally to exist. The law also requires the presence of labor inspectors to witness and legitimize unions’ decisions before the Ministry of Labor. The International Labor Organization (ILO) raised concerns about the ministry’s refusal to register trade union organizations. Under the law employers may negotiate a collective contract only with the union that represents the majority of their workers. Minority organizations may not jointly negotiate in cases where no union represents an absolute majority. The law also places a number of restrictions on unions’ ability to administer their activities. For example, the CNE has the authority to administer internal elections of labor unions, federations, and confederations. By law elections must be held at least every three years. If CNE-administered and -certified elections are not held within this period, the law prohibits union leaders from representing workers in negotiations or engaging in anything beyond administrative tasks. The ILO repeatedly found cases of interference by the CNE in trade union elections and called since 1999 to delink the CNE from the union election process. The law recognizes the right of all public- and private-sector workers to strike, subject to conditions established by law. By law workers participating in legal strikes receive immunity from prosecution, and their time in service may not be reduced by the time engaged in a strike. The law requires that employers reincorporate striking workers and provides for prison terms of six to 15 months for employers who fail to do so. Replacement workers are not permitted during legal strikes. The law prohibits striking workers from paralyzing the production or provision of essential public goods and services, but it defines “essential services” more broadly than ILO standards. The ILO called on the government to amend the law to exclude from the definition of “essential services” activities “that are not essential in the strict sense of the term…so that in no event may criminal sanctions be imposed in cases of peaceful strikes.” The minister of labor and social security may order public- or private-sector strikers back to work and submit their disputes to arbitration if the strike “puts in immediate danger the lives or security of all or part of the population.” Other laws establish criminal penalties for the exercise of the right to strike in certain circumstances. For example, the law prohibits and punishes with a five- to 10-year prison sentence anyone who “organizes, supports, or instigates the realization of activities within security zones that are intended to disturb or affect the organization and functioning of military installations, public services, industries and basic [mining] enterprises, or the socioeconomic life of the country.” In addition, the law provides for prison terms of two to six years and six to 10 years, respectively, for those who restrict the distribution of goods and for “those…who develop or carry out actions or omissions that impede, either directly or indirectly, the production, manufacture, import, storing, transport, distribution, and commercialization of goods.” The government restricted the freedom of association and the right to collective bargaining through administrative and legal mechanisms. Organized labor activists reported that the annual requirement to provide the Ministry of Labor a membership roster was onerous and infringed on freedom of association; they alleged the ministry removed member names from the rosters for political purposes, particularly if members were not registered to vote with the CNE. Labor leaders also criticized the laborious and costly administrative process of requesting CNE approval for elections and subsequent delays in the CNE’s recognition of such union processes. Additionally, there reportedly was a high turnover of Ministry of Labor contractors resulting in a lack of timely follow-through on union processes. Labor unions in both the private and public sectors noted long delays in obtaining CNE concurrence to hold elections and in receiving certification of the election results, which hindered unions’ ability to bargain collectively. The TSJ suspended union elections for the Orinoco Iron Workers Union (Sintraferrominera) three days before the scheduled May 27 vote. The TSJ ruling criticized irregularities in the call for elections, but the media reported that a more likely reason for the suspension was the low support for the PSUV union leader running for re-election. The Venezuelan Unitary Federation of Oil Workers (FUTPV) for Venezuelan Petroleum (PDVSA) workers had scheduled elections for August, but the FUTPV president, who had been due to run for re-election since 2014, again postponed the vote. According to potential opponent Jose Boadas, the government ordered a further delay to avoid “an imminent defeat” of the progovernment candidate and PSUV activist Wills Rangel. According to PROVEA, “large sectors of national, state, and municipal public administrations and an important number of state enterprises continued to refuse to discuss collective agreements.” According to the Autonomous Front in Defense of Employment, Wages, and Unions (FADESS), there were more than 300 expired public-sector union contracts nationwide. Labor leaders reported the majority of unions that failed to negotiate collective agreements were in the public sector. The Model Contract for Public Administration, which covers approximately three million public workers, was last negotiated in 2004. President Maduro promised it would be finalized in 2013, but no further progress was made during the year. The government did not respond to at least two formal ILO requests for information about reports that the majority of collective bargaining agreements in the public sector had expired but continued to be applied, with the right to collective bargaining denied by authorities due to “overdue elections” (not convoking or concluding the electoral process). The government continued to support many “parallel” unions, which sought to dilute the membership and effectiveness of traditional independent unions. In general these government-supported unions were not subject to the same government scrutiny and requirements regarding leadership elections. For example, the Socialist Bolivarian Workers’ Central had not held elections since 2011, yet it was regularly accredited to participate in ILO meetings, including for the ILO International Labor Conference in Geneva in June. The government excluded from consideration other, independent union federations, including the Confederation of Venezuelan Workers, the General Confederation of Venezuelan Workers, Confederation of Autonomous Unions of Venezuela, and National Union of Workers (UNETE). The ILO expressed continuing concern that the government did not consult with representative worker organizations or accredit their members to the ILO conference. In contrast, the Labor and Trade Union Action Unit, an independent organization of labor federations and other labor groups and movements, was able to meet freely to coordinate interventions for the July meeting, analyze conclusions from the meeting, and discuss follow-up actions. According to the labor group FADESS, the ministry did not send labor inspectors to opposition-leaning union meetings to witness and legitimize unions’ decisions, as required by law, thus rendering moot decisions by many unions. The government continued to refuse to adjudicate or otherwise resolve the cases of 19,000 employees of the state oil company, PDVSA, who were fired during and after the 2002-03 strike. The Ministry of Labor continued to deny registration to the National Union of Oil, Gas, Petrochemical, and Refinery Workers (UNAPETROL), a union composed of these workers. Union elections in the state steel conglomerate’s workers’ trade union were suspended in 2014, and the TSJ upheld the suspension in January 2015. Union leaders in the construction sector were subject to violent attacks–some of which resulted in killings. The lack of effective investigations made determining the motives for such attacks difficult; NGOs alleged the killings were the result of rival attacks over contracts. According to OVCS and PROVEA, the government did not make arrests or prosecute anyone for most violent crimes, including those committed between and against union workers, and few were solved. PROVEA reported that fewer than 5 percent of the cases were investigated. The ILO requested the government establish a national tripartite committee on situations of violence and provide information on the findings of the investigations carried out by the national prosecutor appointed to investigate all cases of violence against trade union leaders and members. Union leaders were also subjected to harassment and verbal attacks. For instance, on his weekly television show, the former National Assembly president Diosdado Cabello made accusations against leaders from FADESS and the National Association of Autonomous Workers, Entrepreneurs, and Small Business Persons. The ILO raised concerns about violence against trade union members and government intimidation of the Associations of Commerce and Production of Venezuela (FEDECAMARAS). The OVCS 2015 report on labor conflicts released on May 2 noted there were 969 labor-related protests in 2015. The OVCS’s data revealed that salary increases had been insufficient to offset the impact of high inflation, layoffs, and other deteriorating conditions for workers. The OVCS reported that during the first six months of the year, there were 624 labor rights-related protests related to increased pay and benefits, the need for collective bargaining agreements, and outsourcing and the integration of contract workers. According to media reports, the government blacklisted and punished union leaders and workers for peaceful protests demanding wage increases and better conditions at work. In practice the concept of striking had been demonized since 2002 and periodically used as a political tool to accuse government opponents of coup plotting or other destabilizing activities. Legal provisions on the right to strike were used to target company management as well as labor leaders. Labor activists were charged under legal provisions on impeding the production, manufacture, import, storing, transport, distribution, and commercialization of goods, as well as under provisions for “instigation to commit a crime,” “blocking public access,” and restriction of the “right to work.” According to some business managers, some union leaders had extraordinary power to cause the arrest and prosecution of business managers for actions that could be considered normal aspects of their jobs. Some companies, especially in the public sector, had multiple unions with varying degrees of allegiance to the ruling party’s version of the “socialist revolution,” which could trigger interunion conflict and strife. A 2012 law set a May 7 deadline for the incorporation of all contract workers in both the public and private sectors into the companies for which they worked. (The largest number of contract workers is in the public sector.) The media reported concerns that this deadline was not met and that the status of a large percentage of workers was not regularized. While there were no official statistics, media sources estimated that 40 percent of the contractor force had been transitioned into formal positions. On June 7, dozens of workers from the state-owned electric utility company Corpoelec went on a hunger strike to pressure the government to resume negotiations for a collective bargaining agreement, as well as to protest a prohibition of the right to assembly on Corpoelec premises imposed by Electricity Minister Luis Motta. The collective bargaining negotiations had been suspended since May 3. The secretary general of the Electric Workers Federation (FETRAELEC), Reynaldo Diaz, said the union submitted a proposal of terms for the collective bargaining agreement to Labor Minister Osvaldo Vera on May 9 and had not received a response. After the first six days of the hunger strike, some workers faced health complications, and the strike was halted. FETRAELEC representatives declared they would continue pressuring the government with protests and strikes until the collective bargaining agreement was signed. b. Prohibition of Forced or Compulsory Labor The law prohibits some forms of forced or compulsory labor but does not provide criminal penalties for certain forms of forced labor. The law prohibits human trafficking by organized criminal groups through its law on organized crime, which prescribes 20 to 30 years’ imprisonment for human trafficking carried out by a member of an organized criminal group of three or more individuals. The organized crime law, however, fails to prohibit trafficking by any individual not affiliated with an organized criminal group and fails to prohibit trafficking men. Prosecutors could employ other statutes to prosecute such individuals. The law includes harsher penalties for imposing forced labor on minors. There was no comprehensive information available regarding the government’s enforcement of the law. On July 19, the Ministry of Labor published Resolution 9855 requiring public- and private-sector businesses to provide male and female workers for 60 to 120 days in order to increase agricultural production. Amnesty International criticized the resolution as effectively amounting to forced labor. The resolution noted that the government would pay workers their normal salary while they participated in the program and that workers would not be fired from their ordinary jobs. The government did not implement the resolution during the year. There were isolated reports of children and adults subjected to forced labor, particularly in the informal economic sector, in domestic servitude (see section 7.c.), and of Cubans working in government social programs (such as the Mission Inside the Barrio) in exchange for the government’s provision of oil resources to the Cuban government. Indicators of forced labor reported by some Cubans included chronic underpayment of wages, mandatory long hours, limitations on movement, and threats of retaliatory actions to the workers and their families if they left the program. c. Prohibition of Child Labor and Minimum Age for Employment The law sets the minimum employment age at 14 years. Children younger than 14 may work only if granted special permission by the National Institute for Minors or the Ministry of Labor. Such permission may not be granted to minors under the age for work in hazardous occupations that risk their life or health or could damage their intellectual or moral development, but according to the ILO, the government had not made publicly available the list of specific types of work considered hazardous. Children ages 14 to 18 may not work without permission of their legal guardians or in occupations expressly prohibited by the law, and they may work no more than six hours per day or 30 hours per week. Minors under 18 may not work outside the normal workday. The law establishes fines on employers between BsF 6,420 ($642, or $9.68 at the Dicom exchange rate as of December 1) and BsF 12,840 ($1,284, or $19.36 at the Dicom rate) for each child employed under age 12 or for adolescents between 12 and 14 employed without proper authorization. Anyone employing children under age eight is subject to a prison term between one and three years. Employers must notify authorities if they hire a minor as a domestic worker. The Ministry of Labor and the National Institute for Minors enforced child labor laws effectively in the formal sector of the economy but less so in the informal sector. No information was available on whether or how many employers were sanctioned for violations. The government also continued to provide services to vulnerable children, including street children, working children, and children at risk of working. There was no independent accounting of the effectiveness of these and other government-supported programs. Most child laborers worked in the agricultural sector, street vending, domestic service, or in small to medium-size businesses, most frequently in family-run operations. There continued to be isolated reports of children exploited in domestic servitude, mining, forced begging, and commercial sexual exploitation of children (see section 6). d. Discrimination with Respect to Employment and Occupation The constitution prohibits employment discrimination for every citizen. Labor law prohibits discrimination based on age, race, sex, social condition, creed, marital status, union affiliation, political views, nationality, disability, or any condition that could be used to lessen the principle of equality before the law. No law specifically prohibits employment discrimination on the basis of sexual orientation, gender identity, or HIV/AIDS status. The media and NGOs, such as PROVEA and the Human Rights Center at the Andres Bello Catholic University, reported the government had a very limited capacity to address complaints and enforce the law in some cases and lacked political will in some cases of active discrimination based on political motivations. On January 3, President Maduro signed a presidential decree to protect government workers and shield them against arbitrary dismissals until 2018. Nevertheless, there were numerous reports of public workers who voted for the opposition in the December 2015 parliamentary elections being fired for “counterrevolutionary” activities. The Food Production and Distribution agency (PDVAL) fired 34 workers in the weeks following the December election and posted a listing referring to the dismissed workers as “traitors.” The decision to disclose their names appeared intended to publicly shame the dismissed workers, goad progovernment loyalists into harassing them, and discourage future antiregime political activities. According to the media, workers at several other government agencies reported harassment, threats of firing, and labor discrimination for political reasons following the December election. Both the Children’s Foundation and a mayor’s office in Tachira State received criticism for alleged discrimination toward opposition voters. In May, PSUV First Vice President and National Assembly Deputy Diosdado Cabello publicly announced that opposition supporters working for the public administration should leave their positions. In June Cabello called on governors’ offices, mayors’ offices, and ministries to identify employees that did not support President Maduro. Other progovernment politicians threatened to take actions against those who signed a recall referendum petition against Maduro after the CNE publicly disseminated a complete listing of signatories in early June, stating that government supporters should not tolerate opposition supporters working “in the revolutionary government.” Human Rights Watch reported in July that the National Tax Revenue Service (SENIAT) fired dozens of workers nationwide in apparent retaliation for supporting a recall referendum against Maduro. Other government agencies reportedly fired hundreds of other referendum supporters in similar circumstances. The Venezuelan National Petroleum Workers Federation announced on October 20 that PDVSA had rescinded the contracts of 2,000 temporary oil workers for political reasons. e. Acceptable Conditions of Work The government raised the monthly minimum wage four times between January and October 26, reflecting a 180-percent increase, bringing it to a total of BsF 27,000 ($2,700, or $40.72 at the Dicom exchange rate as of December 1). The minimum wage also included a nonsalary food ticket subsidy of BsF 64,000 ($6,400, or $96.53 at the Dicom rate), bringing the total monthly minimum wage to BsF 91,000 ($9,100, or $137.25 at the Dicom rate). According to the NGO Workers’ Center for Documentation and Analysis, the monthly food basket for a family of five for September cost BsF 465,035 ($46,503, or $701.41 at the Dicom rate), or 7.1 times the minimum wage. The law sets the workweek at 40 hours (35 hours for a night shift). The law establishes separate limits for “shift workers,” who may not work more than an average of 42 hours per week during an eight-week period, with overtime capped at 100 hours annually. Managers are prohibited from obligating employees to work additional time, and workers have the right to two consecutive days off each week. Overtime is paid at a 50-percent surcharge if a labor inspector approves the overtime in advance and at a 100-percent surcharge if an inspector does not give advance permission. The law establishes that after completing one year with an employer, the worker has a right to 15 days of paid vacation annually. The worker has the right to an additional day for every additional year of service, for a maximum of 15 additional days annually. The law provides for secure, hygienic, and adequate working conditions. Workplaces must maintain “protection for the health and life of the workers against all dangerous working conditions.” The law obligates employers to pay workers specified amounts for workplace injuries or occupational illnesses, ranging from two times the daily salary for missed workdays to several years’ salary for permanent injuries. Workers may remove themselves from situations that endanger health or safety without jeopardy to their employment. The law covers all workers, including temporary, occasional, and domestic workers. Reportedly, there was some enforcement by the Ministry of Labor of minimum wage rates and hours of work provisions in the formal sector, but 40 percent of the population worked in the informal sector, where labor laws and protections generally were not enforced. The government did not enforce legal protections on safety in the public sector. According to PROVEA, while the National Institute for Prevention, Health, and Labor Security required many private businesses to correct dangerous labor conditions, the government did not enforce such standards in a similar manner in state enterprises and entities. There was no publicly available information regarding the number of inspectors or the frequency of inspections to implement health and safety, minimum wage, or hours of work provisions. Ministry inspectors seldom closed unsafe job sites. Employers may be fined between BsF 12,840 ($1,284, or $19.36 at the Dicom rate) and BsF 38,520 ($3,852, or $58.08 at the Dicom rate) for failing to pay the minimum wage or provide legally required vacation time. Employers are required to report work-related accidents within 24 hours or face fines between BsF 8,132 ($813, or $12.26 at the Dicom rate) and BsF 10,700 ($1,070, or $16.13 at the Dicom rate). There was no information on whether penalties were sufficient to deter violations.
https://www.state.gov/report/custom/2650555aa9-8/
Janyure And 4 Others v NRZ (HB 3 of 2021; HCA 32 of 2018) [2021] ZWBHC 3 (25 March 2021) - ZimLII Janyure And 4 Others v NRZ (HB 3 of 2021; HCA 32 of 2018) [2021] ZWBHC 3 (25 March 2021) Document detail Jurisdiction Zimbabwe Citation Janyure And 4 Others v NRZ (HB 3 of 2021; HCA 32 of 2018) [2021] ZWBHC 3 (25 March 2021) Copy Media Neutral Citation [2021] ZWBHC 3 Copy Case number HB 3 of 2021 ; HCA 32 of 2018 Court Bulawayo High Court Judges Makonese J , Moyo J Judgment date 25 March 2021 Language English Type Judgment Download Download DOCX (19.6 KB) Download PDF Other documents Download PDF (306.0 KB) 2 HB 03/21 HCA 32/18 ZEDIAS JANYURE And IFONDUKAYIFELI MANGENA And EDWARD CHIMBADWA And WILSON BULALA And SIMON TAKUVINGA TIZAYI Versus NRZ IN THE HIGH COURT OF ZIMBABWE MAKONESE & MOYO JJ BULAWAYO 11 NOVEMBER 2020 & 25 MARCH 2021 Civil Appeal Applicants in person L. Ncube for the respondent MOYO J: The appellants in this matter are former employees of the respondent. Respondent sued the appellants for eviction in the Magistrates’ Court and the court found in respondent’s favour. Dissatisfied with that appellants approached this court. The appeal was dealt with and dismissed ex tempore . They have now requested for written reasons and here are they. The facts of the matter are that the employment of the appellants was terminated with the respondent for various reasons up to 2013. In other words the employee whose employment terminated last in the group left employment in 2013. The facts of this matter are very simple and straight forward. The former employees and the employer were governed by a Collective Bargaining Agreement namely SI 61/99. They had been housed in respondent’s properties prior to cessation of employment. Upon cessation of employment (even if they refute this, they simply had no right of retention over the accommodation they had been provided as employees). There was just 1 issue for determination by the court a quo that is whether the appellants had the right to remain in occupation of respondent’s properties after the cessation of their employment. The appellants did not dispute that their employment was terminated as alleged. What they claim is that they could not be evicted because the respondent owed them $25 000 Zimbabwe dollars at the material time. The respondent disputes that they are owed $25 000 and avers that they were entitled to $10 000,00 which they were paid in full. The only guiding instrument in this regard is SI 61/99 (the Collective Bargaining Agreement). Appellants are clearly former employees but they argue that clause 4 of the Collective bargaining Agreement applies to them. However clause 4 of the Collective Bargaining Agreement is couched in no uncertain terms. It reads as follows: “ The aspect of funding is yet to be concluded. However, in the meantime no employee is to be evicted until funding has been put in place. Meanwhile those with cash can proceed to purchase the houses as agreed above.” Clearly the clause as interpreted by the learned magistrate refers to “employees” not former employees”. Again, in terms of clause 11 (a) of the Collective Bargaining Agreement, termination of employment ends tenancy. So clearly, the tenancy phase of the appellants in respondent’s accommodation ended when they left employment. The case is very clear. It means that and cannot mean anything else. I then turn to the grounds of appeal. The grounds of appeal attack the learned magistrate’s interpretation of the Collective Bargaining Agreement and that the learned magistrate did not regard the Collective Bargaining Agreement and weekly notice 2313 of 14 January 1999. The learned magistrate did interpret the provisions relevant to the appellant’s case and found that the Collective Bargaining Agreement did not support their cause and that is the position. Weekly notice 2313 of 14 th January 1999, whilst its provisions are not clear, cannot supercede a statutory instrument which is the law. The same applies to the letter the appellant says was written by the human resources manager, it also cannot supercede a statutory instrument whatever its provisions were. The appellants also seem to take issue with the magistrate for not following a fellow magistrate’s decision but a magistrate is not bound by a fellow magistrate’s decision, a magistrate is only bound by the decision of a higher court. Again, even if for argument’s sake, the appellants would be entitled to the $25 000,00 they claim is due to them, it does not in itself create a right of retention for them. They could have approached the court to enforce that payment if they felt they were entitled to it as it clearly does not follow that if you are owed certain monies by your former employer, you then create a right of retention of accommodation for yourself. They should have pursued their claim for the sums owed by the respondent if any. It is for these reasons that we found that the appeal lacks merit and accordingly dismiss it. Makonese J ………………………. I agree James, Moyo-Majwabu & Nyoni, respondent’s legal practitioners
https://zimlii.org/akn/zw/judgment/zwbhc/2021/3/eng@2021-03-25
Paleolithic & Mesolithic [Archive] - Eupedia Forum [Archive] Paleolithic & Mesolithic Do modern Europeans partly descend from Neanderthal ? 25,000-year-old Russian Cro-Magnons might have been hg H17 Unknown mtDNA lineage found in 40,000 hominid in Russia : Neanderthal connection ? Solutrean hypothesis: Native American Clovis Culture & NW Europe: (ydna Q, mtdna X2) Homo heidelberg sapiensis New Denisovan DNA results 700,000 year-old horse DNA sequenced AMAZING depictions humans in Europe from 15,000-42,000ybp 24,000 year old Mal'ta Siberians (ydna R* and mtdna U*) Guess the Y-haplogroup(s) of Mesolithic Iberians (Braña 1 & 2) The DNA of the mesolithic hunter. Absent or present in northern European population? The Genetic Legacy of the Neanderthals Clovis culture: Genome of 12,600 year-old boy from Clovis culture confirms origin of Amerindians MtDNA and Skeletal Link between Paleo-americans and Native Americans Video of the Loschbour man Ust-Ishim close to a population ancestral to both Europeans and Asian Denisovians Interbreeding With Unknown Ancient Humans Neandertal origin of MC1R haplotypes related to skin color Ust-Ishim: a 45.000 siberian 36,200YBP European genome Kennewick Man Was Native American 6000 yo EHG pile dwellings near lakes and rivers in NW Russia : R1a1 -M17 Ice Age Europeans On Brink Of Extinction Old Italian mtdna from Aurignacian period 37-42ky Human with Recent Neanderthal Ancestry Pinhasi et al-Ancient dna recovery Revisiting the issue of "Ice Age refugia" in the context of WHG, SHG, EHG ancestries Mesolithic La Brana skeletons were Brothers? ancient J1b-F4306(xZS80) Satsurblia Late Upper Palaeolithic Caucasus Paleolithic Caucasus=UHG+Basal Eurasian+MA1 Evidence for Early Pleistocene Afro-Iberian dispersals Wallace Line and Denisovan Admixture Ancient MtDna from Europe-Single Dispersal from Africa and Population Turnover DNA shows that Homo sapiens and Neanderthals first admixed over 100,000 years ago Who lived during the LGM in Crimean Refugium? Population turn-around 14,500 bp and Europeans derived from 4 populations Genetic Analysis of "Proto-Neanderthals" from Sima de los Huesos The effect of a high protein diet on Neanderthals Neanderthal Ydna Neanderthal differential pathogen resistance" extinction model Did Neanderthals die of diseases brought by AMH newcomers? The genetic history of Ice Age Europe Partial ancient mtDna from the Jomon people of Japan Papuans have at least 2% of ancestry from early Out-of-Africa migration 90,000 ybp Ancient mtDna from the Iberomaurisian LBK mtDNA match with Mesolithic Greece Deep relationships of modern human genetic lineages outside of Africa Three brother's event (Brother lineages survivors) Ust'-Ishim and Oase1 belong to Haplogroup NO* according to a Chinese team The Neolithic Transition in the Baltic Was Not Driven by Admixture with Early Europea To everyone who claims that Malta Boy was "Mongoloid" DNA provides window into early Aboriginal history Did Cro-Magnonon males Interbred with Aborigininal females ? More genomes from Mesolithic Romania and Spain (Gonzales-Fortes et al. 2017) does R1b-V88 originate from the Iron Gate ? Vasilyevka 3 (Ukraine mesolithic) in Eurogenes K36 Who were native europeans in Mesolithic era Neolithic Farmers and Mesolithic Hunter-Gatherers in the Lower Danube Basin Scandinavian match to Clovis? was E1b1b1b1-L19 the founding father of the Ibero-Maurisians? A high-coverage Neandertal genome from Vindija Cave in Croatia 40,000 year old sample from Asia-Tianyuan Cave The Ainu ethnogenesis through ancient mtDna North American Paleo Eskimo genetics Computer Simulation: Neanderthal replacement by migration & random species drift Nasal airflow simulations: convergent adaptation in Neanderthals & Modern Humans Question about the Villabruna Cluster and Cluster in general Mesolithic Scandinavia: Early Postglacial Migration Routes & High-Latitude Adaptation Failed Homo Sapiens Dispersals Out of Africa? Insights into Modern Human Prehistory Using Ancient Genomes First modern Britons had 'dark to black' skin, Cheddar Man DNA analysis reveals Scientists discover genomic ancestry of Stone Age North Africans from Morocco Signals of ghost admixture in Yoruba related populations Sumerians and Native Americans could be related? Homo Sapiens in Arabia by 85,000 years ago Near East Refuge? 50 ka and 30 ka bones found in Buryatia Ancient parallel lineages within North America Multiple episodes of Neanderthal/Human Interbreeding? Into Asia-Review of Current thinking Evolution of Homo Sapiens The Genetics of Modern Wolves More on "Out of Africa" 45,000 yo human teeth show similarities to San Multiple models for the peopling of the Americas 50k Year Old Girl Found to be 1/2 Neaderthal and 1/2 Denisovan Cheddar man Talks from the ISBA Conference 2018 15 ka DNA from Anatolia Prehistoric peopling in southeast Asia Late Pleistocene genome suggests a local origin for the first farmers from Anatolia Paleolithic DNA from the Caucasus How Neanderthals made us sick Levantine and southern Arabian populations have a shared population history Svante Pääbo - Pioneer of Palaeogenetics Ancient Andean genomes show distinct adaptations to farming and altitude The population history of northeastern Siberia since the Pleistocene Reconstructing the Deep Population History of Central and South America Ancient DNA confirms Native Americans’ deep roots in North and South America Early post-glacial dual route colonization of Scandinavia confirmed by "chewing gum" Displaced archaic admixture across the X chromosome Elba, the first Mesolithic woman found in Spain Limits of selection against Neanderthal dna A third archaic introgression into Asia and Oceania? Cheddar Man, Mesolithic Britain, GEDmatch results North Norwegian Mesolithic Hunter, GEDmatch Oldest sample with R1a on GEDmatch "Ghost" Archaic introgression in African populations Anatolian Hunter-Gatherer GEDmatch Question about Behavioral modernity Denisovans may have mated with modern humans as recently as 15,000 years ago Expanding the horizons of Palaeolithic rock art: the site of Romualdova Pećina Multiple Deeply Divergent Denisovan ancestries in Papuans Mesolithic Polish Hunter-Gatherer who were the first Americans? Jomon Woman's Genome Decoded Is the Neanderthal lineage older than we thought Oldest Dna in Scandinavia found in "chewing gum" More on the Jomon people Neanderthal and Denisovan interbred with an archaic hominin Y and mtDna from East Asia, autosomes multi-regional? Sicilian Hunter-Gatherer GEDmatch Late Upper Palaeolithic hunter-gatherers in the Central Mediterranean The geographical range of early Homo Sapiens has been extended to Greece New Samples from Iberomaurisian Taforalt Clues to early social structures may be found in ancient extraordinary graves How CHG did look like? Albrigi A 5700 year-old human genome and oral microbiome from chewed birch pitch The last stand of Homo Erectus Divergence between archaic and modern humans may date to 260,000 years ago. Neanderthal Dna in Africa how, where and when were CHG and steppe ancestry born? new paper on neanderthals Humans may have reached Europe earlier than thought Increased fertility for women with Neanderthal gene Denisovan ancestry and population history of early East Asians Are R1b and R1a ultimately East Asian lineages? Third Neanderthal Genome Sequenced The Gravettian Diffusion How far were ANE/EHG/WSHG spread? Severe genetic bottleneck in Asian HGs after invention of agriculture COVID-19 related to Neanderthal Chromsome 3? Sources for ancient DNA (23andme/ftdna format)? Early Alpine human occupation backdates westward human migration in Late Glacial Euro Early Aurignacian dispersal into westernmost Europe Ancestors of First Americans in East and Northeast Asia Denisovans and Early East Asian pop. history Monozygotic Twins in the Paleolithic Origin of Native Americans and expansion of y line C2a‐L1373 Homo Sapiens in Arabia 85,000 years ago The blood types of the Neanderthals Back to Africa with Deep Learning and Whole Genomes Dzudzuana paper prepint gives a hint of *TWO* Basal Eurasian lineages. The evolution of skin pigmentation-associated variation in West Eurasia. Basal Eurasian in 25,000 yo site? Archaic introgression and local adaptation Earliest paleolithic homo sapiens remains from bacho kiro cave bulgaria New Paper on Ancient Eurasian DNA Nick Patterson of Harvard: Cryptography to Neanderthals. Interesting and insightful take on Iberomaurusians and their relationship with BE. Neanderthal introgression of mechanisms of response to environment Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry A genome sequence from a modern human skull ~45,000 years old from Zlatý kůň Czechia The genome of a woman ∼34,000 ago, reduced diversity, genetic load. denisovan epas1 gen into Tibetans "...only 1.5 to 7% of the modern human genome is uniquely human" Scientists unveil extinct Ice Age lion cubs pulled from Russian permafrost Upper Paleolithic and Mesolithic hunter-gatherers in the modern Caucasus Revisiting the out of Africa event with a deep-learning approach Upper Palaeolithic hunter-gatherers from San Teodoro cave Sicily Ancient DNA and deep population structure in sub-Saharan African foragers. Ancient DNA and deep population structure in sub-Saharan African foragers Beringia and the settlement of the western hemisphere Origin of Y-haplogroup R transition mesolithic to neolithic in sicily repeated expansions into Paleolithic Eurasia from a population hub out of Africa Hoabinhian DNA Haplogroup E from Arabia/Natufian ancestry Between fishing and farming. The Neolithic in the Danube Gorges. Preprint. A Late Pleistocene human genome from Southwest China. WHG arrived in Europe by which route? Hunter-gatherer admixture facilitated natural selection in Neolithic European farmers What was the Y-DNA of Afontova Gora? The Selection Landscape and Genetic Legacy of Ancient Eurasians. Preprint. Basques more WHG or Neolithic British late Paleolithic ancestry is dual Which Y-DNA mostly carried 25.000 BC Siberia and Central Asia? WHG and EEF/CHG in the PCA Genomic ancestry, diet and microbiomes of Upper Palaeolithic hunter-gatherers. 2 million yo DNA from northern Greenland Professor Lee Berger January annoucement 2 new Papers on ancient European DNA from UP to Neolithic Reconstructing past human genetic variation with ancient DNA. History and evolution of the Picene Culture through Ancient DNA analysis
https://www.eupedia.com/forum/archive/index.php/f-264.html?s=f85e541c155d22c640b4a00467e7169a
Vandergriff v. State, 239 Ark. 1119, 396 S.W.2d 818 (1965) | Caselaw Access Project Full text of Vandergriff v. State, 239 Ark. 1119, 396 S.W.2d 818 (1965) from the Caselaw Access Project. Vandergriff v. State, 239 Ark. 1119, 396 S.W.2d 818 (1965) Dec. 13, 1965 · Arkansas Supreme Court · 5-3663 239 Ark. 1119, 396 S.W.2d 818 Case outline majority — frank holt, associate justice. Vandergriff v. State, 239 Ark. 1119, 396 S.W.2d 818 (1965) 239 Ark. 1119, 396 S.W.2d 818 Vandergriff v. State Vandergriff v. State. 5-3663 396 S. W. 2d 818 Opinion delivered December 13, 1965. Bruce Bennett,Attorney General, By: Richard B. Adkisson,Chief Asst. Atty. Gen., and Fletcher Jackson,Asst. Atty. General, for appellee. Frank Holt, Associate Justice. Appellant brings this appeal from a civil proceeding in- circuit court in which he was held in contempt and his premises permanently padlocked pursuant to the provisions of Ark. Stat. Ann. <§ 34-101 et seq (Repl. 1962). The appellee, by the prosecuting attorney, filed a verified petition against the appellant on March 2, 1964 in the First Division of Pulaski Circuit Court alleging that appellant was operating an establishment at 110 Main Street, Little Rock, Arkansas where gaming was being carried on and praying for a temporary and permanent injunction to abate the alleged nuisance. On that day the court granted the temporary order. Upon a hearing before the court on March 27, 1964 the court found that the establishment, consisting of three floors*1120occupied by the appellant, was being operated in violation of Ark. Stat. Ann. § 34-101 in that gaming was being carried on, and that its operation constituted a public nuisance requiring abatement. The court permanently enjoined appellant from operating the establishment contrary to law, removed the temporary padlock, and authorized him to operate any lawful business. See Ark. Stat. Ann. § 34-106-7; Futrellv. State,207 Ark. 452,181 S. W. 2d 680; B & M Land Co.v. State,232 Ark. 815,340 S. W. 2d 395. On January 12, 1965 the prosecuting attorney again filed a verified petition against appellant in the same court, reciting the foregoing facts and alleging that appellant had violated the order of the court by operating his establishment as a public nuisance in that gaming existed in violation of the law. On that day the court granted the appellee’s petition for a temporary injunction and ordered appellant to appear on January 21, 1965 to show cause why he should not be adjudged in contempt for violation of the court’s order rendered in March, 1964. On the date scheduled the court conducted a hearing and found appellant had operated his establishment contrary to the provisions of Ark. Stat. Ann. § 34-101, that such operation constituted a public nuisance, and that appellant had violated the court’s permanent injunction. The court then ordered that appellant’s premises be padlocked for one year, held appellant in contempt, sentenced him to sixty days in jail and fined him $50.00. See Ark. Stat. Ann. § 34-107. From that judgment there is this appeal. Appellant first contends: ‘ ‘ The First Division Circuit Court was devoid of jurisdiction, so the conviction of contempt was and is a nullity.” We find no merit in this contention. Ark. Stat. Ann. § 34-102 expressly confers concurrent jurisdiction upon the chancery and circuit courts of this state to abate public nuisances such as alleged in the case at bar. Further, the proceedings, whether in a chancery or circuit court, must be conducted in accordance with chancery court procedure. Ark. Stat. Ann. § 34-105; Siesta Cafev. State,231 Ark. 1004,*1121333 S. W. 2d 722; Lawsonv. State,226 Ark. 170,288 S. W. 2d 585. The procedings in this type of action, therefore, are civil in nature. The appellant argues that since this is a civil proceeding, the First Division Circuit Court of Pulaski County is without jurisdiction and cites to us Act 3 of 1961 [First Extraordinary Session (Ark. Stat. Ann. §§ 22-326.4 — 22-326.6)]. This Act relates, inter alia,to the assignment of cases in the Pulaski Circuit Courts. Section 3 of the Act [Ark. Stat. Ann. %'22-326.6 (Bepl. 1962)] specifically provides that:"* * * It shall not be reversible error that any civil case is tried in a division to which it has not been specially assigned, provided, that all criminal cases shall be tried in the first division.” Thus, this statute requires criminal cases to be tried in the first division, but does not restrict the first division from also trying other cases. Also, see Blackstad Mercantile Co.v. Bond,104 Ark. 45,148 S. W. 262. Appellant next contends: ‘ ‘ The statute under which the State proceeded is unconstitutional on its face and as applied” since a temporary injunction was granted in each instance without notice. The statute only requires notice with reference to a permanent.injunction. We have recognized that this statute [Act 109 of 1915, Ark. Stat. Ann. § 34-101 et seq], which provides for the abatement of public nuisances by injunction, is constitutional. Hickeyv. State,123 Ark. 180,184 S. W. 459; Marvelv. State,127 Ark. 595,193 S. W. 259; Adamsv. State,153 Ark. 202,240 S. W. 5. The granting of a temporary injunction without notice addresses itself to judicial discretion in granting or withholding the relief. Thus, the requirement of due process is satisfied in a case of such brief restraint. 28 Am. Jur., Injunctions, § 246 and 152 A. L. B. 168. We are of the view that the question, however, becomes moot in the case at bar since following-each temporary injunction there was a full-scale hearing-preceding the issuance of the permanent injunctions. 43 C. J. S., Injunctions, § 180(d). An objection for lack of proper notice cannot be raised after a hearing on the merits in which the injunction is made permanent. *1122The appellant next asserts that the court erred in refusing to suppress the evidence because the affidavit and the search warrant were insufficient as a matter of law and, therefore, invalid. The affidavit reads in part: “I, G. F. Weeks, do solemnly swear that gaming is being-carried on and gaming equipment is concealed in the premises occupied by Bevis Recreational Parlor at 110 and 110% Main in the State and County aforesaid, and pray a warrant from said Court to search said premises.”. Appellant argues that the place to be searched is not sufficiently identified in the affidavit since it describes the premises to be searched as the “Bevis Recreational Parlor at 110 and 110% Main in the State and County aforesaid.” Therefore, it could have referred to some city other than Little Rock. We do not agree with this assertion. The caption of the affidavit reads: “In the Municipal Court of L. R. Arkansas,” and “State of Arkansas, County of Pulaski.” Certainly this indicated sufficiently where the establishment was located. 79 C. J. S., Searches and Seizures, § 75; see, also, United Statesv. Romano,203 F. Supp. (Conn. 1962). The search warrant, based upon this affidavit, describes the place to be searched as “110 and 110% Main in the City of Little Rock, occupied by Bevis Recreational Parlor” and describes the things to be seized as “prohibited gambling devices.” The description of the premises to be searched and the things to be seized was sufficient to enable the officer to locate the premises and identify the concealed articles-. The appellant next asserts that the court committed prejudicial error in the admission of certain evidence offered by the appellee. As we have stated, the rules of chancery procedure are applicable in the ease at bar whether the proceeding is being conducted in chancery or circuit court. Ark. Stat. Ann. § 34-105; Siesta Cafev. State, supra; Lawsonv. State, supra.Therefore, this anneal is reviewed de novoand we consider only the com*1123petent testimony regardless of the ruling of the trial court on the challenged evidence. Walshv. Fairhead,215 Ark. 218,219 S. W. 2d 941. Here we find no incompetent evidence was heard. In his last point appellant questions the sufficiency of the evidence to convict for contempt, asserting that the “proceedings were in criminal contempt” requiring proof of guilt beyond any reasonable doubt. We do not agree with this contention. The G-eneral Assembly is vested with the authority to regulate by law the punishment of contempt for disobedience of process. Article 7, § 26, Arkansas Constitution. Accordingly, our Legislature has regulated the punishment of contempt for disobedience of a temporary or permanent injunction in a proceeding such as the case at bar. Ark. Stat. Ann. § 34-107. Thus, the test is whether the preponderance of the evidence supports the finding of the trial court since the rules of chancery procedure aré applicable. Alstonv. State,216 Ark. 604,226 S. W. 2d 988; Brownv. State,206 Ark. 135,173 S. W. 2d 1016; Lawsonv. State, supra. Further, we think the trial court should be sustained even if appellant were adjudged guilty of criminal contempt. We review the evidence in criminal contempt cases as in ordinary criminal cases. Therefore, we affirm if there is any substantial evidence to support the trial court’s order. Blackardv. State,217 Ark. 661,232 S. W. 2d 977 ; Songerv. State,236 Ark. 20,364 S. W. 2d 155. In the case at bar the appellant was present on his premises when they were searched. The arresting officers found an individual on the otherwise unoccupied second floor of appellant’s establishment sitting alone inside a walk-in steel vault. The officers had to have it opened by a locksmith using a drill when appellant denied that he knew the combination or how to get into the vault. After thus opening the vault, the officers used a key in appellant’s possession to open a locked compartment within the vault. On the table in front of the individual inside the vault were telephones, scratch sheets,*1124betting slips, tally sheets, and football cards. Officer Weeks testified that he accepted calls over these telephones from people placing bets on horses running at race tracks in Louisiana and Florida. There was evidence that the telephones found in the vault were listed in the directory in the name of Jo’s Liquor Store and Pedigo Cleaners at 110% Main Street. There was no cleaning establishment on the premises. The telephones were not “normal” installations. There is no need to detail the other evidence. It is clear that the evidence was amply sufficient to sustain the court’s findings that appellant was operating his establishment in such a manner as to constitute a public nuisance and in violation of the court’s permanent injunction. Affirmed. Robinson, J., not participating.
https://cite.case.law/ark/239/1119/
In the Literature - Page 4 of 6 - The Hospitalist News In the Literature By Alraies Chadi, MD; Anuradha Ramaswamy, MD; Iqbal Masood, MD; Mital Patel, MD; Saurabh Kandpal, MD June 1, 2009 Bottom line: Communication between inpatient physicians and PCPs needs improvement to affect clinical outcomes, especially in high-risk patients. Citation: Bell CM, Schnipper JL, Auerbach AD, et al. Association of communication between hospital-based physicians and primary care providers with patient outcomes. J Gen Intern Med . 2008;24(3):381-386. Gentamicin Use in Staphylococcal Bacteremia or Endocarditis Causes Nephrotoxicity Clinical question: Does gentamicin synergism in Staphylococcal bacteremia and endocarditis achieve faster eradication at the cost of nephrotoxicity? Background: Gentamicin has been used to help with sterilization of blood or cardiac vegetations in patients with Staphylococcal bacteremia or infective endocarditis (IE). However, historic data negate its role in decreasing morbidity or mortality. If its potential nephrotoxicity were better characterized, it could help assess the overall utility of this practice. Study design: Retrospective analysis of a cohort from a published randomized control trial. Setting: 44 hospitals in the U.S. and Europe. Synopsis: Two hundred thirty-six patients with Staphylococcal bacteremia or native-valve IE (mostly right-sided) were randomized to receive standard therapy (vancomycin or antistaphylococcal penicillin) or daptomycin. Patients receiving standard therapy and those with left-side IE in the daptomycin arm also received low-dose gentamicin. Sequential creatinine levels were used to determine primary outcomes of renal impairment events and a decrease in creatinine clearance. Renal impairment events, elevation of mean serum creatinine, and decrease in creatinine clearance were more prevalent with standard therapy, especially in the elderly and those with diabetes. Combination of gentamicin with penicillin caused an earlier creatinine elevation compared with that with vancomycin. Patients on gentamicin had a modest decrease in creatinine clearance (22% vs. 8%; P= 0.005), especially if their baseline was 50 to 80 mL/min. The decrease was early and sustained with gentamicin exposure. Multivariate analysis revealed age (≥65 years) and gentamicin use (not dose and duration) to be independent predictors of renal impairment. The analysis fails to address use of gentamicin in prosthetic-valve IE and left-side IE. Bottom line: Initial low-dose gentamicin use in Staphylococcal bacteremia or endocarditis increases nephrotoxicity with no clear mortality benefit. Citation: Cosgrove SE, Vigliani GA, Fowler VG, et al. Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis . 2009;48(6):713-721. Osteoporotic Fractures Increase Five-Year Mortality, Especially in the Elderly Clinical question: What is the effect of initial osteoporotic fractures and subsequent fractures on mortality? Background: With an aging population, osteoporotic fractures are poised to escalate into a national healthcare problem. Studies have outlined the increase in premature and long-term mortality associated with hip or vertebral fractures. However, other appendicular fractures have not been studied, and little is known about the mortality risk with subsequent fracturing. Study design: Prospective cohort from the Dubbo Osteoporosis Epidemiology Study, a longitudinal, population-based study. Setting: Stable population of men and women 60 and older in Dubbo, Australia. Synopsis: 1,300 people with at least one minimal-trauma fracture were selected. Fractures were grouped as hip, vertebral, major (long bones and ribs), and minor (any remaining). Mortality data were extracted from local media, along with state and national registries. Age- and sex-specific mortality rates in each group were compared with population mortality rates to provide standardized mortality ratios (SMRs) over five-year periods. Osteoporotic fractures increased five-year mortality with SMRs of 1.38 to 2.53 for women and 1.64 to 3.52 for men. An exception was minor fractures in patients 60 to 75 years old with no increase in mortality. Only hip fractures influenced mortality adversely for up to 10 years. Interestingly, the nonhip, nonvertebral group included 50% of the fractures and contributed to 29% of overall mortality. Another five-year increase in mortality was evident in 364 people with a subsequent fracture. Previous 1 2 3 4 5 6 Next Share:
https://www.the-hospitalist.org/hospitalist/article/123964/literature/4/
Buchireddipalli Branch Post Office, Tiruvallur 06, Tamil Nadu Get Buchireddipalli post office address, pincode, phone number, Buchireddipalli speed post tracking, saving scheme and location map. Buchireddipalli Post Office, Tiruvallur Buchireddipalli Post Officeis located at Buchireddipalli, Tiruvallurof Tamil Nadu state. It is a branch office (B.O.). A Post Office (PO) / Dak Ghar is a facility in charge of sorting, processing, and delivering mail to recipients. POs are usually regulated and funded by the Government of India (GOI). Pin code of Buchireddipalli POis 631206. This Postoffice falls under Kanchipuram postal division of the Tamilnadu postal circle. The related head P.O. for this branch office is Tiruvallur head post office and the related sub-post office (S.O.) for this branch office is Madduru post office. Buchireddipalli dak ghar offers all the postal services like delivery of mails & parcels, money transfer, banking, insurance and retail services. It also provides other services including passport applications, P.O. Box distribution, and other delivery services in Buchireddipalli. The official website fo this PO is http://www.indiapost.gov.in. Types of Post Offices are basically classified into 3 types, namely – Head Post Office, Sub-Post Office including E.D. Sub-Office and Branch Postoffice. Buchireddipalli P.O. is a Branch Post Office. So far as the public is concerned, there is basically no difference in the character of the service rendered by Sub-Post Offices and Head-Post Offices except in regard to a few Post Office Savings Bank (SB) transactions. Certain Sub Post Offices do not undertake all types of postal business. Facilities are generally provided at Branch Post Offices for the main items of postal work like delivery and dispatch of mails, booking of registered articles and parcels accepting SB deposits and effecting SB withdrawals, and issue and payment of money orders, though in a restricted manner. Post Office Type Head Post Office Sub-Post Offices including E.D. Sub-Offices Branch Post Office Buchireddipalli Post Office & Its Pin Code Branch Office Information Buchireddipalli Post Office Services Mail Services Parcels Retail Services Premium Services Speed Post India Post Speed Post Tracking Tracking System India Post Tracking Number Formats Express Parcel Post Media Post Greetings Post Logistics Post ePost Office Financial Services Savings Bank (SB) Account Recurring Deposit (RD) Account Monthly Income Scheme (MIS) Monthly Public Provident Fund (PPF) Time Deposit (TD) Senior Citizen Saving Scheme (SCSS) National Savings Certificate (NSC) Kisan Vikas Patra (KVP) Sukanya Samriddhi Accounts (SSA) Post Office Timings India Post Tracking Buchireddipalli Post Office Recruitment Location Map Contact Details About India Post Buchireddipalli Post Office & Its Pin Code Often Post Offices are named after the town / village / location they serve. The Buchireddipalli Post Office has the Postal Index Number or Pin Code 631206. A Pincode is a 6 digit post code of postal numbering system used by India Post. The first digit indicates one of the regions. The first 2 digits together indicate the sub region or one of the postal circles. The first 3 digits together indicate a sorting / revenue district. The last 3 digits refer to the delivery post office type. P.O. Name Buchireddipalli PO Pincode 631 206 The first digit of 631206 Pin Code '6' represents the region, to which this Post Office of Buchireddipalli belongs to. The first two digits of the Pincode '63' represent the sub region, i.e, Tamilnadu. The first 3 digits '631' represent the post-office revenue district, i.e, Kanchipuram. The last 3 digits, i.e, '206' represent the Buchireddipalli Delivery Branch Office. Branch Office Information The Buchireddipalli Post Office is a branch office. The Delivery Status for this PO is that it has delivery facility. Postal division name for this Dak Ghar is Kanchipuram, which falls under Chennai Region region. The circle name for this PO is Tamilnadu and it falls under Tiruvallur Taluka and Tiruvallur District. The state in which this Dakghar is situated or located is Tamil Nadu. The related head postoffice is Tiruvallur post office and the related sub post office is Madduru post-office. The phone number of Buchireddipalli post office is unavailable at present. PO Type Branch Office Delivery Status Delivery Postal Division Kanchipuram Postal Region Chennai Region Postal Circle Tamilnadu Town / City / Tehsil / Taluka / Mandal Tiruvallur District Tiruvallur State Tamil Nadu Related Sub PO Madduru Sub Office Related Head PO Tiruvallur Head Post Office Buchireddipalli Post Office Services Traditionally the primary function of Buchireddipalli post office was collection, processing, transmission and delivery of mails but as of today, a Post Office offers many other vital services in addition to its traditional services. The additional services provided by a Dak Ghar include – Mail Services, Financial Services, Retail Services and Premium Services. Mail Services Mail Services are the basic services provided by Buchireddipalli P.O. Mails and mail services include all or any postal articles whose contents are in the form of message which may include Letters, Postcards, Inland letter cards, packets or parcels, Ordinary mails etc. Parcels Mail Service also includes transmission and delivery of Parcels. A parcel can be anything ranging from a single written letter or anything addressed to an addressee. No parcel shall be by any chance be in a shape, way of packing or any other feature, such that it cannot be carried or transmitted by post or cause serious inconvenience or risk. Every parcel (including service parcels) that needs to be transmitted by post must be handed over at the window of the post office. Any parcel found in a letter box will be treated and charged as a registered parcel. Delivery services are provided by some selected delivery and branch post offices. This dakghar have the facility of delivery, thus the people of Buchireddipalli and nearby localities can avail all the types of mail services. Retail Services Post offices in India serve in various ways and Buchireddipalli Post Office offer most of the retail services. They offer the facility to accept or collect constomer bills like telephone or mobile bills, electricity bills for Government and private organizations through Retail Post. Some of the aditional agency services that Post offices offers through retail services are as follows - Telephone revenue collection, e-Ticketing for Road Transport Corporations and Airlines, Sale of UPSC forms, university applications, Sale of Passport application forms, Sale of Gold Coins, Forex Services, Sale of SIM and recharge coupons, Sale of India Telephone cards, e-Ticketing of Railway tickets etc. The postal customers of Buchireddipalli can pay their bills and avail other retail services from this Dak Ghar. Premium Services Most of the premium services can be availed by the Buchireddipalli peoples and nearby living people. The premium services provided by Buchireddipalli Post Office are - Speed Post, Business Post, Express Parcel Post, Media Post, Greeting Post, and Logistics Post. Speed Post Speed Post is a time bound service in express delivery of letters and parcels. The max weight up to which an article or parcel be sent is 35 kgs between any two specified stations in India. Speed Post delivers 'Value for money' to everyone and everywhere, delivering Speed Post upto 50 grams @ INR 35 across the country and local Speed Post upto 50 grams @ INR 15, excluding applicable Service Tax. Kindly check official website for updated Speed Post service charges. India Post Speed Post Tracking Speed Post offers a facility of on-line tracking and tracing that guarantees reliability, speed and customer friendly service. Using a 13 digit barcode that makes a Speed Post consignment unique and identifiable. A web-based technology (www.indiapost.gov.in/speednettracking.aspx) helps the Buchireddipalli customers track Speed Post consignments from booking to delivery. Tracking System Except Speed Post, India Post also allows people to track their order information for certain products like Parcels, Insured letters, Speed Post, Registered Post, Electronic Money Orders (EMO) and Electronic value payable parcel (EVPPs) etc. The tracking number is available on the receipt given at Buchireddipalli Post Office. Using the tracking number postal customers can find out the date and time of dispatch of an article at various locations. The time of booking and the time of delivery of article. India Post Tracking Number Formats Different types of postal service have different kinds of tracking number formats. The tracking number for Express Parcel is a 13 digit alphanumeric format. The format for Express Parcel is XX000000000XX. The tracking number for a Registered Mail is a 13 digit alphanumeric number and its format is RX123456789IN. But a Electronic Money Order (EMO) has a 18 digit tracking number and its format is 000000000000000000. For domestic Speed Post (EMS) there is a 13 digit alphanumeric tracking number with the format EE123456789IN. Bharatiya Dak Ghar Seva Tracking Number Format Number of Digits Electronic Money Order (eMO) 000000000000000000 18 Express Parcel XX000000000XX 13 International EMS Artilces to be delivered in India EE123456789XX 13 Registered Mail RX123456789IN 13 Speed Post (EMS) Domestic EE123456789IN 13 Express Parcel Post In Express Parcel Post, the Buchireddipalli postal customer gets time bound delivery of parcels. These parcels will be transmitted through air or any other fastest mean available at that time. Minimum chargeable weight for which Express Parcel consignments will be booked is 0.5 Kg. Maximum weight of Express Parcel consignments which shall be booked across the Post Office counter by a retail customer shall be 20 Kg and maximum weight that can be booked by corporate customer is 35 kgs. Media Post India Post offers a unique way or concept to help the Indian corporate organisations and the Government organizations reach potential customers through media post. Through media post people can advertise on postcards, letters, aerogramme, postal stationary etc. Customers get to see the logo or message of the respective corporate or government organizations. The Aerogramme even gives the organizations the opportunity to make their product have a global impact. Greetings Post Greeting Post is yet another innovative or unique step by India Post. It consists of a card with an envelope with pre-printed and pre attached postage stamp on the envelope. The stamp on the envelope is a replica of the design that appears upon the card but in miniature form. Thus there is no need affix postage stamps on the envelope implicitly saving your time of going to post offices and standing in the queue. All the rules and that are applicable for the postage dues will also be applicable to the Greeting Post. Logistics Post Logistics Post manages the entire transmission and distribution side of the parcels. It deals with collection of goods, storage of goods, carriage and distribution of the various parcels or goods, from order preparation to order fulfilment. And that too at the minimum possible price. Logistics Post services provides the Buchireddipalli postal customer with cost-effective and efficient distribution across the entire country. ePost Office The advent of internet made communication very rapid through emails. But, the internet has not yet reached most of the rural parts of India. To change this division between rural & urban life, and to get the benefit of internet technology to Buchireddipalli people's lives, Indian Postal Department has introduced e-post. e-post is a service in which personalized handwritten messages of customers are scanned and sent as email through internet. And at the destination address office, these messages are again printed, enveloped and delivered through postmen at the postal addresses. E-post centres are established in the Post Offices, covering a large geographical area including major cities and districts. These e-post centres are well equipped with internet connection, scanners, printers and other necessary hardware equipment. However, this e-post service doesn’t particularly need a e-post centre, but can this facility can be availed at any normal Post Office or you can visit www.epostoffice.gov.in to access postal services on your desktop, laptop or even on mobile. If a message is booked at Buchireddipalli post office, the post is scanned and sent to an e-post centre by e-mail and a mail received at e-post centre is printed and sent to nearby Post Office for dispatch. A Buchireddipalli customer can also avail these services of an e-post, at his/ her home. All he/ she has do is to register as a user at www.epostoffice.gov.in website. After registration, a user can use e-post by scanning and sending messages, printing and receive messages. The message to be scanned must not be written in a paper not more A4. There is no limit for sending number of sheets of messages in e-post. E-Post Office offers certain services like – Philately, Postal Life Insurance, Electronic Indian Postal Order, Information Services, Track & Trace and Complaints & Guidelines services. Philately Philately service deals with collection, sale and study of postage stamps. Philately includes lot of services Philately Information, Stamp issue Program, Stamps List and Buy Stamps service. Postal Life Insurance (PLI) A service offered by the Government to pay a given amount of money on the death of an individual to his prescribed nominee. The amount may also be paid to the person himself, in case he survives that maturity period. The two services offered under Postal Life Insurance are – Pay Premium service and PLI information. Electronic Indian Postal Order eIPO or Electronic Indian Postal Order is a facility to purchase an Indian Postal Order electronically by paying a fee on-line through e-Post Office. This service is launched by the Department of Posts, Ministry of Communications & IT, Government of India. eIPO can now be used by Indian Citizens living in India for paying online fee, whoever seeks information under the RTI Act, 2005. eIPO offers 2 types of services – eIPO information and payment of online fees. Information Services This helps Buchireddipalli customers to get information regarding certain products like – Pin Code search, Speed post, Banking, Insurance, Business Post, Logistics Post, IMTS and many more other services. Track & Trace The track & trace service is very helpful as it aids in getting information of our valuables. Track & Trace service offers 5 different services – Pin Code search, EMO tracking, Speed Post tracking, WNX tracking and International mail service. Complaints & Guidelines Using e-post office service Buchireddipalli postal costumer can access services based on – complaint registration, complaint status and guidelines on complaints. ePost Office Website www.epostoffice.gov.in Financial Services The customers of Buchireddipalli can enjoy the various savings schemes available in this post office that prove to be highly beneficial for the people living in Buchireddipalli area. The Financial service offered by PO includes Savings and Postal Life Insurance (PLI). There are various options available to save and invest with post-offices. The commonly used ones include - Savings account, Recurring Deposit, Monthly Income Scheme, Monthly Public Provident Fund, Time Deposit, Senior Citizen Saving Scheme, National Savings Certificate, Kisan Vikas Patra and Sukanya Samriddhi Yojana. Post Office also offers Insurance product through Postal Life Insurance (PLI) and Rural Postal Life Insurance (RPLI) schemes that offer low premium and high bonus. Post Office Financial Services Kisan Vikas Patra (KVP) Monthly Income Scheme (MIS) Monthly Public Provident Fund (PPF) National Savings Certificate (NSC) Recurring Deposit (RD) Account Savings Bank (SB) Account Senior Citizen Saving Scheme (SCSS) Sukanya Samriddhi Accounts (SSA) Time Deposit (TD) Savings Bank (SB) Account A Savings bank account serves the need of regular deposits for its customers as well as withdrawals. Cheque facility is also avail by Buchireddipalli postal consumers. Recurring Deposit (RD) Account A post office offers a monthly investment option with handsome return at the time period with an option to extend the investment period. Insurance facility is also available with certain conditions. Monthly Income Scheme (MIS) MIS offers a fixed investment technique for five or more years with monthly interest payment to the account holder. There is also a facility of automatic crediting of interest to SB account of the Buchireddipalli postal customer. Monthly Public Provident Fund (PPF) This service offers intermittent deposits subject to a particular limit for a time period of 15 years with income tax exemptions, on the investment. It also offers loan and withdrawal facilities for the postal customers. Time Deposit (TD) Fixed deposit option for periods ranging from one, two, three to five years with facility to draw yearly interest offered at compounded rates. Automatic credit facility of interest to SB account. Senior Citizen Saving Scheme (SCSS) Offers fixed investment option for senior citizens for a period of five years, which can be extended, at a higher rate of interest that are paid in quarterly instalments. National Savings Certificate (NSC) NSC is offered with a fixed investment for 5 or 10 years on certificates of various denominations. Pledging facility available for availing loan from Banks. Kisan Vikas Patra (KVP) Kisan Vikas Patra is a saving certificate scheme in which the amount Invested doubles in 110 months (i.e. 9 years & 2 months). It is available in denominations of Rs 1,000, 5000, 10,000 and Rs 50,000. Minimum deposit is Rs 1000/- and there is no maximum limit. The KVP certificate can be purchased by any adult for himself or on the behalf of a minor. This certificate can also be transferred from one account holder to another and from one post office to another. This certificate can be en-cashed only after 2 and 1/2 years from the date of issue. Sukanya Samriddhi Accounts (SSA) Sukanya Samriddhi Account Yojana offers a small deposit investment for the girl children as an initiative under 'Beti Bachao Beti Padhao' campaign. This yojana is to facilitate girl children proper education and carefree marriage expenses. One of the main benefits of this scheme is that it is very affordable and offers one of the highest interest rates. Currently its interest rate is set as 8.6% per annum that is again compounded yearly. The minimum deposit allowed in a financial year is INR. 1000/- and Maximum is INR. 1,50,000/-. Subsequent deposits can be made in multiples of INR 100/-. Deposits can be made all at a time. No limit is set on number of deposits either for a month or a financial year. A legal Guardian can open an account in the name of a Girl Child. Account can be closed only after completion of 21 years of the respective child. The normal Premature closure allowed is after completion of 18 years only if that girl is getting married. Post Office Timings The official working hours of Post Offices vary from one another, but the general Post Office opening time starts from 08:00 AM or 09:00 AM or 10:00 AM and the closing time is 04:00 PM or 05:00 PM or 06:00 PM respectively. The working days are from Monday to Saturday, Sunday being a holiday. This doesn't include the public holidays or the extended working hours. You can verify the working hours of Buchireddipalli Branch Post Office from the official resources. India Post Tracking Online tracking of India Post allowed Buchireddipalli people to access their postal article tracking information and confirm the delivery of their postal article by using the tracking number assigned to them at the time of Booking. They can find the tracking number on the Postal acknowledgement handed over to them at the Buchireddipalli Branch Post Office counter at the time of postal article booking. Following items can track through the www.indiapost.gov.in/articleTracking.aspx official website. Business Parcel Business Parcel COD Electronic Money Order (e-MO) Electronic Value Payable Parcel (eVPP) Express Parcel Express Parcel COD Insured Letter Insured Parcel Insured Value Payable Letter Insured Value Payable Parcel International EMS Registered Letter Registered Packets Registered Parcel Registered Periodicals Speed Post Value Payable Letter Value Payable Parcel The India Post tracking system is updated at regular intervals to give the Buchireddipalli postal customers with the most up to date information available about the location and status of their postal article. They'll be able to find out the following: When their postal article was booked When their postal article was dispatched at various locations during its Journey When their postal article was received at various locations during its Journey When their postal article was delivered, or When a delivery intimation notice was issued to notify the recipient that the postal article is available for delivery Buchireddipalli Post Office Recruitment For latest Buchireddipalli post office recruitment kindly visit www.indiapost.gov.in/recruitment.aspx. Location Map Buchireddipalli Branch Post Office is located in Buchireddipalli, Tiruvallur. Contact Details All the queries or complaints regarding Bill Mail Service, Booking Packets, Business Post, Direct Post, Flat Rate Box, Indian Postal Orders, Inland Letters, Instant Money Orders, Insurance of Postal Articles, Insurance of Postal Parcels, Letters, Logistics Posts, MO Videsh, Money Orders, Parcels, Post Office Savings Bank, Postal Life Insurance, Postcards, Registration of Postal Articles, Registration of Postal Parcels, Rural Postal Life Insurance, Saving Certificates, Small Saving Schemes, Speed Post, Value Payable Post etc.services in Buchireddipalli Post Office, can be resolved at Buchireddipalli Branch Post Office. You can send letters to "Postmaster, Buchireddipalli Branch Post Office, Buchireddipalli, Tiruvallur, Tamil Nadu, India, Pincode: 631 206". The official website of the Berhampur University Sub Office is http://www.indiapost.gov.in. Buchireddipalli Branch Office Address: Buchireddipalli Branch Post Office, Buchireddipalli, Tiruvallur , Tamil Nadu , India Pin Code: 631206 Website: www.indiapost.gov.in About India Post India Postis a government-operated postal system, which is part of the Ministry of Communications and Information Technology of the Government of India. It has the largest Postal Network in the Indiawith over 154882 Post Offices. There are around 139182 Post Offices in the rural India and 15700 Post Offices in urban India. The individual post office serves an area of 21.22 Sq. Km. and a population of 8221 people. The slogan of India Post is Dak Seva Jan Seva. There are 25464 departmental post offices and 129418 extra-departmental branch post offices in India. Buchireddipalli Post Office Summary Dak Ghar Name Buchireddipalli Branch Post Office Pincode 631206 Dakghar Type Branch Office Post Office Delivery Status Delivery Branch Office Postal Division Kanchipuram Postal Region Chennai Region Postal Circle Tamilnadu Location Buchireddipalli District Tiruvallur State Tamil Nadu Country India Related Sub Office Madduru Sub Office Related Head Office Tiruvallur Head Post Office Website www.indiapost.gov.in ePost-office Web Site Address www.epostoffice.gov.in Speed Post Tracking Website www.indiapost.gov.in/speednettracking.aspx Recruitment Web Site Address www.indiapost.gov.in/recruitment.aspx Other Post Offices
https://www.postoffices.co.in/tamilnadu-tn/buchireddipalli-tiruvallur-06/
Text of H.R. 6227 (84th): An Act to provide for the control and regulation of bank holding companies, … (Passed Congress version) - GovTrack.us Text of H.R. 6227 (84th): An Act to provide for … as of May 9, 1956 (Passed Congress version). H.R. 6227 (84th): An Act to provide for the control and regulation of bank holding companies, and for other purposes Overview The text of the bill below is as ofMay 9, 1956(Passed Congress). Source: Wikipedia The Bank Holding Company Act of 1956(12 U.S.C. § 1841, et seq.) is a United States Act of Congress that regulates the actions of bank holding companies. The original law (subsequently amended), specified that the Federal Reserve Board of Governors must approve the establishment of a bank holding company and that bank holding companies headquartered in one state are banned from acquiring a bank in another state. The law was implemented,in part, to regulate and control banks that had formed bank holding companies to own both banking and non-banking businesses. The law generally prohibited a bank holding company from engaging in most non-banking activities or acquiring voting securities … 70 S T A T . ] PUBLIC LAW 511-MAY 9, 1966 133 Public Law 511 CHAPTER 240 -^N A C T May 9,1956 To define bank holding companies, control their future expansion, and require [H. R. 6227] divestment of their nonbanking interests. Be it enacted hi/ the Senate and House of RepresentativeH of the United states of Anienca in Congress assembled. That this Act may c o ^ a n y ^/SA*©? be cited as the "Bank Holding Company Act of 1956". i9S6. DEFINITIONS SEC. 2 (a) '"Bank holding company"' means any company (1) which directly or indirectly OAvns, controls, or holds with power to vote, 25 per centum or more of the voting shares of each of two or more banks or of a com])any which is or becomes a bank holding com- ])any by virtue of tliis Act, or (2) which controls in any manner the election of a majority of the directors of each of two or more banks, or (3) for the benefit of whose shareholders or members 25 per centum or more of the voting shares of each of tw'o or more banks or a baiik holding company is held by trustees; and for the purposes of this Act, any successor to any such company shall be deemed to be a baiik holding company from the date as of w^liich such predecessor company became a bank holding company. Xotwdthstanding the foregoing (A) no bank shall be a bank holding company by virtue of its owner- ship or control of shares in a fiduciary capacity, except where such shares are held for the benefit of the shareholders of such bank, (B) no company shall be a bank holding company Avhich is registered under the Investment Company Act of 1910, and Avas so registered 15 usc*8(f»-*5i. prior to May 15, 1955 (or which is affiliated with any such company in such manner as to constitute an affiliated company within the mean- ing of such Act), unless such company (or such affiliated company), as the case may be, directly owns 25 per centum or more of the voting shares of each of two or more banks, (C) no company shall be a bank holding company by virtue of its ow^nership or control of shares acquired by it in connection with its underwriting of securities and which are held only for such period of time as Avill permit the sale thereof upon a reasonable basis, (D) no company formed for the sole purpose of participating in a proxy solicitation shall be a bank holding company by virtue of its control of voting rights of shares acquired in the course of such solicitation, and ( E ) no company shall be a bank holding company if at least 80 per centum of its total assets are com- jjosed of holdings in the field of agriculture. (b) "Company" means any corporation, business trust, association, or similar organization, but shall not include (1) any corporation the majority of the shares of which are owned by the United States or by any State, or (2) any corporation or community chest, fund, or foundation, organized and operated exclusively for religious, charita- ble, or educational purposes, no part of the net earnings of which inures to the benefit of any private shareholder or individual, and no substantial part of the activities of which is carrying on propa- ganda, or otherwise attempting to influence legislation, or (3) any partnership. (c) "Bank" means any national banking association or any State bank, savings bank, or trust company, but shall not include any organ- ization operating under section 25 (a) of the Federal Reserve Act, 12 usc'6^nf6i2. or any organization which does not do business within the United States. "State member bank" means any State bank which is a mem- bal^"*** member ber of the Federal Reserve System. "District bank" means any State "District bank". 134 PUBLIC LAW 511-MAY 9, 1956 [70 S T A T . bank organized or operating under the Code of Law for the District of Columbia. (d) "Subsidiary", with respect to a specified bank holding com- pany, means (1) any company 25 per centum or more of whose voting shares (excluding shares owned by the United States or by any com- pany wholly owned by the United States) is owned or controlled by such bank holding company; or (2) any company the election of a majority of whose directors is controlled in any manner by such bank holding company; or (3) any company 25 per centum or more of whose votmg shares are held by trustees for the benefit of the share- holders or members of such bank holding company. (e) The term "successor" shall include any company which acquires directly or indirectly from a bank holding company shares of any bank, when and if the relationship between such company and the bank holding company is such that the transaction effects no substan- tial change in the control of the bank or beneficial ownership of such shares of such bank. The Board may, by regulation, further define the term "successor" to the extent necessary to prevent evasion of the purposes of this Act. (f) "Board" means the Board of Governors of the Federal Reserve System. (g) "Agriculture", as used in section 2 ( a ) , includes farming in all its branches including fruitgrowing, dairying, the raising of live- stock, bees, fur-bearing animals, or poultry, forestry or lumbering operations, and the production of naval stores, and operations directly related thereto. A C Q U I S I T I O N OF B A N K SHARES OR ASSETS SEC. 3. (a) I t shall be unlawful except with the prior approval of the Board (1) for any action to be taken which results in a company becoming a bank holding company under section 2 (a) of this Act; (2) for any bank holding company to acquire direct or indirect owner- ship or control of any voting shares of any bank if, after such acquisition, such company will directly or indirectly own or control more than 5 per centum of the voting shares of such bank; (3) for any bank holding company or subsidiary thereof, other than a bank, to acquire all or substantially all of the assets of a bank; or (4) for any bank holding company to merge or consolidate with any other bank holding company. Notwithstanding the foregoing this prohibi- tion shall not apply to (A) shares acquired by a bank, (i) in good faith in a fiduciary capacity, except where such shares are held for the benefit of the shareholders of such bank, or (ii) in the regular course of securing or collecting a debt previously contracted in good faith, but any shares acquired after the date of enactment of this Act in securing or collecting any such previously contracted debt shall be disposed of within a period of two years from the date on which they were acquired; or (B) additional shares acquired by a bank holding company in a bank in which such bank holding company owned or controlled a majority of the voting shares prior to such acquisition. (b) Upon receiving from a company any application for approval under this section, the Board shall give notice to the Comptroller of the Currency, if the applicant company or any bank the voting shares or assets of which are sought to be acquired is a national banking association or a District bank, or to the appropriate supervisory authority of the interested State, if the applicant company or any bank the voting shares or assets of which are sought to be acquired is a State bank, and shall allow thirty days within which the views and recommendations of the Comptroller of the Currency or the State 70 S T A T . ] PUBLIC LAW 511-MAY 9, 1956 135 supervisory authority, as the case may be, may be submitted. If the Comptroller of the Currency or the State supervisory authority so notified by the Board disapproves the application in writing within said thirty days, the Board shall forthwith give written notice of that fact to the applicant. Within three days after giving such notice to the applicant, the Board shall notify in writing the applicant and the disapproving authority of the date for commencement of a hear- ing by it on such application. Any such hearing shall be commenced not less than ten nor more than thirty days after the Board has given written notice to the applicant of the action of the disapproving authority. The length of any such hearing shall be determined by the Board, but it shall afford all interested parties a reasonable oppor- tunity to testify at such hearing. A t the conclusion thereof, the Board shall by order grant or deny the application on the basis of the record made at such hearing. (c) I n determining whether or not to approve any acquisition or merger or consolidation under this section, the Board shall take into consideration the following factors: (1) the financial history and condition of the company or companies and the banks concerned; (2) their prospects; (3) the character of their management; (4) the con- venience, needs, and welfare of the communities and the area con- cerned ; and (5) whether or not the effect of such acquisition or merger or consolidation would be to expand the size or extent of the bank holding company system involved beyond limits consistent with ade- quate and sound banking, the public interest, and the preservation of competition in the field of banking. (d) Notwithstanding any other provision of this section, no appli- cation shall be approved under this section which will permit any bank holding company or any subsidiary thereof to acquire, directly or indirectly, any voting shares of, interest in, or all or substantially all of the assets of any additional bank located outside of the State in which such bank holding company maintains its principal office and place of business or in which it conducts its principal operations unless the acquisition of such shares or assets of a State bank by an out-of- State bank holding company is specifically authorized by the statute laws of the State in which such bank is located, by language to that effect and not merely by implication. I N T E R E S T S I N N O N B A N K I N G ORGANIZATIONS SEC. 4, (a) Except as otherwise provided in this Act, no bank hold- ing company shall— (1) after the date of enactment of this Act acquire direct or indirect ownership or control of any voting shares of any com- pany which is not a bank, or (2) after two years from the date of enactment of this Act or from the date as of which it becomes a bank holding company, whichever is later, retain direct or indirect ownership or control of any voting shares of any company which is not a bank or a bank holding company or engage in any business other than that of banking or of managing or controlling banks or of furnishing services to or performing services for any bank of which it owns or controls 25 per centum or more of the voting shares. The Board is authorized, upon application by a bank holding company, to extend the period referred to in paragraph (2) above from time to time as to such bank holding company for not more than one year at a time if, in its judgment, such an extension would not be detrimental to the public interest, but no such extensions shall extend beyond a date 136 PUBLIC LAW 511-MAY 9, 1956 [70 S T A T . five years after the date of enactment of this Act or five years after the date as of which a company becomes a bank holding company, which- ever is later. (b) After two years from the date of enactment of this Act, no certificate evidencing shares of any bank holding company shall bear any statement purporting to represent shares ot any other company except a bank or a bank holding company, nor shall the ownership, sale, or transfer of shares of any bank holding company be conditioned in any manner whatsoever upon the ownership, sale, or transfer of shares of any other company except a bank or a bank holding company, of i^^bmons. '^^^ (c) The prohibitions in this section shall not apply— (1) to shares owned or acquired by a bank holding company in any company engaged solely in holding or operating properties used wholly or substantially by any bank with respect to which it is a bank holding company in its operations or acquired for such future use or engaged solely in conducting a safe deposit business, or solely in the business of furnishing services to or performing services for such holding company and banks with respect to which it is a bank holding company, or in liquidating assets acquired from such bank holding company and such banks; (2) to shares acquired by a bank holding company which is a bank, or by any banking subsidiary of a bank holding company, in satisfaction of a debt previously contracted in good faith, but such bank holding company or such subsidiaries shall dispose of such shares within a period of two years from the date on which they were acquired or from the date of enactment of this Act, whichever is later; (3) to shares acquired by a bank holding company from any of its subsidiaries which subsidiary has been requested to dispose of such shares by any Federal or State authority having statutory power to examine such subsidiary, but such bank holding com- pany shall dispose of such shares within a period of two years from the date on which they were acquired or from the date of enactment of this Act, whichever is later; (4) to shares which are held or acquired by a bank holding company which is a bank or by any banking subsidiary of a bank holding company, in good faith in a fiduciary capacity, except where such shares are held for the benefit of the shareholders of such bank holding company or any of its subsidiaries, or to shares which are of the kinds and amounts eligible for investment by National banking associations under the provisions of section 12 use 24 . 5j^3g fyf fi^Q Revised Statutes, or to shares lawfully acquired and owned prior to the date of enactment of this Act by a bank which is a bank holding company, or by any of its wholly owned subsidiaries; (5) to shares of any company which are held or acquired by a bank holding company which do not include more than 5 per centum of the outstanding voting securities of such company, and do not have a value greater than 5 per centum of the value of the total assets of the bank holding company, or to the ownership by a bank holding company of shares, securities, or obligations of an investment company which is not a bank holding company and which is not engaged in any business other than investing in securities, which securities do not include more than 5 per centum of the outstanding voting securities of any company and do not include any single asset having a value greater than 5 per centum of the value of the total assets of the bank holding com- pany; 70 S T A T . ] PUBLIC LAW 511-MAY 9, 1956 137 (6) to shares of any company all the activities of which are of a financial, fiduciary, or insurance nature and which the Board after due notice and hearing, and on the basis of the record made at such hearing, by order has determined to be so closely related to the business of banking or of managing or controlling banks as to be a proper incident thereto and as to make it unnecessary for the prohibitions of this section to apply in order to carry out the purposes of this Act; (7) to any bank holding company which is a labor, agricultural, or horticultural organization and which is exempt from taxation under section 501 of the Internal Revenue Code of 1954; or f26l^ilr^lnV!^* u s e 501. (8) to shares held or acquired by a bank holding company in any company which is organized under the laws of a foreign country and which is engaged principally in the banking business outside the United States. ADMINISTRATION SEC. 5. (a) Within one hundred and eighty days after the date of enactment of this Act, or within one hundred and eighty days after becoming a bank holding company, whichever is later, each bank holding company shall register with the Board on forms prescribed by the Board, which shall include such information with respect to the financial condition and operations, management, and intercompany relationships of the bank holding company and its subsidiaries, and related matters, as the Board may deem necessary or appropriate to carry out the purposes of this Act. The Board may, in its discretion, extend the time within which a bank holding company shall register and file the requisite information. (b) The Board is authorized to issue such regulations and orders as may be necessary to enable it to administer and carry out the purposes of this Act and prevent evasions thereof. (c) The Board from time to time may require reports under oath to keep it informed as to whether the provisions of this Act and such regulations and orders issued thereunder liave been complied with; and the Board may make examinations of each bank holding company and each subsidiary thereof, the cost of which shall be assessed against, and paid by, such holding company. The Board shall, as far as pos- sible, use the reports of examinations made by the Comptroller of the Currenc}', the Federal Deposit Insurance Corporation, or the appro- priate State bank supervisory authority for the purposes of this section. (d) Before the expiration of two years following the date of enact- Report to C o n - gress. ment of this Act, and each year thereafter in the Board's annual report to the Congress, the Board shall report to the Congress the results of the administration of this Act, stating what, if any, sub- stantial difficulties have been encountered in carrying out the purposes of this Act, and any recommendations as to changes in the law which in the opinion of the Board would be desirable. BORROWING BY B A N K HOLDING COMPANY OR ITS SUBSIDIARIES SEC. 6. (a) From and after the date of enactment of this Act, it shall be unlawful for a bank— (1) to invest any of its funds in the capital stock, bonds, deben- tures, or other obligations of a bank holding company of which it is a subsidiary, or of any other subsidiary of such bank holding company; (2) to accept the capital stock, bonds, debentures, or other obli- gations of a bank holding company of which it is a subsidiary or any other subsidiary of such bank holding company, as collateral 138 PUBLIC LAW 511-MAY 9, 1956 [TO S T A T . security for advances made to any person or company: Provided^ however^ That any bank may accept such capital stock, bonds, debentures, or other obligations as security for debts previously contracted, but such collateral shall not be held for a period of over two years; (3) to purchase securities, other assets or obligations under repurchase agreement from a bank holding company of which it is a subsidiary or any other subsidiary of such bank holding company; and (4) to make any loan, discount or extension of credit to a bank holding company of which it is a subsidiary or to any other subsidiary of such bank holding company. Non-interest-bearing deposits to the credit of a bank shall not be deemed to be a loan or advance to the bank of deposit, nor shall the giving of immediate credit to a bank upon uncollected items received in the ordinary course of business be deemed to be a loan or advance * to the depositing bank. (b) The provisions of this section shall not apply (1) to the capital stock, bonds, debentures, or other obligations of any company described Ante, p. 136. jj^ scctiou 4 (c) (1) of this Act, or (2) to any company whose subsid- iary status has arisen out of a bona fide debt to tlie bank contracted prior to the date of the creation of such status, or (3) to any company whose subsidiary status exists by reason of the ownership or control of voting shares thereof by the bank as executor, administrator, trus- tee, receiver, agent, or depositary, or in any other fiduciary capacity, except where such shares are held for the benefit of all or a majority of the stockholders of such bank. RESERVATION OF RIGHTS TO STATES SEC. 7. The enactment by the Congress of the Bank Holding Com- pany Act of 1956 shall not be construed as preventing any State from exercising such powers and jurisdiction which it now has or may hereafter have with respect to banks, bank holding companies, and subsidiaries thereof. PENALTIES SEC. 8. Any company which willfully violates any provision of this Act, or any regulation or order issued by the Board pursuant thereto, shall upon conviction be fined not more than $1,000 for each day during which the violation continues. Any individual who will- fully participates in a violation of any provision of this Act shall upon conviction be fined not more than $10,000 or imprisoned not more than one year, or both. Every officer, director, agent, and em- ployee of a bank holding company shall be subject to the same pen- alties for false entries in any book, report, or statement of such bank holding company as are applicable to officers, directoi^s, agents, and employees of member banks for false entries in any books, reports, or 62 Stat. 750 . statements of member banks under section 1005 of title 18 , United States Code. JUDICIAL R E V I E W SEC. 9. Any party aggrieved by an order of tlie Board under this Act may obtain a review of such order in the United States Court of Appeals within any circuit wherein such party has its principal ])lace of business, or in the Court of Appeals in the District of Colum- bia, by filing in the court, within sixty days after the entry of the Board's order, a petition praying that the order of the Board be set aside. A copy of such petition shall be forthwith served upon the 70 S T A T . ] PUBLIC LAW 51 1 - M A Y 9, 1956 139 Board, and thereupon the Board shall certify and file in the court a transcript of the record made before the Board. Upon the filing of the transcript the court shall have jurisdiction to affirm, set aside, or modify the order of the Board and to require the Board to take such action with regard to the matter under review as the court deems proper. The findings of the Board as to the facts, if supported by substantial evidence, shall be conclusive. AMENDMENTS TO INTERNAL REVENUE CODE OF 1954 SEC. 10. (a) Subchapter O of chapter 1 of the Internal Revenue f 1^^1*0 lo^oi- Code of 1954 is amended by adding at the end thereof the following io9i. new p a r t : "PART VIII—DISTRIBUTIONS P U R S U A N T TO BANK HOLDING COMPANY ACT OF 1956 "Sec. 1101. Distributions pursuant to Bank Holding Company Act of 1956. "Sec. 1102. Special rules. "Sec. 1103. Definitions. "SEC. 1101. DISTRIBUTIONS PURSUANT TO BANK HOLDING COMPANY ACT OF 1956. "(a) DISTRIBUTIONS OF CERTAIN NON-B.\NKING PROPERTY,— " ( 1 ) DISTRIBUTIONS or PROHIBITED PROPERTY.—If— " ( A ) a qualified bank holding corporation distributes pro- hibited property (other than stock received in an exchange to which subsection (c) (2) applies)— "(i) to a shareholder (with respect to its stock held by such shareholder), without the surrender by such share- holder of stock in such corporation; or "(ii) to a shareholder, in exchange for its preferred stock; or "(iii) to a security holder, in exchange for its secu- rities; and " ( B ) the Board has, before the distribution, certified that the distribution of such prohibited property is necessary or appropriate to effectuate section 4 of the Bank Holding Ante, p« 135* Company Act of 1956, then no gain to the shareholder or security holder from the receipt of such property shall be recognized. " ( 2 ) DISTRIBUTIONS OF STOCK AND SECURITIES RECEIVED I N AN EXCHANGE TO WHICH S U B S E C T I O N ( C ) ( 2 ) APPLIES. I f " ( A ) a qualified bank holding corporation distributes— " ( i ) common stock received in an exchange to which subsection (c) (2) applies to a shareholder (with respect to its stock held by such shareholder), without the sur- render by such shareholder of stock in such corporation; or "(ii) common stock received in an exchange to which subsection (c) (2) applies to a shareholder, in exchange for its common stock; or "(iii) preferred stock or common stock received in an exchange to which subsection (c) (2) applies to a share- holder, in exchange for its preferred stock; or "(iv) securities or preferred or common stock received in an exchange to which subsection (c) (2) applies to a security holder, in exchange for its securities; and " ( B ) any preferred stock received has substantially the same terms as the preferred stock exchanged, and any securi- 140 PUBLIC LAW 511-MAY 9, 1956 [70 S T A T . ties received have substantially the same terms as the securities exchanged, then, except as provided in subsection ( f ) , no gain to the share- holder or security holder from the receipt of such stock or such securities or such stock and securities shall be recognized. "(3) NoN PRO RATA DISTRIBUTIONS.—Paragraphs (1) and (2) shall apply to a distribution whether or not the distribution is pro rata with respect to all of the shareholders of the distributing qualified bank holding corporation. "(4) EXCEPTION.—This subsection shall not apply to any dis- tribution by a corporation which has made any distribution pur- suant to subsection (b). "(5) DISTRIBUTIONS INVOLVING GIFT OR COMPENSATION.— "In the case of a distribution to which paragraph (1) or (2) applies, but which— 26USC 250°^ "(-^^ results in a gift, see section 2501, and following, or „, ,.__ ^, * "(B) has the effect of the payment of compensation, see 2^"^^^^* section 61 (a) (1). "(b) CORPORATION CEASING T O B E A B A N K HOLDING COMPANY.— "(1) DISTRIBUTIONS OF PROPERTY WHICH CAUSE A CORPORATION TO BE A BANK HOLDING COMPANY.—If— " ( A ) a qualified bank holding corporation distributes property (other than stock received in an exchange to which subsection (c) (3) applies) — "(i) to a shareholder (with respect to its stock held by such shareholder), Avithout the surrender by such shareholder of stock in such corporation; or "(ii) to a shareholder, in exchange for its preferred stock; or "(iii) to a security holder, in exchange for its securi- ties; and " ( B ) the Board has, before the distribution, certified that— "(i) such property is all or part of the property by reason of which such corporation controls (within the meaning of section 2 (a) of the Bank Holding Company Ante, p. 133. ^^^.^ ^f 1956) a bank or bank holding company, or such property is part of the property by reason of which such corporation did control a bank or a bank holding com- pany before any property of the same kind was distrib- uted imder this subsection or exchanged under subsection (c) (3) ; and "(ii) the distribution is necessary or appropriate to effectuate the policies of such Act, then no gain to the shareholder or security holder from the receipt of such property shall be recognized. " ( 2 ) IDlSTRIBUTIONS OF STOCK AND SECURITIES RECEIVED IN AN EXCHANGE TO WHICH SUBSECTION ( c ) ( 3 ) APPLIES. I f " ( A ) a qualified bank holding corporation distributes— " ( i ) common stock received m an exchange to which subsection (c) (3) applies to a shareholder (with respect to its stock held by such shareholder), without the sur- render by such shareholder of stock in such corporation; or "(ii) common stock received in an exchange to which subsection (c) (3) applies to a shareholder, in exchange for its common stock; or 70 S T A T . ] PUBLIC LAW 511-MAY 9, 1956 141 "(iii) preferred stock or common stock received in an exchange to which subsection (c) (3) applies to a shareholder, in exchange for its preferred stock; or " (iV) securities or preferred or common stock received in an exchange to which subsection (c) (3) applies to a security holder, in exchange for its securities; and " ( B ) any preferred stock received has substantially the same terms as the preferred stock exchanged, and any se- curities received have substantially the same terms as the securities exchanged, then, except as provided in subsection ( f ) , no gain to the share- holder or security holder from the receipt of such stock or such securities or such stock and securities shall be recognized. "(3) Nox PRO RATA DISTRIBUTIONS.—Paragraphs (1) and (2) shall apply to a distribution whether or not the distribution is pro rata with respect to all of the shareholders of the distributing qualified bank holding corporation. "(4) EXCEPTION.—This subsection shall not apply to any dis- tribution by a corporation which has made any distribution pur- suant to subsection ( a ) . "(5) DISTRIBUTIONS INVOLVING GIFT OR COMPENSATION.— "In the case of a distribution to which paragraph (1) or (2) applies, but- which— "(A) results in a gift, see section 2501, and following, or 26^i<f*2soi* "(B) has the effect of the payment of compensation, see j~, ^.„^ f, section 61 (a) (1). ^^ "^^ ^^' "(c) PROPERTY ACQUIRED AFTER MAY 15, 1955.— " ( 1 ) I N GENERAL.—Except as provided in paragraphs (2) and (3), subsection (a) or (b) shall not apply to— " ( A ] any property acquired by the distributing corpora- tion alter May 15, 1955, unless (i) gain to such corporation with respect to the receipt of such property was not recog- nized by reason of subsection (a) or ( b ) , or (ii) such prop- erty was received by it in exchange for all of its stock in an exchange to which paragraph (2) or (3) applies, or (iii) such property was acquired b^ the distributing corporation in a transaction in which gain was not recognized under section 305 (a) or section 332, or under section 354 with 354 , ,5!*^!^^°*'^^^ 368. respect to a reorganization described in section 368 (a) (1) (E) or ( F ) , o r " ( B ) any property which was acquired by the distributing corporation in a distribution with respect to stock acquired by such corporation after May 15,1955, unless such stock was acquired by such corporation (i) in a distribution (with respect to stock held by it on May 15, 1955, or with respect to stock in respect of which all previous applications of this clause are satisfied) with respect to which gain to it was not recognized by reason of subsection (a) or ( b ) , or (ii) in exchange for all of its stock in an exchange to which para- graph (2) or (3) applies, or (iii) in a transaction in which gain was not recognized under section 305 (a) or section 332, or under section 354 with respect to a reorganization described in section 368,(a) (1) ( E ) or ( F ) , o r " ( C ) any property acquired by the distributing corpora- tion in a transaction in which gain was not recognized under section 332, unless such property was acquired from a corpo- ration which, if it had been a qualified bank holding corpora- tion, could have distributed such property under subsection (a) (1) or (b) (1). 70 S T A T . ] PUBLIC LAW 511-MAY 9, 1956 143 tributing corporation retains, or transfers after May 15, 1955, to any corporation, property (other than property described in subsection (b) (1) (B) ( i ) ) as part of a p i a n one of the principal purposes of which is the distribution of the earnings and profits of any corporation, "(3) CERTAIN CONTRIBUTIONS TO CAPITAL.—In the case of a dis- tribution a portion of which is attributable to a transfer which is a contribution to the capital of a corporation, made after May 15, 1955, and prior to the date of the enactment of this part, if subsection (a) or (b) Avould apply to such distribution but for the fact that, under paragraph (1) or (2) (as the case may be) of this subsection, such contribution to capital is part of a plan one of the principal purposes of which is to distribute the earnings and profits of any corporation, then, notwithstanding paragraph (1) or (2), subsection (a) or (b) (as the case may be) shall apply to that portion of such distribution not attributable to such con- tribution to capital, and shall not apply to that portion of such distribution attributable to such contribution to capital. "(e) F I N A L CERTIFICATION.— "(1) FOR SUBSECTION (a).—Subsection (a) shall not apply with respect to any distribution by a corporation unless the Board certifies that, before the expiration of the period permitted under section 4 (a) of the Bank Holding Company Act of 1956 (includ- Ante, p» 135* ing any extensions thereof granted to such corporation under such section 4 ( a ) ) , the corporation has disposed of all the property the disposition of which is necessary or appropriate to effectuate section 4 of such Act (or would have been so necessary or appropriate if the corporation had continued to be a bank hold- ing company). "(2) FOR SUBSECTION (b).— " ( A ) Subsection (b) shall not apply with respect to any distribution by any corporation unless the Board certifies that, before the expiration of the period specified in subpara- graph ( B ) , the corporation has ceased to be a bank holding company. " ( B ) The period referred to in subparagraph (A) is the period which expires 2 years after the date of the enactment of this part or 2 years after the date on which the corporation becomes a bank holding company, whichever date is later. The Board is authorized, on application by any corporation, to extend such period from time to time with respect to such corporation for not more than one year at a time if, in its judgment, such an extension would not be detrimental to the public interest; except that such period may not in any case be extended beyond the date 5 years after the date of the enactment of this part or 5 years after the date on which the corporation becomes a bank holding company, whichever date is later. " ( f ) CERTAIN EXCHANGES OF SECURITIES.—In the case of an ex- change described in subsection (a) (2) (A) (iv) or subsection (b) (2) (A) (iv), subsection (a) or subsection (b) (as the case may be) shall apply only to the extent that the principal amount of the securi- ties received does not exceed the principal amount of the securities exchanged. "SEC. 1102. SPECIAL RULES. " (a) BASIS OF PROPERTY ACQUIRED IN DISTRIBUTIONS.—If, by reason of section 1101, gain is not recognized with respect to the receipt of any Ante, p . 139. property, then, under regulations prescribed by the Secretary or his delegate— Ii4 PUBLIC LAW 511-MAY 9, 1956 [70 S T A T . "(1) if the property is received by a shareholder with respect to stock, without the surrender by such shareholder of stock, the basis of the property received and of the stock with respept to which it is distributed shall, in the distributee's hands, be deter- mined by allocating between such property and such stock the adjusted basis of such stock; or "(2) if the property is received by a shareholder in exchange for stock or by a security holder in exchange for securities, the basis of the property received shall, in the distributee's hands, be the same as the adjusted basis of the stock or securities exchanged, increased by— " ( A ) the amount of the property received which was treated as a dividend, and " ( B ) the amount of gain to the taxpayer recognized on the property received (not including any portion of such gain which was treated as a dividend). " (b) PERIODS OF LIMITATION.—The periods of limitation provided 68A Stat. 803 . in section 6501 (relating to limitations on assessment and collection) 26 u s e 6501. shall not expire, with respect to any deficiency (including interest and additions to the tax) resulting solely from the receipt of property by shareholders in a distribution which is certified by the Board under subsection ( a ) , ( b ) , or (c) of section 1101, until five years after the distributing corporation notifies the Secretary or his delegate (in such manner and with such accompanying information as the Secretary or his delegate may by regulations prescribe) that the Ante, p. 135. period (including extensions thereof) prescribed in section 4 (a) of Ante, p. 143. the Bank Holding Company Act of 1956, or section 1101 (e) (2) ( B ) , whichever is applicable, has expired; and such assessment may be made notwithstanding any provision of law or rule of law which would otherwise prevent such assessment. " ( c ) AlXOCATION OF EARNINGS AND P R O F I T S . "(1) DISTRIBUTION OF STOCK I N A CONTROLLED CORPORATION.— I n the case of a distribution by a qualified bank holding corpora- Ante, p. 139. tion under section 1101 (a) (1) or (b) (1) of stock in a controlled corporation, proper allocation with respect to the earnings and profits of the distributing corporation and the controlled corpora- tion shall be made under regulations prescribed by the Secretary or his delegate. "(2) E X C H A N G E S D E S C R I B E D I N SECTION 1 1 0 1 ( o ( 2 ) OR ( s ) . — I n Ante, p. 142. the case of any exchange described in section 1101 (c) (2) or ( 3 ) , proper allocation with respect to the earnings and profits of the corporation transferring the property and the corporation receiv- ing such property shall be made under regulations prescribed by the Secretary or his delegate. "(3) DEFINITION OF CONTROLLED CORPORATION.—For purposes of paragra])h ( 1 ) , the term 'controlled corporation- means a corporation with respect to which at least 80 percent of the total combined voting power of all classes of stock entitled to vote and at least 80 percent of the total number of shares of all other classes of stock is owned by the distributing qualified bank holding corporation. " ( d ) ITEMIZATION OF PROPERTY.—In any certification under this j)art, the Board shall make such specification and itemization of prop- erty as may be necessary to carry out the provisions of this part. "SEC. 1103. DEFINITIONS. " ( a ) B A N K HOLDING COMPANY.—For purposes of this part, the term 'bank holding company' has the meaning assigned to such term Ante, p. 133. by section 2 of the Bank Holding Company Act of 1956. 70 S T A T . ] PUBLIC LAW 511-MAY 9, 1956 145 "(b) QUALIFIED B A N K HOLDING CORPORATION.— "(1) I N GENERAL.—Except as provided in paragraph (2), for purposes of this part the term 'qualified bank holding corpora- tion' means any corporation (as defined in section 7701 (a) (3)) 68A Stat. 911 . 26 u s e 7701. which is a bank holding company and which holds prohibited property acquired by it— " ( A ) on or before May 15, 1955, " ( B ) in a distribution in which gain to such corporation with respect to the receipt of such property was not recog- Ante, p. 139. nized by reason of subsection (a) or (b) or section 1101, or " ( C ) in exchange for all of its stock in an exchange de- scribed in section 1101 (c) (2) or (c) (3). Ante, p . 142* "(2) LIMITATIONS.— " ( A ) A bank holding company shall not be a qualified bank holding corporation, unless it would have been a bank holding company on May 15,1955, if the Bank Holding Com- pany Act of 1956 had been in effect on such date, or unless it is a bank holding company determined solely by reference to— " ( i ) property acquired by it on or before May 15, 1955, "(ii) property acquired by it in a distribution in which gain to such corporation with respect to the re- ceipt of such property was not recognized by reason of subsection (a) or (b) of section 1101, and Ante, p . 139. "(iii) property acquired by it in exchange for all of its stock in an exchange described in section 1101 (c) (2) or (3). Ante, p . 142* " ( B ) A bank holding company shall not be a qualified bank holding corporation by reason of property described in subparagraph (B) of paragraph (1) or clause (ii) of subparagraph (A) of this paragraph, unless such property was acquired in a distribution with respect to stock, which stock was acquired by such bank holding company— " ( i ) on or before May 15, 1955, "(ii) in a distribution (with respect to stock held by it on May 15, 1955, or with respect to stock in respect of which all previous applications of this clause are satisfied) with respect to which gain to it was not recognized by reason of subsection (a) or (b) of section 1101, or Ante, p. 139. "(iii) in exchange for all of its stock in an exchange described in section 1101 (c) (2) or (3). Ante, p . 142. " ( C ) A corporation shall be treated as a qualified bank holding corporation only if the Board certifies that it satisfies the foregoing requirements of this subsection. "(c) PROHIBITED PROPERTY.—^For purposes of this part, the term 'prohibited property' means, in the case of any bank holding com- pany . p r o p e r t y (other than nonexempt property) the disposition of which* would be necessary or appropriate to effectuate section 4 of the Bank Holding Company Act of 1956 if such company continued Ante, p . 135, to be a bank holding company beyond the period (including any exten- sions thereof) specified in subsection (a) of such section or in section 1101 (e) (2) (B) of this j>art, as the case may be. The term 'pro- "Prohibited proper^". hibited property' does not include shares of any company held by a bank holding company to the extent that the prohibitions of section 4 of the Bank Holding Company Act of 1956 do not apply to the owner- ship by such bank holding company of such property by reason of subsection (c) (5) of such section. 69225 O - 57 - 14 (Vol. 70) U6 PUBLIC LAW 512-MAY 9, 1956 [70 S T A T . " ( d ) NoNEXEMPT PRorERTY.—For purposes of this part, the term 'iionexempt property' means— "(1) obligations (including notes, drafts, bills of exchange, and bankers' acceptances) having a maturity at the time of issuance of not exceeding 24 months, exclusive of days of grace; "(2) securities issued by or guaranteed as to principal or in- terest by a government or subdivision thereof or by any instru- mentality of a government or subdivision; or "(3) money, and the right to receive money not evidenced by a security or obligation (other than a security or obligation de- scribed in paragraph (1) or ( 2 ) ) . "(e) BOARD.—For purposes of this part, the term 'Board' means the Board of Governors of the Federal Reserve System." (b) The table of parts for subchapter O of chapter 1 of the Internal 2V^us°c 10^01- Revenue Code of 1954 is amended by adding at the end thereof the 1091. following: " P a r t V I I I . Distribiitions p u r s u a n t to Bank Holding Company Act of 1956." (c) The amendments made by this section shall apply "with respect to taxable years ending after the date of the enactment of this Act. SAVING P R O V I S I O X SEC. 11. Nothing herein contained shall be interpreted or construed as approving any act, action, or conduct which is or has been or may be in violation of existing law, nor shall anything herein contained constitute a defense to any action, suit, or proceeding pending or here- after instituted on account of anj' prohibited antitrust or monopolistic act, action, or conduct. SEPARABILITY OF PROVISIONS SEC. 12. If any provision of this Act, or the application of such provision to any person or circumstance, shall be held invalid, the remainder of the Act, and the application of such provision to persons or circumstances other than those to which it is held invalid, shall not be affected thereby. Approved May 9, 1956. Public Law 512 CHAPTER 241 M«y9.1956 ^ ACT [H. R. 6573] rj^Q authorize renewals of a lease of the Annette Island Airport to t h e United States. Be it enacted hy the Senate and House of Repremntatives of the Ai^rt^'Aiask^** United States of America in Congress assembled^ That the Congress of the United States hereby approves the extension, from year to year, until June 30, 1999, of a lease of certain land comprising part of Annette Island, Alaska, for use by the Civil Aeronautics Administra- tion as an airport, entered into by the United States of America and the Council of the Annette Island Keserve on December 13,1948, section 5 of which lease provides that no renewal thereof shall extend beyond June 30, 1959, unless approved by Congress. Approved May 9, 1956.
https://www.govtrack.us/congress/bills/84/hr6227/text
Hecate | Oxford Classical Dictionary " Hecate" published on by Oxford University Press. Hecate<here is a image c6b444266ddcae6c-5058ed57d83d241d> Hecate<here is a image c6b444266ddcae6c-5058ed57d83d241d> A. Henrichs https://doi.org/10.1093/acrefore/9780199381135.013.2957 Published online:22 December 2015 Subjects Greek Myth and Religion Hecate was a popular and ubiquitous goddess from the time ofHesioduntil late antiquity. Unknown inHomerand harmless in Hesiod, she emerges by the 5th cent. as a sinister divine figure associated with magic and witchcraft, lunar lore and creatures of the night, dog sacrifices and illuminated cakes, as well as doorways and crossroads. Her name is the feminine equivalent of Hekatos, an obscure epithet ofApollo(Chantraine, Dictionnaire étymologique de la langue grecque(Paris 1968–80) 1. 328 on ἔκατος‎, ἑκατηβόλος‎), but the Greek etymology is no guarantee that her name or cult originated in Greece. Possibly of Carian origin (seecaria), and certainly outlandish in her infernal aspects, she is more at home on the fringes than in the centre of Greek polytheism. Intrinsically ambivalent and polymorphous, she straddles conventional boundaries and eludes definition. In Hesiod's Theogonyshe is the granddaughter of theTitansPhoebeand Coeus, daughter of Perses andAsteria, and first cousin of Apollo andArtemis(for other genealogies see schol. Ap. Rhod. Argon.3. 467). In a remarkable digression ( Theog.411–52), the authenticity of which has been unduly doubted, Hecate is praised as a powerful goddess who ‘has a share’ of earth, sea, and sky—but not the Underworld—and who gives protection to warriors, athletes, hunters, herders, and fishermen. As with all gods, she may choose to withhold her gifts. But, because her functions overlap with those of other divinities, she lacks individuating features. Furthermore, the Hesiodic Hecate contrasts sharply with the goddess's later manifestations, which tend to be much more menacing. Where and how this differentiation happened remains uncertain. Throughout her long history, Hecate received public as well as private cult, the latter often taking forms that were anything but normal. She was worshipped in liminal places, and sacrifices to her were as anomalous as the goddess herself. The earliest archaeological evidence is a dedication to Hecate on a circular altar in the precinct of Apollo Delphinios atMiletus( A. Rehm, Milet.1. 3 (Berlin, 1914), no. 129, before 500 bce); she had her own shrine ‘outside the gates’—as opposed to the Coan cult (seecos) of Hecate ‘in the city’ ( LSCG169 A 5)—where she received libations of unmixed wine ( LSAM50. 25–9, 450 bce). In AthensHermesPropylaios and Hecate Epipyrgidia (‘On the Ramparts’) guarded the entrance to the Acropolis (Paus. 1. 22. 8, 2. 30. 2). Similarly, altars and cult images of the trimorphic Hecate ( hekataia) stood in front of private homes (Aesch. fr. 388 Radt, Ar. Vesp.804) and especially at forks in the road (Apollodorus of Athens, FGrH244 F 110), after which she was named τριοδῖτις‎ and Trivia. The documentation for the Hecate cult in Classical Athens is particularly rich and varied. Her favourite food offerings consisted of a scavenging fish (seefish, sacred) tabooed in other cults—the red mullet ( τρίγλα‎, Apollodorus 244 F 109; Antiphanes fr. 69. 14 f. K–A)—of sacrificialcakesdecorated with lit miniature torches (Soph. fr. 734 Radt; Diphilus fr. 27 K–A; LIMC‘Hekate’, no. 47), and, most notoriously, of puppies (Ar. frs. 209, 608 K-A). The illuminated cakes were offered at the time of the full moon (Philochorus, FGrH328 F 86). So-called ‘suppers of Hecate’ ( Ἑκαταῖα‎ sc. δεῖπνα‎)—consisting of various breadstuffs, eggs, cheese, and dog-meat—were put out for her at the crossroads each month to mark the rising of the new moon ( Ari. Plut.594 ff. with schol., fr. 209 K–A). On an Attic lecythus, a woman deposits a puppy and a basket with sacrificial cakes in front of burning torches ( Beazley, ARV 21204. 2). Attested for Athens, Colophon,Samothrace, andThrace, dog sacrifices to Hecate were alimentary as well as cathartic (Sophron fr. 4.7 K-A; Plut. Quaest. Rom.280c, 290d). During Hellenistic and Roman times, she was worshipped as the regional mother-goddess at her main Carian sanctuary at Lagina nearStratonicea. There, the ritual carrying of a sacred key ( κλειδαγωγία‎) was part of her cult, the clergy of which included a priest and priestess as well as eunuchs. On the temple frieze, Hecate carries toCronusthe stone that represents the newbornZeus; in another scene, she participates in the Gigantomachy ( LIMCnos. 98–100; seegiants). No dogs were sacrificed in the Lagina cult, but the puppy sacrifices, prominent inHittiteand Carian purification rituals, point to an early Anatolian connection. Seeanatolian deities. Hecate was identified with other divine figures such as Ereschigal, the Babylonian goddess of the Underworld ( PGM lxx); the Thessalian Enodia (Soph. fr. 535. 2 Radt; Eur. Hel.569 f.) andBrimo(Ap. Rhod. Argon.3. 861 f., 1211; LIMCnos. 303, 305); the Sicilian Angelos (schol. Theocr. 2. 11/12b; cf. R. Arena, Iscrizioni greche arcaiche di Sicilia e Magna Grecia1 ( 1989), no. 38 = L. Dubois, Inscriptions grecques dialectales de Sicilie(1989), no. 55, c.450 bce);Persephone(Soph. Ant.1199 f., Eur. Ion1048 f.);Iphigenia(Stesichorus fr. 215 Davies, PMGF; Paus. 1. 43. 1, cf. Hesiod fr. 23a. 26 M–W); and especially Artemis ( IG12. 8. 359, Thasos, c.450 bce; IG4 2. 499, Epidaurus, imperial period). In Athens, too, she was worshipped as Artemis Hecate ( IG1 3. 383. 125–7, 429/ 8 bce) and as Kalliste, another of Artemis' cult titles (Hesychius κ‎ 489; cf. IG2 2. 4665–8). Sacrifices to Artemis Hecate and to Kourotrophos were performed in Hecate's shrine at Erchia in Attica ( LSCG18 B 6–13, 375/ 50 bce). Hecate was also associated with various male gods, including Apollo Delphinios,Asclepius, Hermes,Pan, Zeus Meilichios, and Zeus Panamaros. Like allchthoniandivinities, Hecate was perceived as simultaneously terrible and benign. Her ‘good’ side is addressed by her Hesiodic epithet ‘nurturer of the young’ (Hes. Theog.450 κουροτρόφος‎, echoed in later sources). In Aeschylus, the title ‘Hekata’ refers to Artemis in her association with childbirth (H. F. Johansen and E. W. Whittle, Aeschylus: The Suppliants( 1980) on Supplices676) and young animals ( Aga.140 West). The Hecate seen in Eleusinian myth and cult is propitious and caring. She assistsDemeterin her search for Persephone (Kore), and after the reunion of mother and daughter becomes Kore's ‘minister and attendant’ (Richardson on Hym. Hom. Cer.24 f. and 440). Attic vase-painters included Hecate in their depictions of the return of Kore and the mission ofTriptolemus( LIMCnos. 10–23); in the Atticdemeof Paiania, Hecate's cult and priestess were attached to the local Eleusinion ( IG1 3. 250 = LSS18, 450/ 30 bce). In later versions of the myth, Hecate is another daughter of Demeter and retrieves Persephone from the Underworld (Callim. fr. 466 Pf., Orph. fr. 400 Bernabé). Mystery cults (seemysteries) of Hecate also existed, as onAeginaand Samothrace; a woman initiate claims on her tombstone to have been immortalized in death as the ‘goddess Hecate’ ( GVI438a, Thrace, imperial period). Although Hecate lacked a mythology of her own, her nocturnal apparitions, packs of barking hell-hounds, and hosts of ghost-like revenants occupied a special place in the Greek religious imagination. As ‘the one of the roadways’ ( ἐνοδία‎), she protected the crossroads as well as the graves by the roadside. She also guarded the gates to Hades. According to one of the hymns toSelene-Hecate embedded in the Paris magical papyrus, Hecate keeps the keys that ‘open the bars of Cerberus’ and wears ‘the bronze sandal of her who holdsTartarus’ ( PGM iv2291–5, 2334 f.; cf. Suppl. Mag.49. 57–61). A permanent fixture of the Greek and Roman Underworld, she gives Virgil'sSibyl, a priestess of Apollo and Hecate, a guided tour of Tartarus ( Aen.6. 35, 564 f.). Because of her association with the chthonian realm and the ghosts of the dead, Hecate looms large in ancientmagic. Sorceresses of all periods and every provenance, such as Medea, Simaetha, and Canidia, invoke her name as one who makes powerful spells more potent (Soph. frs. 534–5 Radt; Eur. Med.397; Ap. Rhod. Argon.3. 1035 ff.; Theoc. Id.2. 12–16; Hor. Sat.1. 8. 33). On curse tablets (seecurses) dating from the Classical to the imperial period, Hecate is conjured in conjunction withHermesChthonios, Gē (seegaia) Chthonia, Persephone, or Pluton (seehades) ( Def. tab.A. Audollent, nos. 38, 41, Wünsch, nos. 104–7). In a specimen from Hellenistic Athens, Hecate Chthonia is invoked ‘along with the maddeningErinyes’ (no. 108b 2 Wünsch = Gager no. 69). Hecate is equally prominent in the magical papyri, where she is often identified withBaubo,Brimo,Persephone /Koreand Selene (Fauth 2006, 27–76). In thetheurgyof the Chaldaean Oraclesadopted by the Neoplatonists, Hecate, though still linked to demons, has become an epiphanic celestial deity (seeepiphany) and cosmological principle—the Cosmicsoul—accessible through ritual as well as contemplation. Representations of Hecate in art fall into two broad categories: her images are either single-faced or three-faced. The earliest example of the former type may be an inscribed terracotta figurine of a woman seated on a throne, dedicated by ‘ Aigonto Hecate’ ( Athens, late 6th cent. bce; IG1 2. 836; LIMCno. 105). After c.430 bce, the goddess of the crossroads is often represented as a standing female figure with three faces or bodies, each corresponding to one of the crossing roads. The trimorphous Hecate is said to be the creation ofAlcamenes( LIMCno. 112). She is often shown wearing the polos(divine head-dress) and holding torches in her hands ( Hym. Hom. Cer.52; LIMCnos. 1–94), and occasionally with a phiale, a sword, snakes, boughs, flowers, or a pomegranate. Central to her cult, the three-faced image of Hecate is depicted on two Attic vases from the Classical period ( LIMCnos. 48, 206). On the Altar of Zeus atPergamum, Hecate and her dog attack a serpentine giant; her single body supports three heads and three pairs of arms ( LIMCno. 191). Exceptionally, on a calyx crater with the death ofActaeon, a winged Hecate urges on his maddened dogs while Artemis looks on ( LIMCno. 96). On an equally unique vase, Hecate has man-eating dogs for feet and is accompanied by threeErinyes( LIMCno. 95). Greek wordsmiths went to great lengths in their efforts to verbalize the triple aspects of the trimorphic goddess. In one of the comedies of Chariclides, she is humorously invoked as ‘Lady Hecate of the triple roads, of the triple form, of the triple face, enchanted by triple-fish [mullets]’ (fr. 1 K–A δέσποιν᾽ Ἑκάτη τριοδῖτι‎, τρίμορφε‎, τριπρόσωπε τρίγλαις κηλευμένη‎). A curse tablet from the imperial period addresses her similarly as ‘Lady Hecate of the heavens, Hecate of the Underworld, Hecate of the three roads, Hecate of the triple face, Hecate of the single face’ ( SEG30. 326 = Gager no. 84; cf. iv2525–30, 2820–6). Playing withsacred numbersadded to her mystery. Bibliography J. Heckenbach, Realencyclopädie der Classischen Altertumswissenschaft, 2769–2782, s.v. ‘Hekate’. U. von Wilamowitz-Moellendorff, Der Glaube der Hellenen(1931–2), 169–77. T. Kraus, Hekate(1960). M. L. West, Hesiod, Theogony(1966), 276–80. A. Kehl, Reallexikon für Antike und Christentum14 (1988), 310–38, ‘Hekate’. S. I. Johnston, Zeitschrift für Papyrologie und Epigraphik88 (1991), 217–24. S. I. Johnston, Restless Dead(1999), 203–249. W. Fauth, Hekate Polymorphos(2006). Local cults M. P. Nilsson, Griechische Feste v. religiöser Bedeutung m. Ausschluss d. attischen(1906), 394–401. L. R. Farnell, The Cults of the Greek States(1896–1909), 2. 501–519, 549–557, 596–602. A. Laumonier, Les Cultes indigènes en Carie(1958), 344–425. F. Graf, Nordionische Kulte(1985), 229 f., 257–9. A. Henrichs, in H. Hofmannand A. Harder(eds.), Fragmenta dramatica(1991), 180–7 (Athens). K. Clinton, Myth and Cult: The Iconography of the Eleusinian Mysteries(1992), esp. 116–120. ‘Hecate's suppers’ K. Meuli, Gesammelte Schriften(1975), 2. 923 f. C. H. Greenewalt, Ritual Dinners in Early Historic Sardis, University of California Publications in Classical Studies, 1978, esp. 42–45. W. Burkert, in Le Sacrifice dans l'antiquité, Entretiens Hardt 27 (1981), 117 f. R. Parker, Miasma: Pollution and Purification in Early Greek Religion(1983), 222–4, 357 f., 362 f. Hecate in magic and theurgy H. D. Betz(ed.), The Greek Magical Papyri in Translation1 (1986, 2nd edn. 1992), esp. 78–92. S. I. Johnston, Hekate Soteira(1990). J. G. Gager, Curse Tablets and Binding Spells from the Ancient World(1992). Iconography E. Simon, Mitteilungen des deutschen archäologischen Instituts, Athenische Abteilung1985, 271–284. H. Sarian, Lexicon Iconographicum Mythologiae Classicae6 (1992), 1. 985–1018, 2. 654–73 (plates). N. Werth, Hekate(2006).
https://oxfordre.com/classics/display/10.1093/acrefore/9780199381135.001.0001/acrefore-9780199381135-e-2957;jsessionid=B93D0FE0E1CAC76E9F75F6C30D8C932A
Vegetative responses under different soil amending mulches on western Kentucky strip mine spoil (Conference) | OSTI.GOV The U.S. Department of Energy's Office of Scientific and Technical Information Title: Vegetative responses under different soil amending mulches on western Kentucky strip mine spoil Full Record Other Related Research Abstract In May of 1979, eleven test plots were established to test the effectiveness of mulch and grass and legume mixtures. Test plots of hardwood bark, whole tree chips, straw, hay, five wood fiber products, one soil sealant and a control were established with five grass and legume seed mixtures. Bark and whole tree chips were applied at 45 ton/a, straw and hay at 1 1/2 ton/a, five wood fiber products at 1500 pound/a and the soil sealant at 5 gal/a. Seed mixtures were about 40 pounds/a. Bark and whole tree chips were found to promote the best total ground cover. Bark was also found to promote the best legume cover. Hay promoted the best grass cover. The best seed mixture consisted of 15 pounds/a KY-31 tall fescue, 8 pounds/a Gladiator Alfalfa, 6 pounds/a hulled Korean Lespedeza, 3 pounds/a Timfor Timothy and 6 pounds/a of Medium Red Clover. In general, the wood fiber products did not develop a better grass-legume stand than the control. The soil sealant was generally worse than the control. Authors: Vail, J A ; Koon, D L Publication Date: 1980-12-01 Research Org.: Madisonville Community College, KY OSTI Identifier: 5380539 Report Number(s): CONF-801263- Journal ID: CODEN: UKOBD Resource Type: Conference Journal Name: Univ. Ky., Off. Eng. Serv., (Bull.); (United States) Additional Journal Information: Conference: Symposium on surface mining hydrology, sedimentology and reclamation, Lexington, KY, USA, 1 Dec 1980 Country of Publication: United States Language: English Subject: 54 ENVIRONMENTAL SCIENCES ; 60 APPLIED LIFE SCIENCES ; REVEGETATION ; COMPARATIVE EVALUATIONS ; CULTIVATION TECHNIQUES ; SPOIL BANKS ; SURFACE MINING ; LAND RECLAMATION ; FERTILIZERS ; FIELD TESTS ; KENTUCKY ; SOIL CHEMISTRY ; CHEMISTRY ; FEDERAL REGION IV ; MINING ; NORTH AMERICA ; TESTING ; USA ; 510500* - Environment, Terrestrial- Site Resource & Use Studies- (-1989) ; 553000 - Agriculture & Food Technology Citation Formats MLA APA Chicago BibTeX Vail, J A, and Koon, D L. Vegetative responses under different soil amending mulches on western Kentucky strip mine spoil . United States: N. p., 1980. Web. Copy to clipboard Vail, J A, & Koon, D L. Vegetative responses under different soil amending mulches on western Kentucky strip mine spoil . United States. Copy to clipboard Vail, J A, and Koon, D L. 1980. "Vegetative responses under different soil amending mulches on western Kentucky strip mine spoil". United States. Copy to clipboard @article{osti_5380539, title = {Vegetative responses under different soil amending mulches on western Kentucky strip mine spoil}, author = {Vail, J A and Koon, D L}, abstractNote = {In May of 1979, eleven test plots were established to test the effectiveness of mulch and grass and legume mixtures. Test plots of hardwood bark, whole tree chips, straw, hay, five wood fiber products, one soil sealant and a control were established with five grass and legume seed mixtures. Bark and whole tree chips were applied at 45 ton/a, straw and hay at 1 1/2 ton/a, five wood fiber products at 1500 pound/a and the soil sealant at 5 gal/a. Seed mixtures were about 40 pounds/a. Bark and whole tree chips were found to promote the best total ground cover. Bark was also found to promote the best legume cover. Hay promoted the best grass cover. The best seed mixture consisted of 15 pounds/a KY-31 tall fescue, 8 pounds/a Gladiator Alfalfa, 6 pounds/a hulled Korean Lespedeza, 3 pounds/a Timfor Timothy and 6 pounds/a of Medium Red Clover. In general, the wood fiber products did not develop a better grass-legume stand than the control. The soil sealant was generally worse than the control.}, doi = {}, url = {https://www.osti.gov/biblio/5380539}, journal = {Univ. Ky., Off. Eng. Serv., (Bull.); (United States)}, number = , volume = , place = {United States}, year = {1980}, month = {12} } Copy to clipboard Conference: Other availability Please see Document Availability for additional information on obtaining the full-text document. Library patrons may search WorldCat to identify libraries that hold this conference proceeding. Save / Share: Export Metadata Endnote RIS CSV / Excel XML JSON Save to My Library You must Sign In or Create an Account in order to save documents to your library. Facebook Twitter Email Print More share options LinkedIn Pinterest Tumblr Similar records in OSTI.GOV collections: Vegetative responses of grasses and legumes planted under differing rates of soil amending mulches on Kentucky surface mines Conference Koon, D ; Graves, D - Univ. Ky., Off. Eng. Serv., (Bull.); (United States) A replicated block design was established in March, 1978 on Falcon Coal Company land in eastern Kentucky to evaluate grass and legume vegetation responses to different soil mulching agents. Within each replication twelve one-tenth acre plots were seeded and fertilized at a constant rate. Each plot was mulched with bark, wood fiber mulch (WFM), composted municipal waste, or with a mixture of bark and chicken manure, or bark and composted municipal waste. WFM was applied at the rates of 250, 500, 750, and 1500 pounds per acre. Bark was tested at rates of 35 and 70 cubic yards per acre. more » Composted municipal waste was applied at rates of 10 and 20 tons per acre. Mixtures of bark and chicken manure and bark and composted municipal waste were also evaluated. Percent ground cover, percent grasses and legumes composition, and vegetative vigor data were collected for the first growing season. Initially the vegetative establishment on all plots was good with legume to grass ratios being the lowest on the WFM plots. Plots mulched with organic mulches resulted in a higher percentage of vegetative cover than plots mulched with WFM. Percent vegetative cover occupied by legumes were significantly higher for plots treated with organic mulches. « less Growth responses of Kentucky-31, Kenhy, and Kenwell tall fescues established under differing rates of wood fiber and hardwood bark mulches on eastern Kentucky surface mines Conference Koon, D ; Graves, D - Univ. Ky., Off. Eng. Serv., (Bull.); (United States) In August, 1977 Kentucky-31, Kenwell, and the newly released Kenhy variety of tall fescue (Festuca arundinacea (L.) Schreb.) were planted on Falcon Coal Company land in eastern Kentucky to evaluate their establishment and vegetative responses to wood fiber mulch (WFM) and hardwood tree bark. Each of the one-half acre plots were fertilized at a constant rate of four hundred (400) pounds of 16-32-8 fertilizer and seeded at the rate of twenty (20) pounds and four (4) pounds per acre with a tall fescue variety and sweet clover (Melilotus officinalis (L.) Lam.) respectively. Plot mulch treatments included a control, 35 and more » 70 cubic yards per acre of hardwood bark, and 300 and 750 pounds per acre of WFM. Percent total ground cover and percent cover occupied by grasses and by legumes were collected for two growing seasons. Reduced seeding rates were utilized to increase the length of time for establishment so that each variety could be easily compared over several growing seasons, indicating adaptability for establishment on eastern Kentucky mine spoil. « less Plant-growth response to various combinations of mulches and spoil substrates on a Walker County, Alabama, surface coal mine Technical Report Cross, E ; Gabrielson, F ; Hughes, T In 1978-1979, Walker County, Alabama, was the site of an experiment designed to assess plant growth and soil erosion. The experiment utilized 6 mulch treatments applied to each of 3 coal surface mine substrates. The mulches (wood fiber, hardwood bark, pine bark, waste compost, paper-slag, and no mulch application) were randomly combined with either A + B horizon soil, shale, or a mixture of the two. The resulting 18 plots were replicated on two slopes (N-S). A standard seed-fertilizer regimen was applied to all plots. Plots were read in June and October 1979 for species composition, density, and plane cover. more » Overall grass growth, as measured by plane cover, was best on mixed substrate, and growth was not significantly different between shale and topsoil plots. Density and cover provided by volunteer species varied according to slope, substrate, and mulch combinations. Overall, numbers of spoil arthropods did not show great differences according to slope or substrate. « less Bark mulch promotes establishment of vegetation on minesoils with south and west exposures Conference Dyer, K ; Sencindiver, J - Univ. Ky., Off. Eng. Serv., (Bull.); (United States) In early July 1976, a non-topsoiled head-of-hollow fill in Breathitt County, Kentucky, was seeded to grasses and legumes. From July 12 to July 16, a hardwood bark mulch was applied in a band around this fill. After late August 1976, the mulched areas were nearly fully sodded, regardless of aspect. South- and west-facing unmulched slopes were nearly void of vegetation. At this time, the north-facing slope had the best vegetative cover even though no mulch had been applied. By the end of the second growing season, nearly the entire head-of-hollow fill was well vegetated, regardless of aspect or whether mulch more » had been applied. The mulch protected the exposed minesoil from erosion during the first year and speeded the establishment of vegetative cover on the south- and west-facing slopes. On a nearby mountain top removal tract, hardwood bark and black locust chips were compared on gentle north- and south-facing slopes. After to growing seasons, vegetative cover was much heavier on the north-facing than on the south-facing slopes. In April 1985, almost 9 years after these tracts had been seeded, it was apparent that the south- and west-facing slopes had a much heavier vegetative cover than the north-facing slopes. The initial slow growth of vegetation on the south-facing slopes apparently had been more than overcome by (1) greater growth potential due to more available sunlight and warmer temperatures, and (2) greater fertility due to the better survival of legumes. 8 references, 2 figures, 3 tables. « less Surface mine reclamation at the Elkins Mine drainage demonstration project after 17 years Conference Hill, R ; Grube, Jr, W - Univ. Ky., Off. Eng. Serv., (Bull.); (United States) In 1968 approximately 640 acres of land disturbed by coal mining were reclaimed and revegetated. The revegetation approach included the use of lime and fertilizer followed by seeding with a grass-legume mixture. In the steeper areas pine trees were also planted. In areas designated for forest planting, a mixture of pines and deciduous trees was utilized. The revegetated areas were evaluated in 1971, 1973, 1976, 1984, and 1985. This paper discusses the results of the latter two evaluations. After 17 years observations show that a substantial degree of long-term success had been achieved with the revegetation approach taken. The introduced more » vegetative cover either persisted or was replaced by a higher successional order. Shortleaf and Virginia pine were the most successful conifers planted. Black alder had been a good nurse tree but died after 10 years. S. lespedeza was the superior legume. Soil pH was in the range of 3-5, with the best cover occurring at the higher pH. 2 references, 4 figures, 2 tables. « less Similar Records
https://www.osti.gov/biblio/5380539
Congressional Hearing – Building Consumer Confidence by Empowering FDA to Improve Cosmetic Safety | National Women's Health Network Congressional Hearing – Building Consumer Confidence by Empowering FDA to Improve Cosmetic Safety Thank you for the opportunity to testify. My name is M. Isabelle Chaudry and I am the Senior Policy Manager at the National Women’s Health Network, a D.C. – based women’s health advocacy organization. We are supported by a national network of individual members and do not accept financial support from drug- or device-makers or personal care product manufacturers. We shape policy, support consumer health decisions, and monitor the actions of federal regulatory and funding agencies, the health care industry, and the health professions. We also identify and expose health care abuses, and mobilize grassroots action for women’s health issues. On average, women use 12 products containing 168 unique ingredients every day. By contrast, men use six products daily, with 85 unique ingredients. There are several critical issues and loopholes in federal cosmetic regulationthat allow manufacturers to use dangerous ingredients in their products and evade full disclosure of the chemicals contained in those products, and then sell those products to the American public, all of which puts consumers’ health at risk. Understanding the safety of the ingredients in cosmetics is imperative to the overall health of women and girls, both their long-term health and the significant impact on their reproductive health. What is at issue here is the ability to conceive and carry a pregnancy to term as well as the ability to survive through and post menopause without experiencing certain diseases, such as ovarian cancer. Practicing good hygiene and self- care should not create a risk for infertility. Cosmetics and personal care products include skin moisturizer, soap, perfume, lipstick, fingernail polish, makeup, hair products, and deodorant, as well as any substance intended for use as a component of a cosmetic or personal care product. Cosmetic and personal care products are a disproportionately large source of chemical exposure for women and girls in this country. On average, women use 12 products containing 168 unique ingredients every day. By contrast, men use six products daily, with 85 unique ingredients. Vulnerable and underserved women, and girls in particular, may be disproportionately affected by environmental chemical exposures.The data on U.S. reproductive-age women suggest that the bodies of women of color have higher levels of certain endocrine-disrupting chemicals, such as phthalates and parabens, than those of white women, and that these racial and ethnic differences are not explained by socioeconomic status. Research shows that even low exposures to toxic chemicals during critical periods of development, such as pregnancy, can trigger adverse health consequences, including impacts on fertility and pregnancy, cancer, and neurodevelopment. The Federation for Obstetrics and Gynecology recommended that reproductive health professionals recognize the disproportionate burden to toxic chemical exposure in certain patient populations and also to champion policies that secure environmental justice. Their report concludes that: Policies to address toxic chemicals must shift the burden of proof of safety of chemicals from the individual healthcare provider, the patient, and the public to the manufacturers before they are released into the environment. Under current law, dangerous chemicals used in personal care products are still not banned, restricted, or even required to be studied for their safety. Take talc, for instance, which can be contaminated with asbestos and also can be linked to cancer. It is typically found in cosmetic products such as facial powders and personal care products, including baby powder. The FDA was first warned about this type of contamination in the early 1970s, and it has gotten renewed attention in recent years. In December of 2017, independent testing uncovered possible asbestos contamination in makeup kits sold by Claire’s, a national makeup and accessories retail store for girls. Independent testing in 2019 once again found asbestos contamination in products sold by Claire’s, Justice – another national retail chain for girls – and cosmetics maker Beauty Plus Global. Just as recently as October of this year, Johnson & Johnson recalled 33,000 bottles of a product after the FDA discovered evidence of asbestos in one of the bottles. As with many public policy issues, however, Black women are disproportionately affected. According to a 2015 case control study conducted in Los Angeles, 44 percent of Black women use talcum powder as part of a feminine hygiene routine, compared to only 30 percent of white women. Genital powder use, however, may be a modifiable risk factor for epithelial ovarian cancer, the deadliest of all gynecologic cancers.12 In 2016, a University of Virginia study found that African American women who used talcum powder for feminine hygiene had more than a 40 percent increased risk of cancer. We know that, in many cases, companies have actively targeted and marketed talc-based products contaminated with asbestos to Black and Latina women, who remain most affected by a range of reproductive health and comprehensive care barriers and related adverse maternal health risks and outcomes. "Out of 1,177 beauty and personal care products marketed to Black women, about one in 12 was ranked highly hazardous."- Environmental Working Group Study And we now know more about how companies targeted certain populations, despite having evidence that their products may be harmful. Internal documents Johnson & Johnson, one of the country’s largest producers of personal care products containing talc, showed how its marketing efforts focused on the “right place,” and “under developed geographical areas with hot weather, and higher AA [African American] population.” Johnson & Johnson distributed Baby Powder samples through churches and beauty salons in African-American and Hispanic neighborhoods, ran digital and print promotions with weight-loss and wellness company Weight Watchers, and launched a $300,000 radio advertising campaign in a half-dozen markets aimed at reaching “curvy Southern women 18-49 skewing African American.” Black women and women of color are particularly at risk because the cosmetic and personal care products marketed and sold to them often contain the most harmful ingredients. In one study by the Environmental Working Group “of 1,177 beauty and personal care products marketed to Black women, about one in 12 was ranked highly hazardous.”Another study found similar results – personal care products marketed to Black women were found to include “highly hazardous” ingredients at a far higher rate than products marketed to the general population. Under current law, the FDA is not required to review any of these ingredients and indeed has not done so. What’s more, many of these ingredients do not have to be disclosed to consumers but can instead be hidden behind words such as “fragrance.” Companies are not required to disclose the ingredients in the fragrances used in their products, which leaves consumers unaware of the actual chemicals included in the products they purchase. Studies have shown the harmful ingredients often used to formulate “fragrance” are linked to cancer, reproductive health effects, developmental health effects, birth defects and more. We know that “fragrance” can include one or more of about 3,000 chemicals. In 2015, Woman Voices for the Earth published a study examining the thousands of chemicals used by the fragrance industry and demonstrating that many have been identified as chemicals of concern by authoritative governing bodies but were not being examined by the International Fragrance Association and its research arm. Many of the chemicals were linked to cancer or reproductive harm. The report was a result of more than six years of research and persistent watch-dogging of the fragrance and cosmetic industries. In 2016, the Breast Cancer Prevention Partners, the BCPP, set out to investigate whether some of the biggest beauty, personal care, and cleaning brands were hiding unlabeled toxic ingredients in their products. Their report tested 140 cleaning products and personal care products for volatile organic compounds, and 32 personal care and cleaning products for hidden fragrance ingredients. Black women experience one of the highest rates of pre-term births, preeclampsia, fibroids and a host of other maternal health issues. Many factors contribute to the disproportionate disease burden Black women experience, including structural racism and discrimination in the health care system. Other vulnerable populations affected by this issue include workers.Research shows that salon workers are at greater risk for certain health problems compared to other occupations. Salon workers face disproportionate incidence of cancer, neurological diseases, immune diseases, birth defects, reproductive disorders, skin diseases, asthma, and breathing problems. Workers in the beauty industry, who are predominantly women of color and immigrant women, can also face occupational health hazards from chemicals in professional cosmetic products. Other countries have far surpassed the U.S. in assuring cosmetic safety. The EU29 and Canada require cosmetic manufacturers to list any fragrance allergen on the package. The EU has also banned or restricted more than thirteen hundred (1,300) toxic ingredients for cosmetic use. Numerous states, including Minnesota, California, and Washington, have adopted safe cosmetics legislation. The state of California passed the Cleaning Product Right to Know Act, S.B. 258, which requires cleaning companies to disclose all of the chemicals linked to cancer or reproductive or developmental harm, either on the package or on their website. Starting January 1, 2020, the manufacturer of a cleaning product will now have to disclose whether any of the chemicals in its products are linked to these issues. Why are we doing this for cleaning products and not for cosmetic and personal care products? Most people use cleaning products once a week, but we use cosmetic and personal care products every day. It seems that the only reason this category is not regulated is that it is a category that overwhelmingly serves women and disproportionately affects women of color. At the federal level,proposals such as Rep. Schakowsky’s Safe Cosmetics and Personal Care Products Act of 2019 provide meaningful protections for consumers. For example, Ms. Schakowsky’s bill would mandate full fragrance ingredient disclosure by manufacturers, the FDA, the suppliers to manufacturers, and by manufacturers to consumers. Dangerous fragrance ingredients, including allergens and chemicals linked to cancer and reproductive harm, should be disclosed to consumers to allow them to protect their health and avoid the substances they wish to avoid. Chairman Pallone has also introduced a proposal on cosmetic safety that would finally give the FDA the power to review cosmetic ingredients and actually recall products that pose a health risk. I strongly recommend that this committee continue to consider legislation that meaningfully protects women and girls from harmful cosmetic ingredients. Optimally, cosmetics companies should be required to be prove that their products are safe before they can market them to consumers. However, at a minimum, FDA must have the capacity to ban or restrict chemicals that are known to be dangerous to human health must be able to be banned or restricted. Legislation should allow consumers to be able to know what is in the products they use. Cosmetic companies should be forced to actively monitor the safety of their products and to alert the FDA about dangerous products, like talc products contaminated with asbestos. The FDA should absolutely have the power to recall products that threaten our health. Finally, states should not be precluded from providing additional protections against harmful cosmetic products to their residents. For far too long, women and girls have been subject to dangerous products that negatively affect their health. In June of this year,the National Women’s Health Network wrote a letter to the Energy and Commerce Committee, which was signed by 42 other national, state, and local organizations. Today we urge you, as we did in June, “to include the strongest possible safeguards to protect women’s health,” in cosmetics legislation.We thank you, Chairman Pallone, for your efforts to modernize cosmetics law, and we stand ready to work with the committee to pass meaningful legislation that fully protects the public health. M. Isabelle Chaudry, J.D., is the Senior Policy Manager for the NWHN and an advocate for marginalized communities of women. Isabelle actively lobbies and provides expert testimony before Congress and the FDA for women’s health and cosmetic policies. She is an LL.M candidate in International Human Rights and Humanitarian Law and a Board Member for Women’s Voices for the Earth. References [1] Environment Working Group, https://www.ewg.org/Personal-Care-Products-Safety-Act-Would-Improve- Cosmetics-Safety. [2] Environmental Working Group, https://www.ewg.org/Personal-Care-Products-Safety-Act-Would-Improve- Cosmetics-Safety. [3] Ami R. Zota and Bhavna Shamasunder, The Injustice of Beauty: Framing Chemical Exposures From Beauty Products as a Health Disparities Concern , AJOG, (2017) https://www.ajog.org/article/S0002-9378(17)30862- 1/fulltext. [4] James-Todd, T.M., Chiu, Y.-H., and Zota, A.R, Racial/ethnic disparities in environmental endocrine disrupting chemicals and women’s reproductive health outcomes: epidemiological examples across the life course , Curr Epidemiol Rep, 2016; 3: 161–180, https://www.ncbi.nlm.nih.gov/pubmed/28497013 ; Varshavsky, J.R., Zota, A.R., and Woodruff, T.J. A novel method for calculating potency-weighted cumulative phthalates exposure with implications for identifying racial/ethnic disparities among US reproductive-aged women in NHANES 2001-2012, Environ Sci Technol, 2016, 50: 10616–10624, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748889/ : Branch, F., Woodruff, T.J., Mitro, S.D., and Zota, A.R., Vaginal douching and racial/ethnic disparities in phthalates exposures among reproductive-aged women: National Health and Nutrition Examination Survey 2001-2004 , Environ Health, 2015, 14: 1–8 https://ehjournal.biomedcentral.com/articles/10.1186/s12940-015-0043-6 ; Kobrosly, R.W., Parlett, L.E., Stahlhut, R.W., Barrett, E.S., and Swan, S.H., Socioeconomic factors and phthalate metabolite concentrations among United States women of reproductive age , Environ Res, 2012; 115: 11–17, https://www.sciencedirect.com/science/article/abs/pii/S0013935112000916 . [5] Ami R. Zota, Bhavna Shamasunder, The environmental injustice of beauty: framing chemical exposures from beauty products as a health disparities concern , AJOG, (2017) https://www.ajog.org/article/S0002-9378(17)30862- 1/fulltext. [6] Di Renzo, G.C., Conry, J.A., Blake, J. et al., International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals , Int J Gynaecol Obstet, 2015; 131: 219– 225, https://www.figo.org/sites/default/files/uploads/News/Final%20PDF_8462.pdf. [7] Di Renzo, G.C., Conry, J.A., Blake, J. et al., International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals, Int J Gynaecol Obstet, 2015; 131: 219– 225, https://www.figo.org/sites/default/files/uploads/News/Final%20PDF_8462.pdf. [8] Emily Volz, Wjar , Consumer Advocate: Claire’s pulls children’s makeup after family finds asbestos , (December 22, 2017) https://turnto10.com/i-team/consumer-advocate/claires-pulls-childrens-makeup-after-barrington-family- finds-asbestos. [9] Asbestos found in Claire’s, Beauty Plus Global cosmetics , beasleyallen, (June 11, 2019) https://www.beasleyallen.com/news/asbestos-found-in-claires-beauty-plus-global-cosmetics/. [10] Tiffany Hsu and Roni Caryn Rabin , Johnson & Johnson Recalls Baby Powder Over Asbestos Worry , (October 18, 2019) https://www.nytimes.com/2019/10/18/business/johnson-johnson-baby-powder-recall.html. [11] Ronnie Cohen, Why You Shouldn’t Put Baby Powder Down There , Huffington Post, (June 3, 2016) https://www.huffpost.com/entry/talc-linked-to-ovarian-cancer-risk-in-african-american- women_n_5751a1dbe4b0ed593f142915. [12] Association between Body Powder Use and Ovarian Cancer: the African American Cancer Epidemiology Study , AACES, (2016), https://cebp.aacrjournals.org/content/early/2016/05/12/1055-9965.EPI-15-1281.full-text.pdf. [13] Association between Body Powder Use and Ovarian Cancer: the African American Cancer Epidemiology Study, AACES, (2017), https://cebp.aacrjournals.org/content/early/2016/05/12/1055-9965.EPI-15-1281.full-text.pdf. [14] Susan Berfield, Jef Feeley, and Margaret Cronin Fisk, Johnson & Johnson Has a Baby Powder Problem , Bloomberg, (March 31, 2016) https://www.bloomberg.com/features/2016-baby-powder-cancer-lawsuits/. [15] Chris Kirkham and Lisa Girion, As worries about Baby Powder’s safety mounted, J&J focused its pitches on minority, overweight women , Reuters, (April 9, 2019) https://www.reuters.com/investigates/special- report/johnsonandjohnson-marketing/. [16] Chris Kirkham and Lisa Girion, As worries about Baby Powder’s safety mounted, J&J focused its pitches on minority, overweight women , Reuters, (April 9, 2019) https://www.reuters.com/investigates/special- report/johnsonandjohnson-marketing/. [17] Paul Pestano, Nneka Leiba, and Brit’ny Hawkins , Big Market For Black Cosmetics, But Less Hazardous Choices Limited , Environmental Working Group (2016), https://www.ewg.org/research/big-market-black-cosmetics-less- hazardous-choices-limited. [18] Helm, Nishioka, Brody et al., Measurement of endocrine disrupting and asthma-associated chemicals in hair products used by Black women , Environmental Research 2018 (165): 448-458. www.sciencedirect.com/science/article/pii/S0013935118301518. [19] Paula I. Johnson et al., Cosmetics Containing Ingredients Linked to Cancer or Reproductive Harm, Data Reported to the California Safe Cosmetics Program 2009-2015, https://www.cdph.ca.gov/Programs/CCDPHP/DEODC/OHB/CSCP/CDPH%20Document%20Library/DataReport.pdf [20] Alexandra Scranton, Unpacking the Fragrance Industry: Policy Failures, the Trade Secret Myth and Public Health, Woman’s Voices for the Earth , Women’s Voices for the Earth, (2015) https://www.womensvoices.org/wp- content/uploads/2015/11/Fragrance_Industry_Report_Final.pdf. [21] Janet Nudelman and Connie Engel, Right to Know: Exposing toxic fragrance chemicals in beauty, personal care and cleaning products , Breast Cancer Prevention Partners (2018) https://d124kohvtzl951.cloudfront.net/wp- content/uploads/2018/09/26092837/BCPP_Right-To-Know-Report_Secret-Toxic-Fragrance- Ingredients_9_26_2018.pdf. [22] Janet Nudelman and Connie Engel, Right to Know Exposing toxic fragrance chemicals in beauty, personal care and cleaning products , Breast Cancer Prevention Partners (2018) https://d124kohvtzl951.cloudfront.net/wp- content/uploads/2018/09/26092837/BCPP_Right-To-Know-Report_Secret-Toxic-Fragrance- Ingredients_9_26_2018.pdf. [23] Janet Nudelman and Connie Engel, Right to Know Exposing toxic fragrance chemicals in beauty, personal care and cleaning products , Breast Cancer Prevention Partners (2018) https://d124kohvtzl951.cloudfront.net/wp- content/uploads/2018/09/26092837/BCPP_Right-To-Know-Report_Secret-Toxic-Fragrance- Ingredients_9_26_2018.pdf. [24] Janet Nudelman and Connie Engel, Right to Know Exposing toxic fragrance chemicals in beauty, personal care and cleaning products , Breast Cancer Prevention Partners (2018) https://d124kohvtzl951.cloudfront.net/wp- content/uploads/2018/09/26092837/BCPP_Right-To-Know-Report_Secret-Toxic-Fragrance- Ingredients_9_26_2018.pdf. [25] Beauty and It’s Beast: Unmasking the Impacts of toxic chemicals on salon workers , Women’s Voices for the Earth (2014) https://womensvoices.org/wp-content/uploads/2014/11/Beauty-and-Its-Beast.pdf. [26] The U.S. Bureau of Labor Statistics estimates there are 1.2 million people employed in this sector working as hairdressers, hairstylists, cosmetologists, barbers, nail salon workers, and other beauty and personal care workers. 94.8% of hairstylists and hairdressers and 85.1% of other personal appearance workers are women. House Hold Data Annual Averages, Bureau of Labor Statistic, https://www.bls.gov/cps/cpsaat11.pdf. [27] Beauty and It’s Beast: Unmasking the Impacts of toxic chemicals on salon workers , Women’s Voices for the Earth (2014) https://womensvoices.org/wp-content/uploads/2014/11/Beauty-and-Its-Beast.pdf. [28] Adewumi-Gunn, T.A., Ponce, E., Flint, N., and Robbins, W. A preliminary community-based occupational health survey of black hair salon workers in South Los Angeles , J Immigr Minor Health. 2016; 1–7 https://www.ajog.org/article/S0002-9378(17)30862-1/fulltext#back-bib21 ; Quach, T., Gunier, R., Tran, A. et al., Characterizing workplace exposures in Vietnamese women working in California nail salons , Am J Public Health, 2011; 101: S271–S276, https://www.ajog.org/article/S0002-9378(17)30862-1/fulltext#back-bib22; Quach, T., Tsoh, J.Y., Le, G. et al., Identifying and understanding the role of key stakeholders in promoting worker health and safety in nail salons , J Health Care Poor Underserved, 2015; 26: 104–115, https://www.ajog.org/article/S0002- 9378(17)30862-1/fulltext#back-bib23. [29] Fragrance Allergens Labelling, European Commission, https://ec.europa.eu/growth/sectors/cosmetics/products/fragrance-allergens-labelling_en. [30] Cosmetic advertising, labelling and ingredients, Government of Canada, https://www.canada.ca/en/health- canada/services/cosmetics/cosmetic-advertising-labelling-ingredients.html. [31] Oliver Milman, US cosmetics are full of chemicals banned by Europe – why ?, The Guardian, (May 22, 2019) https://www.theguardian.com/us-news/2019/may/22/chemicals-in-cosmetics-us-restricted-eu. [32] Minnesota (House Bill 458) banned formaldehyde, a cancer-causing chemical, in children’s personal care products like lotions, shampoos and bubble baths in 2013. The ban against the use of formaldehyde and formaldehyde-releasing preservatives applies to products intended for children under eight. https://legiscan.com/MN/text/HF458/id/731206. [33] California passed state legislation governing the safety and reporting of cosmetic ingredients. The California Safe Cosmetics Act requires manufacturers to disclose to the state any product ingredient that is on state or federal lists of chemicals that cause cancer or birth defects. http://www.leginfo.ca.gov/pub/05-06/bill/sen/sb_0451- 0500/sb_484_bill_20051007_chaptered.pdf. [34] The state of Washington adopted the Children’s Safe Product Act (CSPA – Chapter 70.240 RCW), which requires manufacturers of children’s products, including personal care products, sold in Washington to report to the state if their product contains a Chemical of High Concern to Children. https://app.leg.wa.gov/RCW/default.aspx?cite=70.240 [35] California Legislative Information, https://leginfo.legislature.ca.gov/faces/billNavClient.xhtml?bill_id=201720180SB258
https://nwhn.org/testimony-of-m-isabelle-chaudry-building-consumer-confidence-by-empowering-fda-to-improve-cosmetic-safety/?lcp_page0=2
Notice of copyright infringement | Statista Find statistics, consumer survey results and industry studies from over 22,500 sources on over 60,000 topics on the internet& #39;s leading statistics database Skip to main content statista.com statista.es statista.de statista.fr Prices & Access Single Accounts Business Solutions Academia and Government Statistics All Industries Consumer Goods & FMCG Internet Media & Advertising Retail & Trade Sports & Recreation Technology & Telecommunications Transportation & Logistics Travel, Tourism & Hospitality Most-viewed Statistics Recent StatisticsPopular Statistics Facebook: quarterly number of MAU (monthly active users) worldwide 2008-2023 Quarterly smartphone market share worldwide by vendor 2009-2023 Number of apps available in leading app stores Q3 2022 OPEC oil price annually 1960-2023 Big Mac index worldwide 2023 Topics Topic Overview Smartphones - statistics & facts Social media - Statistics & Facts Top Report View Report Industry Overview Reports Report Shop Search our report database Digital & Trend reports Overview and forecasts on trending topics Industry & Market reports Industry and market insights and forecasts Companies & Products reports Key figures and rankings about companies and products Consumer & Brand reports Consumer and brand insights and preferences in various industries Politics & Society reports Detailed information about political and social topics Country & Region reports All key figures about countries and regions Find your information in our database containing over 20,000 reports New Market Insights Market forecast and expert KPIs for 1000+ markets in 190+ countries & territories Explore Market Insights Consumer Digital Mobility Consumer Insights Insights on consumer attitudes and behavior worldwide 2,000,000+ interviews 15,000+ brandsExplore Consumer Insights Company Insights Business information on 70m+ public and private companies 100+ industries 200+ countries and territories Explore Company Insights eCommerce Insights Detailed information for 35,000+ online stores and marketplaces 70+ KPIs per store Revenue analytics and forecastsExplore eCommerce Insights Daily Data Services The Statistics Portal Directly accessible data for 170 industries from 150+ countries and over 1 Mio. facts. About Statista Why trust Statista First Steps and Help Centre Live webinars & recordings Tools Business Plan Export Publication Finder Statista Services Statista Q Customized Research & Analysis projects:Statista Q askStatista Get quick analyses with our professional research serviceaskStatista Statista R The best of the best: the portal for top lists & rankings:Statista R Statista Content & Design Transforming Data into Design: Customized infographic service Presentation Design Animated videos Whitepapers, E-Books, etc. Statista Content & Design nxt statista Strategy and business building for the data-driven economy:nxt statista Single Accounts Business Solutions Academia and Government Popular Statistics Topics Markets Reports Market Insights Consumer Insights Company Insights eCommerce Insights Daily Data Content & Design Research projects Ask Statista Business Plan Export Publication Finder Statista R DE ES FR Notice of copyright infringement Information on when we delete personal data, the countries where we save data (e.g., US, EU, Singapore), and the companies we collaborate with can be found in ourprivacy statement. Home About Statista Career Contact Help & FAQ Report Bug Our Media Partners Privacy Imprint Menu Prices & Access Popular Statistics Industries Daily Data Content & Design projects Research projects AskStatista statista.de statista.es statista.fr Cookie Consent Manager General Information General Information When you visit any website, it may store or retrieve information on your browser, mostly in the form of cookies. This information might be about you, your preferences or your device and is mostly used to make the site work as you expect it to. The information does not usually directly identify you, but it can give you a more personalized web experience. Because we respect your right to privacy, you can choose not to allow some types of cookies. Click on the different category headings to find out more and change our default settings. However, blocking some types of cookies may impact your experience of the site and the services we are able to offer. More information Necessary Cookies Necessary Cookies Always Active These cookies are necessary for the website to function and cannot be switched off in our systems. They are usually only set in response to actions made by you which amount to a request for services, such as setting your privacy preferences, logging in or filling in forms. You can set your browser to block or alert you about these cookies, but some parts of the site will not then work. These cookies do not store any personally identifiable information. Functional Cookies Functional Cookies Functional CookiesInactive These cookies enable the website to provide enhanced functionality and personalisation. They may be set by us or by third party providers whose services we have added to our pages. If you do not allow these cookies then some or all of these services may not function properly. Performance Cookies Performance Cookies Performance CookiesInactive These cookies allow us to count visits and traffic sources so we can measure and improve the performance of our site. They help us to know which pages are the most and least popular and see how visitors move around the site. All information these cookies collect is aggregated and therefore anonymous. If you do not allow these cookies we will not know when you have visited our site, and will not be able to monitor its performance. Targeting Cookies Targeting Cookies Targeting CookiesInactive These cookies may be set through our site by our advertising partners. They may be used by those companies to build a profile of your interests and show you relevant adverts on other sites. They do not store directly personal information, but are based on uniquely identifying your browser and internet device. If you do not allow these cookies, you will experience less targeted advertising. Back Vendor Search ConsentLeg.Interest checkbox labellabel checkbox labellabel checkbox labellabel Name cookie name checkbox labellabel By clicking “Accept all,” you agree to the storage of cookies on your device to improve website navigation, analyze website usage, and assist with our marketing efforts. If you click on "Only necessary," only cookies that are required for technical reasons to operate the website will be used.Privacy Statement
https://www.statista.com/statistics/report-content/statistic/440198
Citation Nr: 0310523 Decision Date: 05/30/03 Archive Date: 06/02/03 DOCKET NO. 97-28 954 ) DATE ) ) On appeal from the Department of Veterans Affairs (VA) Regional Office (RO) in St. Petersburg, Florida THE ISSUES 1. Entitlement to an increased (compensable) rating for the service-connected iritis of the right eye. 2. Entitlement to service connection for headaches, claimed as secondary to the service-connected iritis of the right eye. REPRESENTATION Appellant represented by: Disabled American Veterans WITNESSES AT HEARINGS ON APPEAL The veteran and E.C. ATTORNEY FOR THE BOARD L. Cryan, Counsel INTRODUCTION The veteran had active service from September 1983 to May 1985 and from May 1987 to July 1990. This case initially came to the Board of Veterans' Appeals (Board) on appeal from a March 1996 rating decision by the RO that denied a compensable rating for the service-connected iritis. In a July 1997 rating decision, the RO denied the veteran's claim of service connection for headaches, as secondary to the service-connected iritis. The veteran testified at personal hearings before the undersigned Veterans Law Judge at the RO, the first in February 1999, and again in January 2003. The Board remanded the case to the RO in May 1999 and in November 2002 for additional development of the record. FINDINGS OF FACT 1. The service-connected chronic right eye iritis is shown to be productive of recurrent incapacitating episodes manifested by pain, watering and impaired vision. 2. The veteran currently is shown to suffer from a separately ratable headache manifestations that as likely as not are caused or aggravated by his service-connected right eye iritis. CONCLUSIONS OF LAW 1. The schedular criteria for a 30 percent disability rating for the veteran's iritis of the right eye have been met. 38 U.S.C.A. §§ 1155, 5107, 7104 (West 2002); 38 C.F.R. §§ 4.1- 4.14, 4.20, 4.84a, including Diagnostic Codes 6003 6009 (2002). 2. By extending the benefit of the doubt to the veteran, his headache disability is proximately due to or the result of the service-connected iritis of the right eye. 38 U.S.C.A. §§ 1131, 5107, 7104 (West 2002); 38 C.F.R. §§ 3.303, 3.310 (2002). REASONS AND BASES FOR FINDING AND CONCLUSION I. Factual Background The veteran asserts that his service-connected iritis of the right eye is severe enough to warrant a compensable rating. In addition, the veteran asserts that his current headache disability is proximately due to, or the result of the service-connected iritis of the right eye. Service connection for iritis of the right eye was granted by way of an August 1990 RO rating decision which assigned a 10 percent evaluation for the service-connected right eye iritis based on a finding that the veteran was being treated for active iritis in the right eye and, in spite of aggressive treatment, the veteran presented with active iritis resulting in complaints of discomfort, pain, photosensitivity, and inability to focus at near because of cycloplegia. An August 1991 VA outpatient record notes a history of chronic iritis of the right eye with continued complaints of photophobia and 4+ cells in the right eye. The veteran also complained of pain, redness and sensitivity to light in the right eye. In a November 1992 VA examination report, the examiner noted an ongoing severe iritis of the right eye, in spite of medication to control. The examiner also noted that the veteran had been to the clinic several times over the past 5 months with an active iritis of the right eye. In a January 1993 rating decision, the RO increased the rating to 20 percent for the service-connected iritis, based on a finding that the veteran had an "active process in the right eye," and that best corrected visual acuity in the right eye was 20/60. The 20 percent rating was assigned based on the decrease in visual acuity during an active, chronic process of iritis. The veteran was examined again in June 1993. A history of chronic iritis of the right eye was noted. Visual acuity was corrected to 20/20 in the right eye. The diagnosis was that of evidence of previous iritis in the right eye, with current 1+ cells; acuity in the right eye is decreased when iritis is active. In light of the June 1993 examination report, the RO proposed to reduce the veteran's service-connected iritis rating to noncompensable. An August 1993 VA outpatient treatment record notes complaints of recurring chronic iritis. The examiner noted that if the veteran remained on medications, the iritis was minimal. Going off all medications resulted in increase of iritis, with symptoms of photophobia and eye pain and potential and real loss of acuity. The examiner noted that the iritis was a chronic condition with exacerbations. In an August 1993 letter to the RO, a private doctor noted that the veteran was examined by him for chronic uveitis in the right eye. The doctor noted that the veteran's uveitis was chronic, recurrent, and progressive and could cause long term damage to the eye. Despite the medical evidence from August 1993, the RO reduced the rating for the service-connected right eye iritis to noncompensable in an October 1993 rating decision. VA outpatient treatment records from December 1993 through August 1995 show multiple complaints of frequent recurrent iritis of the right eye. In a March 1996 rating decision, the RO denied the veteran's claim for an increased (compensable) rating for the service- connected right eye iritis. The veteran timely appealed that determination. In the veteran's April 1997 Notice of Disagreement, he reported that the service-connected iritis of the right eye caused chronic headaches on the right side of his head, 4-6 times per week. One of the veteran's private doctors submitted a memorandum to the RO indicating that he had treated the veteran for uveitis since 1992 and that headaches could be associated with the uveitis. In light of the foregoing, the veteran submitted a claim of service connection for headaches, claimed as secondary to the service-connected iritis of the right eye in April 1997. The RO denied the veteran's claim of service connection for headaches in a July 1997 rating decision. The veteran timely appealed that determination. In February 1999, the veteran testified before the undersigned Veterans Law Judge that he got headaches over the right eye as a precursor to the iritis attacks. The veteran reported that the headache was like a warning sign, and that once he had the headache, he would take medication for the iritis to hopefully avoid a full-blown iritis attack. The veteran testified that the iritis was very painful during a full-blown attack, and that during service, he received Tylenol 3 with Codeine for the pain. Any sunlight made the pain worse. The veteran testified that his headaches associated with the iritis occurred about 4 times per week, and that at least once per year the headache would render him incapacitated for at least a day. Finally, the veteran testified that he had about 6 severe headaches per year. In May 1999, the Board remanded the case to the RO for further development of the record. In particular, the Board requested that the RO schedule the veteran for a VA examination to determine the current severity of the service- connected iritis of the right eye. In addition, the examiner was requested to opine as to whether the veteran's headaches were a manifestation of the iritis, or whether they constituted a separate ratable disability, as secondary to the service-connected iritis of the right eye. The examination was conducted in October 1999. The examiner noted that the veteran had a long history of iritis of the right eye, with the last flare-up requiring treatment occurring seven months prior. The veteran complained of headaches 2-3 times per month which were relieved by aspirin. The examiner noted that he had evaluated the veteran 12 times from November 1992 to August 1995, but only once since August 1995. The examiner concluded that from November 1992 to August 1995 the veteran was very troubled by the iritis of the right eye, as the pupil stayed dilated secondary to treatment, headaches were more pronounced and the light sensitivity was significant. Since that time, however, the iritis had not been severe, according to the examiner. The veteran noted only one episode in the past year that required treatment and there was no evidence of active iritis on the day of the examination. The examiner doubted that the headaches were a result of subclinical episodes of iritis, but indicated that it was impossible to know for sure since the veteran had not been examined during the time of the headaches. The veteran reported that the headaches were controlled by aspirin. The examiner opined that if the aspirin relieved the headaches, then the headaches were probably not secondary to the iritis since aspirin is not an effective treatment for iritis. However, the examiner did note that in April 1997, the veteran was treated at that facility for complaints of headaches and indeed had an iritis with 2+ cells which required treatment. The headache was relieved with topical eye drops. VA outpatient treatment records from 2000-2002 show that the veteran was treated for active iritis, with complaints of blurriness, pain and burning. The case was thereafter remanded in November 2002 to afford the veteran another personal hearing. The second personal hearing before the undersigned Veterans Law Judge was held in January 2003. The veteran testified that he has had frequent episodes of active iritis in the past year, manifested by headaches on the right side of his head, burning in the right eye and sensitivity to sunlight. II. Legal Analysis A. Service Connection Service connection may be established for disability resulting from personal injury suffered or disease contracted in line of duty, or for aggravation of a pre-existing injury suffered or disease contracted in line of duty. 38 U.S.C.A. § 1131 (West 2002); 38 C.F.R. § 3.303 (2002). The regulations also provide that service connection may be granted for any disease diagnosed after discharge when all the evidence, including that pertinent to service, establishes that the disease was incurred in service. 38 C.F.R. § 3.303(d) (2002). Service connection also may be granted for disability which is proximately due to or the result of a service-connected disease or injury. 38 C.F.R. § 3.310(a) (2002). When aggravation of a veteran's nonservice-connected condition is proximately due to or the result of a service-connected condition, the veteran shall be compensated for the degree of disability over and above the degree of disability existing prior to aggravation. Allen v. Brown, 7 Vet. App. 439 (1995). When all the evidence is assembled, VA is responsible for determining whether the evidence supports the claim or is in relative equipoise, with the appellant prevailing in either event, or whether a preponderance of the evidence is against a claim, in which case, the claim is denied. Gilbert v. Derwinski, 1 Vet. App. 49 (1990); 38 C.F.R. §§ 3.102, 4.3 (2002). When, after consideration of all of the evidence and material of record in an appropriate case before VA, there is an approximate balance of positive and negative evidence regarding the merits of an issue material to the determination of the matter, the benefit of the doubt doctrine in resolving each such issue shall be given to the veteran. 38 U.S.C. § 5107 (West Supp. 2001); Alemany v. Brown, 9 Vet. App. 518, 519 (1996). In this case, the examiner in October 1999 indicated that it was impossible to determine if the veteran's headaches were the result of subclinical episodes of iritis because the veteran had not reported to the facility at the time of the headaches. The examiner also noted that since aspirin apparently relieved the headaches, that they were probably not secondary to iritis since aspirin is not an effective treatment for iritis. Nonetheless, the examiner did note that the veteran complained of a headache in April 1997 at that facility and indeed had an iritis with 2+ cells which required treatment. The Board finds that the examiner's rationale appears flawed. First, the mere fact that aspirin relieved the headaches does not, in and of itself, confirm that the headaches are not secondary to the iritis. Aspirin is a pain reliever and etiology of a claimed disability is not determined by whether aspirin does or does not bring pain relief. Likewise, it does not appear that the etiology of the veteran's headaches could be determined solely based on if aspirin did not relieve the pain in this case. The examiner did note, however, that the veteran did complain of headaches in April 1997 when he was treated for having an iritis attack. The Board points out that the veteran testified at two personal hearings before the undersigned Veterans Law Judge. The veteran consistently maintained that his headaches were a precursor to the iritis attacks and that he could sometimes ward off an attack by using the headache pain as a warning signal to use the prescribed drops for the iritis. The Board finds the veteran's testimony credible. In this regard, the Board finds that the evidence serves to show that the veteran as likely as not has a separately ratable disability manifested by headaches which is proximately due to the service-connected iritis of the right eye. In other words, it is established by the competent evidence of record that the veteran has currently demonstrated headaches that are shown as likely as not to have been proximately due to or the result of his service-connected iritis of the right eye. By extending the benefit of the doubt to the veteran in this case, the Board finds that service connection for headaches is warranted. B. Increased Rating Disability ratings are determined by applying the criteria set forth in the VA Schedule for Rating Disabilities, found in 38 C.F.R. Part 4 (2002). The Board attempts to determine the extent to which the veteran's service-connected disability adversely affects his ability to function under the ordinary conditions of daily life, and the assigned rating is based, as far as practicable, upon the average impairment of earning capacity in civil occupations. 38 U.S.C.A. § 1155 (West 2002); 38 C.F.R. §§ 4.1, 4.10 (2002). Where there is a question as to which of two evaluations shall be applied, the higher evaluation will be assigned if the disability picture more nearly approximates the criteria required for that rating; otherwise, the lower rating will be assigned. 38 C.F.R. § 4.7 (2002). The rating schedule provides that when an unlisted disability is encountered, it will be permissible to rate under a closely related disease or injury in which not only the functions affected, but the anatomical localization and symptomatology are closely analogous. 38 C.F.R. § 4.20 (2002). The veteran's service-connected right eye iritis is evaluated as noncompensable under 38 C.F.R. § 4.84, Diagnostic Code 6003 (2002). According to Diagnostic Code 6009, ratings for unhealed eye injuries and other diseases of the eyes listed in Diagnostic Codes 6000 through 6008 (uveitis, keratitis, scleritis, iritis, cyclitis, choroiditis, retinitis, recent intra-ocular hemorrhage and detachment of the retina), in chronic form, are to be rated from 10 to 100 percent under the criteria for impairment of visual acuity or field loss, pain, rest-requirements or episodic incapacity, combining an additional rating of 10 percent during continuance of active pathology, with 10 percent being the minimum rating during active pathology. 38 C.F.R. § 4.84a, Diagnostic Codes 6003, 6009 (2002). A compensable rating for loss of visual acuity requires that corrected vision be 20/40 in one eye and 20/50 in the other. 38 C.F.R. § 4.84(a), Diagnostic Codes 6078, 6079 (2002). Upon review of the evidence of record, the Board finds that a 30 percent disability rating is warranted for the veteran's right eye iritis. Private and VA medical records dated from 1991 to May 2002 noted a history of chronic, recurrent iritis. The records do show that the veteran has had periods of a decrease in the frequency of flare-ups, however, the records confirm that the overall disability has remained chronic and recurrent over the years. He has complained of pain over and on the right eye and a watering right eye, recently worse with light sensitivity and blurred vision. Moreover, the veteran testified that he is often able to self medicate the iritis before it gets out of control, but that he still experiences occasional incapacitating episodes. Under the criteria of Diagnostic Codes 6003 and 6009, chronic iritis is to be rated at the minimum 10 percent rating if it is chronic. As the medical evidence shows that the veteran's iritis is recurrent and, therefore, chronic, and in consideration of the veteran's hearing testimony that he has occasional incapacitating episodes, the Board finds that a 30 percent rating more closely represents the level of disability due to the service-connected right eye iritis. 38 U.S.C.A. §§ 1155, 5107 (West 2002); 38 C.F.R. §§ 4.7, 4.84, Diagnostic Codes 6003, 6009 (2002). In this regard, the Board notes that Diagnostic Code 6009 further provides that the assignment of a minimum 10 percent rating during active pathology, but that additional ratings between 10 percent and 100 percent may be assigned based on the severity of the active pathology manifested. The Board thus concludes that the preponderance of the evidence is against the assignment of a disability rating in excess of 30 percent, as there is no medical evidence of impairment of visual acuity or field loss, and the pain, rest-requirements and episodic incapacity is sufficiently compensated for by the 30 percent rating. 38 U.S.C.A. § 5107 (West 2002). In order to warrant even the minimal compensable rating of 10 percent for impaired vision, the veteran would have to demonstrate a minimum corrected vision of 20/50 in his service-connected eye. See 38 C.F.R. § 4.75, 4.84a, Diagnostic Codes 6078, 6079 (2002). The most recent medical records revealed corrected vision of no worse than 20/25 bilaterally. Thus, a higher rating is not warranted for impaired vision. The Board has considered the veteran's testimony regarding his pain, discomfort and blurred vision associated with his service-connected iritis of the right eye, and finds him credible. However, as noted above, the veteran simply has not demonstrated a minimum corrected vision of 20/50 in his service-connected eye to warrant a compensable rating on this basis. See 38 C.F.R. § 4.84a, Diagnostic Codes 6078, 6079 (2002). Accordingly, resolving the benefit of the doubt in the veteran's favor to this extent, the Board finds that a 30 percent rating for the veteran's service-connected iritis of the right eye is warranted, based on a chronic disability, with active pathology manifested by pain with occasional incapacitating episodes. 38 U.S.C.A. §§ 1155, 5107 (West 2002); 38 C.F.R. § 4.84, Diagnostic Code 6003 (2002). However, the preponderance of the evidence is against a rating in excess of 30 percent, based upon the veteran's loss of visual acuity. Finally, the Board points out that on November 9, 2000, the President signed into law the Veterans Claims Assistance Act (VCAA) of 2000, which has since been codified at 38 U.S.C.A. §§ 5100, 5102, 5103, 5103A, 5106, 5107, 5126 (West Supp. 2001). Among other things, this law eliminated the concept of a well-grounded claim, redefined the obligations of VA with respect to the duty to assist, and superseded the decision of the United States Court of Appeals for Veterans Claims in Morton v. West, 12 Vet. App. 477 (1999), withdrawn sub nom. Morton v. Gober, No. 96-1517 (U.S. Vet. App. Nov. 6, 2000) (per curiam order), which had held that VA cannot assist in the development of a claim that is not well grounded. This change in the law is applicable to all claims filed on or after the date of enactment of the Veterans Claims Assistance Act of 2000, or filed before the date of enactment and not yet final as of that date. 38 U.S.C.A. §§ 5102, 5103, 5103A, 5107. The regulations implementing the VCAA are now published at 66 Fed. Reg. 45,620, 45,630-32 (August 29, 2001) (which have since been codified at 38 C.F.R. § § 3.102, 3.156(a), 3.159 and 3.326). Except as specifically noted, the new regulations are effective November 9, 2000. Because of the change in the law brought about by the Veterans Claims Assistance Act of 2000, compliance with the notice and duty to assist provisions contained in the new law is now required. See Veterans Claims Assistance Act of 2000, Pub. L. No. 106-475, §§ 3-4, 114 Stat. 2096, 2096-2099 (2000) (codified as amended at 38 U.S.C. §§ 5102, 5103, 5103A, and 5107). The RO, in the July 2002 Supplemental Statement of the Case, has had an opportunity to address this new legislation with regard to the veteran's claim for increase. In this regard, the veteran has been informed of what information was needed to support his claim in rating decisions, Statements of the Case, and letters sent to his by the RO as noted hereinabove. Moreover, the veteran was afforded a VA examination and two personal hearings at which he testified as to the severity of the service-connected disability. In light of the first hearing testimony, the case was thereafter remanded for further development of the record. Most importantly, in light of the favorable action taken hereinbelow, the Board finds that the veteran is not prejudiced thereby and no further assistance in developing the facts pertinent to his claim is required. In this case, the Board finds that there is sufficient evidence of record to decide his claim properly. ORDER Entitlement to an increased rating of 30 percent for the service-connected iritis of the right eye is granted, subject to the laws and regulations governing the award of monetary benefits. Entitlement to service connection for headaches is granted. ____________________________________________ Veterans Law Judge, Board of Veterans' Appeals IMPORTANT NOTICE: We have attached a VA Form 4597 that tells you what steps you can take if you disagree with our decision. We are in the process of updating the form to reflect changes in the law effective on December 27, 2001. See the Veterans Education and Benefits Expansion Act of 2001, Pub. L. No. 107-103, 115 Stat. 976 (2001). In the meanwhile, please note these important corrections to the advice in the form: ? These changes apply to the section entitled "Appeal to the United States Court of Appeals for Veterans Claims." (1) A "Notice of Disagreement filed on or after November 18, 1988" is no longer required to appeal to the Court. (2) You are no longer required to file a copy of your Notice of Appeal with VA's General Counsel. ? In the section entitled "Representation before VA," filing a "Notice of Disagreement with respect to the claim on or after November 18, 1988" is no longer a condition for an attorney-at-law or a VA accredited agent to charge you a fee for representing you.
https://www.va.gov/vetapp03/files/0310523.txt
MLB Stats, Scores, History, & Records | Baseball-Reference.com Complete source for baseball history including complete major league player, team, and league stats, awards, records, leaders, rookies and scores. Baseball Stats and HistoryThe complete source for current and historical baseball players, teams, scores and leaders. 22,920 Major League Players View any Active Player: Choose a TeamArizona DiamondbacksAtlanta BravesBaltimore OriolesBoston Red SoxChicago CubsChicago White SoxCincinnati RedsCleveland GuardiansColorado RockiesDetroit TigersHouston AstrosKansas City RoyalsLos Angeles AngelsLos Angeles DodgersMiami MarlinsMilwaukee BrewersMinnesota TwinsNew York MetsNew York YankeesOakland AthleticsPhiladelphia PhilliesPittsburgh PiratesSan Diego PadresSan Francisco GiantsSeattle MarinersSt. Louis CardinalsTampa Bay RaysTexas RangersToronto Blue JaysWashington Nationals Then a playerReally select a team Select a Hall of Famer: Select a playerHenry AaronGrover AlexanderRoberto AlomarWalter AlstonSparky AndersonCap AnsonLuis AparicioLuke ApplingRichie AshburnEarl AverillJeff BagwellHarold BainesHome Run BakerDave BancroftErnie BanksAl BarlickEd BarrowJake BeckleyCool Papa BellJohnny BenchCharles BenderYogi BerraCraig BiggioBert BlylevenWade BoggsJim BottomleyLou BoudreauRoger BresnahanGeorge BrettLou BrockDan BrouthersMordecai BrownRay BrownWillard BrownMorgan BulkeleyJim BunningJesse BurkettRoy CampanellaRod CarewMax CareySteve CarltonGary CarterAlexander CartwrightOrlando CepedaHenry ChadwickFrank ChanceHappy ChandlerOscar CharlestonJack ChesbroNestor ChylakFred ClarkeJohn ClarksonRoberto ClementeTy CobbMickey CochraneEddie CollinsJimmy CollinsEarle CombsCharlie ComiskeyJocko ConlanTommy ConnollyRoger ConnorAndy CooperStan CoveleskiBobby CoxSam CrawfordJoe CroninCandy CummingsKiki CuylerRay DandridgeGeorge DavisAndre DawsonLeon DayDizzy DeanEd DelahantyBill DickeyMartín DihigoJoe DiMaggioLarry DobyBobby DoerrBarney DreyfussDon DrysdaleHugh DuffyLeo DurocherDennis EckersleyBilly EvansJohnny EversBuck EwingRed FaberBob FellerRick FerrellRollie FingersCarlton FiskElmer FlickWhitey FordBill FosterRube FosterBud FowlerNellie FoxJimmie FoxxFord FrickFrankie FrischPud GalvinLou GehrigCharlie GehringerBob GibsonJosh GibsonWarren GilesPat GillickTom GlavineLefty GomezJoe GordonGoose GoslinRich GossageFrank GrantHank GreenbergKen Griffey Jr.Clark GriffithBurleigh GrimesLefty GroveVladimir GuerreroTony GwynnChick HafeyJesse HainesRoy HalladayBilly HamiltonNed HanlonWill HarridgeBucky HarrisGabby HartnettDoug HarveyHarry HeilmannRickey HendersonBilly HermanWhitey HerzogPete HillGil HodgesTrevor HoffmanHarry HooperRogers HornsbyWaite HoytCal HubbardCarl HubbellMiller HugginsWilliam HulbertCatfish HunterMonte IrvinReggie JacksonTravis JacksonFergie JenkinsHughie JenningsDerek JeterBan JohnsonJudy JohnsonRandy JohnsonWalter JohnsonChipper JonesAddie JossJim KaatAl KalineTim KeefeWillie KeelerGeorge KellJoe KelleyGeorge KellyKing KellyHarmon KillebrewRalph KinerChuck KleinBill KlemSandy KoufaxBowie KuhnTony La RussaNap LajoieKenesaw Mountain LandisBarry LarkinTommy LasordaTony LazzeriBob LemonBuck LeonardFreddie LindstromJohn Henry LloydErnie LombardiAl LopezTed LyonsConnie MackBiz MackeyLarry MacPhailLee MacPhailGreg MadduxEffa ManleyMickey MantleHeinie ManushRabbit MaranvilleJuan MarichalRube MarquardEdgar MartinezPedro MartinezEddie MathewsChristy MathewsonWillie MaysBill MazeroskiJoe McCarthyTommy McCarthyWillie McCoveyJoe McGinnityBill McGowanJohn McGrawFred McGriffBill McKechnieBid McPheeJoe MedwickJosé MéndezMarvin MillerMinnie MinosoJohnny MizePaul MolitorJoe MorganJack MorrisEddie MurrayStan MusialMike MussinaHal NewhouserKid NicholsPhil NiekroHank O'DayWalter O'MalleyBuck O'NeilJim O'RourkeTony OlivaDavid OrtizMel OttSatchel PaigeJim PalmerHerb PennockTony PerezGaylord PerryMike PiazzaEddie PlankAlex PompezCum PoseyKirby PuckettOld Hoss RadbournTim RainesPee Wee ReeseJim RiceSam RiceBranch RickeyCal Ripken Jr.Mariano RiveraEppa RixeyPhil RizzutoRobin RobertsBrooks RobinsonFrank RobinsonJackie RobinsonWilbert RobinsonIvan RodriguezBullet RoganScott RolenEdd RoushRed RuffingJacob RuppertAmos RusieBabe RuthNolan RyanRyne SandbergRon SantoLouis SantopRay SchalkMike SchmidtRed SchoendienstJohn SchuerholzTom SeaverFrank SeleeBud SeligJoe SewellAl SimmonsTed SimmonsGeorge SislerEnos SlaughterHilton SmithLee SmithOzzie SmithJohn SmoltzDuke SniderBilly SouthworthWarren SpahnAl SpaldingTris SpeakerWillie StargellTurkey StearnesCasey StengelBruce SutterMule SuttlesDon SuttonBen TaylorBill TerryFrank ThomasJim ThomeSam ThompsonJoe TinkerJoe TorreCristóbal TorrienteAlan TrammellPie TraynorDazzy VanceArky VaughanBill VeeckRube WaddellHonus WagnerLarry WalkerBobby WallaceEd WalshLloyd WanerPaul WanerJohn WardEarl WeaverGeorge WeissMickey WelchWillie WellsZack WheatDeacon WhiteSol WhiteHoyt WilhelmJ.L. WilkinsonBilly WilliamsDick WilliamsJoe WilliamsTed WilliamsVic WillisHack WilsonJud WilsonDave WinfieldGeorge WrightHarry WrightEarly WynnCarl YastrzemskiTom YawkeyCy YoungRoss YoungsRobin Yount Trending Player PagesShohei Ohtani,Matt Harvey,Mike Trout,Justin Verlander,Matt Mervis,Ronald Acuna Jr.,Juan Soto,Wander Franco,Max Scherzer,Masataka Yoshida Recent DebutsAustin Cox(KCR),Sammy Peralta(CHW),Miguel Amaya(CHC),Brandon Pfaadt(ARI),Gavin Stone(LAD) andZach Muckenhirn(NYM) Minor, Foreign, College, & Black BaseballOur professional baseball register has stats from the Minor, Negro, Japan, Cuban, and Korean leagues, as well as NCAA Division I, II, and III, NAIA, and summer collegiate leagues. In MemoriamTampa Bay Rays play-by-play radio broadcaster Dave Wills,Mike Shannon,Dick Groat,Dennis Ribant,Dave Frost,Don LeppertandMike Baxes Born On This DayJose Altuve,Jose Alvarez,Jim Chamblee,Larry Andersen,Charlie BeverlyandFrankie Libran Player pages include basic statistics and links to player's gamelogs, splits, and more. Every Major League Team 2023 MLB Standings MLB Summary·Scores·Schedule·Leaders·Standings·Transactions AL Summary· Leaders:Batting·Pitching·Standings·Attendance NL Summary· Leaders:Batting·Pitching·Standings·Attendance Table ALWLGBSRS East TBR266--3.3 BAL21104.50.4 BOS19147.51.3 TOR18148.00.2 NYY17159.00.1 Central MIN1814--0.4 CLE14173.5-1.3 DET13174.0-0.8 CHW10228.0-1.1 KCR82410.0-1.5 West TEX1812--1.8 LAA18141.00.1 HOU16152.51.1 SEA15163.5-0.4 OAK62613.0-3.5 Table NLWLGBSRS East ATL2210--1.3 MIA16166.0-1.6 NYM16166.0-0.6 PHI15177.0-1.0 WSN13188.5-0.3 Central PIT2012--1.4 MIL18131.50.5 CHC15164.51.3 CIN13186.5-0.3 STL102210.0-0.5 West LAD1913--1.5 ARI17141.50.4 SDP17152.00.1 SFG13175.0-0.9 COL12207.0-1.4 2023 MLB Rules Changes Effect on Stats and Pace of Play Game time, batting average, stolen bases, clock violations Most Likely Playoff Scenario NL: Byes: LAD, ATL. Wild Card Series: MIL vs SDP and NYM vs ARI AL: Byes: TBR, HOU. Wild Card Series: MIN vs BAL and TOR vs NYY See Full Playoff Odds Interleague Play AL leads NL 62-61 (554 runs to 541)Go to a team page: Choose a TeamArizona DiamondbacksAtlanta BravesBaltimore OriolesBoston Red SoxChicago CubsChicago White SoxCincinnati RedsCleveland GuardiansColorado RockiesDetroit TigersHouston AstrosKansas City RoyalsLos Angeles AngelsLos Angeles DodgersMiami MarlinsMilwaukee BrewersMinnesota TwinsNew York MetsNew York YankeesOakland AthleticsPhiladelphia PhilliesPittsburgh PiratesSan Diego PadresSan Francisco GiantsSeattle MarinersSt. Louis CardinalsTampa Bay RaysTexas RangersToronto Blue JaysWashington Nationals Choose a pageFranchise Index2023 Stats2023 Schedule and Results2023 Roster2023 Transactions2023 Uniform Numbers202220212020All-Time Franchise PagesCareer Batting LeadersSeason Batting LeadersCareer Pitching LeadersSeason Pitching LeadersYear-By-Year Team BattingYear-By-Year Team Pitching Team pages include statistics, rosters, payroll, schedule, gamelogs, splits, and more. Stathead Baseball Powered By Baseball Reference The sports search engine that was made forfans like you POWERED BY Exploring the Baseball Reference database just got easier Start your FREE trial Learn More Benefits of Stathead: Access to the most complete sports database on the internet Affordable (as low as $8/month) Discovery tools to search the Baseball Reference database Customized leaderboards Ad free viewing on Baseball Reference Which team had the most wins over a 162-game span in the expansion era?See it on Stathead Stathead Resources Tips & TricksContact UsTutorialsSample Searches If Baseball Reference creates more questions, find the answers on Stathead. Go beyond the basics.Go to Stathead. Sign Up - First Month Free Sign Up MLB Scores (Thursday, May 4) Chicago Cubs3Final Washington Nationals4 WKyle Finnegan (1-1) LBrad Boxberger (0-1) New York Mets0Final Detroit Tigers2 WEduardo Rodriguez (3-2) LJustin Verlander (0-1) SAlex Lange (5) Pittsburgh Pirates2Final Tampa Bay Rays3 WZach Eflin (4-0) LVince Velasquez (4-3) SJason Adam (2) Los Angeles Angels11Final St. Louis Cardinals7 WGriffin Canning (2-0) LJack Flaherty (2-4) Minnesota Twins7Final Chicago White Sox3(12) WEmilio Pagán (2-0) LAlex Colomé (0-1) Baltimore Orioles13Final Kansas City Royals10 WYennier Cano (1-0) LAroldis Chapman (1-2) Milwaukee Brewers6Final Colorado Rockies9 WBrad Hand (1-1) LPeter Strzelecki (2-2) Seattle Mariners5Final Oakland Athletics3 WGeorge Kirby (3-2) LDrew Rucinski (0-2) SPaul Sewald (9) Atlanta Braves6Final Miami Marlins3 WDylan Dodd (2-1) LJesús Luzardo (2-2) SA.J. Minter (7) Toronto Blue Jays5Final Boston Red Sox11 WBrayan Bello (1-1) LKevin Gausman (2-3) Box scores contain team and player stats.All Major League Box Scores From 1901 to Present Yesterday's Top Performers (Thursday, May 4) Batters Freddy FerminKCR3-4, 1 hr, 2 rbi, 2 rbox Luis RengifoLAA3-4, 1 hr, 4 rbi, 2 rbox Ramón UríasBAL2-2, 4 rbi, 2 sbbox Masataka YoshidaBOS3-5, 1 hr, 3 rbi, 3 rbox Eloy JiménezCHW3-5, 1 hr, 3 rbi, 1 rbox View all Batters Pitchers Eduardo RodriguezDET8.0 ip, 0 er, 9 k, 1 bbbox Zach EflinTBR7.0 ip, 0 er, 10 k, 0 bbbox Lucas GiolitoCHW7.0 ip, 1 er, 7 k, 3 bbbox Patrick CorbinWSN7.0 ip, 2 er, 6 k, 0 bbbox Pablo LópezMIN7.0 ip, 2 er, 8 k, 1 bbbox View all Starting Pitchers by Game Score Create your own list of hot (or not) players What's Happening Follow the impact of the new MLB rule changes Women's Stats Added to College Basketball Reference! Congratulations to this year's Hall of Fame inductees: Fred McGriff,Scott Rolen 2023 Hall of Fame Voting Results 2024 Hall of Fame Projected Ballot 2023 Marcel Projections are Live! Sign up for the Baseball Reference newsletter! A daily recap of top performers, scores and statistical highlights, straight to your inbox! Free FBref World Cup 2023 Newsletter With the 2023 Women's World Cup around the corner, don't miss any of it by signing up for the FBref World Cup newsletter! Get previews, game recaps, advanced stats, and more delivered to your inbox every morning bysigning up today! Dive Deeper with Stathead Baseball Subscribe to Stathead Baseball powered by Baseball Reference. Its your all-access pass to go inside the Baseball Reference database. Get your first month free! Want to see more? Check out Foolish Baseball’s review of Stathead here. Team Head to Head Records Tool The Negro Leagues Are Major Leagues 2023 Negro Leagues Data Update Including Expanded Stats and Bio Info New book!The Negro Leagues Are Major Leagues: Overdue Recognitionavailable now The Negro Leagues Are Major Leagues: A Resource for Educators Site News Additional Baseball Reference Updates from Seamheads 2023 Preseason WAR Updates! Updated Play by Play Info Give us your feedback(please be polite) MLB Trade Rumors Astros’ Luis Garcia To Undergo Tommy John Surgery Latest On Carlos Rodon Dodgers Select Wander Suero, Option Gavin Stone Austin Warren To Undergo Tommy John Surgery Red Sox Acquire Zack Littell From Rangers Twins Select Dereck Rodríguez, Recall Alex Kirilloff Kyle Isbel To Miss Six Weeks With Grade 2 Hamstring Strain Sports Reference Blog 2023 MLB Rule Changes Page Live on Baseball Reference Additional Baseball Reference Updates from Seamheads Versus Finder Launches on Stathead Hockey Baseball Reference Blog and Articles Best Left Fielders of All Time 2022 Baseball Hall of Fame Inductees Out of the Park 24, the award-winning sports strategy baseball game, is available now Upcoming Dates June 2: Lou Gehrig Day June 24-25: Cubs and Cardinals play in London July 10: MLB Home Run Derby July 11: MLB All-Star Game at T-Mobile Park in Seattle August 20: Little League Classic in Williamsport, PA (Phillies/Nationals) September 15: Roberto Clemente Day October 1: Final day of MLB regular season ViewMoreItems Today in Baseball History Site Last Updated:Friday, May 5, 2:36AM MLB Leaders — 2023 & All-Time Season-by-Season Top 20s 2023 Batting Leaders Select a season2023 Leaders2022 Leaders2021 Leaders2020 Leaders2019 Leaders2018 Leaders2017 Leaders2016 Leaders2015 Leaders2014 Leaders2013 Leaders2012 Leaders2011 Leaders2010 Leaders2009 Leaders2008 Leaders2007 Leaders2006 Leaders2005 Leaders2004 Leaders2003 Leaders2002 Leaders2001 Leaders2000 Leaders1999 Leaders1998 Leaders1997 Leaders1996 Leaders1995 Leaders1994 Leaders1993 Leaders1992 Leaders1991 Leaders1990 Leaders1989 Leaders1988 Leaders1987 Leaders1986 Leaders1985 Leaders1984 Leaders1983 Leaders1982 Leaders1981 Leaders1980 Leaders1979 Leaders1978 Leaders1977 Leaders1976 Leaders1975 Leaders1974 Leaders1973 Leaders1972 Leaders1971 Leaders1970 Leaders1969 Leaders1968 Leaders1967 Leaders1966 Leaders1965 Leaders1964 Leaders1963 Leaders1962 Leaders1961 Leaders1960 Leaders1959 Leaders1958 Leaders1957 Leaders1956 Leaders1955 Leaders1954 Leaders1953 Leaders1952 Leaders1951 Leaders1950 Leaders1949 Leaders1948 Leaders1947 Leaders1946 Leaders1945 Leaders1944 Leaders1943 Leaders1942 Leaders1941 Leaders1940 Leaders1939 Leaders1938 Leaders1937 Leaders1936 Leaders1935 Leaders1934 Leaders1933 Leaders1932 Leaders1931 Leaders1930 Leaders1929 Leaders1928 Leaders1927 Leaders1926 Leaders1925 Leaders1924 Leaders1923 Leaders1922 Leaders1921 Leaders1920 Leaders1919 Leaders1918 Leaders1917 Leaders1916 Leaders1915 Leaders1914 Leaders1913 Leaders1912 Leaders1911 Leaders1910 Leaders1909 Leaders1908 Leaders1907 Leaders1906 Leaders1905 Leaders1904 Leaders1903 Leaders1902 Leaders1901 Leaders1900 Leaders1899 Leaders1898 Leaders1897 Leaders1896 Leaders1895 Leaders1894 Leaders1893 Leaders1892 Leaders1891 Leaders1890 Leaders1889 Leaders1888 Leaders1887 Leaders1886 Leaders1885 Leaders1884 Leaders1883 Leaders1882 Leaders1881 Leaders1880 Leaders1879 Leaders1878 Leaders1877 Leaders1876 Leaders1875 Leaders1874 Leaders1873 Leaders1872 Leaders1871 Leaders All-Time Leaderboards Go to a leaderboard using the form below. For Example: Batter | Career | Runs Scored Pitcher | Single-Season | Strikeouts Single-SeasonCareer TotalsActive PlayersRecord EvolutionYear-by-Year LeadersYear-by-Year Top 10 WAR Position PlayersOffensive WARDefensive WARBatting AverageOn-Base%Slugging %On-Base Plus SluggingGames PlayedAt BatsPlate AppearancesRuns ScoredHitsTotal BasesDoublesTriplesHome RunsRuns Batted InBases on BallsStrikeoutsStolen BasesSinglesAdjusted OPS+Runs CreatedAdj. Batting RunsAdj. Batting WinsExtra Base HitsTimes On BaseOffensive Win %Hit By PitchSacrifice HitsSacrifice FliesIntentional Bases on BallsDouble Plays Grounded IntoCaught StealingSB %Power-Speed #AB per SOAB per HROuts MadeBase-Out Runs Added (RE24)Win Probability Added (WPA)Situ. Wins Added (WPA/LI)Championship WPA (cWPA)Base-Out Wins Added (REW)WAR for PitchersEarned Run AverageWinsWin-Loss %Walks & Hits per IPHits per 9 IPBases On Balls per 9 IPStrikeouts per 9 IPGames PlayedSavesInnings PitchedStrikeoutsGames StartedComplete GamesShutoutsHome RunsBases on BallsHitsStrikeouts / Base On BallsHome Runs per 9 IPLossesEarned RunsWild PitchesHit By PitchBatters FacedGames FinishedAdjusted ERA+Fielding Independent PitchingAdj. Pitching RunsAdj. Pitching WinsBase-Out Runs Saved (RE24)Win Probability Added (WPA)Sit. Wins Saved (WPA/LI)Championship WPA (cWPA)Base-Out Wins Saved (REW)Wins Above ReplacementPutoutsAssistsErrors CommittedTotal Zone RunsDef. Games as CPutouts as CAssists as CErrors Committed as CDouble Plays Turned as CPassed BallsStolen Bases Allowed as CCaught Stealing as CCaught Stealing %Def. Games as 1BPutouts as 1BAssists as 1BErrors Committed as 1BDouble Plays Turned as 1BDef. Games as 2BPutouts as 2BAssists as 2BErrors Committed as 2BDouble Plays Turned as 2BDef. Games as 3BPutouts as 3BAssists as 3BErrors Committed as 3BDouble Plays Turned as 3BDef. Games as SSPutouts as SSAssists as SSErrors Committed as SSDouble Plays Turned as SSDef. Games as LF (s.1901)Putouts as LF (s.1901)Assists as LF (s.1901)Errors Committed as LF (s.1901)Double Plays Turned as LF (s.1901)Def. Games as CF (s.1901)Putouts as CF (s.1901)Assists as CF (s.1901)Errors Committed as CF (s.1901)Double Plays Turned as CF (s.1901)Def. Games as RF (s.1901)Putouts as RF (s.1901)Assists as RF (s.1901)Errors Committed as RF (s.1901)Double Plays Turned as RF (s.1901)Def. Games as OFPutouts as OFAssists as OFErrors Committed as OFDouble Plays Turned as OFDef. Games as PPutouts as PAssists as PErrors Committed as PDouble Plays Turned as PTotal Zone Runs as C (s.1953)Range Factor/9Inn as CRange Factor/Game as CFielding % as CTotal Zone Runs as 1B (s.1953)Range Factor/9Inn as 1BRange Factor/Game as 1BFielding % as 1BTotal Zone Runs as 2B (s.1953)Range Factor/9Inn as 2BRange Factor/Game as 2BFielding % as 2BTotal Zone Runs as 3B (s.1953)Range Factor/9Inn as 3BRange Factor/Game as 3BFielding % as 3BTotal Zone Runs as SS (s.1953)Range Factor/9Inn as SSRange Factor/Game as SSFielding % as SSTotal Zone Runs as LF (s.1953)Range Factor/9Inn as LF (s.1948)Range Factor/Game as LF (s.1901)Fielding % as LF (s.1901)Total Zone Runs as CF (s.1953)Range Factor/9Inn as CF (s.1948)Range Factor/Game as CF (s.1901)Fielding % as CF (s.1901)Total Zone Runs as RF (s.1953)Range Factor/9Inn as RF (s.1948)Range Factor/Game as RF (s.1901)Fielding % as RF (s.1901)Total Zone Runs as OF (s.1953)Range Factor/9Inn as OFRange Factor/Game as OFFielding % as OFRange Factor/9Inn as PRange Factor/Game as PFielding % as P View Upcoming Player Milestones 2023 MLB Season 2023 MLB Season Summary·Expanded Standings·Batting Leaders·Pitching Leaders·Batting Stats·Pitching Stats·Starting Lineups·Pitching Staffs·Transactions·Uniform Numbers·Debuts Or go to a season page: Choose a Season & League2023 MLB2022 MLB2021 MLB2020 MLB2019 MLB2018 MLB2017 MLB2016 MLB2015 MLB2014 MLB2013 MLB2012 MLB2011 MLB2010 MLB2009 MLB2008 MLB2007 MLB2006 MLB2005 MLB2004 MLB2003 MLB2002 MLB2001 MLB2000 MLB1999 MLB1998 MLB1997 MLB1996 MLB1995 MLB1994 MLB1993 MLB1992 MLB1991 MLB1990 MLB1989 MLB1988 MLB1987 MLB1986 MLB1985 MLB1984 MLB1983 MLB1982 MLB1981 MLB1980 MLB1979 MLB1978 MLB1977 MLB1976 MLB1975 MLB1974 MLB1973 MLB1972 MLB1971 MLB1970 MLB1969 MLB1968 MLB1967 MLB1966 MLB1965 MLB1964 MLB1963 MLB1962 MLB1961 MLB1960 MLB1959 MLB1958 MLB1957 MLB1956 MLB1955 MLB1954 MLB1953 MLB1952 MLB1951 MLB1950 MLB1949 MLB1948 MLB1947 MLB1946 MLB1945 MLB1944 MLB1943 MLB1942 MLB1941 MLB1940 MLB1939 MLB1938 MLB1937 MLB1936 MLB1935 MLB1934 MLB1933 MLB1932 MLB1931 MLB1930 MLB1929 MLB1928 MLB1927 MLB1926 MLB1925 MLB1924 MLB1923 MLB1922 MLB1921 MLB1920 MLB1919 MLB1918 MLB1917 MLB1916 MLB1915 MLB1914 MLB1913 MLB1912 MLB1911 MLB1910 MLB1909 MLB1908 MLB1907 MLB1906 MLB1905 MLB1904 MLB1903 MLB1902 MLB1901 MLB1900 MLB1899 MLB1898 MLB1897 MLB1896 MLB1895 MLB1894 MLB1893 MLB1892 MLB1891 MLB1890 MLB1889 MLB1888 MLB1887 MLB1886 MLB
https://www.baseball-reference.com/?__hsfp=3465878509&__hssc=213859787.1.1683153551264&__hstc=213859787.287dc4d7949435ce1b20825f6898782f.1683153551262.1683153551262.1683153551262.1
Cyclic Irrigation Improves Irrigation Application Efficiency and Growth of Sawtooth Oak | Request PDF Request PDF | Cyclic Irrigation Improves Irrigation Application Efficiency and Growth of Sawtooth Oak | Two studies were conducted to evaluate differ- ent irrigation regimes for production of container-grown sawtooth oak. Three irrigation treatments... | Find, read and cite all the research you need on ResearchGate Cyclic Irrigation Improves Irrigation Application Efficiency and Growth of Sawtooth Oak July 1999 Arboriculture & Urban Forestry 25(4) DOI: 10.48044/jauf.1999.029 Authors: Auburn University Abstract Two studies were conducted to evaluate differ- ent irrigation regimes for production of container-grown sawtooth oak. Three irrigation treatments (single, 3 times daily, and 6 times daily) and 2 substrate treatments (100% pinebark and 4:1 (v:v) pinebark:coir) were evaluated to determine their effects on irrigation application efficiency and growth of sawtooth oak (Quercus acutissima Carruthers) in a pot-in-pot production system. Irrigation application efficiency increased with cyclic treatments compared to a single application and was increased with the pinebark:coir substrate compared to pinebark alone in the single application treatment. Growth was greater when irrigation was applied in 6 cycles than in 1 single application. Trees grown in pinebark:coir substrate were larger than those grown in the pinebark substrate. ... One potential method of conserving water is cyclic irrigation, in which a fraction of a plant's daily water allowance is applied several times a day. Plant responses to cyclic irrigation include higher growth index, root growth, trunk diameter, shoot dry weight, height, and crop yield than plants receiving one irrigation event per day (Beeson and Haydu, 1995; Fain et al., 1999; Ismail et al., 2007;Keever and Cobb, 1985;Ruter, 1998;Witmer, 2000). In some cases, caliper growth was 25% greater using cyclic irrigation compared with the traditional method of applying a single cycle in the morning (Beeson and Haydu, 1995;Fain et al., 1999;Witmer, 2000). ... ... Plant responses to cyclic irrigation include higher growth index, root growth, trunk diameter, shoot dry weight, height, and crop yield than plants receiving one irrigation event per day (Beeson and Haydu, 1995;Fain et al., 1999;Ismail et al., 2007;Keever and Cobb, 1985;Ruter, 1998;Witmer, 2000). In some cases, caliper growth was 25% greater using cyclic irrigation compared with the traditional method of applying a single cycle in the morning (Beeson and Haydu, 1995; Fain et al., 1999; Witmer, 2000). These studies, however, were conducted in the southeastern United States or in greenhouses and may not reflect conditions common in nurseries in cooler climates such as the upper midwestern United States. ... ... Cyclic irrigation increased relative height and caliper growth of Pinus strobus (Table 2). This growth increase associated with cyclic irrigation is consistent with previous nursery studies testing cyclic irrigation (Beeson, 1992;Beeson and Haydu, 1995; Fain et al., 1999; Haydu and Beeson, 1997;Ruter, 1998;Witmer, 2000). Counter to our hypothesis, however, cyclic irrigation did not increase relative height or caliper growth in three other species investigated. ... Carbon Isotope Discrimination, Gas Exchange, and Growth of Container-grown Conifers Under Cyclic Irrigation Article Full-text available Jul 2013 HORTSCIENCE Amanda Taylor Rodney Thomas Fernandez Pascal Nzokou Bert Cregg The objective of this study was to quantify the effects of cyclic irrigation on growth and physiology of container-grown conifer species in pot-in-pot (PIP) production in the upper Midwest. Trees of four conifer species (Picea glauca var. densata, Picea pungens, Abies fraseri, and Finns strobus) were grown in 25-L containers and assigned to one of four combinations of irrigation rate (low or high) and daily irrigation cycle frequency (one or four). Irrigation rates were based on common nursery practice in the region (2 cm rainfall equivalent/day) and one-half the standard rate (1 cm rainfall equivalent/day). Cyclic irrigation increased relative height growth and relative caliper growth of Pinus strobus by over 80% and 35%, respectively, compared with once-daily irrigation. The high-rate irrigation increased relative caliper growth of Picea pungens by 40% compared with the low rate. The effects of irrigation regime on needle- or shoot-level gas exchange varied by species and date of measurement. Carbon isotope discrimination (Delta C-13) of needle and wood tissue was positively correlated (r >= 0.64, P < 0.001) with needle conductance to water vapor (g(wv)) and negatively correlated (r <= -0.60, P< 0.001) with intrinsic water use efficiency (WUEi). Carbon isotope discrimination of wood and needle tissue decreased with the low irrigation rate, indicating increased WUEi associated with reduced g(wv). Cyclic irrigation had relatively little effect on Delta C-13 except for Pinus strobus. Our findings suggest that carbon isotope composition of wood and needle tissue provides a sensitive and accurate representation of plant response to varying moisture availability. From a water management perspective, identifying optimal irrigation rates appears to be more important than number of daily cycles for these crops grown in the midwestern United States. ... Growers use cyclic irrigation to optimize crop irrigation through increased lateral flow, reduced preferential flow within the substrate, and replacement of water as used, thus improving water retention and potentially reducing the quantity of water used on a daily basis (Karam and Niemiera, 1994;Warren and Bilderback, 2005). Cyclic irrigation often can be implemented without making significant changes in irrigation equipment or setup (Fain et al., 1999) . However, in other cases, growers may need to modify their existing irrigation infrastructure and possibly add an irrigation controller for scheduling and implementing multiple water applications. ... ... Beeson and Keller (2003) found that cyclic irrigation applied using microspray heads increased southern magnolia (Magnolia grandiflora) height and increased trunk diameter over single application. Similarly, Fain et al. (1999) found that sawtooth oak (Quercus acutissima) growth (height and trunk diameter) was greater with cyclic irrigation than with single application. However, Tyler et al. (1996a) found that shoot and root growth of 'Goldsturm' orange coneflower was the same for cyclic and standard-irrigation methods, and irrigation type did not affect shoot and root N and P concentrations, suggesting that plant nutrient uptake was unaffected by the irrigation method. ... Validation of Nursery and Greenhouse Best Management Practices through Scientific Evidence Article Full-text available Aug 2019 HORTTECHNOLOGY Rachel Mack James S. Owen Jr. Alex X. Niemiera David James Sample Nursery and greenhouse growers use a variety of practices known as best management practices (BMPs) to reduce sediment, nutrient, and water losses from production beds and to improve efficiency. Although these BMPs are almost universally recommended in guidance manuals, or required by regulation in limited instances, little information is available that links specific BMPs to the scientific literature that supports their use and quantifies their effectiveness. A previous survey identified the most widely used water management, runoff, and fertilizer-related BMPs by Virginia nursery and greenhouse operators. Applicable literature was reviewed herein and assessed for factors that influence the efficacy of selected BMPs and metrics of BMP effectiveness, such as reduced water use and fertilizers to reduce sediment, nitrogen (N), and phosphorus (P) loads in runoff. BMPs investigated included vegetative zones (VZs), irrigation management strategies, and controlled-release fertilizers (CRFs). Use of vegetative buffers decreased average runoff N 41%, P 67%, and total suspended solids 91%. Nitrogen, P, and sediment removal efficacy increased with vegetative buffer width. Changes in production practices increased water application efficiency >20% and decreased leachate or runoff volume >40%, reducing average N and P loss by 28% and 14%, respectively. By linking BMPs to scientific articles and reports, individual BMPs can be validated and are thus legitimized from the perspective of growers and environmental regulators. With current and impending water use and runoff regulations, validating the use and performance of these BMPs could lead to increased adoption, helping growers to receive credit for actions that have been or will be taken, thus minimizing water use, nutrient loss, and potential pollution from nursery and greenhouse production sites. ... Supplemental irrigation management has been suggested to ameliorate the negative impact of soil water stress on landscape trees in summer (Fain et al. 1999; Vico et al. 2014). However, a smaller irrigation interval and amount of water are essential for the effective and sustainable management of landscape trees. ... Photosynthetic responses to soil water stress in summer in two Japanese urban landscape tree species (Ginkgo biloba and Prunus yedoensis): effects of pruning mulch and irrigation management Jun 2016 TREES-STRUCT FUNCT Keisuke Nishida Yuko T. Hanba Key message Stomatal regulation involves beneficial effects of pruning mulch and irrigation on leaf photosynthesis in Prunus yedoensis and Ginkgo biloba under moderate drought. G. biloba showed conservative water use under drought. Abstract Leaf photosynthesis is highly sensitive to soil water stress via stomatal and/or biochemical responses, which markedly suppress the growth of landscape trees. Effective irrigation management to maintain leaf photosynthesis and information on species-specific photosynthetic responses to soil water stress are essential for the sustainable management of landscape trees in Japan, in which summer drought often occurs. In order to investigate effective irrigation management, we used plants with moderate soil water stress as controls, and examined the effects of daily irrigation and pruning mulch on leaf photosynthesis in container-grown Ginkgo biloba and Prunus yedoensis, which are the first and second main tall roadside trees in Japan. Stomatal conductance was significantly increased by pruning mulch and daily irrigation, with similar increases in leaf photosynthesis being observed in P. yedoensis and G. biloba. In order to obtain information on species-specific photosynthetic responses to soil water stress, we compared the responses of leaf photosynthesis and leaf water status to reductions in soil water content (SWC) between the two species. G. biloba maintained a constant leaf water potential, leaf water content, maximum carboxylation rate, and electron transport rate with reductions in SWC, whereas reductions were observed in P. yedoensis. We concluded that pruning mulch and irrigation effectively offset the negative impact of moderate water stress on leaf photosynthesis in summer in P. yedoensis and G. biloba via stomatal regulation, and also that G. biloba maintained its photosynthetic biochemistry and leaf water status better than P. yedoensis under severe water stress. Apr 2003 HORTTECHNOLOGY Paul W. Wilson Fig. 1. Schematic representation of effluent collection apparatus. tion of salts in the growing medium (Mason, 1994). More research is needed to determine irrigation requirements for large [≥15-gal (56.8-L)] container production optimizing plant growth and decreasing nutrient runoff. One method of irrigation management for nursery crops is monitoring the percentage ef-fluent passing through container sub-strate for each irrigation event (Yeager et al., 1997). Measuring percent efflu-ent can be used as a method of increas-ing irrigation precision and reducing fertilizer runoff. Considering the po-tential high soil bulk density and daily water evaporation potential a sturdy effluent collection device is needed. Therefore, a closed-capture system was designed, constructed, and tested for the purpose of determining irriga-tion volume and quality to monitor large nursery container effluent. ADDITIONAL INDEX WORDS. container effluent, irrigation volume, irrigation efficiency SUMMARY. Irrigation management is essential in producing quality woody ornamentals and minimizing off-site runoff. The closed-capture effluent device provided an inexpensive method of monitoring effluent in large containers throughout the year with minimal effort. Daily irrigation requirements for 'Little Gem' southern magnolia (Magnolia grandifolia) were established throughout an entire growing season. The maximum daily water requirement was approximately 3 gal (11.4 L). Application Method Affects Water Application Efficiency of Spray Stake- irrigated Containers Jun 1993 HORTSCIENCE William F Lamack Alex X. Niemiera Studies were conducted to evaluate the effect of water application medium moisture deficit, water application rate, and intermittent application on water application efficiency {[(amount applied - amount leached)/amount applied] x 100} of spray stake-irrigated, container-grown plants. Pine bark-filled containers were irrigated to replace moisture deficits of 600, 1200, or 1800 ml; deficits were returned in single, continuous applications of 148, 220, or 270 ml·min -l . Efficiency was unaffected by application rate but decreased with increased medium moisture deficit. In the second experiment, container medium at a 600-ml deficit was irrigated with 400 or 600 ml (6570 and 100% water replacement, respectively); deficits were returned in a single, continuous application or in intermittent 100-ml applications with 30-min intervals between irrigations. Application efficiency was greater with intermittent irrigation (95% and 84% for 400- and 600-ml replacement, respectively) than with continuous irrigation (84% and 67% for 400- and 600-ml replacement, respectively). In the third experiment, pine bark was irrigated with 600 ml water (100% replacement) in 50-, 100-, or 150-ml aliquots with 20, 40, or 60 min between applications in a factorial design. Efficiency increased with decreasing application volume and increasing time between applications. Highest efficiency (86%) was achieved with an irrigation regimen of 50-ml applications with at least 40 min between applications, compared to 62% for the control treatment (a single, continuous application of 600 ml). Our results suggest that growers using spray stakes would waste less water by applying water intermittently rather than continuously.
https://www.researchgate.net/publication/237397840_Cyclic_Irrigation_Improves_Irrigation_Application_Efficiency_and_Growth_of_Sawtooth_Oak
| Download Scientific Diagram Download scientific diagram | from publication: Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program | Initiation of X inactivation depends on the coordinated expression of the sense/antisense pair Xist/Tsix. We show here that a precisely defined Xist promoter region flanked by CTCF is maintained by Tsix in a heterochromatic-like state in undifferentiated embryonic stem (ES)... | Epigenetics, Epigenomics and Untranslated RNA | ResearchGate, the professional network for scientists. Figure 3 - uploaded by Pablo Navarro Source publication Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program Article Full-text available Pablo Navarro Damian R Page Philip Avner Claire Rougeulle Initiation of X inactivation depends on the coordinated expression of the sense/antisense pair Xist/Tsix. We show here that a precisely defined Xist promoter region flanked by CTCF is maintained by Tsix in a heterochromatic-like state in undifferentiated embryonic stem (ES) cells and shifts to a pseudoeuchromatic structure upon Tsix truncation. We... Contexts in source publication Context 1 ... insulation of the Xist 5 region, capable of limiting the spreading of H3K9 trimethylation and/or CpG methylation to the overall Xist/Tsix region, may be occurring. Importantly, the region showing varia- tion of chromatin modification levels appears to be pre- cisely defined and restricted to the −1-to +1.5-kb interval of the Xist promoter region (Fig. ... Context 2 ... epigenetic marks embed- ded within a region of euchromatin-associated histone modifications. We therefore searched for CTCF binding on both sides of the −1-to +1.5-kb interval. Using two independent antibodies against CTCF ( Supplementary Fig. 2A,B), we were able to immunoprecipitate CTCF at the predicted positions in both undifferentiated female (Fig. 3B) and male ES cells (Fig. 3C, dotted line). The binding profile of CTCF was found to be altered in Tsix-truncated cells (Fig. 3C, plain line). In all chromatin preparations analyzed, the binding over site c1 was sys- tematically noted to be higher in mutant than in wild- type cells. Although more variability was observed in CTCF binding ... Context 3 ... within a region of euchromatin-associated histone modifications. We therefore searched for CTCF binding on both sides of the −1-to +1.5-kb interval. Using two independent antibodies against CTCF ( Supplementary Fig. 2A,B), we were able to immunoprecipitate CTCF at the predicted positions in both undifferentiated female (Fig. 3B) and male ES cells (Fig. 3C, dotted line). The binding profile of CTCF was found to be altered in Tsix-truncated cells (Fig. 3C, plain line). In all chromatin preparations analyzed, the binding over site c1 was sys- tematically noted to be higher in mutant than in wild- type cells. Although more variability was observed in CTCF binding at the c2 site, higher levels in the ... Context 4 ... on both sides of the −1-to +1.5-kb interval. Using two independent antibodies against CTCF ( Supplementary Fig. 2A,B), we were able to immunoprecipitate CTCF at the predicted positions in both undifferentiated female (Fig. 3B) and male ES cells (Fig. 3C, dotted line). The binding profile of CTCF was found to be altered in Tsix-truncated cells (Fig. 3C, plain line). In all chromatin preparations analyzed, the binding over site c1 was sys- tematically noted to be higher in mutant than in wild- type cells. Although more variability was observed in CTCF binding at the c2 site, higher levels in the mutant than in the wild-type were never observed. Interestingly, the modification of CTCF-binding ... Context 5 ... more variability was observed in CTCF binding at the c2 site, higher levels in the mutant than in the wild-type were never observed. Interestingly, the modification of CTCF-binding profile occurring upon truncation of Tsix leads to a profile similar to that of female MEFs, in which Tsix is transcriptionally si- lenced (cf. the plain line in Fig. 3C and Supplementary Fig. 2C). Based on these results, we propose that CTCF defines the boundaries of chromatin domains differen- tially regulated by ... Context 6 ... the second Xist promoter in female and on the single X in male cells, the repressive chromatin conformation, initially maintained by continuous transcription of Tsix, is sub- sequently propagated by Tsix-independent mechanisms. This is supported by the fact that in male MEFs, the inactive Xist promoter is devoid of active histone marks although Tsix is silenced (Supplementary Fig. 3). ... View in full-text Similar publications Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions Article Full-text available Zhihu Zhao Gholamreza Tavoosidana Mikael Sjölinder [...] Rolf Ohlsson Accumulating evidence converges on the possibility that chromosomes interact with each other to regulate transcription in trans. To systematically explore the epigenetic dimension of such interactions, we devised a strategy termed circular chromosome conformation capture (4C). This approach involves a circularization step that enables high-throughp... Noncoding RNA localisation mechanisms in chromatin regulation Article Full-text available Richard Gareth Jenner An important challenge in biology has been to understand how cell-type-specific expression programs are orchestrated through regulated access to chromatin. Knowledge of the interaction between noncoding RNAs (ncRNAs) and chromatin regulators has the potential to help answer such questions, but how ncRNAs target chromatin regulators to specific site... Nonallelic transvection of multiple imprinted loci is organized by the H19 imprinting control region during germline development Article Full-text available Kuljeet Singh Sandhu Chengxi Shi Mikael Sjölinder [...] Rolf Ohlsson Recent observations highlight that the mammalian genome extensively communicates with itself via long-range chromatin interactions. The causal link between such chromatin cross-talk and epigenetic states is, however, poorly understood. We identify here a network of physically juxtaposed regions from the entire genome with the common denominator of... View Citations ... Distinct from miRNAs that can only target mRNAs, lncRNAs not only have the ability to directly perform gene modification, but also can "sponge" bound miRNAs and reverse the repressive effect of miRNAs on mRNAs (Quinn and Chang, 2016). Previous studies on genetic imprinting have shown that lncRNAs can perform epigenetic modification of genes by recruiting chromatin remodeling complexes to specific sites (Navarro et al., 2006; Gupta et al., 2010). For example, the lncRNA named HOTAIR in the Hox locus of primary breast tumor is highly expressed in epithelial cancer cells and induces genome-wide transformation of polycomb repressive complex 2 (PRC2), ultimately enhancing gene expression and cancer invasiveness (Gupta et al., 2010). ... Promising roles of non-exosomal and exosomal non-coding RNAs in the regulatory mechanism and as diagnostic biomarkers in myocardial infarction Article J ZHEJIANG UNIV-SC B Jingru Li Haocheng Ma Xinyu Wu Guihu Sun Luqiao Wang Non-exosomal non-coding RNAs (non-exo-ncRNAs) and exosomal ncRNAs (exo-ncRNAs) have been associated with the pathological development of myocardial infarction (MI). Accordingly, this analytical review provides an overview of current MI studies on the role of plasma non-exo/exo-ncRNAs. We summarize the features and crucial roles of ncRNAs and reveal their novel biological correlations via bioinformatics analysis. The following contributions are made: (1) we comprehensively describe the expression profile, competing endogenous RNA (ceRNA) network, and "pre-necrotic" biomarkers of non-exo/exo-ncRNAs for MI; (2) functional enrichment analysis indicates that the target genes of ncRNAs are enriched in the regulation of apoptotic signaling pathway and cellular response to chemical stress, etc.; (3) we propose an updated and comprehensive view on the mechanisms, pathophysiology, and biomarker roles of non-exo/exo-ncRNAs in MI, thereby providing a theoretical basis for the clinical management of MI. ... The expression of XIST, lncRNA responsible for X-chromosome inactivation in females, is regulated by Tsix (noncoding antisense transcript to XIST) via histone modifications [120] . In males, Tsix induces H3K9 trimethylation and DNA methylation [120] and prevents H3K27 trimethylation [120,121] making the embryonic stem cells unable to transcribe XIST, thereby preventing X-inactivation. ... ... The expression of XIST, lncRNA responsible for X-chromosome inactivation in females, is regulated by Tsix (noncoding antisense transcript to XIST) via histone modifications [120]. In males, Tsix induces H3K9 trimethylation and DNA methylation [120] and prevents H3K27 trimethylation [120,121] making the embryonic stem cells unable to transcribe XIST, thereby preventing X-inactivation. In the case of females, there is asymmetric regulation of Tsix where Tsix is repressed and XIST expression is induced only on the future inactive X [122]. ... ... The expression of XIST, lncRNA responsible for X-chromosome inactivation in females, is regulated by Tsix (noncoding antisense transcript to XIST) via histone modifications [120]. In males, Tsix induces H3K9 trimethylation and DNA methylation [120] and prevents H3K27 trimethylation [120, 121] making the embryonic stem cells unable to transcribe XIST, thereby preventing X-inactivation. In the case of females, there is asymmetric regulation of Tsix where Tsix is repressed and XIST expression is induced only on the future inactive X [122]. ... The Epigenetics of Noncoding RNA Chapter Sep 2022 Ravindresh Chhabra DNA, RNA, and the proteins are the major players in the flow of genetic information. Out of these, RNA is the most versatile biomolecule as it exists in multiple forms and each form carries out specified functions in the cell. RNA can be classified into coding and noncoding RNA (ncRNA). The noncoding RNA is further subdivided into long noncoding RNA (>200 nucleotides) and small noncoding RNA (<200 nucleotides). The coding RNA is the one which gets translated into proteins; whereas, the ncRNA is usually responsible for the regulation of gene expression. The ncRNA has been implicated in a number of pathological conditions including cancer, diabetes, neurological disorders and developmental defects. The interplay between ncRNAs and epigenetics often plays a significant role in the onset and progression of some of the aforementioned diseases. This chapter elaborates on the different ways in which epigenetic phenomenon is regulated by ncRNA and the effect of epigenetic modification on the expression of ncRNA. ... Although the current treatment strategies have prolonged the overall survival of patients, the 5-years survival rate of patients remains low, at just over 50% (Frampton and Houlston, 2016). Long noncoding RNAs (lncRNAs) are involved in a great diversity of biological processes, and various mechanisms of lncRNA transcriptional regulation of gene expression have been demonstrated (Navarro et al., 2006; Rinn et al., 2007;Gupta et al., 2010). Increasing evidence suggests that the abnormal expression of lncRNAs is closely related to tumor progression. ... Identification and validation of an inflammation-related lncRNAs signature for improving outcomes of patients in colorectal cancer Article Full-text available Sep 2022 Mengjia Huang Yuqing Ye Yi Chen Junkai Zhu Fangrong Yan Background: Colorectal cancer is the fourth most deadly cancer worldwide. Although current treatment regimens have prolonged the survival of patients, the prognosis is still unsatisfactory. Inflammation and lncRNAs are closely related to tumor occurrence and development in CRC. Therefore, it is necessary to establish a new prognostic signature based on inflammation-related lncRNAs to improve the prognosis of patients with CRC. Methods: LASSO-penalized Cox analysis was performed to construct a prognostic signature. Kaplan-Meier curves were used for survival analysis and ROC curves were used to measure the performance of the signature. Functional enrichment analysis was conducted to reveal the biological significance of the signature. The R package “maftool” and GISTIC2.0 algorithm were performed for analysis and visualization of genomic variations. The R package “pRRophetic”, CMap analysis and submap analysis were performed to predict response to chemotherapy and immunotherapy. Results: An effective and independent prognostic signature, IRLncSig, was constructed based on sixteen inflammation-related lncRNAs. The IRLncSig was proved to be an independent prognostic indicator in CRC and was superior to clinical variables and the other four published signatures. The nomograms were constructed based on inflammation-related lncRNAs and detected by calibration curves. All samples were classified into two groups according to the median value, and we found frequent mutations of the TP53 gene in the high-risk group. We also found some significantly amplificated regions in the high-risk group, 8q24.3, 20q12, 8q22.3, and 20q13.2, which may regulate the inflammatory activity of cancer cells in CRC. Finally, we identified chemotherapeutic agents for high-risk patients and found that these patients were more likely to respond to immunotherapy, especially anti-CTLA4 therapy. Conclusion: In short, we constructed a new signature based on sixteen inflammation-related lncRNAs to improve the outcomes of patients in CRC. Our findings have proved that the IRLncSig can be used as an effective and independent marker for predicting the survival of patients with CRC. ... In mice, Jpx RNA activates Xist transcription in a dose-dependent manner by evicting CTCF 30 (Fig. 1B), a DNA-binding insulator capable of repressing Xist expression. 34, 35 Ftx promotes the transcription of Xist through the proximity of their gene loci, which is independent of the Ftx RNA products 28 (Fig. 1B). The X-encoded E3 ubiquitin ligase RNF12 31 upregulates mouse Xist expression by targeting for degradation the pluripotency factor REX1, 36 which normally activates Tsix and represses Xist expression through binding to regulatory regions 36,37 (Fig. 1B). ... Long noncoding RNA XIST: Mechanisms for X chromosome inactivation, roles in sex-biased diseases, and therapeutic opportunities Article Full-text available Apr 2022 Jianjian Li Zhe Ming Liuyi Yang Tingxuan Wang Qing Ma Sexual dimorphism has been reported in various human diseases including autoimmune diseases, neurological diseases, pulmonary arterial hypertension, and some types of cancers, although the underlying mechanisms remain poorly understood. The long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in X chromosome inactivation (XCI) in female placental mammals, a process that ensures the balanced expression dosage of X-linked genes between sexes. XIST is abnormally expressed in many sex-biased diseases. In addition, escape from XIST-mediated XCI and skewed XCI also contribute to sex-biased diseases. Therefore, its expression or modification can be regarded as a biomarker for the diagnosis and prognosis of many sex-biased diseases. Genetic manipulation of XIST expression can inhibit the progression of some of these diseases in animal models, and therefore XIST has been proposed as a potential therapeutic target. In this manuscript, we summarize the current knowledge about the mechanisms for XIST-mediated XCI and the roles of XIST in sex-biased diseases, and discuss potential therapeutic strategies targeting XIST. ... The asymmetric binding of RIF1 (and KAP1) seems to be downstream of fluctuations of antisense transcription across the Xist locus [81], while YY1 binding is due to differential DNA methylation of Xist alleles at the onset of XCI [82]. This has also been reported downstream of antisense transcription across the Xist locus [83][84] [85] . Together, these findings suggest that the asymmetric binding of these trans-factors serve as "bookmarks" for the future active and inactive X (though most likely not irreversibly), reinforcing asymmetries derived from cis-acting mechanisms. ... Mechanisms of Choice in X-Chromosome Inactivation Article Full-text available Feb 2022 Giulia Furlan Rafael Galupa Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nucleus are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to the environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved. ... A very similar role has been proposed for YY1 [82], while KAP1 binds to the allele with no Xist expression, due to the absence of RIF1 [81]. The asymmetric binding of RIF1 (and KAP1) seems to be downstream of fluctuations of antisense transcription across the Xist locus [81], while YY1 binding is due to differential DNA methylation of Xist alleles at the onset of XCI [82], which has also been reported as downstream to antisense transcription across the Xist locus [83][84] [85] . Together, these findings suggest that the asymmetric binding of these trans-factors serve as "bookmarks" for the future active and inactive X (though most likely not irreversibly), reinforcing asymmetries derived from cis-acting mechanisms. ... Inversion of a topological domain leads to restricted changes in its gene expression and affects inter-domain communication Preprint Full-text available Jan 2022 Rafael Galupa Christel Picard Nicolas Servant Elphège Pierre Nora Edith Heard The interplay between the topological organization of the genome and the regulation of gene expression remains unclear. Depletion of molecular factors underlying genome topology, such as CTCF and cohesin, leads to modest alterations in gene expression, while genomic rearrangements involving boundaries of topologically associating domains (TADs) disrupt normal gene expression and can lead to pathological phenotypes. Here we inverted an almost entire TAD (245kb out of 300kb) within the X-inactivation centre (Xic), leaving its boundaries intact. This led to a significant rearrangement of topological contacts within the TAD, mostly in accordance to the orientation of underlying CTCF binding sites but suggesting heterogeneity in the "contact" potential of different CTCF sites. The inversion also led to increased contact insulation with the neighbouring TAD. Expression of most genes within the inverted TAD remained unaffected in mouse embryonic stem cells and during differentiation. Interestingly, expression in the neighbouring TAD of the noncoding transcript Xist, which controls X-chromosome inactivation, was ectopically upregulated. The same inversion in mouse embryos led to a bias in Xist expression, but X-inactivation choice ratios did not significantly deviate from wild type. Smaller deletions and inversions of specific clusters of CTCF sites within the TAD led to similar results: rearrangement of contacts, limited changes in local gene expression but significant changes in Xist expression. Our study suggests that the wiring of regulatory interactions within a TAD can influence the expression of genes in neighbouring TADs, highlighting the existence of mechanisms for inter-TAD communication. ... The asymmetric binding of RIF1 (and KAP1) seems to be downstream of fluctuations of antisense transcription across the Xist locus [81], while YY1 binding is due to differential DNA methylation of Xist alleles at the onset of XCI [82]. This has also been reported downstream of antisense transcription across the Xist locus [83][84] [85] . Together, these findings suggest that the asymmetric binding of these trans-factors serve as "bookmarks" for the future active and inactive X (though most likely not irreversibly), reinforcing asymmetries derived from cis-acting mechanisms. ... Mechanisms of Choice in X-Chromosome Inactivation Preprint Full-text available Jan 2022 Giulia Furlan Rafael Galupa Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nuclei are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved. We also call for a revised manner in which to think about choice during random X-inactivation. ... Indeed, TSIX was transcribed only from the inactive X chromosome and was coexpressed with XIST, implying that the repression of Xist by mouse Tsix has no counterpart in humans, and TSIX is not the gene that protects the active X chromosome from random inactivation [60]. Regarding the role of Tsix in the chromatin modifications at the Xist locus, of note is the "dual effect" exerted by "opening" the chromatin structure along the Xist gene and "closing" it at the Xist promoter itself [61, 62]. ... The lncRNAs at X Chromosome Inactivation Center: Not Just a Matter of Sex Dosage Compensation Article Full-text available Non-coding RNAs (ncRNAs) constitute the majority of the transcriptome, as the result of pervasive transcription of the mammalian genome. Different RNA species, such as lncRNAs, miRNAs, circRNA, mRNAs, engage in regulatory networks based on their reciprocal interactions, often in a competitive manner, in a way denominated “competing endogenous RNA (ceRNA) networks” (“ceRNET”): miRNAs and other ncRNAs modulate each other, since miRNAs can regulate the expression of lncRNAs, which in turn regulate miRNAs, titrating their availability and thus competing with the binding to other RNA targets. The unbalancing of any network component can derail the entire regulatory circuit acting as a driving force for human diseases, thus assigning “new” functions to “old” molecules. This is the case of XIST, the lncRNA characterized in the early 1990s and well known as the essential molecule for X chromosome inactivation in mammalian females, thus preventing an imbalance of X-linked gene expression between females and males. Currently, literature concerning XIST biology is becoming dominated by miRNA associations and they are also gaining prominence for other lncRNAs produced by the X-inactivation center. This review discusses the available literature to explore possible novel functions related to ceRNA activity of lncRNAs produced by the X-inactivation center, beyond their role in dosage compensation, with prospective implications for emerging gender-biased functions and pathological mechanisms. ... A more promising candidate for the cis repressor is Xist's antisense transcription unit Tsix, which overlaps the complete Xist gene including its promoter [20,173]. Tsix transcription establishes a repressive chromatin state at the Xist promoter [25][26] [27] [28]. Heterozygous Tsix deletions skew the choice of the inactive X towards the mutated allele, as expected from a cis repressor [20][21][22][23]. ... ... Upon successful dosage compensation, global DNA methylation levels also increase in female cells, and the binding cluster on the Xa becomes methylated, preventing Yy1 binding (Fig 3.4a, left). Possibly, the methylation of the binding site is promoted specifically on the Xa by active Tsix transcription, which has been shown to promote DNA methylation [27] . ... ... However, DNA methylation is not essential for the establishment of alternative Xist expression patterns, because they are set up correctly in the absence of de novo DNA methylation [185]. Possibly, in the establishment phase DNA methylation acts together with other mechanisms to repress Xist, such as Tsix transcription, which also reinforces DNA methylation [27] . As cells differentiate, Tsix expression is shut off, and DNA methylation becomes essen- RNA-mediated silencing of X-linked genes is required to reinforce Xist expression: Deletion of the repeat A region, which has been shown to be essential for silencing, results in failure to stably upregulate Xist [12,73]. ... Experimental and theoretical analysis of X-chromosome inactivation as a paradigm for epigenetic memory and molecular decision-making Thesis Verena Mutzel X-Chromosom-Inaktivierung (XCI) ist der Mechanismus, den Säuger zur Dosiskompensierung zwischen weiblichen und männlichen Zellen verwenden. XCI wird ausgelöst durch die monoallelische Hochregulation der langen nicht-kodierenden RNA Xist von einem der zwei X-Chromosomen in weiblichen Zellen. Die Xist RNA vermittelt dann das Ausschalten der Gene auf diesem X-Chromosom. Das wirft einige interessante Fragen auf: Wie zählen Zellen ihre X-Chromosomen und stellen sicher, dass genau eines aktiv bleibt? Wie entscheiden sie, welches X-Chromosom aktiv bleibt und welches ausgeschaltet wird? Und wie erinnern sie sich an diese Entscheidung und behalten sie stabil bei durch alle weiteren Zellteilungen? Mithilfe eines stochastischen Modells zeigen wir, dass diese XCI Regulation prinzipiell durch nur zwei Regulatoren erklärt werden kann: Ein global (in trans) agierender XCI Aktivator und ein lokal (in cis) agierender XCI Repressor. Dieses Netzwerk aus nur zwei Regulatoren kann die Xist Expressionsmuster in verschiedenen Säugerspezies reproduzieren, von der Maus bis zum Mensch. Es sagt außerdem voraus, dass Zellen in der Lage sind, biallelische zu monoallelischer Xist Expression zu korrigieren, eine Vorhersage, für die wir tatsächlich experimentelle Belege finden. Mit einem mechanistischen Modell zeigen wir, dass das cis-Gedächtnis über den Xist Expressionszustand durch Antisense-Transkription zustande kommen könnte. Auf dieser Hypothese aufbauend untersucht der zweite Teil der Arbeit das Potential von Antisense-Transkription, ein lokales Gedächtnis über den Expressionszustand eines Gens zu generieren, genauer. Diese Analyse sagt vorher, dass Antisense-Repression den Expressionszustand eines Lokus tatsächlich für einige Tage stabil erhalten kann. ... Previous work from the Avner laboratory has demonstrated that transcription of Xist and the Tsix lncRNA, its major antagonist, is precisely controlled by pluripotency factors [17][18][19] . Other laboratories have investigated the role of nearby genes encoding lncRNAs such as Jpx and Ftx and protein factors such as Rnf12 (also known as Rlim) and YY1/CTCF in the allelic regulation of Xist and Tsix [20] [21][22][23][24][25][26][27] . The current model comprises a complex interaction network that is in a dynamic transcriptional equilibrium in undifferentiated ES cells 28 . ... ... Whilst many aspects of Xist regulation have been intensely studied over the years [17][18][19] [20] [21][22][23][24]62 , little is known about the role of chromatin remodelers in the context of XCI. Here we show that Chd8 is a likely critical factor involved in the regulation of Xist expression. ... Chd8 regulates X chromosome inactivation in mouse through fine-tuning control of Xist expression Article Full-text available Andrea Cerase Alexander N Young Nerea Blanes Ruiz Andreas Buness Philip Avner Female mammals achieve dosage compensation by inactivating one of their two X chromosomes during development, a process entirely dependent on Xist, an X-linked long non-coding RNA (lncRNA). At the onset of X chromosome inactivation (XCI), Xist is up-regulated and spreads along the future inactive X chromosome. Contextually, it recruits repressive histone and DNA modifiers that transcriptionally silence the X chromosome. Xist regulation is tightly coupled to differentiation and its expression is under the control of both pluripotency and epigenetic factors. Recent evidence has suggested that chromatin remodelers accumulate at the X Inactivation Center (XIC) and here we demonstrate a new role for Chd8 in Xist regulation in differentiating ES cells, linked to its control and prevention of spurious transcription factor interactions occurring within Xist regulatory regions. Our findings have a broader relevance, in the context of complex, developmentally-regulated gene expression.
https://www.researchgate.net/figure/fig3_6752901
Commons Chamber Debates in the Commons on 10th February 2015 Bills Live Bills Government Bills Private Members' Bills Acts of Parliament Created Departments Department for Business and Trade Department for Culture, Media and Sport Department for Education Department for Energy Security & Net Zero Department for Environment, Food and Rural Affairs Department of Health and Social Care Department for Levelling Up, Housing & Communities Department for Transport Department for Science, Innovation & Technology Department for Work and Pensions Cabinet Office Foreign, Commonwealth & Development Office Home Office Leader of the House Ministry of Defence Ministry of Justice Northern Ireland Office Scotland Office HM Treasury Wales Office Department for International Development (Defunct) Department for Exiting the European Union (Defunct) Department for Business, Energy and Industrial Strategy (Defunct) Department for International Trade (Defunct) Reference Stakeholder Targetting APPGs The Glossary Inquiries Upcoming Events Petitions Tweets Publications Written Questions Parliamentary Debates Parliamentary Research Non-Departmental Publications Secondary Legislation MPs / Lords Members of Parliament Lords Pricing About Login Home Debates 10 Feb 2015 Commons Commons Chamber All 14 Commons Chamber debates in the Commons on 10th Feb 2015 Mon 9th Feb 2015 House of Commons (30) - Commons Chamber (14) / Written Statements (8) / Westminster Hall (6) / Petitions (2) House of Lords (24) - Grand Committee (13) / Lords Chamber (11) Wed 11th Feb 2015 Share Page Copy Link 14 Debates - Show / Collapse List Tue 10th Feb 2015 House of Commons Commons Chamber Tue 10th Feb 2015 Prayers Commons Chamber Tue 10th Feb 2015 Oral Answers to Questions Commons Chamber Tue 10th Feb 2015 Accident prevention measures for Redbridge roundabout Commons Chamber Tue 10th Feb 2015 Green belt land in Redbridge Commons Chamber Tue 10th Feb 2015 Ukraine Commons Chamber Tue 10th Feb 2015 Tuition Fee (Transparency and Accountability) Commons Chamber Tue 10th Feb 2015 Police Commons Chamber Tue 10th Feb 2015 Local Government Finance Commons Chamber Tue 10th Feb 2015 deferred divisions Commons Chamber Tue 10th Feb 2015 Counter-terrorism and Security Bill Commons Chamber Tue 10th Feb 2015 Business without Debate Commons Chamber Tue 10th Feb 2015 Petitions Commons Chamber Tue 10th Feb 2015 Transport (Tees Valley) Commons Chamber (Adjournment Debate) House of Commons Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Tuesday 10 February 2015 The House met at half-past Eleven o’clock Return to start of debate - Return to top of page Prayers Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Info: What are Prayers? Prayers mark the daily opening of Parliament. The occassion is used by MPs to reserve seats in the Commons Chamber with 'prayer cards'. Prayers are not televised on the official feed. This information is provided by Parallel Parliament and does not comprise part of the offical record [Mr Speaker in the Chair ] Return to start of debate - Return to top of page Oral Answers to Questions Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Read Debate Ministerial Extracts The Deputy Prime Minister was asked— Sarah Newton (Truro and Falmouth) (Con) - Hansard - Copy Link - - Excerpts 1. What discussions he has had with Cornwall local enterprise partnership on devolving powers and responsibilities from Whitehall. The Deputy Prime Minister (Mr Nick Clegg) - Hansard - Copy Link - - Excerpts The Government have already devolved powers and responsibilities to the Cornwall and Isles of Scilly local enterprise partnership through the growth deal, which was agreed last summer and extended just two weeks ago. It will mean that around £60 million is invested in Cornwall and Isles of Scilly, including in a range of infrastructure investments in the area. In Truro, that will mean money for seven new low-floor buses to provide additional capacity for the city’s successful park and ride scheme. Sarah Newton - Hansard - Copy Link - - Excerpts I thank the right hon. Gentleman for his answer, but when will the European regional development funds for Cornwall be available to spend, and will the LEP make the decisions on how that vital money for the future of Cornwall is spent? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts I strongly agree with my hon. Friend that it is essential that we get clarity as soon as possible on the use of the European structural investment funds through the so-called operational programmes. She may be aware that there has been lots of to-ing and fro-ing between the Government and the European Commission to ensure that the operational programmes are agreed as soon as possible. We are looking at everything to mitigate the impact of any delay. For example, we are looking at extending the deadline for spending on the 2007 to 2013 ERDF programme for some projects from the end of June to the end of September this year. Of course, every step of the way, the local enterprise partnerships are rightly involved in how that money is subsequently spent. Andrew George (St Ives) (LD) - Hansard - Copy Link - - Excerpts Further to that exchange, I would be grateful if the Deputy Prime Minister ensured that he impresses on the Communities and Local Government Secretary the importance of Cornwall achieving intermediate body status, because only by doing so can we proceed with making decisions. The Deputy Prime Minister - Hansard - Copy Link - - Excerpts As much as my hon. Friend points the finger of blame, it is pointed not so much at Departments in Whitehall but at the European Commission, which appears to struggle with the idea that there can be lots of different intermediate bodies within the United Kingdom. As he knows, London already has intermediate status. We have found it very difficult to persuade the European Commission to grant similar or analogous powers to other parts of the UK. We want to ensure that, while we make that case—everyone in the Government is making that case—we do not lose the use of the money. That is the balance we are trying to strike. Kevin Brennan (Cardiff West) (Lab) - Hansard - Copy Link - - Excerpts 2. What recent assessment he has made of the effect of his policies on the completeness of the electoral register. The Minister for the Constitution (Mr Sam Gyimah) - Hansard - Copy Link - - Excerpts I am pleased to report that the implementation of individual electoral registration is proceeding smoothly. [ Laughter. ] We have safeguarded the register by automatically transferring nine out of 10 existing electors on to the new system, and by ensuring that no one registered to vote at the last canvass will lose their vote in May. More than 5 million people have registered to vote since May; there have been more than 1 million applications since December; 35,000 people per day are registering on the Government’s new online system; and 166,000 people registered to vote on national voter registration day. In addition, the Government have invested £14 million in the completeness and accuracy of the register, working with local authorities and national bodies. Kevin Brennan - Hansard - Copy Link - - Excerpts I missed the beginning of the Minister’s answer because of the hilarity it caused in the House. I understand that 1 million people have been lost from the register in the past 12 months. I asked him about the completeness of the register and the impact of his policies on that. Despite his very long previous answer, can he add anything that is pertinent to the question I asked? Mr Gyimah - Hansard - Copy Link - - Excerpts Absolutely. The hon. Gentleman revels in his 2011 nomination for the Total Politics Labour point-scorer of the year. In fact, he has plastered the information all over his website. To answer his question specifically, since December, 1.3 million have been added to the register. Each day and each month, more people are being added to the register, so it is about time the Labour party stopped creating fear and uncertainty where there is none. Bob Blackman (Harrow East) (Con) - Hansard - Copy Link - - Excerpts 15. What measures is my hon. Friend taking to ensure that people who live overseas and wish to register to vote are able to do so? Equally, has he taken account of the fact that people who have lived overseas for longer than 15 years should also have the opportunity to vote in this country? Mr Gyimah - Hansard - Copy Link - - Excerpts My hon. Friend asks a very good question. With the introduction of online voting, people who live overseas can register to vote more easily. We have made it easier for them as they do not now need another British citizen to attest to their citizenship before they register to vote. There is no consensus within the Government to change the 15-year rule at the moment, but, as he well knows, the Conservative party’s manifesto pledge is that, when elected after 7 May, we will get rid of it. Debbie Abrahams (Oldham East and Saddleworth) (Lab) - Hansard - Copy Link - - Excerpts 14. In 2010, the Deputy Prime Minister talked about the need for the biggest shake up of democracy since the Great Reform Act 1832. As my hon. Friend the Member for Cardiff West (Kevin Brennan) said, is not the reality that, instead of extending the franchise, millions of voters are being lost from the electoral register, including 4,000 from my own constituency. Will the Minister agree to delay IER implementation? If not, why not? Mr Gyimah - Hansard - Copy Link - - Excerpts The hon. Lady talks about the register. Let me make it clear: Electoral Commission data show that 3 million people were missing from the register in 2000. By 2011, 7.5 million people were missing from the register. The deterioration of the register happened when the Labour party was in government. IER is part of the solution to get the register right. Under the old system, people moved house but the register did not. With online registration, we are making it simpler and easier for people to get on the register. That is how we will ensure that more people get on the register. Sir Oliver Heald (North East Hertfordshire) (Con) - Hansard - Copy Link - - Excerpts Will the Minister join me in welcoming the initiative, by Facebook and the Electoral Commission, to contact 35 million users of Facebook and encourage them to register online? Does he agree that this sort of innovative approach will lead to better use of online registration? Mr Gyimah - Hansard - Copy Link - - Excerpts My hon. and learned Friend is absolutely right. The way forward for the completeness and accuracy of the register is not to go back to the old system of block registration—I know the Labour party likes its block votes—but to use initiatives, such as using Facebook, to market to the vast majority of the British public who should be on the register but are not. Stephen Twigg (Liverpool, West Derby) (Lab/Co-op) - Hansard - Copy Link - - Excerpts I join the Minister in welcoming the huge success of national voter registration day. Will he join me in praising the brilliant work of Bite the Ballot, which organised national voter registration day last week? If we are to maximise the number of young people on the register, will he think again about extending the Northern Ireland schools initiative so that it applies in the rest of the United Kingdom? Mr Gyimah - Hansard - Copy Link - - Excerpts The Northern Ireland schools initiative was introduced after the introduction of IER, when Northern Ireland did not have the annual canvass, and voter registration rates plummeted to about 11%. In contrast, in the rest of the UK we moved to IER, but nine out of 10 electors are on the register. Specifically on schools, we are funding national organisations with experience of working with schools and getting attainers on to the register. I know the Labour party would like us to introduce some kind of duty on schools, but that would increase the burden on schools. We can do this through national organisations and electoral registration officers, who know their local area. In some local areas, the issue will be to do with the elderly population; in others, it will be to do with young people. There is no need for a legislative sledgehammer. We should leave it to EROs, who have a duty to maximise their local registers. Stephen Twigg - Hansard - Copy Link - - Excerpts The Minister says it would be a burden on schools, but I spoke to the Association of School and College Leaders, which represents school head teachers. It says that to have such a scheme would be “easily organised” and deliver real benefits. The Northern Ireland electoral registration officer says that the schools initiative has been “very successful in improving the rate of registration amongst young people”. The Minister talks about nine in 10 being carried across. That is right, but the one in 10 are disproportionately students and young people. Why is he so afraid of getting more young people registered to vote in this country? Mr Gyimah - Hansard - Copy Link - - Excerpts If it is so easily organised, as the organisations the hon. Gentleman spoke to have said, then we do not need legislation. As I said, every local area would have differing circumstances as far as the register is concerned. What we do not want is EROs spending their time having to go to schools because of legislation, when to maximise the register in their areas they should be going to care homes and talking to elderly people. Sadiq Khan (Tooting) (Lab) - Hansard - Copy Link - - Excerpts What are you scared of? Mr Gyimah - Hansard - Copy Link - - Excerpts The shadow Justice Secretary asks me what I am scared of. What we know is that the Labour party is not against IER. Labour Members are pretending in this House that they are interested in students and young people when they are not. It is all about the block vote—that is what they want. Nick Smith (Blaenau Gwent) (Lab) - Hansard - Copy Link - - Excerpts 3. What steps he is taking to address low levels of electoral turnout. The Minister for the Constitution (Mr Sam Gyimah) - Hansard - Copy Link - - Excerpts The low levels of electoral turnout are an important and long-standing issue. Turnout was 78% in 1992, it declined steadily to 61% in 2005, and it rose to 65% in 2010. The Government’s responsibility is to ensure that everybody eligible to vote is on the register—because if someone is not on the register, they cannot vote—which is why we are committed to maximising the register. However, it is the responsibility of politicians to set out an attractive offer that makes people want to vote, so the job of increasing turnout is a job not for the Government but for all of us in the House. Nick Smith - Hansard - Copy Link - - Excerpts Does the Minister believe that holding elections on Thursdays best maximises voter turnout? Mr Gyimah - Hansard - Copy Link - - Excerpts I have seen several proposals—some argue that moving elections to weekends would somehow increase turnout, others argue for compulsory voting—but the answer is not to introduce new processes and systems, but for us politicians to engage and excite the electorate. The huge turnout for the Scottish referendum had nothing to do with the day on which it was held—in fact, I think it was held on a Thursday. Mr David Nuttall (Bury North) (Con) - Hansard - Copy Link - - Excerpts I am pleased to hear my hon. Friend restate that it is the job of politicians and those who stand for election to enthuse voters and persuade them to vote. Does he agree that we should never blame voters if they choose to exercise their right to stay at home and abstain? Mr Gyimah - Hansard - Copy Link - - Excerpts We want everyone in the country to have a say in who governs them, and we would encourage all people to vote, but it is the job of politicians to do so, not the Government. Mr Angus Brendan MacNeil (Na h-Eileanan an Iar) (SNP) - Hansard - Copy Link - - Excerpts On electoral turnout, does the Minister think he can learn from the Scottish referendum and that the non-delivery of the vow will increase turnout, as Scots vote for a strong SNP voice to counter the failure of the three parties, the three amigos, at Westminster? Mr Gyimah - Hansard - Copy Link - - Excerpts I know that the hon. Gentleman would like to rewrite history, but there was a decisive result in the Scottish referendum, and the vow has been delivered completely and faithfully. Rehman Chishti (Gillingham and Rainham) (Con) - Hansard - Copy Link - - Excerpts 4. What assessment he has made of progress on implementing Medway’s growth deal. The Minister for Universities, Science and Cities (Greg Clark) - Hansard - Copy Link - - Excerpts The South East local enterprise partnership has a large portfolio of projects ready to start in April, including 22 in the Thames Gateway, 12 of which will have a direct impact in Medway. For example, a new Kent and Medway growth hub will deliver improved advice services to local businesses. Rehman Chishti - Hansard - Copy Link - - Excerpts I thank the Minister for his answer and the Government for the £33.4 million given to Medway, which will create more jobs and businesses and get Medway moving with better transport infrastructure. I know that local authorities have received a letter, but when will the formal agreements be signed with them? Greg Clark - Hansard - Copy Link - - Excerpts The money will be available from April, and my colleagues and I are going around signing the agreements, but no LEPs should wait to have the signature on the dotted line: they can plan with confidence in the projects that have been funded. Several hon. Members - Hansard - Copy Link rose — Mr Speaker - Hansard - Copy Link - - Excerpts Order. I realise that hon. Members from Lincolnshire and Huddersfield feel that Medway could benefit from their wisdom, but on this occasion I am afraid we are going to move on, because there are many more questions. Mrs Mary Glindon (North Tyneside) (Lab) - Hansard - Copy Link - - Excerpts 5. In how many local authority areas people in more than 90% of households are registered to vote. The Minister for the Constitution (Mr Sam Gyimah) - Hansard - Copy Link - - Excerpts I am sorry to disappoint the hon. Lady, but data are not available on the number of local authority areas in which people in more than 90% of households are registered to vote. As she is aware, each register is held locally. Aggregated electoral statistics are available from the Office for National Statistics, but these are not broken down by household. However, the ONS will publish its data at the end of February, by which time the Electoral Commission will also publish its assessment of the December register. Mrs Glindon - Hansard - Copy Link - - Excerpts Ahead of that information being published, will the Minister explain to the House why his Department’s advice to local authorities made such a massive mess of capturing information on voters approaching the age of 18? The evidence suggests a catastrophic collapse in the number of attainers on the register. What will he do about that? Mr Gyimah - Hansard - Copy Link - - Excerpts I do not agree that a catastrophic mess was made of the system. If the hon. Lady looks at the forms issued by the Electoral Commission to local authorities to get households to input all the names, she will see that it was clearly stated that people under the age of 18 should appear. This was user tested as well. In addition to the write out, electoral registration officers can knock on doors to make sure that people’s names are on the register. We have given EROs everything they need and everything they have asked for to get on the register everyone eligible to vote. Mr Andrew Robathan (South Leicestershire) (Con) - Hansard - Copy Link - - Excerpts I am sure my hon. Friend would agree that registering involves faith in the political system. I am sure he agrees with me and the Deputy Prime Minister who said on 6 September 2010: “Fewer, more equally sized and more up-to-date constituencies will help to bolster the legitimacy of parliamentary elections.” —[ Official Report , 6 September 2010; Vol. 515, c. 40.] Does the Minister agree that a failure of the Liberal Democrats, and particularly of the Deputy Prime Minister, to vote for his own Bill in 2013—he voted against bolstering the legitimacy of the parliamentary elections—has led to this diminution of faith in politicians, showing opportunism and political advantage at its worst? Mr Gyimah - Hansard - Copy Link - - Excerpts I thank my right hon. Friend for his question. Of course we regret going into another election with some constituencies such as Arfon having 38,000 electors and others such as the Isle of Wight having 110,000. Those are not equally sized boundaries, but, as they say, we are where we are. Barbara Keeley (Worsley and Eccles South) (Lab) - Hansard - Copy Link - - Excerpts 6. What the Government's policy is on increasing participation among young voters. The Minister for the Constitution (Mr Sam Gyimah) - Hansard - Copy Link - - Excerpts For getting young people on the register, I believe online registration makes it quicker, simpler and more convenient. It takes roughly three minutes and it will help get young people on the register. Indeed, more than 1 million applications from young people have been through the online process. We are funding a number of youth organisations who have a share of £2.5 million to promote voter registration among young people. These include the British Youth Council, UK Youth and the NUS. Finally, data sharing goes on at universities where academic registrars have to give data on enrolment to EROs, which is helping to boost registration rates at universities, as we have seen at Sheffield university. Mr Speaker - Hansard - Copy Link - - Excerpts That was too long. Barbara Keeley - Hansard - Copy Link - - Excerpts Let me return to the value of enforcing the schools initiative from Northern Ireland, to which the Opposition are committed. As we have heard, it has been instrumental in bringing a 50% increase in the total population of young people on the register, which is really important. Why are Ministers, including the Deputy Prime Minister, who appears not to be answering questions today as he should be, not bothered about this? Why do they mention care homes, but do not want young people to get registered and get into the habit of voting? Mr Gyimah - Hansard - Copy Link - - Excerpts If we did not want young people to get on the register, we would not be funding the very organisations that have the experience and expertise for getting young people to vote. That is the first point. The second is that the Northern Ireland system was paper-based, but we have an online system spanning 363 local authorities. This is a much superior system for getting young people to register from their laptops, smartphones or tablets and computers. Andrew Gwynne (Denton and Reddish) (Lab) - Hansard - Copy Link - - Excerpts T1. If he will make a statement on his departmental responsibilities. The Deputy Prime Minister (Mr Nick Clegg) - Hansard - Copy Link - - Excerpts rose— Hon. Members - Hansard - Copy Link Hooray. The Deputy Prime Minister - Hansard - Copy Link - - Excerpts I am grateful for such applause as I rise to my feet. As Deputy Prime Minister, I support the Prime Minister on a full range of Government policy initiatives. Within government, I take special responsibility for this Government’s programme of political and constitutional reform. Andrew Gwynne - Hansard - Copy Link - - Excerpts The Deputy Prime Minister talks a lot about cleaning up political donations, yet his Liberal Democrats were perfectly willing to take a donation of £34,000 from the managing director of Autofil Yarns, a company that is removing 160 British jobs to Bulgaria to protect its profits. Does the Deputy Prime Minister regret that? Is he going to repay it, or is this just another yarn that is being spun by the Liberal Democrats? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts The puns come thick and fast. Perhaps the hon. Gentleman will explain why his party blocked party political funding reform recently, and whether his question was written by one of his trade union paymasters. Being lectured by the Labour party on how parties are funded really takes the biscuit. Bob Blackman (Harrow East) (Con) - Hansard - Copy Link - - Excerpts T3. Will my right hon. Friend tell us what proposals are being made to devolve stamp duty to local authorities, and will he tell us about the other fiscal measures which, I understand, are being announced elsewhere today? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts As my hon. Friend will know, a number of steps have been taken to devolve and decentralise what has traditionally been the very over-centralised way in which we raise and spend money. We are not just devolving unprecedented fiscal powers to the various nations in the United Kingdom, but, for instance, giving greater borrowing powers to local government in England. However, the journey is not yet complete, and, in my view, further steps towards further fiscal devolution and decentralisation should be taken in the years ahead. Sadiq Khan (Tooting) (Lab) - Hansard - Copy Link - - Excerpts We are fast approaching the 800th anniversary of Magna Carta. Over the last five years, the Deputy Prime Minister’s Government have extended the use of secret courts, curtailed judicial review, and radically reduced access to justice by making massive cuts in legal aid. Which of those policies of his Government does he consider to be most in keeping with the spirit of Magna Carta? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts Does the right hon. Gentleman not remember what his Government did to habeas corpus, and that great tradition? Does he not remember his Government’s flawed attempt to impose an identity card database, which we brought to an end? Does he not remember his push to fingerprint innocent children in schools throughout the country, and does he not remember wanting to store the DNA of innocent citizens throughout the country? For heaven’s sake, let him remember his own record and that of his own party before he starts trying to cast aspersions on this Government. Sadiq Khan - Hansard - Copy Link - - Excerpts The Deputy Prime Minister has had five years’ experience of this arrangement. It works like this: we ask the questions, and he tries to answer them. Let me try one more question. It may be the last. It is, of course, important for our country to use its influence with its allies to improve human rights abroad. As the Deputy Prime Minister will know, the Ministry of Justice wants to enter into a £6 million contractual arrangement with the Saudi Arabian justice system to share “best practice”. Many people are rightly concerned about the sentence of 1,000 lashes that was given to Raif Badawi, and the regular use of execution by beheading in Saudi Arabia. What does the Deputy Prime Minister think about the British Government’s making money out of the Saudi Arabian justice system, and what is he going to do about it? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts The issue is not whether the right hon. Gentleman has the right to ask questions. The issue is his absolute amnesia about what his Government got up to, from invading Iraq illegally to shredding civil liberties on an industrial scale. As for the question that he has asked, the Minister of State, Ministry of Justice, my right hon. Friend the Member for Bermondsey and Old Southwark (Simon Hughes), says that no contract has been entered into with Saudi Arabia. Like the right hon. Gentleman and, I suspect, many Members on both sides of the House, I consider some of the practices that we have seen in Saudi Arabia to be absolutely abhorrent, and completely in conflict with our values. What every Government, including his own, have done in such circumstances is make a judgment on whether to cut off relations with other Governments with whom we disagree, or whether to try to influence them and bring them more into line with our values. That is clearly what his Government did, and it is what this coalition Government are trying to do as well. Sir Edward Leigh (Gainsborough) (Con) - Hansard - Copy Link - - Excerpts T4. I understand that if the United Kingdom votes to leave the European Union in a referendum—the United Kingdom as a whole—the Scottish Parliament will, under the vow, have to pass a legislative consent motion before it can happen. Is that not a recipe for constitutional crisis? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts The right hon. Gentleman’s views and my views on Britain’s continued membership of the European Union may be at a variance, but I am starting to agree with him that stumbling into a referendum on such a momentous matter without really thinking through the implications for the country as a whole would not only result in a constitutional quagmire, but would possibly jeopardise millions of jobs in this country. That is why I would counsel him and his party not to make breezy commitments in the run-up to a general election which could leave this country much poorer. Barbara Keeley (Worsley and Eccles South) (Lab) - Hansard - Copy Link - - Excerpts T2. We have talked a great deal about students this morning, but the students about whom I am concerned are young adult carers, who often struggle financially because their caring means that they cannot take on paid work. Indeed, a survey by the National Union of Students found that financial difficulties were the main reason why young carers considered abandoning their courses. Enabling carers to fulfil their educational potential is meant to be one of the Government’s priorities, so will the Deputy Prime Minister tell us why so little has been done to help young adult carers to fulfil theirs? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts I certainly agree that the hon. Lady identifies a problem that is by no measure solved. Carers young and old work under huge pressures. They are unsung heroes and heroines for society. We have taken a number of measures, for instance to try to give greater respite care to carers of all ages, but I accept the hon. Lady’s challenge that we need to do more. Andrew Bridgen (North West Leicestershire) (Con) - Hansard - Copy Link - - Excerpts T7. Given reports over the weekend that Tony Blair will play a prominent role in Labour’s election campaign and given the fact that he still draws the maximum allowance—£115,000 of taxpayers’ money—for his public duties, does the Deputy Prime Minister agree that he and all former Prime Ministers should be covered by the Nolan principles of public life? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts The public duty cost allowance limited to £115,000 per year was created to help cover expenses incurred by former Prime Ministers in meeting the continuing additional costs they incur because of their special position in public life. The Nolan principles apply to public office holders. There are no plans to extend their application to present or former politicians, whether Prime Ministers or not. Mr Stephen Hepburn (Jarrow) (Lab) - Hansard - Copy Link - - Excerpts T5. May I ask the Deputy Prime Minister at this eleventh hour to step in and save Jarrow’s NHS walk-in centre? I have made a plea to the Prime Minister, and I have made a plea to the Secretary of State for Health. Can the Deputy Prime Minister stop this? Some 27,000 people are going to be dumped on overloaded local GPs and A and Es. It is deliberate sabotage of the NHS, to get the private sector involved through the backdoor. I ask the Deputy Prime Minister to help. The Deputy Prime Minister - Hansard - Copy Link - - Excerpts I am, of course, more than willing to look into that. I doubt very much, however, that it could remotely be as the hon. Gentleman characterises it, as this Government outlawed the sweetheart deals with the private sector that the previous Labour Government indulged in, and, of course, decisions on how local health services are commissioned are taken by local commissioners, not decision-makers in London. Stuart Andrew (Pudsey) (Con) - Hansard - Copy Link - - Excerpts T10. Traditional industries in my constituency such as the mills at Abraham Moon and Hainsworth have had growing exports recently and have expanded, but they have concerns about the skilled work force they will need. Can the Deputy Prime Minister assure me that the skills funding in the local growth deals will help such important businesses to address their needs? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts Yes, I absolutely can. As my hon. Friend will know, the local growth deal in his area places a particular emphasis on making sure that there are, over time, no youngsters whatsoever who are not in employment, education or training—the so-called NEETs—and the skills provided to youngsters in the area continue to be boosted. One of the achievements that everybody in the coalition parties can be proudest of is that we have massively expanded the number of apprenticeships available across the country: 2 million new apprentices have been taken on over the past several years. Douglas Carswell (Clacton) (UKIP) - Hansard - Copy Link - - Excerpts T6. When the lobbying Act went through the House concerns were expressed that it would prevent organisations from engaging in the democratic process. Have any concerns been put to the Deputy Prime Minister about how the law is actually working with an election looming? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts The hon. Gentleman is absolutely right. A number of concerns have been expressed, but I think they are misplaced. It is clear from the way in which the legislation was crafted that there was no intention to stop anyone making their views known at any time; the intention was simply to expect anyone who wants to influence a particular election in a particular constituency to abide by the same rules as those who are competing in those elections in those areas. Henry Smith (Crawley) (Con) - Hansard - Copy Link - - Excerpts T11. A recent growth deal saw tens of millions of pounds being invested in the future of Gatwick airport station. May I seek assurances from my right hon. Friend that further growth deals will focus on improving transport infrastructure for the area? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts : I am pleased that we were able to support Gatwick airport station redevelopment as part of the growth deal. The growth deals that have been announced are not, of course, the end of the story. In total, I think we have announced £7 billion of the £12 billion that it was envisaged would be committed to growth deals over time. Local enterprise partnerships have been encouraged to identify their own local growth priorities, so that they can submit their own ideas to future growth deals, which I hope will continue in the next Parliament. Stephen Doughty (Cardiff South and Penarth) (Lab/Co-op) - Hansard - Copy Link - - Excerpts T8. According to the latest figures, a staggering 23,500 voters appear to be missing from the electoral registration lists in Cardiff. We have already heard how the scandal is affecting young people and students, but it also appears that a significant number of people in the black and minority ethnic community across the city are missing from the register. What is the Deputy Prime Minister going to do about this? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts Nobody will have their right to vote taken away from them as we move to individual voter registration. What I find so fascinating as I listen to all this heat and fury from the Opposition is that when they were in government they supported the move to individual voter registration, and for good reasons. The previous system was patronising and out of date; it rested on the idea that the head of a household would register everyone in that household on to the electoral register. Do the Opposition now want to revert to that system? It was patronising, out of date and unfair to many voters. Mr Philip Hollobone (Kettering) (Con) - Hansard - Copy Link - - Excerpts T12. Since 2010, unemployment has fallen sharply and employment has risen dramatically, but all the while, we have had a large and growing trade deficit with the European Union. How does the Deputy Prime Minister square that with the Liberal Democrat myth that 3 million British jobs depend on our EU membership? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts The figures cited are certainly not mythological; they have been arrived at independently by Government Departments and other researchers. It is not difficult to work out the economic value, given that the European Union, whatever its flaws and its present difficulties, is the world’s largest borderless single market, with more than 500 million consumers. It is also by far the largest destination for goods and services produced in this country, for the simple reason that we are a European country located in the European hemisphere. Mr William Bain (Glasgow North East) (Lab) - Hansard - Copy Link - - Excerpts T13. The most recent figures from the Office for National Statistics show a rise in youth unemployment of 30,000 compared with the previous quarter. May I offer the Deputy Prime Minister the opportunity to have a deathbed conversion tomorrow and to support Labour’s proposed bank bonus tax, which would help to get tens of thousands of young people into decent jobs? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts It is—how can I put this politely?—brave of Labour to select jobs as the subject of its Opposition day debate. It is the party that crashed the economy in the first place. Youth unemployment is lower today than it was when the hon. Gentleman’s party left office. We have created countless more apprenticeships than Labour made available, and 1.8 million more people are in work now than when the Labour Government left office. Inequality, income inequality and relative child poverty are lower under this Government. He might not like the facts, but they speak for themselves. Mark Hunter (Cheadle) (LD) - Hansard - Copy Link - - Excerpts May I welcome the announcement by the Deputy Prime Minister yesterday on schools funding? I particularly welcome the fact that two schools in my constituency—Cheadle primary and Great Moor junior—will benefit as a consequence. Can he give me an assurance that investment in education will be protected while we continue to address the deficit? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts I am very pleased that we have been able to make that significant announcement of a further £6 billion to be allocated from central Government to refurbish, rebuild and maintain school buildings up and down the country. We are now assisting twice as many schools across the country than were being helped under Labour’s school building programme. My hon. Friend makes an important point. All the political parties will need to set out their stall in the run-up to the general election. The Liberal Democrats have said clearly that we want to protect funding from cradle to college and from nursery to 19, and not to implement the kind of real-terms cut in the money going to our schools that other parties have recently revealed. Debbie Abrahams (Oldham East and Saddleworth) (Lab) - Hansard - Copy Link - - Excerpts T14. The Electoral Commission’s own research shows that the electoral registration of private renters stands at 63%, compared with the overall level of 85%. Is not this yet another example of how this Government are totally disregarding “generation rent”? What is the Deputy Prime Minister going to do about it? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts Again, the facts speak for themselves. Since last summer, 5 million people have been entered on to the new individual voter registration system. Nine in 10 voters are transferred automatically on to it, and 1.3 million more people have been entered on to it since December alone. Of course we need to do more, across the parties and across the nation, to encourage people to register to vote, but it is the worst form of shameless scaremongering to suggest that a transition to individual voter registration—which the Labour Government advocated and introduced—is somehow entirely responsible for the fact that some groups are more under-registered than others. Richard Graham (Gloucester) (Con) - Hansard - Copy Link - - Excerpts I recently welcomed the Minister for Universities, Science and Cities, my right hon. Friend the Member for Tunbridge Wells (Greg Clark) to Gloucester, where he saw at first hand the regeneration in Blackfriars. That regeneration will be helped by the recent growth award via the local enterprise partnership. Does the Deputy Prime Minister agree that there is potential for small city deals or county deals to help to devolve and boost regeneration projects in cities such as Gloucester, or would he encourage us to bid for the next growth deal via the LEP? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts I would encourage the hon. Gentleman to do the latter. First, he is right to point out that decentralisation should not be only an urban phenomenon or just something granted to larger cities, although they were the pioneer areas where the city deals and growth deals first happened. We have made a good start, with the £12 billion growth deals that are under way, on ensuring that every part of the country—county, city, rural, urban—gets more powers handed down to it from Whitehall, and I very much want to see that. Mr Frank Roy (Motherwell and Wishaw) (Lab) - Hansard - Copy Link - - Excerpts Can the Deputy Prime Minister explain to 16 and 17-year-olds in my constituency why they were deemed mature enough to vote in the recent Scottish referendum yet his Government do not think they are mature enough to vote in the forthcoming general election? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts I wholeheartedly agree with the hon. Gentleman; I have long believed that 16 and 17-year-olds should be able to vote. They take on responsibilities and duties as adults in so many other walks of life, and they showed themselves to be enthusiastic, informed and impassioned participants in the Scottish referendum. Unfortunately, we have not been able to secure agreement between the two coalition parties on this, but I look forward to the day when the House, on a cross-party basis, votes finally to give the democratic rights to 16 and 17-year-olds that they deserve. Mr Peter Bone (Wellingborough) (Con) - Hansard - Copy Link - - Excerpts I was reading the Hansard record of the previous Deputy Prime Minister’s questions, and the Deputy Prime Minister answered the first topical question in the same way as he did today. He said that his main purpose is to “support the Prime Minister” over a whole range of activities—after that, in brackets, was the word, “Laughter.” Can the Deputy Prime Minister name one thing he has done to support the Prime Minister? The Deputy Prime Minister - Hansard - Copy Link - - Excerpts I would like to correct the hon. Gentleman, as I have it here. I said: “As Deputy Prime Minister, I support the Prime Minister on a full range”. —[ Official Report , 6 January 2015; Vol. 590, c. 143.] That does not mean “complete range”; it does not mean the whole, as the hon. Gentleman suggests. Of course there are disagreements between myself and the Prime Minister, and of course there are disagreements between the coalition parties. I know the hon. Gentleman has not taken to the give and take of coalition government as readily as some Government Members have, but I think history will judge the two coalition parties kindly for having put the national interest first and working together, supporting each other, in order to fix the broken economy inherited from the previous Government. As he talks about support, I am delighted to hear that the Prime Minister and his party now support my party in, for instance, giving tax cuts to millions and millions of people on low and middle incomes—that was always our policy. Mr David Winnick (Walsall North) (Lab) - Hansard - Copy Link - - Excerpts Will the Deputy Prime Minister be attending the lectures being given by the Rev. Lord Green, the chap who ran HSBC in such an ethical way? Apparently, he is giving lectures on “ethical banking”. Does the Deputy Prime Minister stand by the comments made by the Business Secretary when the Rev. Lord Green was made a trade Minister? The Business Secretary described Lord Green in terms of “a powerful philosophy for ethical business.” Even George Orwell could not have made that one up! The Deputy Prime Minister - Hansard - Copy Link - - Excerpts Again, the hon. Gentleman is a brave man to talk about regulation of the banking system from the Labour Benches, given his party’s total, singular failure to heed the warnings of my right hon. Friend the Business Secretary. I recall him standing there saying to the then Prime Minister, week in, week out, that the Labour party was heading for trouble because it did not regulate the banks properly. Perhaps the hon. Gentleman might want to ask questions of his own colleagues about why HSBC was able to get away with such outrageous business practices back in 2007 and 2008. The Attorney-General was asked— Steve Rotheram (Liverpool, Walton) (Lab) - Hansard - Copy Link - - Excerpts 1. What recent discussions he has had with his Cabinet colleagues on implementation of the UK’s domestic and international legal obligations on human rights. Paul Blomfield (Sheffield Central) (Lab) - Hansard - Copy Link - - Excerpts 6. What recent discussions he has had with his Cabinet colleagues on implementation of the UK’s domestic and international legal obligations on human rights. [R] Mr David Anderson (Blaydon) (Lab) - Hansard - Copy Link - - Excerpts 7. What recent discussions he has had with his Cabinet colleagues on implementation of the UK’s domestic and international legal obligations on human rights. The Attorney-General (Jeremy Wright) - Hansard - Copy Link - - Excerpts Hon. Members will know that I cannot discuss legal advice that I may have given to members of the Government, but I have regular discussions with colleagues about a large number of issues. Domestic and international human rights are an important aspect of our law and are a key consideration in the Law Officers’ work. Steve Rotheram - Hansard - Copy Link - - Excerpts Can the Attorney-General tell the House whether he supports the Human Rights Act and the European convention on human rights, and whether he and the Solicitor-General are completely in agreement with the Government’s position? The Attorney-General - Hansard - Copy Link - - Excerpts The answer to the latter part of the hon. Gentleman’s question is yes. On the first part, I do not support the Human Rights Act, but I do support the European convention on human rights. There is a misunderstanding here, perhaps on his part and certainly among some of his Labour colleagues, as the abolition of the Human Rights Act does not mean the abolition of human rights. The Conservative party is in favour of human rights and we have a proud record on human rights. What we do not agree with is the mess his party made of the relationship between this country’s courts and the European Court of Human Rights in Strasbourg—we will do something about it. Paul Blomfield - Hansard - Copy Link - - Excerpts May I follow up on the Attorney-General’s response to my hon. Friend the Member for Liverpool, Walton (Steve Rotheram) by asking whether he agrees that last week’s ruling by the European Court of Human Rights that British courts can hand down whole-life sentences without breaching human rights is a fine example of dialogue between our courts and Strasbourg? As we mark the 50th anniversary of Winston Churchill’s death, will the Attorney-General join me in celebrating the European convention as Churchill’s legacy and one that provides vital protections that we would be unwise to deny our people? The Attorney-General - Hansard - Copy Link - - Excerpts I welcome clarification from the European Court of Human Rights on whole-life tariffs, but I remind the hon. Gentleman that it is not just the outcome of these cases that can be problematic but the time, effort and taxpayers’ money spent defending them. He is quite right that the convention is an excellent document; there is very little to disagree with in it. The problem is the way in which the European Court of Human Rights has interpreted that document. Once again, the Conservative party will do something about that, but, as far as I can tell, the Labour party in government would do nothing whatever about it. Mr Anderson - Hansard - Copy Link - - Excerpts One of the basic human rights is the right of association and, through that, the right to combine together in trade unions. Will the Attorney-General say why his Government are making it harder for civil servants to exercise that basic human right by withdrawing the right to have trade union subscriptions taken off pay at source? The Attorney-General - Hansard - Copy Link - - Excerpts I do not accept that we are taking human rights away from civil servants. Let me repeat the point that I made: the Conservative party in government has a proud record on human rights. I remind the hon. Gentleman that it was a Conservative Home Secretary who brought forward the Modern Slavery Bill, of which we are very proud. Clearly, it was a “human-rights enhancing measure”. Those are not my words but those of the Joint Committee on Human Rights. It was a Conservative Foreign Secretary, now Leader of the House, who has done excellent work on preventing the use of sexual violence in conflict—again, huge steps forward in the defence of human rights in this country and abroad. We are proud of that record, but see no reason to combine that pride with a blind and meek acceptance that every judgment of the European convention on human rights by the European Court of Human Rights, however eccentric, should be meekly accepted. Miss Anne McIntosh (Thirsk and Malton) (Con) - Hansard - Copy Link - - Excerpts The Council of Europe and the European convention on human rights were set up to protect the citizens of Ukraine from the former Soviet Union. Should we not be doing more to protect the citizens of Ukraine with regard to their human rights at this present time? The Attorney-General - Hansard - Copy Link - - Excerpts I understand my hon. Friend’s point. Of course she is right that when the convention was originally drafted, it was precisely to deal with the most egregious examples of breaches of human rights across the world. That is what we have always supported, and we will continue to do so. What we do not support is the extension of that franchise to discussing things such as the insemination of prisoners in prison, and whether prisoners should be given the right to vote in British elections. That is in no way comparable to what my hon. Friend is discussing. Sir Alan Beith (Berwick-upon-Tweed) (LD) - Hansard - Copy Link - - Excerpts Will the Attorney-General confirm that neither the repeal of the Human Rights Act nor a British Bill of Rights could in any way diminish Britain’s obligations under the European convention on human rights, or does he disagree with his predecessor on that point? The Attorney-General - Hansard - Copy Link - - Excerpts As I have said, there is no direct connection between what we decide to do on the Human Rights Act and what we decide to do in support of human rights, both nationally and internationally. We remain wholly committed to the preservation of human rights, both in this country and abroad. As for my predecessor, I think that he would wholeheartedly support that position. Mr David Burrowes (Enfield, Southgate) (Con) - Hansard - Copy Link - - Excerpts The Attorney-General refers to the Government’s leadership in tackling modern slavery. Given that traffickers operate across jurisdictions, what is he doing to support other countries to have effective justice systems to protect the victims and enforce the law? The Attorney-General - Hansard - Copy Link - - Excerpts My hon. Friend is right that we need to think about how we assist other countries in the way in which they implement their justice systems so that we can work together to confront what is, as he says, cross-border problems. It comes back to the dilemma that was being discussed with my right hon. Friend the Deputy Prime Minister around what we do in countries that do not have the best records in the preservation of justice and human rights. We have to get the balance right, but it is important that we continue to co-operate. Mr Nigel Evans (Ribble Valley) (Con) - Hansard - Copy Link - - Excerpts 2. What assessment he has made of the potential effect of introducing an offence of coercive control on prosecutions for domestic abuse. The Solicitor-General (Mr Robert Buckland) - Hansard - Copy Link - - Excerpts I have been taking this welcome new measure through Committee with the support of Members from all parties. The new law of coercive control will help protect victims by criminalising sustained patterns of behaviour that stop short of serious physical violence but amount to extreme psychological and emotional abuse. It is likely to increase the number of cases of domestic abuse reported, which should result in an increase in the number of prosecutions. Mr Evans - Hansard - Copy Link - - Excerpts I am grateful for that response. As the number of domestic abuse referrals has increased, which must be welcomed as people now have the confidence to refer such crimes of abuse, does the Solicitor-General agree that it is apparent that just as physical abuse should be consigned to the history books so should mental control, which is a form of torture that is equally unacceptable in this country today? The Solicitor-General - Hansard - Copy Link - - Excerpts I welcome my hon. Friend’s remarks. Only today on the radio, we heard about people using mobile apps to control the movements and behaviour of their partners. Modern technology can be a wonderful thing, but it can also be very dangerous in the wrong hands. I believe that the new law will embrace that, too. Keith Vaz (Leicester East) (Lab) - Hansard - Copy Link - - Excerpts Female genital mutilation is a form of domestic abuse. Is the Solicitor-General as concerned as I am that there has been no successful prosecution for FGM in this country, following the acquittal last week of two of those prosecuted? The Solicitor-General - Hansard - Copy Link - - Excerpts The right hon. Gentleman and I share a passion for ending this scourge. It was important that the prosecution was brought and the number of referrals continues to increase—we did not have any referrals before 2010. That shows that both the police and the Crown Prosecution Service are taking the matter very seriously. The message must be sent out to everybody that those who indulge in this form of abuse will be subject to the law and to prosecution. Robert Neill (Bromley and Chislehurst) (Con) - Hansard - Copy Link - - Excerpts May I welcome the Solicitor-General’s recognition of the importance of dealing with the psychological intimidation of witnesses, which, as those of us who have prosecuted a case of this kind will know, can be every bit as difficult as physical intimidation? I congratulate him personally on the initiatives he has taken in this matter and the work he has been doing. The Solicitor-General - Hansard - Copy Link - - Excerpts I am grateful to my hon. Friend for those remarks. It was important that we fill the loopholes in the law. We now have the stalking and harassment legislation introduced by this Government and legislation on coercive control. We are doing everything we can to deal with the scourge of emotional and psychological abuse. Mr Elfyn Llwyd (Dwyfor Meirionnydd) (PC) - Hansard - Copy Link - - Excerpts May I commend the Solicitor-General on his co-operative and informed attitude to the issue of coercive control and on the way in which he took the matter through Committee? I also thank him for sponsoring my ten-minute rule Bill on the subject last year; it would be remiss of me not to say that. On a more serious note, will he assure the House that prior to the commencement of the new law, welcome as we all say it will be, there will be sufficient time to train the police and prosecuting authorities and the necessary guidelines will be produced? The Solicitor-General - Hansard - Copy Link - - Excerpts I thank the right hon. Gentleman for his question and I entirely agree that we must ensure that full training of the police, the Crown Prosecution Service and all the authorities that will be responsible for dealing with the new legislation is put in place before we bring it into force. Heidi Alexander (Lewisham East) (Lab) - Hansard - Copy Link - - Excerpts 3. What recent discussions he has had with the Chancellor of the Exchequer on funding for the Crown Prosecution Service to ensure effective prosecution of historical sex abuse cases. The Attorney-General (Jeremy Wright) - Hansard - Copy Link - - Excerpts The CPS is working closely with the Treasury to manage the impact of the increasing numbers of large and complex cases, including non-recent sex abuse cases, and to ensure that the CPS has the resources to prosecute serious crime effectively and efficiently. Future funding will be determined as part of the spending review process in the usual way. Heidi Alexander - Hansard - Copy Link - - Excerpts The victims of historical sexual abuse have a right to justice, like anyone else, but, as the right hon. and learned Gentleman says, these cases are complex and require adequate funding. How confident is he that the CPS will be able to cope with the demands on it and can he categorically say that such cases will not be consigned to the dustbin of history for want of extra resources? The Attorney-General - Hansard - Copy Link - - Excerpts I understand the hon. Lady’s concern and it is important to put on record that every case, regardless of the alleged crime, must be considered carefully by the CPS. The CPS must conduct the appropriate tests on evidence and on public interest, and these cases should be no different in that regard. We must certainly talk about resources, but we also need to talk about what also matters to victims, which includes being listened to in the first place, ensuring that the court process is as conducive as it can be to the giving of their evidence and ensuring that those who prosecute such cases are expert in what they do. All those things are important and we must ensure that the CPS is doing them. At the moment, the CPS is engaged in doing those things. Philip Davies (Shipley) (Con) - Hansard - Copy Link - - Excerpts In his answer, the Attorney-General made it clear that funding is an issue and that discussions are going on with the Chancellor. Given that, is it sensible for the Crown Prosecution Service to commit millions of pounds to a retrial of journalists from The Sun when there is clearly no realistic prospect of conviction? The money could be much better spent pursuing some of the historical sex abuse cases mentioned by the hon. Member for Lewisham East (Heidi Alexander). Are the cost of a trial and the likelihood of conviction together part of a public interest test that the Crown Prosecution Service should go through, because it seems to many people that a retrial is not justified on that basis? The Attorney-General - Hansard - Copy Link - - Excerpts My hon. Friend will understand that, as Attorney-General, I do not decide which cases should be prosecuted or commenced. He will also understand that whether there is a realistic prospect of conviction is already part of the test that the Crown Prosecution Service applies. Of course, it should also consider the public interest, which is what it has done in each and every case involving journalists—some have been convicted at the end of the process and some have been acquitted. However, I think that it is important to recognise two things. First, there should be no cases in which who a person is or what they do prevents the Crown Prosecution Service following the evidence where it leads—it should do so in every case. Secondly, some cases are complex and difficult and take time to prepare and to try, which increases their cost, but I do not think that we can say that we should not prosecute something because it is too expensive. Karl Turner (Kingston upon Hull East) (Lab) - Hansard - Copy Link - - Excerpts I welcome what the Attorney-General says, but the Director of Public Prosecutions has been to him on bended knee, begging for £50 million so that she can prosecute serious cases. Has he asked the Chancellor for that emergency funding—and if not, why not? If he has asked the Chancellor, what did he say about helping to plug the funding gap caused by the ill thought through cuts to the Crown Prosecution Service? The Attorney-General - Hansard - Copy Link - - Excerpts I do not think that the cuts to the Crown Prosecution Service have been ill thought through. They have certainly been significant, as I am afraid they had to be, given the huge economic mess we inherited when the hon. Gentleman’s party left office. We had to take those decisions, but I think that the Crown Prosecution Service has managed the reductions in its budget extremely well. It has not decided—I think that he would support this approach—not to prosecute cases where it thinks that it is appropriate to do so. However, we must recognise—the DPP recognises this in what she is saying—that there has no doubt been an increase in the number of complex and difficult historical sex abuse cases. We are talking with the Treasury about exactly that, and I am sure that it will understand the case we are making. Pat Glass (North West Durham) (Lab) - Hansard - Copy Link - - Excerpts 4. What recent discussions he has had with the Home Secretary on the future of the Serious Fraud Office. Fiona Mactaggart (Slough) (Lab) - Hansard - Copy Link - - Excerpts 10. What recent discussions he has had with the Home Secretary on the future of the Serious Fraud Office. The Attorney-General (Jeremy Wright) - Hansard - Copy Link - - Excerpts I meet the Home Secretary regularly to discuss issues of common interest. The UK anti-corruption plan, published in December, announced that the Cabinet Office will take forward a review of the enforcement response to bribery and corruption more broadly and will report to the inter-ministerial group on anti-corruption in June. Pat Glass - Hansard - Copy Link - - Excerpts Is the Attorney-General concerned that there is now a conflict, with the Solicitor-General allegedly involved in tax avoidance schemes? [ Interruption. ] Can he properly oversee the work of the Serious Fraud Office, given its role in prosecuting serious fraud and tax evasion? [ Interruption. ] Mr Speaker - Hansard - Copy Link - - Excerpts Order. I fear that, in so far as I could hear, the terms of the question did not engage with the question on the Order Paper. Therefore—forgive me—I do not think that it would be proper to ask for an answer. Fiona Mactaggart - Hansard - Copy Link - - Excerpts In view of the fact that the police are being ineffective in prosecuting fraud, and given that reports to Action Fraud have gone up by 10%, what is the Attorney-General doing to ensure that the Serious Fraud Office has sufficient resources to deal with the most complex frauds? How much money has it got from fraudsters to enable it to fund future work? The Attorney-General - Hansard - Copy Link - - Excerpts The hon. Lady is right to refer to the fact that there are different kinds of fraud, which are dealt with in different ways in our system. The Serious Fraud Office, which falls within the ambit of the Law Officers’ superintendence, deals with the most exceptionally complex cases of fraud. To answer her question directly, in this financial year the Serious Fraud Office has recovered financial orders of £10.7 million. It is right to point out also that the way in which the Serious Fraud Office is funded is unusual. It relies on some core funding and also on what is called blockbuster funding for unanticipated, large and complex cases. I think that that is the right way to do it. Sir Edward Garnier (Harborough) (Con) - Hansard - Copy Link - - Excerpts Will my right hon. and learned Friend confirm that the invitation from some to subsume the Serious Fraud Office into the National Crime Agency is not one that he will accede to? The Attorney-General - Hansard - Copy Link - - Excerpts There is huge value always in looking at the way in which Government agencies do their business and in finding efficiencies and changes if it is beneficial to do so, but I think the Roskill model on which the Serious Fraud Office is based—that is, the combination of lawyers, investigators, prosecutors, accountants and the like, all in multidisciplinary teams—is a sensible model, and it is delivering effective results. Stephen Mosley (City of Chester) (Con) - Hansard - Copy Link - - Excerpts With the Serious Fraud Office doing some incredibly complex investigations into companies such as Barclays, Tesco and G4S, does my right hon. and learned Friend agree that there is a need for very close working between the Serious Fraud Office and other Government agencies, such as the NCA, the police and Her Majesty’s Revenue and Customs? The Attorney-General - Hansard - Copy Link - - Excerpts I agree with my hon. Friend. Close working is always important and the Serious Fraud Office tries to do that. I am sure the intergovernment review will find better ways of co-ordinating if there are better ways to be found. Karen Lumley (Redditch) (Con) - Hansard - Copy Link - - Excerpts 5. What steps the Crown Prosecution Service is taking to increase the number of successful prosecutions for human trafficking offences. The Solicitor-General (Mr Robert Buckland) - Hansard - Copy Link - - Excerpts The number of successful prosecutions in human trafficking cases has increased each year since April 2010, from 73 to 155, which is more than double. The Director of Public Prosecutions is seeking to increase the number of prosecutions further through the CPS contribution to the Government strategy on modern slavery. Karen Lumley - Hansard - Copy Link - - Excerpts Does my hon. and learned Friend agree that the Modern Slavery Bill is a groundbreaking measure that will send a clear message to perpetrators? The Solicitor-General - Hansard - Copy Link - - Excerpts I do, and I am grateful to Members in all parts of the House for their sterling support for legislation which is among the first in the world and the first in Europe. Mr Barry Sheerman (Huddersfield) (Lab/Co-op) - Hansard - Copy Link - - Excerpts rose— Mr Speaker - Hansard - Copy Link - - Excerpts The moment has arrived. Mr Sheerman - Hansard - Copy Link - - Excerpts Is the Solicitor-General aware that those of us who for many years have been involved in such cases, and involved in the problem of runaway children particularly, are still concerned about the number and level of prosecutions of those people, and now of gangs organising human trafficking? When will we see results—more people apprehended, charged, convicted and in prison? Mr Speaker - Hansard - Copy Link - - Excerpts Even if the hon. Gentleman’s palate is not yet fully satisfied, I hope he feels he has now had his hors d’oeuvre for the day. The Solicitor-General - Hansard - Copy Link - - Excerpts The hon. Gentleman is right to be impatient—we all are—for progress in tackling this scourge. It exists not just here at home, but internationally. We have criminal justice advisers and liaison magistrates in 20 countries where we know that human trafficking is a source problem. Human trafficking will not be tackled just within these shores. The effort has to be international. Bob Blackman (Harrow East) (Con) - Hansard - Copy Link - - Excerpts 8. What assessment he has made of the benefits of increased digital working by the Crown Prosecution Service; and what estimate he has made of potential savings from such changes. The Solicitor-General (Mr Robert Buckland) - Hansard - Copy Link - - Excerpts The Crown Prosecution Service (CPS) has made substantial progress in implementing digital working with other criminal justice agencies. Almost all police forces are now transferring over 90% of case files electronically. Savings are being made through business process change and other economies. By 2015-16, the CPS estimates that savings of approximately £30 million per annum will be achieved. Bob Blackman - Hansard - Copy Link - - Excerpts Clearly, there are benefits from not losing documents and removing huge piles of paper from cases. What further measures can my hon. and learned Friend take to speed up the process so that the interests of justice are served? The Solicitor-General - Hansard - Copy Link - - Excerpts My hon. Friend is right to talk about more measures. That will come through initiatives such as the common platform between the Courts and Tribunals Service and the Crown Prosecution Service, so that everybody in the courts system is using digital technology. That will achieve real savings in the long term. Mr David Hanson (Delyn) (Lab) - Hansard - Copy Link - - Excerpts 9. What recent discussions he has had with the Director of Public Prosecutions on dealing with vulnerable victims and witnesses. The Solicitor-General (Mr Robert Buckland) - Hansard - Copy Link - - Excerpts Measures to support vulnerable victims and witnesses are regularly discussed by the Crown Prosecution Service and the Attorney-General’s office. The CPS works closely with the police and the voluntary sector to ensure that vulnerable victims and witnesses are well supported through the criminal justice system. The results of the first national CPS survey of victims and witnesses due in the summer will inform future actions. Mr Hanson - Hansard - Copy Link - - Excerpts The Crown Prosecution Service draft document, “Speaking to Witnesses at Court”, was published in January, and it is broadly welcome. However, will the Solicitor-General give some reassurance to those who are concerned that it might involve coaching of witnesses? The Solicitor-General - Hansard - Copy Link - - Excerpts It is vital that everybody involved in witness care understands the old and well-established rule that witnesses must not be coached. Educating them in the process is absolutely right, but talking about the evidence and trying to coach them in some way would be wholly wrong. Mr Speaker - Hansard - Copy Link - - Excerpts Last but not least, I call Peter Bone. Mr Peter Bone (Wellingborough) (Con) - Hansard - Copy Link - - Excerpts Thank you, Mr Speaker. Victims of human trafficking are the most vulnerable witnesses that can be had before the courts. Adult victims of human trafficking are looked after very well under the Government’s scheme, but child victims are not. Will the Solicitor-General look at ways in which we can improve protection and help for the child victims of human trafficking? The Solicitor-General - Hansard - Copy Link - - Excerpts I am grateful to my hon. Friend, whose track record in fighting modern-day slavery is well known to us all. The Crown Prosecution Service has clear guidelines that ask prosecutors to consider very carefully the public interest in prosecuting young people who are identified as victims of human trafficking where there is clear evidence of exploitation. That approach will turn people who used to be regarded as defendants into true victims of modern-day slavery. Return to start of debate - Return to top of page Accident prevention measures for Redbridge roundabout Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Mr Lee Scott (Ilford North) (Con) - Hansard - - Excerpts I have a petition signed by 676 people declaring that they are extremely concerned, as I am, at the high level of reported accidents—averaging one per week—as well as the potential for fatal accidents at the Redbridge roundabout, which is a major junction of the M11, the north circular and the A12. There needs to be urgent action to stop what has become a nightmare for residents of the area and anyone travelling through it. The petition states: The Petitioners therefore request that the House of Commons urges the Government to direct Transport for London to install traffic lights at the Redbridge Lane East junction or to at least put measures in place (such as adjusting the existing traffic light timings) so that at least 6 or 8 cars can safely get onto the roundabout on each traffic light cycle. Following is the full text of the petition: [The Petition of residents of Ilford North, Declares that the Petitioners are extremely concerned at the high level of reported accidents (which averages at one accident per week) as well as the potential for more fatal accidents on the Redbridge roundabout (LBR); further that this is a major road junction on the east of London which carries heavy traffic from the M11, North Circular Road and the A12; further that it is reputed to be one of the busiest and most dangerous road junctions in Europe; further that all connecting roads on the gyratory have traffic lights apart from one road, Redbridge Lane East; further that traffic from Redbridge Lane East is unable to safely join this constantly busy roundabout and only two or three cars can enter the roundabout on each cycle of the lights; further that this causes up to 45 minute delays on reaching the roundabout, generates pollution levels above safe limits, causes inconsiderate driving by frustrated drivers and results in stress and anxiety experienced by drivers contemplating taking the high-risk strategy of attempting to get across the roundabout without having an accident; and further that a local petition on this matter in the Ilford North constituency and the surrounding area was signed by 2187 individuals. The Petitioners therefore request that the House of Commons urges the Government to direct Transport for London to install traffic lights at the Redbridge Lane East junction or to at least put measures in place (such as adjusting the existing traffic light timings) so that at least 6 or 8 cars can safely get onto the roundabout on each traffic light cycle. And the Petitioners remain, etc.] [P001432] Return to start of debate - Return to top of page Green belt land in Redbridge Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Mr Lee Scott (Ilford North) (Con) - Hansard - - Excerpts I have a petition signed by 4,864 people to save the Oakfield site, which covers playing fields and a sports area on green-belt land. Sadly, the London borough of Redbridge has put out to consultation a proposal to build homes on the site. There are brownfield sites in the area that have not yet been built on and should perhaps be looked at as a matter of urgency before the proposal is even considered. The proposal must be thrown out: it is a rape of our countryside and our green-belt land, and it is a misuse of land needed by children and adults for recreational purposes. The Petitioners therefore request that the House of Commons urges the London borough of Redbridge to reconsider any proposal to develop the Oakfield site for housing, and further request that the House of Commons urges the Government to reject any requests to remove green-belt status from Oakfield. Following is the full text of the petition: [The Petition of the Save Oakfield Site (SOS) campaign group, Declares that the precious, high quality sports field known as Oakfield has twelve full size and nine junior size grass football pitches and four cricket grounds as well as two large pavilions which together act as an inclusive social hub contributing to community cohesion; further that the Petitioners believe that there are proposals to concrete over this irreplaceable green belt land and to destroy the pavilions; further that this would be a massive and irreversible loss to the residents of the Borough of Redbridge, to the many sportsmen and sportswomen in the surrounding London Boroughs and in the County of Essex and beyond, and to the many voluntary and other organisations that provide services to local schools and the wider public; further that the London Borough of Redbridge has planned to seek de-classification of green belt status for Oakfield; further that the Petitioners believe that these plans have occurred without good reason following a flawed process; further that at a time when sport is seen as the Olympic Legacy and as the solution to ever-increasing obesity in the nation, removal of such facilities represents a loss of opportunity for exercise for the existing and growing number of potential users and increases the risk of ill health and will also put further strain on NHS resources; further that the Borough Council would be failing to supply conveniently located, good quality playing fields to satisfy the current demand and the likely future demand in line with the policy of Sport England; further that the proposed development of the stated 800 units of housing on the site will increase already chaotic traffic congestion to intolerable levels and will increase the local pollution level which currently exceeds the rate that is identified as acceptable by the EU and the WHO and will reduce safety without contributing anything significant to social and key-worker homes; and further that all this is based on long-term population projections for the Borough that extrapolate from past trend analysis to produce unrealistic, and unfounded housing demands on the Borough that ignore the needs and rights of the existing population for a sustainable quality of life and are unfair in relation to other London Boroughs and national Government demographic policies. The Petitioners therefore request that the House of Commons urges Redbridge Borough Council to reconsider the proposal to develop the Oakfield site for housing and further request that the House of Commons urges the Government to reject any requests to remove green belt status from Oakfield. And the Petitioners remain, etc.] [P001433] Return to start of debate - Return to top of page Ukraine Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Read Debate Ministerial Extracts 12:36 The Secretary of State for Foreign and Commonwealth Affairs (Mr Philip Hammond) - Hansard - Copy Link - - Excerpts With permission, Mr Speaker, I would like to make a statement on the situation in Ukraine. The past month has seen an escalation of violence in the eastern regions of Ukraine. Fighting has been intense around the town of Debaltseve, a strategically important rail and road hub between the cities of Donetsk and Luhansk. The Ukrainians have suffered indiscriminate missile attacks on buses in Donetsk and Volnovakha and on the port city of Mariupol. What is happening on the ground now resembles, to all intents and purposes, a small-scale conventional war. Over 5,000 people have been killed since the crisis began last spring, and over 1.5 million people have been displaced from their homes. In recent weeks, Russia has aggravated the effects of its initial incursion by stepping up the military support it provides to its proxies. It has transferred hundreds of heavy weapons, including rocket launchers, heavy artillery, tanks and armoured vehicles; and it maintains hundreds of regular soldiers, including special forces, in Ukraine, as well as command and control elements, air defence systems, unmanned aerial vehicles, and electronic warfare systems. The Russian army is also the source of ex-regulars who resign their army posts to fight in Donbass as “volunteers”. The recent escalation in fighting would not have been possible without the military support and strategic direction that Russia provides. In these circumstances, it is vital that all the countries who have a stake in the rules-based international system remain clear and united against Russian aggression. In Normandy last summer, we agreed with the US and our European partners that the most effective channel of communication with the Kremlin would be through a small group. This is known as the Normandy Format, comprising Germany, France as the host of the Normandy meeting, Ukraine and Russia. Chancellor Merkel and President Hollande met President Poroshenko in Kiev last Thursday, and President Putin in the Kremlin on Friday. On Saturday, in Munich, I held meetings with Secretary of State Kerry and German Foreign Minister Steinmeier to assess the prospects for a diplomatic resolution of the crisis. On Sunday, the German Chancellor and the French President held a conference call with Poroshenko and Putin, agreeing to meet in the Normandy format in Minsk tomorrow. Their aim is to reach agreement on an implementation plan for the Minsk ceasefire agreements that the Russians entered into last September, updated, as they need to be, to reflect subsequent changes on the ground. The UK welcomes these efforts to achieve a peaceful resolution of the situation in eastern Ukraine, while remaining sceptical of Russian commitment to such a resolution. It is clear that Putin respects strength, so Britain’s focus has been, and will continue to be, on ensuring that the EU remains robust, resolved and united on the maintenance of economic sanctions, and closely aligned with the US. The consensus within the European Union that Russia must pay a price for its disregard of the international rules-based system remains strong. Equally, there is a clear consensus that the EU does not, and will not, recognise Russia’s illegal annexation of Crimea. The emergency EU Foreign Affairs Council on 29 January agreed to roll over all the Crimea-related tier 2 sanctions against individuals and companies. That is another clear sign that the EU remains united in its response to Russian action in Ukraine. The package of economic sanctions which the European Union and the US has imposed on Russia, coupled with the catastrophic impact on the Russian economy of the decline in the oil price, is a critical element of the pressure on President Putin to change his behaviour. Britain was and remains at the forefront of the successful effort to build and maintain an EU-wide consensus on a sanctions regime on Russia, to the evident surprise and dismay of the Kremlin. Yesterday in Brussels I represented the UK at the EU Foreign Affairs Council, which discussed Ukraine and reconfirmed its decision to apply additional sanctions, but, at the suggestion of the Ukrainian Foreign Minister and as a gesture of support for the political process, decided to delay their entry into force until next Monday. The informal European Council of Heads of State and Government will have further discussions about Ukraine on Thursday. The crisis has inflicted substantial damage on Ukraine’s economy. The World Bank estimates that it shrank by 8.2% in 2014. Public debt has risen sharply, foreign exchange reserves have fallen and the currency has lost nearly half its value against the US dollar. Ukraine clearly needs support from international partners to stabilise the economy, in return for which it must pursue the reforms to which it has committed under the association agreement with the European Union and the International Monetary Fund programme. Britain is providing £10 million in technical assistance to support economic and governance reforms and the humanitarian effort. The EU will make a substantial contribution to the immediate estimated $15 billion financing needs of the country, the majority of which will be provided through an IMF-led package. We shall also continue to work through NATO to offer technical support to the Ukrainian armed forces and reassurance to our eastern NATO allies. At the NATO Wales summit last September, NATO allies sent a strong message to Russia, agreeing to maintain NATO’s long-standing capacity building work in Ukraine by setting up five dedicated trust funds for Ukraine, one of which will be co-led by the UK. The Wales summit also agreed a readiness action plan to reassure our eastern allies. As part of the package, NATO allies agreed to a new spearhead unit—the very high readiness joint taskforce—within the NATO response force, which, supported by the newly created forward integration units in the Baltic and eastern European states, will be able to deploy at very short notice wherever they are needed. On 5 February, NATO Defence Ministers agreed the size and scope of that mission. My right hon. Friend the Defence Secretary has announced that the UK will lead the force in 2017 and on a rotational basis thereafter. The UK also made a commitment to contribute to headquarters in Poland and Romania and the six NATO forward integration unit headquarters in the Baltic states, Poland, Romania and Bulgaria. In addition, the UK will contribute four RAF Typhoons to operate alongside Norway in support of the Baltic air policing mission. The UK also remains a strong supporter of the OSCE’s monitoring mission in eastern Ukraine. We have provided funding of more than £2 million, the second largest number of monitors and 10 armoured vehicles to allow monitors to move around dangerous areas in a more secure manner. Our policy since the start of the crisis has been to supply non-lethal assistance to Ukrainian armed forces, in line with our assessment that there must be a political solution to this crisis. We have increased our defence engagement with Ukraine and are providing additional support on crisis management, anti-corruption, defence reform and strategic communications. We have offered three members of the Ukrainian armed forces who were wounded in the Donbass life-changing specialist medical assistance in the form of reconstructive surgery at the Queen Elizabeth hospital in Birmingham. We are providing a substantial package of non-lethal equipment to Ukraine, comprising medical kits, winter clothing and equipment, body armour, helmets and fuel. The package is focused on reducing fatalities and casualties among members of the Ukrainian armed forces. It is a national decision for each country in the NATO alliance to decide whether to supply lethal aid to Ukraine. The UK is not planning to do so, but we reserve the right to keep this position under review. Different members of the alliance take nuanced positions on this question, and are entitled to do so. However, we share a clear understanding that while there is no military solution to this conflict, we could not allow the Ukrainian armed forces to collapse. By its illegal annexation of Crimea and its destabilising activities in eastern Ukraine, including its direct military support of the separatists, Russia has demonstrated its disregard for international law. It is clear that President Putin respects only strength, and by standing united, using our combined economic muscle to impose significant economic costs on Russia, the international community has shown its determination to rebuff Russia’s anachronistic behaviour. The ball is now firmly in Russia’s court. Until we see Russia complying with the terms of the Minsk agreement on the ground—withdrawing troops, stopping the flow of weapons and closing the border—there must be no let-up in the pressure. Fine words in a declaration tomorrow will, of course, be welcome, but we have seen them before. The proof of the pudding will be in actions on the ground. We will monitor the situation carefully, and we will agree to a relaxation of the pressure only when we see clear evidence of changed Russian behaviour and systematic compliance with Russia’s obligations under the original Minsk agreement. Meanwhile, there will be no let-up in our efforts—with the US, in the EU and through NATO—to ensure that Mr Putin hears a clear and consistent message: civilised nations do not behave in the way Russia under Putin has behaved towards Ukraine, and those of us who live by the rules-based international system will be steadfast in defending it against such aggression. I commend this statement to the House. 12:47 Mr Douglas Alexander (Paisley and Renfrewshire South) (Lab) - Hansard - Copy Link - - Excerpts I thank the Foreign Secretary for his statement, and for advance sight of it. Although the conflict in Ukraine is clearly a geopolitical crisis, it is also a conflict of profound civilian suffering. As the Foreign Secretary has just reminded us, in a neighbouring European state more than 5,000 lives have already been lost, 5 million civilians are living in conflict-affected areas, and nearly 1 million people are internally displaced as a result of the fighting. The House was united in welcoming the Minsk agreement negotiated last year, but even after it was reached, the fighting, although it briefly subsided, did not stop. The situation has yet again deteriorated, with more than 200 civilians killed in the last week of January alone. President Putin appears to have miscalculated the west’s commitment to sustained economic diplomacy. So long as the Russian Government refuse to change course, we must continue with a robust and united international response. With the collapse of the oil price in recent months, the sanctions still hold out the prospect of altering the calculus of risk in President Putin’s mind regarding Russian actions in eastern Ukraine. The Foreign Secretary made it clear that, at the request of the European Foreign Minister, a decision was taken yesterday to delay the implementation of a further set of EU restrictive measures. While credible negotiations are ongoing, all efforts must be focused on ensuring that they are successful. In the absence of an agreed deal this week, however, does the Foreign Secretary believe that new EU restrictive measures, as opposed to simply an extension of existing measures, should be on the table at the upcoming EU Council meeting? In particular, in the absence of meaningful progress tomorrow, will the Prime Minister call for new tier 2 or 3 sanctions when he meets European Union leaders? In recent days, attention has turned to the question of sending lethal arms to the Ukrainian army. I welcome the Foreign Secretary’s reassurance that the UK will continue to work through NATO to offer technical support to the Ukrainian armed forces. This weekend, he said that “the UK is not planning to supply lethal aid”. He repeated that statement in the House today. The Foreign Secretary has said: “Ukrainians can’t beat the Russian army”, and that the policy remains “under review” by the UK Government. Given those two statements, will he tell the House in what context he envisages that Britain could decide to export lethal arms to the Ukrainians? I welcome the recent German and French initiative to help broker an agreement between President Putin and President Poroshenko. Talks in Moscow with Russia, Ukraine, France and Germany were held alongside US Secretary of State Kerry’s visit to Kiev, and followed up by Chancellor Merkel’s visit to Washington yesterday. Further talks are scheduled in Minsk for tomorrow. The ultimate test is whether these talks are successful in ending the conflict, and it is in that sprit that I ask the Foreign Secretary about the extent of British engagement. Does the Foreign Secretary agree that given Britain’s unique assets and alliances, we could make a key contribution to help ensure that the diplomatic effort is successful? If so, why has the UK chosen to take such a back seat in trying to resolve the crisis? The Foreign Secretary does not need to take my word for that judgment. As General Sir Richard Shirreff—the top British commander in NATO until last year—warned last weekend, the Prime Minister is a “foreign policy irrelevance” and a “bit player” on the world stage. When questioned about the former general’s comments, the Foreign Secretary rather flippantly quipped: “Having a sort of committee of ten traipsing in and out trying to talk to the Russians would simply not be effective”. I agree with that judgment, but suggestions that Britain’s diplomatic role could only ever be part of a so-called “traipsing committee of 10”, tells us a great deal more about the Foreign Secretary than it does about the United Kingdom. Does the Foreign Secretary agree that under past Governments of all complexions, Britain has played a leading role in diplomatic negotiations of this sort? In his statement the Foreign Secretary tried to defend the British absence from the latest talks by claiming that the Franco-German leadership role was established in Normandy last year. Nevertheless, whether last year, this year or this month, the decision to exclude Britain, or to be excluded, raises real questions and concerns on the Opposition Benches. Can the Foreign Secretary offer any more hope that Britain in the months ahead—unlike in past months—will be an active, engaged and influential part of efforts to resolve the crisis? The starting point surely must be to remain on guard against Russia’s efforts to find and exploit weaknesses among its European neighbours. Some European states have, of course, been weakened by recession and are vulnerable to subversion, subsidy and corruption, but the challenge is surely to sustain western unity in advancing robust economic diplomacy, while continuing with a more engaged effort to find a resolution to the crisis. If that is the approach of the British Government in the months ahead, they will have our support. Mr Hammond - Hansard - Copy Link - - Excerpts Despite the slightly churlish remarks towards the end of his remarks, I welcome the right hon. Gentleman’s generally supportive approach to this issue, and he is right that Vladimir Putin evidently miscalculated the resolve of the international community to stand firm on this issue. That resolve did not appear without prompting, however, and required a lot of consensus building. Candidly, I will say also that the catalyst of the destruction of Malaysia Airways flight MH17 pulled some of, shall we say, the weaker brethren into line, and ensured a clear and robust alliance on this issue. In particular, the UK and the Netherlands can claim credit for having been key elements in stiffening resolve in that crucial European Council meeting last July. The right hon. Gentleman asked a sensible question about new restrictive measures, and our priority will be to achieve an early roll-over of the tier 3 sanctions. The package of tier 3 sanctions is due to expire at the end of July, and the strongest possible signal that could be sent to the Kremlin would be an early decision to extend that sanctions period, perhaps to the end of 2015. The Kremlin’s knowledge that sanctions will continue, and—most importantly—that it will not have the leverage point of the EU, at 28 member states, having to re-agree a consensus to renew them, removes a lot of its incentives for mischief making, so that will be our priority. I expect that tomorrow, if matters have not progressed or there is bad news from Minsk, the European Council will task the European External Action Service to scope options for further sanctions. A number of perfectly robust allies are now beginning to be slightly concerned about the scale of damage being inflicted on Russia’s economy. We want to hurt the Russians and we want them to pay a price for their aggression in Ukraine, but we do not want the Russian economy to collapse. There is now concern about the scale of damage being inflicted. The right hon. Gentleman asked me to clarify the position on lethal aid. He is right to say that Ukraine cannot beat the Russian army—it does not have the scale of forces, and the Russian army has enormous reserves that it could potentially throw into the conflict. He asked about the circumstances in which we would supply lethal aid, but we have not defined those circumstances. All I have said is that we will not rule out the possibility of supplying lethal aid, and we want to reserve the right to review that position. In my statement I said clearly that we cannot afford to see the Ukrainian army collapse, so perhaps he will take from that a steer as to where our thinking lies. The right hon. Gentleman asked about the UK contribution to the diplomatic effort, and there are two strands to that. There is a forward strand that includes discussions with the Ukrainians and the Russians. In my judgment—being perfectly objective about this and not waving a little flag for the sake of it—the German Chancellor is in the best position to conduct such discussions with the Kremlin. She has channels open with the Kremlin that we, the Americans, and others do not have. The right hon. Gentleman asked about opening out the Normandy process, but if we were to open out that grouping—it is currently four: Russia, Ukraine, Germany and France—we would not be able just to insert the UK but would have to widen that group quite significantly. The United States, naturally, would say, “Well, if the UK is going to join, we must have a seat,” and other European Union partners would also expect to be present, most obviously Poland and Italy. We would therefore have a significantly wider group, and our judgment is that for this phase of the process, maintaining that Normandy format is the best way forward. The second strand of diplomatic activity is behind-the-scenes activity to hold together the European Union consensus and ensure that the EU is aligned with the US, Australia, Japan and other partners. That is a significant diplomatic-legwork task—unglamorous but vital—and I assure the right hon. Gentleman that the UK has played a leading role in designing the sanctions packages, identifying the individuals, companies and sectors to be targeted by sanctions, and building and maintaining consensus in Brussels and around the capitals of Europe. General Sir Richard Shirreff says that the Prime Minister is a “diplomatic irrelevance”, but I suggest that perhaps he should consider carefully the meaning of the word “irrelevance” and where it might best be applied. The right hon. Gentleman talked about Russian coercion and the energy exposure of the European Union to Russian pressure, all of which we are acutely aware of. There is also Russian corruption and the influence of Russian money in the politics of some Balkan countries—even now, one party in the recent Bulgarian general election launched its manifesto in the Kremlin, which may provide a clue, and we are acutely aware of all those things. Europe must make itself more resilient against Russian influence, and that is an important part of the agenda going forward. Sir Malcolm Rifkind (Kensington) (Con) - Hansard - Copy Link - - Excerpts The Foreign Secretary and I were both at the Munich security conference when Chancellor Merkel explained her position and her opposition to helping with military assistance to the Ukrainians on the grounds that, even with that assistance, Ukraine would not be able to defeat the Russians. The Foreign Secretary has repeated that observation today, but may I respectfully suggest that that is missing the point? The question at issue is not whether the Ukrainians could defeat the Russians—of course they could not. At the moment, however, as the Foreign Secretary has pointed out, the Russians are flooding in a whole supply of military equipment—heavy weapons, rocket launchers, heavy artillery, tanks and armoured vehicles—to their supporters in Donetsk and Luhansk. If the Ukrainians are deprived of the military means to defend their territory, that matter will be resolved in the next few weeks. It will be no use coming to the aid of the Ukrainian army when it has already been defeated and when the territory controlled by the Russians has greatly expanded. At this stage, the objective must surely be to impress upon President Putin that Ukraine will be able to defend itself, and therefore that, if the Russians try to resolve the matter by military means, it will take not days or weeks, but months. Against that background, would there not be a much greater likelihood that President Putin would also see the inevitable need for a political and not a military solution? Mr Hammond - Hansard - Copy Link - - Excerpts I am afraid that my right hon. and learned Friend and I will probably have to agree to disagree on that. The position is this: if Russia was intending to make a full-scale military push into Ukraine, it has the forces available to do it. Approximately 10,000 Russian forces are along the border with eastern Ukraine, and it has sophisticated weaponry in large quantities and air forces that could be mobilised. The Russians are already able to do that. We judge that the intervention the Kremlin is making is carefully calculated to improve the position of the separatists on the ground and to apply pressure to the Ukrainian regime, but there has not so far been a wholesale land grab—it has been the consolidating of separatists’ positions. We judge that the Ukrainian army at the moment is able to hold the line and that, broadly speaking, it is doing so. I have said that we will reserve the right to keep under review the question of supplying lethal aid. As my right hon. and learned Friend very well knows, many in the United States are debating openly whether a large package of military equipment assistance should be provided to Ukraine. That would clearly change the parameters of the debate. We are watching that debate very closely. Mr Jack Straw (Blackburn) (Lab) - Hansard - Copy Link - - Excerpts The right hon. Gentleman said in his statement that it was a national decision for each country in the NATO alliance whether to supply lethal aid to Ukraine. He is absolutely right—that is a matter of fact—but does he accept that this cannot be left to unilateral decisions by individual countries? The Russians, for certain, would regard any provision of lethal aid—I certainly do not rule that out in certain circumstances—as a consequence of collective decision making within NATO and seek to respond in a similar way. While accepting the reality the Foreign Secretary describes—it is a national decision—what efforts is he making to ensure that there is some co-ordination, not least so that we do not end up with a situation in which, within the NATO alliance, two policies are being pursued, which the Russians would skilfully exploit? Mr Hammond - Hansard - Copy Link - - Excerpts I am afraid that the reality is that, if the United States decides to supply lethal aid, there will be two policies within the NATO alliance, because the German Chancellor could not have been clearer about her position, which she set out on Saturday, as my right hon. and learned Friend the Member for Kensington (Sir Malcolm Rifkind) said. This is a matter for individual national Government decision, and individual countries will make their own decisions. As far as I am aware, no countries within the NATO alliance apart from the United States are actively contemplating the supply of lethal assistance to the Ukrainians. Mr Kenneth Clarke (Rushcliffe) (Con) - Hansard - Copy Link - - Excerpts Will my right hon. Friend stick to his opinion that, however well trained and equipped the Ukrainian army is, it is inconceivable that it could resist the Russian army, or even slow it down significantly, so long as President Putin determined that he was going to put in the necessary resources? Does my right hon. Friend therefore agree that the British contribution must be to remain resolute and comparatively hawkish on stepping up economic sanctions if Putin maintains his present stance of military aggression, because the President of Russia cannot protect himself against economic sanctions, and it is the only reasonable response we can make? Mr Hammond - Hansard - Copy Link - - Excerpts I agree with my right hon. and learned Friend. That is indeed the role we have defined for ourselves, being the most forward-leaning partner within the European Union, urging, cajoling and persuading the others about the need to remain robust. When I say that we are the most forward-leaning country, I mean that we are the most forward-leaning large country—some of our small Baltic partners are very much forward leaning on this issue. The underlying truth is this: hon. Members know, and the history of the Soviet Union reminds us, that, in the end, we cannot ignore the economics. Russia spends something like 20% of its GDP on defence and security. That is unsustainable in the long term. A small and shrinking economy—it is much smaller than the UK economy—attached to a very large military force is ultimately an unsustainable and unstable situation. Mr Peter Hain (Neath) (Lab) - Hansard - Copy Link - - Excerpts I agree with much of what the Foreign Secretary says, including that President Putin is a calculating, ruthless and lethal authoritarian. Does not the whole crisis spring from the failure after the cold war ended to establish a common European security system to which Russia felt attached? Instead, there has been a kind of cold peace. Surely the way forward is a negotiated solution, or an attempt at one, in which there are limits to NATO expansion and European Union expansion in return for an end to Russian aggression. Mr Hammond - Hansard - Copy Link - - Excerpts The situation is that, after the cold war, when 19 ex-Soviet republics, or whatever it was, liberated themselves from the Soviet Union and became independent countries able to set their own path in the world, we sought to build a normal relationship with Russia—one in which Russia would join the community of nations and become richer and more normalised, and one in which the Russian people were able to become more prosperous. President Putin has chosen to set his face against that future and to hark backwards to the Soviet Union or perhaps to the Russian empire. We should remember that he is on public record as saying that the collapse of the Soviet Union was the worst disaster of the 20th century. Many of us would think it was one of the great achievements of the 20th century. I do not think we can compromise with somebody whose avowed intention is to exercise control over independent neighbouring countries in such a way that they cannot determine their own future, whether that is a future aligned with the European Union and NATO or a future aligned with Russia and other allies. That must be for those people in those independent countries to choose for themselves. Martin Horwood (Cheltenham) (LD) - Hansard - Copy Link - - Excerpts I strongly welcome the clarity of the Foreign Secretary’s statement and his commitment to a united European response to the invasion. Does he agree that it is vital to pursue the diplomatic path, but equally important to ensure that diplomacy does not simply provide the space and time for the great chess player Putin to weaken Ukraine, regroup and attack again at a later date? Mr Hammond - Hansard - Copy Link - - Excerpts That is the great risk—that the Russian objective is simply to achieve a frozen conflict, and a situation in which, de facto, Russia exercises very extensive leverage over Ukraine, and Ukraine operates not as a truly independent sovereign nation, but as a semi-independent nation. We have seen Russian attempts elsewhere to manage frozen conflicts. I sometimes think that one of the diseases we suffer from in the west is tidy-mindedness. We tend to think of conflicts such as this one as things that have to be solved and that have to have an end. I suspect that the mindset in the Kremlin is that the Russians can have any number of those conflicts, and that they can remain open, simmering for ever. That would suit them quite nicely. Ms Gisela Stuart (Birmingham, Edgbaston) (Lab) - Hansard - Copy Link - - Excerpts It sounds to me as if President Putin is getting exactly what he wants. The right hon. and learned Member for Kensington (Sir Malcolm Rifkind) was absolutely right. I was at Munich, too. Not only was it obvious that the UK’s views were utterly irrelevant—nobody in the room asked what the United Kingdom thought—but it was clear that Chancellor Merkel was not going to arm the Ukrainians. More remarkably, she did not mention the possibility of further sanctions. The Secretary of State said that we should not weaken Russia any further. It seems to me that we are not supplying arms and not applying any more serious sanctions, with the explanation that that would destabilise Russia even further. If so, Putin will have got what he wanted. Mr Hammond - Hansard - Copy Link - - Excerpts No. If the existing sanctions are rolled over for a further period, the pressure on Russia will be maintained. It is not the case that we have imposed a bunch of sanctions that are not having any effect, and now we should be asking whether we should impose more. We have imposed a bunch of sanctions. Alongside the declining oil price the absence of access to the capital markets is having a crippling impact on Russia. While the hon. Lady was listening to Mrs Merkel in the room at Munich, I was talking to the Iranian Foreign Minister, so I did not listen to the speech, but I spoke to the German Foreign Minister afterwards. We are actively discussing the maintenance and extension of the sanctions regime with the Germans. Of course, they want to explore the opportunity that tomorrow’s meeting, if it goes ahead, might offer, but the Germans, and the German Chancery in particular, are robust. They have been admirably robust on the case for maintaining sanctions. Sir Gerald Howarth (Aldershot) (Con) - Hansard - Copy Link - - Excerpts This is a very serious and growing crisis. As my right hon. Friend knows, I have consistently warned that Russia plans to complete its illegal annexation of Crimea by forming a land link. Are Her Majesty’s Government content for that to happen? If not, at what point do we exercise that demonstration of strength, which the Foreign Secretary mentioned Mr Putin respects, to show we are no longer prepared to see him completely redraw the boundaries of Europe? Mr Hammond - Hansard - Copy Link - - Excerpts Sometimes we underestimate the influence that we have collectively. If Russia wanted to force a land link to the Crimea, it easily has the military capability in the area to do so and would have done so some time ago. However, it understands clearly that there would be a significantly higher price to pay. In circumstances where it is already suffering very significant impacts from the international response to its behaviour, it has shown no inclination to use the military capability it has in the area to achieve that objective. Angus Robertson (Moray) (SNP) - Hansard - Copy Link - - Excerpts We wish Chancellor Merkel and President Hollande well in their search for peace. I personally wish my constituents from RAF Lossiemouth well. They have been deployed to the Baltic as part of the air policing mission. In the past few years, the Russians have been restructuring their armed forces around professional personnel and units that are deployable, based entirely around deployable personnel. What analysis has been done by the UK Government on the reports that have emerged in recent days that the Russians are extending the period in which their conscripts are being made to serve, and what impact that may have on the situation in Ukraine? Mr Hammond - Hansard - Copy Link - - Excerpts I am not aware of any specific analysis relating to the Russian decision on the conscription period. I suspect that that may reflect a demographic challenge that the Russian Federation faces. It has a dramatically ageing population and it is clear that maintaining force numbers when there are declining cohorts of young men will be a challenge. However, the hon. Gentleman is absolutely right. The Russian military has been modernising and professionalising itself. There are now two parts to the Russian armed forces: a mass conscript body and an elite professional force. In our military planning, we need to be conscious of that evolution. Dr Julian Lewis (New Forest East) (Con) - Hansard - Copy Link - - Excerpts NATO was formed originally so that no aggressor could try to pick off one country after another without knowing that he would immediately be at war with the major powers. Is it not vital that we maintain the distinction between NATO countries and non-NATO countries? Is not the best way to reinforce the impression of the strength of NATO to give an open-ended commitment in future, as we have in the past, that we will spend 2% of GDP—the NATO recommended minimum on defence? Mr Hammond - Hansard - Copy Link - - Excerpts As my hon. Friend knows, at the Wales summit all NATO partners signed up either to maintaining that level, for those who are already spending 2% of GDP on defence, or to making progress towards achieving that level. My hon. Friend is absolutely right that the cornerstone of our security in the UK is the article 5 guarantee. Our allies and partners in the Baltic states are acutely conscious that their position is different from that of Ukraine, simply because they are inside NATO and benefit from the article 5 guarantee. He is absolutely right that we need to maintain the clear distinction between the guarantee that we extend to NATO, which is absolute, and the opprobrium we heap on those who launch the kind of attacks we have seen on non-NATO members, but we will deal with attacks on non-NATO members in a different way from attacks on NATO members. Mike Gapes (Ilford South) (Lab/Co-op) - Hansard - Copy Link - - Excerpts The commitments to give support to the front-line states in the Baltic and Romania, Poland and Bulgaria, and very firmly to enforce and maintain article 5 are absolutely vital at this time. Can it be made absolutely clear to the British public that we are in a very, very potentially dangerous situation given the pattern of Russia’s behaviour—Georgia, the frozen conflict in Transnistria and behaviour towards Armenia in trying to get it away from the European Union—and that we face a fundamental problem here unless there is a change of behaviour by Putin? Mr Hammond - Hansard - Copy Link - - Excerpts I agree with the hon. Gentleman. I am almost sick of hearing myself say it, but this is not just a Ukraine problem. This is a Russia problem. Even if the problem in Ukraine solved itself tomorrow, we would still have a Russia problem. Other former Soviet Union republics are looking nervously at the scope for Russian intervention or interference in their affairs. The disappointment is that public opinion, neither in the UK nor in other EU countries, appears to have understood the significance of this threat. I was personally hoping that the events in the Crimea and the threat to gas supplies might have galvanised German public opinion into feeling willing to support a more forward-leaning German response on strategic and defence matters, but the opinion polling suggests that attitudes have hardly moved at all since the incursion in Ukraine. Hopefully, we can have a cross-party consensus to alert public opinion to the significance of this challenge to the established international order. Mr John Whittingdale (Maldon) (Con) - Hansard - Copy Link - - Excerpts Does my right hon. Friend agree that, while the immediate priority must be to try to stop the bloodshed in eastern Ukraine, if Ukraine is to have a future and avoid complete financial collapse it will require an international bail-out on a scale that is not yet under discussion, as well as very urgent political and economic reform to deal with the endemic corruption at every level throughout the country? Mr Hammond - Hansard - Copy Link - - Excerpts I am grateful to my hon. Friend and I thank him for the important work his all-party group on Ukraine does to maintain Anglo-Ukrainian relations. He is right that Ukraine is going to need massive international support, but it cannot be delivered unconditionally. We cannot pour the money of our taxpayers and our international financial institutions into the sink of corruption that is, frankly, the Ukrainian economy at the moment. Ukraine has to make progress on sorting out the endemic corruption if we are to be able to support it towards a better economic future. Jeremy Corbyn (Islington North) (Lab) - Hansard - Copy Link - - Excerpts I thank the Foreign Secretary for his statement. I wish the summit well and hope some good comes out of it. May I take him back to the answer he gave to my right hon. Friend the Member for Neath (Mr Hain)? There is an issue that goes back to the early 1990s, when there was an agreement that Ukraine would become independent and non-aligned—it would not join NATO. In return, Russia would respect its neutrality and divest itself of nuclear weapons. That was a very good statement and very good progress. Does he not think that there would be a better chance of reaching some kind of agreement with Russia if there was a clearer statement that NATO does not intend to expand into Ukraine, and that in return Russia should withdraw from its border regions, so that we do not build up to two huge armed forces meeting in central Europe yet again? Mr Hammond - Hansard - Copy Link - - Excerpts On that last point—two huge armed forces meeting in central Europe—the hon. Gentleman will know that NATO has refrained from stationing non-national NATO troops in the front-line new NATO member states precisely to avoid that build-up. It is part of the Russia-NATO agreement to avoid that build-up of forces in a confrontational way. I am personally rather reluctant to dictate to independent third countries what they can and cannot do. I think Ukraine is perfectly entitled to aspire to membership of the EU or NATO if it chooses to do so. However, it is very, very clear that membership of either organisation would be many, many years away. Ukraine would have a huge amount of work to do before it was ready for membership of either organisation. Duncan Hames (Chippenham) (LD) - Hansard - Copy Link - - Excerpts I welcome the Foreign Secretary’s clear articulation of the economic limits to Russia’s stance, but what is his assessment of the economic impact on Ukraine’s ability to sustain its position and the period of conflict with Putin’s proxies? Mr Hammond - Hansard - Copy Link - - Excerpts The Ukrainian Government are facing significant financial constraints. As the hon. Gentleman will know, they entered a Government-to-Government agreement on the supply of gas from Russia that required them to prepay and clear some old gas debts. That is why we are focused, alongside the strategic channel, on facilitating the $15 billion facility from the IMF, to which the EU will contribute $2.3 billion. That will give the Ukrainians some breathing space. They have to get their economy in order, deal with the corruption issues and make essential reforms, and if they do so, $15 billion will not be the last of it; it will be the first instalment of an ongoing support programme for the country. Mr Barry Sheerman (Huddersfield) (Lab/Co-op) - Hansard - Copy Link - - Excerpts Does the Foreign Secretary agree that the guarantee of peace in Europe and the world has been largely based on a strong EU and NATO and the strong defence capacity of this country? Does he believe that the reason some people say we are peripheral to the main foreign policy discussions in Ukraine at the moment has been the weakness of our support for the EU and NATO and the fact that we have had to be begged by President Obama not to run down our military forces any further? Mr Hammond - Hansard - Copy Link - - Excerpts I shall take that question in two parts. I agree with the first part. It is important that we have a strong EU response. We have already demonstrated, in relation to Iran, that the economic weapon can be a hugely important strategic tool. The EU and the US together represent about 46% of the world’s GDP, so if they align to impose economic sanctions on a third party, they will have an impact. We have shown that that is an important strategic weapon. NATO, of course, remains the cornerstone of our hard defence, and we must maintain the strength of that organisation, including by maintaining European NATO members’ level of defence spending in order to make a fair contribution and balance that of the US. It is simply not true, however, that we are peripheral in this debate. It is true that we are not leading the discussions with Mr Putin. Mrs Merkel talks to him in Russian, and he talks to her in German; they have common languages and communicate with each other. We should use the best channel available, and that communication channel is the best available for that part of the task. We, on the other hand, are focusing on maintaining the backbone of the EU. Any of my EU colleagues who have been present in the Foreign Affairs Council meetings will confirm that we have been boringly insistent on the need to maintain these sanctions, however long the discussions take. We cannot afford casually to reduce our stance, because the Russians will take any sign of weakness or division, and open it out in a way that will be fatal to our position. Sir Edward Leigh (Gainsborough) (Con) - Hansard - Copy Link - - Excerpts With respect to my right hon. and learned Friend the Member for Kensington (Sir Malcolm Rifkind), there is no point making war-like noises unless we are prepared to engage in war and see our sons and daughters die. The reason European public opinion is so relaxed is that we do not have a great stake in this matter. We talk about, “Putin this, Putin that”, but it is not just him; the overwhelming majority of Russians believe, for better or worse, that eastern Ukraine is inhabited by Russians who want to be autonomous and for centuries have been associated with Russia. If we go down the route advocated by my right hon. and learned Friend, we will have war without end. Russia could be in Kiev within four days. Surely we should support the present Foreign Secretary and the German Chancellor in trying to find a peaceful solution based on an autonomous eastern Ukraine. Mr Hammond - Hansard - Copy Link - - Excerpts My hon. Friend could hardly expect me to disagree with that last sentiment. His point about Russian public opinion is, of course, true. Sadly, nationalism is easy to whip up, and at the moment Mr Putin is riding on a tide of nationalist sentiment, but as we move through 2015 and the consequences of his actions begin to bite on Russian consumers—let us remember that the entire burden of the economic sanctions and the decline in the oil price is effectively being transferred to Russian consumers in the depreciation of the rouble—they will find life getting very difficult, and I suggest that such a level of public support might not last. Mr Frank Roy (Motherwell and Wishaw) (Lab) - Hansard - Copy Link - - Excerpts There are many thousands of Ukrainians and people of Ukrainian descent living in all parts of the UK, and obviously they are becoming ever more worried for the safety of their family and friends. Will the Foreign Secretary ensure that the UK-based Ukrainian organisations can make representations to the Foreign Office and will be kept informed as the situation unfolds? Mr Hammond - Hansard - Copy Link - - Excerpts Yes, I assure the hon. Gentleman that they do make representations to the Foreign Office, and of course we take them into account. I should be clear, however, that we have excellent communications with the Ukrainian authorities. I met the President and the Foreign Minister of Ukraine the week before last at the Auschwitz commemorations. We have regular dialogue with them, and they are hugely active in their engagement with the EU and hugely appreciative of how we collectively have responded to their plight. Mr Bernard Jenkin (Harwich and North Essex) (Con) - Hansard - Copy Link - - Excerpts Will my right hon. Friend describe what he thinks a successful outcome to the French and German-led talks with Russia would look like? Would it involve the de facto partition of Ukraine, and how would that be anything else than a permanent reward for Russian aggression? Mr Hammond - Hansard - Copy Link - - Excerpts No, a good outcome would not look like that. It would look like an agreement to a ceasefire and a withdrawal from the current lines of contact, along the lines already suggested, and not just an agreement to its happening tomorrow, but evidence by the end of the week that Russian forces were pulling back; it would look like an agreement on the effective policing of the Russian-Ukrainian border so that once Russian equipment had moved back across the border into Russia, there was an effective, transparent regime for monitoring further equipment crossing the border; and it would look like an explicit withdrawal of Russian support for and endorsement of the separatist forces. Mr Christopher Chope (Christchurch) (Con) - Hansard - Copy Link - - Excerpts If it does not look like that, what will happen? It is clear already that Russia denies it even has troops in eastern Ukraine, and the Speaker of the Duma denied at the recent meeting of the Parliamentary Assembly of the Council of Europe that Russia was even a party to the Minsk agreement and protocol, saying it was a mere bystander. What will happen? Russia could be playing for time, and in the meantime the frozen conflict is increasing. What will my right hon. Friend do to ensure that something happens? For starters, how about expelling Russia from the Council of Europe for being in breach of its statutes? Mr Hammond - Hansard - Copy Link - - Excerpts We do not know the Russian game plan—one difficulty is the absence of a debate about this in Russia; it is one man making all the decisions. We do not know whether Mr Putin has agreed to this process over the last few days because he has seen the light, understood the pressure on him and genuinely wants to find a solution, or because there is an EU Council meeting on Thursday. Traditionally, his tactic has been to ramp up the rhetoric of peace ahead of Council meetings, and then to drop it like a stone afterwards. In response to my hon. Friend’s specific question, however, the single most effective measure we could take to signal our continued displeasure at the failure of this initiative would be to extend the tier 3 sanctions to the end of 2015. That would send a clear message to the Russians. Sir Oliver Heald (North East Hertfordshire) (Con) - Hansard - Copy Link - - Excerpts Does my right hon. Friend agree that there is an opportunity for peace at present, and that by suspending further sanctions, having Chancellor Merkel, who understands Russian interests, negotiating, and not at this stage reinforcing the Ukrainians, rather than proceeding with further economic pressure, particular given Russia’s circumstances at the moment, there is the chance of an honourable peace that the Russians would be wise to accept? Mr Hammond - Hansard - Copy Link - - Excerpts My hon. and learned Friend is right. The key term is that there is a chance for “an honourable peace”. We understand that face will be important to Mr Putin. The German Chancellor grew up in East Germany under Russian control, so she understands the Russian mentality and how to engage with the Russians to try to reach a constructive solution. I am optimistic that we may see something coming from these discussions, but I will not believe it until I see it being delivered on the ground. David Tredinnick (Bosworth) (Con) - Hansard - Copy Link - - Excerpts Is my right hon. Friend aware that President Putin’s grievances with the west can be traced back to the comments of the US Secretary of State James Baker at the time of the negotiations over the reunification of Germany, when he categorically said that there would be “no extension of NATO’s jurisdiction or NATO’s forces one inch to the East”. Having gone to Moscow and met President Yeltsin with John Major, at his request when he was Prime Minister, and having personally talked to President Gorbachev in Moscow, I tell my right hon. Friend that I think we completely underestimate Russia’s security concerns and insecurity. The very minimum we are going to need for a negotiated settlement is a land corridor to Crimea, which most Russians believe to be part of Russia—whatever administrative changes President Khrushchev introduced. Mr Hammond - Hansard - Copy Link - - Excerpts I do not underestimate Russian paranoia, as Russia’s fears of encirclement are an historical phenomenon. Living as we do in a free, democratic NATO member state, we all know that NATO represents no offensive threat to anyone. That is not the way NATO works. It would be inconceivable that public opinion in the NATO countries could be persuaded to support any kind of offensive action against a peaceful neighbour. So Russia has nothing to fear from NATO. As for a land corridor, I have to say to my hon. Friend that I do not think it is our business to sit here discussing whether bits of the Ukraine’s sovereign territory should be given away to a foreign power. If the Ukrainians want to negotiate territory with the Russians, it is of course their prerogative to do so, but it is certainly not for us to do. Mr Jonathan Djanogly (Huntingdon) (Con) - Hansard - Copy Link - - Excerpts I personally would support further immediate economic sanctions led by the EU, but, whatever happens there, for how much longer can we in this country allow Russian nationals to have the benefit of secure and fine living here and to enjoy our banking facilities, for example, while their country wages war and terrorises people on our own continent? Mr Hammond - Hansard - Copy Link - - Excerpts Many Russians living in this country are not exactly friends of the current regime. Indeed, some of them live in pretty much permanent fear of the long arm of the current regime, so I do not think we should tar all Russians with the same brush. We need to be clear that while we have a fundamental disagreement with Mr Putin’s Government, we do not have a fundamental disagreement with the people of Russia. In the medium to long term, we must want to see Russia joining the international community of nations, becoming a normalised economy and the Russian population getting richer, more integrated and freer as the populations of the eastern European countries that lived under the Soviet yoke for so long have now done. Richard Drax (South Dorset) (Con) - Hansard - Copy Link - - Excerpts I agree with my right hon. Friend that a full-scale invasion could be mounted by Russia if she wanted to—she has the resources and there is nothing we could do about it. Her policy is “softly, softly catchee monkey”—not full-scale invasion, which would of course alert NATO, whose reaction to that would be far more aggressive than it has been to date. I agree, too, that jaw-jaw is better than war-war. However, there surely comes a time when the jaw-jaw no longer works, and we have to ensure that NATO’s counter-measures are up to the standard to meet such a threat. Let me reiterate a point made by my hon. Friend the Member for New Forest East (Dr Lewis) that we in this country and the rest of NATO must meet this minimum 2% commitment to NATO. I hope my right hon. Friend can tell us today that this will be in our manifesto for the general election. Mr Hammond - Hansard - Copy Link - - Excerpts It is not my role to write the election manifesto for the Conservative party, and still less to announce the details of it from this Dispatch Box today. I have a certain degree of sympathy for what my hon. Friend says, as he will be well aware. It is essential to maintain our defences against Russia’s asymmetric aggression, but it is also important to understand that economic sanctions are now a weapon in our toolbox alongside military forces. We have used them against Iran, and we are using them in respect of Ukraine. They are part of the new pattern of asymmetric warfare. We should hone and nurture these sanctions so that we can use them effectively in the future. Henry Smith (Crawley) (Con) - Hansard - Copy Link - - Excerpts I welcome my right hon. Friend’s statement. What discussions have taken place with Latvia, which currently has the presidency of the EU and indeed is a Baltic neighbour of Russia and former Soviet republic? Mr Hammond - Hansard - Copy Link - - Excerpts We have excellent relationships with our Latvian counterparts. I recently visited Latvia because it holds the current presidency. Various UK Ministers will be in Riga over the course of the next weeks and months. I had a discussion in Brussels yesterday with the Latvian Foreign Minister. As one of the Baltic states, Latvia is quite forward leaning on these issues, but in its role as EU president it takes a more measured position, stewarding the EU. We have good relations; we well understand the Latvian position; we greatly appreciate the insight that its knowledge of its Russian neighbour allows us. David Morris (Morecambe and Lunesdale) (Con) - Hansard - Copy Link - - Excerpts It seems to me that the current sanctions are having a limited effect in halting the incursions into Ukraine. What will happen if these current sanctions fail? Further sanctions are implied, so what would those sanctions look like? Mr Hammond - Hansard - Copy Link - - Excerpts We have two levels of sanctions in place at the moment. We have sanctions targeted on individuals and companies—named individuals and companies—that include asset freezes, travel bans and so forth. Then we have the tier 3 sanctions, which are sectoral. These impose prohibitions on the export of goods and on trade with certain sectors of the Russian economy. In particular, there is an exclusion of Russian institutions, public and private, from the capital markets of the free world. We could clearly extend both lists if we chose to do so. We have to make a judgment about the balance of economic harm. There are costs to us as well as costs to Russia, so we need to target our sanctions carefully to make sure that the balance of harm is to the disadvantage of the Russians. Return to start of debate - Return to top of page Tuition Fee (Transparency and Accountability) Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Motion for leave to bring in a Bill (Standing Order No. 23) 13:37 Oliver Colvile (Plymouth, Sutton and Devonport) (Con) - Hansard - Copy Link - - Excerpts I beg to move, That leave be given to bring in a Bill to require universities to report to those paying tuition fees on how those fees are treated and spent; and for connected purposes. The aim is that letters should be sent by vice-chancellors and governors explaining in detail how they spend their students’ tuition fees. We have to remember that students are the universities’ clients and customers. They are paying a significant amount of money to receive a service. I firmly believe that students deserve accountability from their institutions. As you know, Mr Speaker, Plymouth is the largest urban conurbation west of Bristol, with a population of 256,384, and it is a significant seat for higher education. Its institutions include Plymouth university, Plymouth college of art and the university of St Mark and St John, commonly known as Marjon. Plymouth university also includes the Peninsula school of medicine and dentistry, but this is split between Plymouth and Exeter universities, with a total of 1,500 students. The Plymouth sites are shared between my constituency and Plymouth, Moor View, which is represented by the shadow Minister for Defence, the hon. Member for Plymouth, Moor View (Alison Seabeck). Plymouth university is the 15th largest university in the UK, with over 28,625 full and part-time students, including the medical students. I understand that 50% of Plymouth university’s income comes from tuition fees. Plymouth college of art, which is soon to become a university, caters for about 1,500 students. Marjon, also in the Moor View seat, caters for 2,665 students. The total undergraduate and graduate student population within Plymouth is 32,790—just below 13% of the city’s population. I am very conscious that students in England are paying up to £9,000 a year in tuition fees, and that the vast majority must rely on student loans. It should be borne in mind that the Bill would not affect students in Scotland, Northern Ireland and Wales, where university policy is devolved. I tabled it because I believe that accountability is essential, and that all university students throughout England should be allowed to know how their money is spent, including the money spent on development, facilities and staffing. In last year’s annual grant letter, my right hon. Friends the Secretary of State for Business, Innovation and Skills and my right hon. Friend the Member for Havant (Mr Willetts), who was then Minister for Universities and Science, expressed concern about the substantial upward drift of the salaries of some top managements at our universities. I believe that if universities were more accountable to their students, they would ensure that they could justify that expenditure. According to Times Higher Education, the best-paid 10 vice-chancellors of English universities earned between £365,432 and £480,000 in 2012-13. I am delighted to report that none of Plymouth’s universities features in the top 10. Members may wish to compare those academic fat cats’ salaries with the £142,500—including his parliamentary salary—that I understand the Prime Minister earns for running the whole country, rather than just one university. Needless to say, those amounts do not include any redundancy money that might have had to be paid. Last year, one university paid 25 members of staff more than £100,000, despite having spent £3.9 million on redundancy and restructuring costs. I am convinced that if students keep an eagle eye on what university managements are spending, the institutions will be forced to make better use of the considerable funds with which their student populations provide them. I therefore propose that all university governors and vice-chancellors should not only send every student who is paying tuition fees a detailed letter—as the Chancellor of the Exchequer has begun to do for taxpayers—but give students an opportunity to question how the money is being spent. This Government have taken the lead in putting transparency, openness and accountability at the heart of this parliamentary term, and the English universities should follow. Question put and agreed to. Ordered, That Oliver Colvile, John McDonnell, Chris Heaton-Harris, Chloe Smith, Mark Garnier, Jonathan Evans, Mr Andrew Turner, Philip Davies, Mr Brian Binley, Mr Andrew Love, Sheryll Murray and Mr Brooks Newmark present the Bill. Oliver Colvile accordingly presented the Bill. Bill read the First time; to be read a Second time on Friday 27 March and to be printed (Bill 173 ). Return to start of debate - Return to top of page Police Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Read Debate Ministerial Extracts Divisions during this debate: 15:22 - The House divided: - Ayes: 285 / Noes: 212 - Question accordingly agreed to. 13:43 The Minister for Policing, Criminal Justice and Victims (Mike Penning) - Hansard - Copy Link - - Excerpts I beg to move, That the Police Grant Report (England and Wales) for 2015–16 (HC 930), which was laid before this House on 4 February, be approved. I announced that the provisional police grant report had been laid before the House in a written ministerial statement on 17 December, so that there would be plenty of opportunity for it to be read and analysed before today’s debate. It is an honour and a privilege to be the Minister responsible for what I often say—and I should often say—is the greatest police force in the world, and it is a great honour to be here today. Policemen and women, and backroom staff, do a fantastic job for us every day, keeping us safe in our homes and tackling crime. I now want to outline the way in which policing has been transformed under this coalition Government in the last four and a half years, and to describe the fantastic work that the police are doing and the innovation that we are seeing on a daily basis. The funding settlement reflects the difficult economic times that we are still experiencing as a result of what we inherited from the last Government, but the police have done a simply fantastic job in reducing crime by 20% over those four and half years, and I think that the whole House should applaud them for that. The police have been responsible for some unbelievable achievements in the United Kingdom. I am thinking of, for instance, the G8 summit which was held in Lough Erne, in Northern Ireland, when I was Northern Ireland Minister of State. I know that it is not relevant to today’s debate, but I have to say that that excellent summit could never have taken place without the mutual aid provided by police forces that came to Northern Ireland from all over Great Britain to provide their assistance. Last September, that same mutual aid was an integral part of the NATO summit in Wales. I also pay tribute to the members of the intelligence services who ensured that we were safe at those summits, and who keep us safe on a daily basis. Reforms have been made in difficult economic times during which the funding for our forces has been cut, and I believe that some of the innovation that we have seen would not have been possible had it not been for those difficult times. I recently had the privilege of visiting Hampshire, where I met the police and crime commissioner, the chief constable, and many of the officers who are doing such a fantastic job in the county. I was amazed to discover that what I, an ex-fireman, had assumed was a fire station was actually a joint fire and police station, something that I had not seen before. The two forces had come together to share their facilities and keep their costs down. I went to the police building at the bottom of the old-fashioned drill yard—as a former fireman, I still call it that—and met members of the armed response unit and officers who were based at the fire station as part of Hampshire’s police authority. Sir George Young (North West Hampshire) (Con) - Hansard - Copy Link - - Excerpts I entirely agree with what my right hon. Friend is saying about the Hampshire police force, which is one of the most efficient forces in the country, but which receives one of the lowest per capita grants. Will he ensure, as he reviews the formula, that authorities such as Hampshire are not penalised for being efficient? Mike Penning - Hansard - Copy Link - - Excerpts My right hon. Friend has raised an important point, which I discussed in depth with the chief constable and the PCC, Simon Hayes, during my visit. The 2016-17 formula is under review. As I would expect, a great deal of discussion and negotiation is taking place, involving chief constables, Members of Parliament and PCCs around the country who are all trying to make their case. I emphasise that they should be sure to submit their views to the consultation so that we can examine carefully the way in which the original formula was drawn up. I am determined that the new formula should not merely tweak the old one, and should represent the type of policing that we need in England and Wales today. I wish not merely to echo what has been said by my right hon. Friend, but to pay tribute to the front-line officers in Hampshire, and to the bravery of one of them in particular. A uniformed female sergeant whom I met had been beaten so severely that she had become unconscious, after about the third time that her head was banged on the kerb. We know that her head hit the kerb about six more times, because the body-worn camera that has been piloted so brilliantly in Hampshire provided the evidence, and the person responsible then got the conviction that that person deserved. It was a real pleasure to see that brave officer back in uniform and back on the front line. Sarah Newton (Truro and Falmouth) (Con) - Hansard - Copy Link - - Excerpts Police officers in Devon and Cornwall are doing a great job with fewer resources, and I am very pleased to hear about the review of the funding formula. Can my right hon. Friend assure me about the costs of policing tourism and students? We are very pleased to have universities in my constituency, but of course they bring policing costs. Will those extra costs be borne in mind in the review of the funding formula? Mike Penning - Hansard - Copy Link - - Excerpts I completely agree with my hon. Friend, and I know lots of colleagues from across the House will be standing up today and asking whether, as part of the review, there could be extra money for their constituencies. I fully understand that, but I also need the House to understand that policing in many parts of the country has fundamentally changed over the years. The demands and needs are now completely different from before, particularly in rural forces. As I suggested in response to the intervention from my right hon. Friend the Member for North West Hampshire (Sir George Young), we must put the arguments together into the consultation, which will be taking place across the summer, so that, although I am not sure everybody will be happy, the 2016-17 formula will be much fairer than the current system. Dr Julian Lewis (New Forest East) (Con) - Hansard - Copy Link - - Excerpts It is encouraging that the review of the formula will bear in mind the need to ensure that more efficient police forces, such as those in Hampshire, are not penalised for their efficiency. What does my right hon. Friend think about the recent survey carried out in Hampshire which showed that more than 70% of respondents would be willing to pay more and see an increase in the council tax precept to 1.99% because they value the services they get from the constabulary? Mike Penning - Hansard - Copy Link - - Excerpts When we introduced PCCs, who are elected by the local people, we gave them the ability to make local decisions. Where PCCs have decided to raise the precept to a level below the need for a referendum, I fully understand and respect that. There is at least one force area at the moment—Bedfordshire—where the PCC is looking to go beyond that, so there will be a referendum there. If it goes ahead, it will be held on the general election date. I do not want to talk only about Hampshire—although a couple of colleagues from Hampshire have intervened so far, and it was a pleasure to be in Hampshire only the other day—as I want now to touch a little more on the changes that have been taking place within the police in England and Wales. Mr Stewart Jackson (Peterborough) (Con) - Hansard - Copy Link - - Excerpts I would like to pay tribute to Cambridgeshire constabulary, which has seen a drop of 21% in recorded crime in the last five years. Will my right hon. Friend look in his ongoing review of funding at the impact of demographic change on policing? He will know that Operation Pheasant, which was tackling illegal gangmasters in the fens in northern Cambridgeshire, was a great success story, but that costs money so will he bear in mind the need for good funding streams for local police forces to deal with these demographic and population issues? Mike Penning - Hansard - Copy Link - - Excerpts Cambridgeshire is also doing a fantastic job under the Conservative PCC, who I had the pleasure of knowing before he was PCC. So that I am not being too party political, may I say that fantastic jobs are being done around the country by PCCs of all political persuasions, including independents? They are not shy in coming to my door and explaining their areas’ needs. As PCCs go forward and we see the elections for them in 2016, I think we will see not only an uptake in the number of people voting for them, but that being in touch with the local community is vitally important. Collaboration has not in the past exactly been top of the agenda with the police forces around England and Wales; it was talked about a lot, but not much came to fruition. However, it is where some of the recent savings have come from. Communities want to see their local bobbies, and see their local constabulary badge on them, but that is only a tiny proportion of what goes on in England and Wales police forces. That is what the public care about most, but we must make sure they are also aware of the work that goes on elsewhere. Collaboration is vital as we continue to look at making savings, with boundaries and silos having been broken down not only, as we have seen in Hampshire, with other local government agencies, but across borders and across the country. To get the benefits of collaboration does not mean it necessarily has to be between neighbouring forces. Mark Reckless (Rochester and Strood) (UKIP) - Hansard - Copy Link - - Excerpts The Minister just said that visible public-facing policing constitutes only a tiny proportion of what the police do. Does he think that proportion is too low and should be increased? Mike Penning - Hansard - Copy Link - - Excerpts No, what I was saying was that there is also a lot of ongoing work behind the scenes—whether in counter-terrorism, the serious organised crime agencies and the National Crime Agency, or the backroom staff, such as in administering the out-of-court disposals we have in this country now—to allow those officers to be on the front line and us to feel safe in our homes. I was saying that that work is just as vital, but that does not mean that the brilliant and vital and brave work our officers do on a day-to-day basis is unimportant—far from it. As I have said before, I have never said police forces should not have as many people on the front line as possible, but that is also very much a local decision; it is for the chief constable and the PCC to decide how they want to disperse their officers under their powers. Andrew Gwynne (Denton and Reddish) (Lab) - Hansard - Copy Link - - Excerpts On the issue of co-operation and collaboration, I am very much with the right hon. Gentleman. As he will know, in yesterday’s Home Office questions I asked about the waste of police time whereby police in Stockport are having to parade on in central Stockport and move out to places like Reddish, wasting time in getting on to the beat. May I commend to him the other part of my constituency: Labour-controlled Tameside council, which has co-operated with Greater Manchester police so that Denton police post is now located in Denton town hall allowing Denton police officers to parade on in Denton? Mike Penning - Hansard - Copy Link - - Excerpts I welcome what is going on in the hon. Gentleman’s local authority, and it is exactly the same as what is happening in my local council, where the police front-line desk is coming into the local authority new forum building, freeing up space for things to be moved into a more cost-effective space where a better police station is going to be built. I therefore pay tribute to what is going on in his constituency and with his local authority, and I pay tribute to what is going on in mine, too. I would say, however, that this collaboration is all relatively new, and is happening somewhat sporadically around the country. The collaboration I was referring to before I took the intervention of the hon. Member for Rochester and Strood (Mark Reckless) is between forces. I am truly amazed that historically—and I still hear this quite a lot—forces would say, “We’re doing collaboration with the force directly next to us,” perhaps on human resources or IT. Well, that is great, as long as we are getting the most bang for our buck, because we are talking about taxpayers’ money, but Cheshire is, I believe, doing HR for Nottinghamshire, which is not exactly right next door, and is doing procurement and other things, and getting better value from these schemes. I have therefore been encouraging, and pushing for more joined-up procurement to make sure we get value for the taxpayer, while at the same time leaving that local decision to the PCCs. One PCC said to me, “I want to buy my officers’ white shirts locally.” I said, “I can perfectly understand that, as long as you’re getting value for money.” That is the crucial point. This is not about taking away localism from the PCCs and the chief constables: yes, there should be such localism, but they are spending taxpayers’ money and they must get value for money. I think that view is shared across the House, and I noted that the shadow Home Secretary was talking this morning about getting value for money. We know that the public trust localism more than they trust us in this House, and we should trust them to do what we need for us as we go forward. The other change coming through that will also save money, time and effort within the criminal justice system is technology. I remember about four and a half years ago in the Conservative manifesto we had a commitment to bring forward roadside drug testing where the police felt that the driver was impaired. If they breathalysed a person who then passed the test and the officers still felt they were impaired, it was very difficult if they had not done the impairment course to arrest at roadside so the driver could be tested for drugs. As an ex-fireman I thought that was very important because on many occasions I had been to what used to be called RTAs—road traffic accidents are now road traffic collisions—and are now called RTCs—when I could smell the cannabis smoke still in the vehicle. The officers could smell that, but did not have the powers to do what they needed to do. They now have those powers, which have been approved. On 2 March officers will have the powers given to them by this House to arrest at the roadside based on a saliva test, which initially will be for two drugs. I have seen the type-approvals coming through from the manufacturers, and the tests will be for not only illegal drugs, but synthetic drugs—often called legal highs, but actually completely different—and prescribed drugs. There are many prescribed drugs that people should not take while driving. We need to work with the Department of Health to ensure that we give more details on the prescription: if it warns against driving heavy plant or operating heavy machinery, it actually means a motor vehicle in many cases. Steve McCabe (Birmingham, Selly Oak) (Lab) - Hansard - Copy Link - - Excerpts I agree with the Minister’s central point, but if someone who is driving has taken prescribed drugs and has not been advised of the risk, is it the Government’s intention for that person to be treated in the same way as someone who is caught driving having taken illegal drugs? Mike Penning - Hansard - Copy Link - - Excerpts Being impaired when driving a motor vehicle is just that. When the legislation was taken through the House, that argument was put forward, but it is the responsibility of drivers who are driving a vehicle on the road to know what is in their bloodstream. This is a very important area, which is why I alluded to the need to ensure that the advice from the pharmacist when the drugs are given out is not confined to advising whether to take them after or before a meal, or not to operate heavy machinery. The hon. Gentleman is right, but it will always be the responsibility of people driving a vehicle to know what is in their bloodstream and whether it will impair them. The level has been set by a scientific committee, so this is not about people who take one co-codamol that morning being over the limit; it is about ensuring that we have the necessary technology. Technology is moving fast and we expect another manufacturer to have type-approval on a roadside saliva test in the next few months. We expect to ensure that we keep officers on the streets as much as possible, because the time involved in implementing the existing scheme means that they are tied up for too long. We also expect the technology to come through soon so that we have a roadside evidential base for drink-driving. At the moment our legislation is based back in the 1960s, when the breathalyser bag provided the base, then we could arrest and the machinery was in the station. If we can get an evidential base at the roadside, that will eliminate a whole swath of the bureaucracy that we have to go through to ensure that we get the necessary conviction of impaired drivers. Such drivers cause death, dismay and injury on our roads every day. We should not in any way be lightening the pressure on drink-drivers as we work on drug-drivers. The most obvious piece of technology that will free up officers’ time is body-worn cameras. They are freeing up time, protecting officers and giving us an evidence base. We have already seen, in the brilliant work in Hampshire, Kent and other forces, that when the evidence is put to the accused, they almost immediately say—on advice from their solicitors, usually—that they will plead guilty. The amount of assaults on officers is down. When officers arrive somewhere on a Friday night obviously wearing cameras, the dispersal is interesting to watch, as I have seen myself from the videos. We need to take things further. We need to ensure that the body-worn camera cannot be ripped easily from the body armour—some of the early cameras could be because they were on a clip system—and we are looking into that in my own force in Hertfordshire. We also need to ensure that the evidence that the camera is capturing cannot be tampered with. In other words, someone might rip the camera off and dispose of it, so we need to stream away the evidence from the scene. At the same time I am working closely with the Crown Prosecution Service and the rest of the criminal justice system to ensure that the technology flows through the system. When officers store the evidence, whether in the cloud or a secure system, the CPS should be able to enter that system and see the evidence without having to wait for it to be downloaded or burnt on to a CD-ROM. I have also been asked whether Kent could trial statements being taken on camera, so we would not need to have them transcribed. That could be exciting, because it could put officers on to the streets for much longer, so that they did not have to sit in the stations transcribing something picked up on the body-worn camera. Such developments are world-leading. Police forces from around the world are coming to see us to see how we are using the technology. Only the other day, at a two-day international crime and policing conference in London, leading academics and other criminal justice professionals from around the world came to see how we had managed to lower not only crime, but the costs of it—in other words, how we were getting more bang for our buck—and to see the technology. Australia, for example, has had roadside drug testing for many years, but the Australian police need to take a 44-tonne articulated lorry to the roadside in order to test everyone passing through, which has huge cost implications. They are very interested in the technology that we have type-approved and are introducing. We are still in difficult economic times. Money to the police has been cut, which was a difficult decision to make. Police forces around the country have predominantly done well at dealing with the cut. Most of them have budgeted for 2015-16 and the review for 2016-17 is still taking place—consultation continues to work—and I suggest that all colleagues, whether in the Chamber or not, work with their local police to see how best that consultation can be used for the benefit of their constituents. John McDonnell (Hayes and Harlington) (Lab) - Hansard - Copy Link - - Excerpts I want to make several points. The Minister congratulated the police on the reduction in crime overall, and I concur with that, but a real issue remains. For example, in London and in my constituency in particular, the safer neighbourhood teams were introduced and were extremely popular and successful, but they are now being penalised as a result of their success. The teams reduce crime, but then lose resources, which are shifted elsewhere, and crime increases; we go around in circles time and time again. It is important that discussions on the new formula result in a new settlement that will reward those forces that are successfully operating to reduce crime, giving them consistency of funding over time. The undermining of the safer neighbourhood teams is deeply unpopular in my constituency. Mike Penning - Hansard - Copy Link - - Excerpts Recently, I had long discussions with the Metropolitan Police Commissioner on that very subject. Only the other day I was at Hendon, sadly the day before the passing-out parade before the commissioner of about 400 new officers. I understand that by March the Metropolitan police will be just under the 32,000 level; it will then recruit at 175 per month, which will reflect the steady level of natural wastage in London. That is a remarkable feat achieved by the Mayor of London for the people of London. I accept that in the old days the Policing Minister would look at things in exactly the way the hon. Gentleman suggests, but it is now a matter for the commissioner and for the Mayor. Such matters would also be for the mayor and commissioner in Manchester, if it is successful in its bid to proceed with the mayoral system, which will include the police. Key to everything is that we have managed remarkably well to reduce crime, as the hon. Gentleman said, and at the same time to reduce the cost of policing. The public’s opinion of our police in general has never been better. I always say, “Yes, I have the honour of being the police Minister for the best police force in the world.” Some police officers let us down, but they are a tiny minority and we should be proud of every single one of our officers, who represent us every single day of the year. 14:08 Jack Dromey (Birmingham, Erdington) (Lab) - Hansard - Copy Link - - Excerpts Five years ago, not one single Conservative candidate went to the electorate and said, “Vote for me and we will cut the police.” Not one single Liberal Democrat candidate went to the electorate and said, “Vote for me and we will cut the police.” On the contrary, Liberal Democrats up and down the country said, “Vote for us and we will put 3,000 more police officers on the beat.” In addition, the Prime Minister himself pledged to protect the front line. When it comes to writing the history of great broken political promises of our time, what has happened to the police service will rank alongside the commitments from the Prime Minister that there should be no more top-down reorganisations of the national health service and from the Deputy Prime Minister that there would not be an increase in tuition fees. Instead, we have seen the biggest cuts to our police service of any in Europe. Mr Stewart Jackson - Hansard - Copy Link - - Excerpts On election manifestos and hyperbole, does the hon. Gentleman recall that his party told the electorate prior to the 2010 general election that any reconfiguration, any sharing of services, any co-operation between services would inevitably result in a massive hike in crime? In fact, the opposite has happened. Jack Dromey - Hansard - Copy Link - - Excerpts The short answer is no, the reverse is the case; my right hon. Friend the Member for Delyn (Mr Hanson), as Policing Minister, encouraged such things. When the hon. Gentleman went to his electorate, did he say, “Vote for me and 117 police officers will be cut”? That is what has happened to his local police service. The Minister spoke about inheritance, and there was an inheritance on the police, because a Labour Government put 17,000 extra police officers and 16,000 police community support officers on the beat. Local policing, local roots with local people having a say proved to be both popular and highly effective. Andrew Gwynne - Hansard - Copy Link - - Excerpts My hon. Friend is absolutely right to say that neighbourhood policing was a success story of the last Labour Government. May I draw his attention to the work of the Poet’s Corner residents association in north Reddish, ably led by Brenda Bates who is really concerned about the lack of response by the PCSOs now that they have to parade in Stockport? For example, they used to do school gate work but they are now unable to get to the school gates in time for when children are dropped off because they are too busy parading in the town centre, several miles away. Jack Dromey - Hansard - Copy Link - - Excerpts Unlike what we heard from the Minister, my hon. Friend speaks from the heart about the reality in his locality, and it is unsurprising, given that the police service that covers the constituency he so ably represents has seen more than 1,300 police officers go, with more to follow at the next stages. There was a good inheritance on the police, but a generation of progress made—the formation of that British model of neighbourhood policing—is now being reversed. I wish to make one other point about what the Minister said. He paid tribute to our police service and discussed remarkable innovation, which I have seen all over the country. Let me give but one example. Essex police, under its excellent chief constable, Stephen Kavanagh, has developed a groundbreaking system that tracks both the perpetrators and potential perpetrators of domestic violence, and the victims and potential victims of domestic violence, and enables the police to drill all the way down to hot spots of domestic violence to inform other interventions. We see such innovation by our police all over the country. But the Minister, who was previously a firefighter, will know from his experience that the police service in England and Wales is a demoralised one. It is demoralised by the scale of what is happening to the service and by the remorselessly negative tone set by the Government, from the Home Secretary downwards. Mike Penning - Hansard - Copy Link - - Excerpts rose — Jack Dromey - Hansard - Copy Link - - Excerpts I will gladly give way, but will the Minister confirm that every index, be it sick, stress or anxiety leave, is shooting up because of the combination of the growing pressures on the police service and the fact that the police feel—people tell me this all over the country—that the Government never have a good word to say about them? Mike Penning - Hansard - Copy Link - - Excerpts If the hon. Gentleman has ever heard me run down the police in this country or destroy their morale, he should stand up and say so now, because I have never done that. The police force’s morale is being destroyed by the sort of commentary we have just heard from the Opposition Dispatch Box, but he is better than that. The first thing he should have done was congratulate the police, but he went into a political rant. That is what destroys morale in our police force. Jack Dromey - Hansard - Copy Link - - Excerpts Over the past 12 months, I have visited 34 of the 43 police services, and there is without doubt an unprecedented collapse of morale, from the chief constables to the police constables and PCSOs, because of that combination of the mounting pressures on the police service and the negative tone set by our Government. We believe that a different approach and a fresh start are essential. Today’s vote on policing is a choice between a Tory plan to cut 1,000 more police officers next year and a Labour plan of reform and savings to protect the front line, so that chief constables can prevent those 1,000 police officer posts from being cut. The Home Secretary should be straining every sinew to protect the front line, but she is not. The Home Secretary and the Tories, and their human shield, the Liberal Democrats, just do not get what pressure the public services and the police are under, and they are turning their backs on obvious savings that could keep those much needed police on our streets. The Home Secretary has said that it does not matter that thousands more police officers are set to go, on top of the 16,000 already lost, reversing a generation of progress under the previous Labour Government; she says that under her plans all is well because crime is falling. The truth is that crime is changing, pressures on the police are going up, and this is the worst possible time to inflict the biggest cuts on the police service of any country in Europe, just when the police are facing mounting and serious demands. Over the past 20 years, volume crime, as it is often called, has indeed been falling. Cars are more difficult to steal than they once were, because crime has been substantially designed out, and homes are more difficult to burgle than they once were. That has been a worldwide trend over the past 20 years, because of a combination of advances of the kind I have described and the success of neighbourhood policing, with its emphasis on prevention. But the figures are clear: police recorded violent crime is increasing, and online crime has shot through the roof. For example, Financial Fraud Action UK has said that online banking crime has increased by 71%, e-commerce crime has increased by 23% and card crime has increased by 15%. We have also seen the mounting terrorist threat posing an ever more serious challenge to our police service, and just this weekend assistant commissioner Mark Rowley, the national anti-terror lead, warned that he needs more resources to respond. At the same time, the police are struggling to deal with crimes that are ever more complex in terms of what it takes to investigate them properly. Hate crime, one of the most hateful of crimes, is up. I have seen this at first hand in my constituency. A fine woman was out with her disabled son, who was in a motorised wheelchair, when he had stones thrown at him because of a whispering campaign about how anyone who has a car or Motability vehicle on benefits somehow has to be a scrounger. I sometimes think that Ministers should be ashamed of the tone they set, because of what it leads to in communities all over the country. Hate crime is up. Reports of rape and domestic violence are up, yet the number of prosecutions and convictions is down. Reports of child sexual abuse have increased by 33%, but referrals to the CPS from the police have decreased by 11%. There are serious delays in investigating online child abuse. That means that victims are finding it much harder to get justice and more criminals and abusers are walking away scot-free. After the exposés of the past two years, there is now a great national will to tackle the obscenity of child sex exploitation and abuse, both historical and current. But, because of the mounting pressures on the police, there are serious question marks over the effectiveness of their response. The National Crime Agency, for example, has, thus far, failed to bring to account those identified under Operation Notarise. Some 20,000 people were found to be accessing child pornography, thousands of whom will be contact abusers of children, but only 700 have faced any action. Police services in Lincolnshire and all over the country say that such are the pressures on their resources that they will find it difficult to do anything other than cope with current cases, and that they will not be able to look into historical cases of abuse and exploitation. I have seen the effect of those mounting pressures in my own police service in the west midlands, where 10% and rising of police resources are now dedicated to doing nothing else but dealing with child sex exploitation and abuse. Even in basic responsibilities, such as road safety, the police are being over-stretched. The number of traffic police on our roads has fallen by 23%. The number of driving offence penalties has fallen substantially while the number of fatalities and casualties has gone up—the number of child fatalities and casualties has gone up by 6%. Neighbourhood policing is being badly undermined. Mark Reckless - Hansard - Copy Link - - Excerpts Does the hon. Gentleman recall how the Government used to stress the need to protect the front line and to put the emphasis on visible policing? But just now, the Minister said that that accounted for only a tiny proportion of activity and he seemed very happy with that and had no desire to increase it. Jack Dromey - Hansard - Copy Link - - Excerpts The hon. Gentleman is right to be concerned, because his police service has lost 604 members of staff since 2010. It is certainly true that policing is complex and requires investigatory teams, not all of which will be on the front line. None the less, front-line policing is essential. We created neighbourhood policing, and it worked; we saw substantial falls in traditional forms of crime and it was popular with the public. It is about not just detecting crime, but working with communities to prevent crime and to divert people from crime. Lord Stevens rightly said that neighbourhood policing is the bedrock of policing, but under this Government it is now being hollowed out. Many forces all over the country are taking officers off the neighbourhood beat, putting them back into cars and forcing them to deal with only emergency response. They are now off the front line and into response, when they should be building community partnerships and intelligence and preventing crime. Mr Jim Cunningham (Coventry South) (Lab) - Hansard - Copy Link - - Excerpts Given the rise in the number of racial and anti-Semitic attacks, is not community policing important because it brings people closer to understanding different communities? Jack Dromey - Hansard - Copy Link - - Excerpts I agree with my hon. Friend, and I will come to that in just a moment. Neighbourhood policing, which took a generation to build, is now being systematically undermined, and the consequences of that are increasingly serious. Let me give two examples. My first relates to terrorism. It was said by a former Member of this House that neighbourhood policing was the “fluffy end” of policing. That could not be further from the truth, especially when we consider how we now have to rise to the challenge of terrorism. Two weeks ago, Peter Clark, a former head of counter terrorism, said: “In the past decade the UK has built a counterterrorist structure that is in many ways the envy of the world. The almost seamless link between local, national and international units is remarkable. Instead of a London-centric force descending on communities, there are regional hubs where community police and counterterrorist officers work together. They understand their local communities, pick up vital intelligence and reassure the public.” He went on to say: “Neighbourhood police hold one end of the thread that can take us from Britain’s streets to wherever in the world terrorists are trained, equipped and radicalised. The chief constable of Merseyside has warned that if police numbers continue to fall, ‘neighbourhood policing as people understand it will not be possible’. Chief constables and police and crime commissioners have tough choices ahead in deciding what to cut. Cutting the counterterrorist policing thread could be fraught with danger.” I know that that is an uncomfortable message for Government Members, but let me give them an example from the west midlands. Some 40 people have been brought before the courts for serious terrorist crimes in the past five years, and there have been 31 convictions. Overwhelmingly, those individuals were identified as a consequence of good neighbourhood policing and the patient building of good community relationships. The community co-operated to identify the wrongdoers, so neighbourhood policing is key to combating the mounting threat of terrorism. What the Home Secretary now wants is a similar scale of cuts all over again, with the Association of Chief Police Officers warning that at least 16,000 more officers will go. Next year, police forces are expecting to cut more than 1,000 officers, and that is what today’s vote is all about. Labour would take an alternative approach. Yes, budgets will be tight, and we have already said that the 2015-16 budget the Government have set will have to be our starting point, because the Chancellor’s failure to secure strong growth in this Parliament means that more still needs to be done to get the deficit down. His long-term economic plan has certainly boosted borrowing. We have had to borrow £200 billion more than he planned back in 2010, putting additional pressures on budgets, including that of the Home Office. But there are alternative ways to make savings— [ Interruption .] Mike Penning - Hansard - Copy Link - - Excerpts The hon. Gentleman, who is a bit of a friend of mine, is actually reading out, word for word, the article that the shadow Home Secretary put in the press this morning. He is better than that. He should be talking about the debate today and not doing the lackey’s job for the shadow Home Secretary. Jack Dromey - Hansard - Copy Link - - Excerpts The Minister may be surprised to hear that the Labour party is united in defence of our police service. That is in contrast to what we see all over the country, which is Government Members, including the hon. Member for South Dorset (Richard Drax), expressing growing concerns over what is happening to the police service. [ Interruption. ] Members will hear my speech. Now, there are alternative ways to make those savings— [Interruption.] Madam Deputy Speaker (Mrs Eleanor Laing) - Hansard - Copy Link - - Excerpts Order. The House well appreciates that a little bit of banter is in order, but continuing banter from a sedentary position is not in order. Jack Dromey - Hansard - Copy Link - - Excerpts Thank you, Madam Deputy Speaker. I appreciate that this is an uncomfortable message for a Government who have been oblivious to the consequences of their actions. There are alternative ways to make smart savings, and that is what we will do. We will require forces to sign up to national procurement, and that would save— Mike Penning - Hansard - Copy Link - - Excerpts £100 million. Jack Dromey - Hansard - Copy Link - - Excerpts Is the Minister aware that the Association of Police and Crime Commissioners has brought forward a proposal on ICT savings alone that would save £400 million, so £100 million is a conservative estimate—please forgive the bad pun. The Home Secretary has simply refused to go down that path and instead has promoted the view that 43 forces can be trusted to do their own thing with 43 police and crime commissioners arguing over contracts of the kind that make nonsense of any sensible approach towards procurement. That is not what we would see in the best of the private sector or, indeed, in the public sector elsewhere. The Government have failed to drive a strategic approach towards procurement, which has been heavily criticised by the National Audit Office, Her Majesty’s inspectorate of constabulary and, increasingly, police officers across the country. Let me move on to the next saving that we will make and ask the Minister a question—perhaps he will want to get up to defend this. Why should the police have to continue to subsidise gun licences? The Minister is not a member of the Chipping Norton shooting set, but perhaps he could justify to the House why it costs £50 for a gun licence and £72 for a salmon and trout licence—£22 more—when it typically costs the police £200 to process each application for a gun licence. Had the Government done the sensible thing and said that they would have full cost recovery, which is what the Association of Chief Police Officers has called for, there would have been substantial savings of £20 million, but that was vetoed by the Prime Minister who, as a fully paid-up member of the Chipping Norton shooting set, declined to do the best and most obvious thing. Would the Minister care to justify that? Mike Penning - Hansard - Copy Link - - Excerpts What is the shadow Minister trying to say to anyone who has a shotgun licence and happens to be working class, like me? I do not have a shotgun licence, but I do shoot clay occasionally at my local shooting club and I enjoy that very much. For many people who are not from an affluent set and who did not go to public school, like those on the shadow Front Bench and on the Government Front Bench, this is an important part of their social life. People do not have to be part of the Chipping Norton set to have a shotgun licence; they just need to enjoy clay shooting or something like that. Jack Dromey - Hansard - Copy Link - - Excerpts Under this Government, proposals have been made in the Home Office to move on this matter but they have been vetoed by the Prime Minister. Why should the taxpayer subsidise gun licences? Why should the police service subsidise gun licences when we need to find ways to keep police officers on the front line? Does the Minister choose to come back to me on that point? Mike Penning - Hansard - Copy Link - - Excerpts All I would say is that there is selective memory loss of 13 years of a Labour Government. Did the Labour Government do anything about this during their last term? No, they did not. Jack Dromey - Hansard - Copy Link - - Excerpts I think that the public listening to the debate will find it incredible that the Policing Minister can get up and say that despite the fact that the police have been calling for movement on this for years the police should continue to subsidise gun licences rather than that money going into our police service. We have made a number of other proposals, such as the £9 million from driver offending retraining courses, and we have also proposed not to proceed with the police and crime commissioner elections in 2016. All those things could be done and they could be done now. If they were, those 1,000 police officers who face being cut would not go. At a time when the overall police budget is being squeezed, sensible action on four fronts, as outlined in our proposals today, would mean that the 1,000 police officers who will otherwise go will remain in the police service and on the front line. The Home Secretary could do all these things now, but she has refused. Without those policies in place, we will not support the Government’s proposal today. That is why we will vote against the Home Secretary’s plans and why we will challenge Conservative and Liberal Democrat candidates throughout the country on why they are voting to cut hundreds more police officers from their local force next year. The Government are turning their backs on neighbourhood policing. The impact on our police service is ever more serious. The Government are taking us back to the 1930s. A Labour Government would not allow this to happen. We face unprecedented challenges as crime changes—from terrorism through banking and online fraud to the emerging child abuse and exploitation cases—and we must rise to them. We want to rebuild the neighbourhood policing that helped to cut local crime and helped our citizens to remain safe. We want to rise to those new challenges, which is why we have set out sensible reforms that better protect the front line, and stand up for communities that depend on public services. The first duty of any Government is the safety and security of their citizens where they live and work. Unlike the Government, we will not fail the public we serve. 14:35 Richard Drax (South Dorset) (Con) - Hansard - Copy Link - - Excerpts I pay tribute to the chief constable of Dorset, Debbie Simpson, and our police and crime commissioner, Martyn Underhill, both of whom do a superb job, and to the 1,200 officers and 156 PCSOs who serve in difficult conditions and extreme circumstances, often under threat of their lives. We owe them a huge debt of gratitude and our thanks. I will not speak for long, but I first want quickly to touch on the comments made by the shadow Minister, whom I respect. Part of his speech was dripping with the old envy, almost hatred, which I thought was sad in such a serious debate. Yes, I am here to stand up for my police force and I will probably say things that are unpalatable to the Government, but I hope I shall say them in a balanced way, based on the evidence and the fact that I have worked closely over the past five years with the Dorset police force. In part, I shall speak personally about what I have seen and heard. Dorset police force has had an appalling history and has been at the bottom of the funding ladder for years. I know that the Minister is aware of that; I have spoken to him about it and he has listened intently on many occasions. We are now in the bottom quartile, so the situation has not improved that much. Even now, further savings will inevitably put pressure on the work that the police do. The funding takes into account the Home Office, the Department for Communities and Local Government and council tax legacy, and in 2014-15 it was £69.42 million. In 2015-16, it will drop to £66.82 million, a loss of about £2.6 million, which crudely equates to 75 police officers. Interestingly, Her Majesty’s inspectorate of constabulary shows in its value-for-money profile that Dorset police force is already one of the leanest forces in the land, due to the fact that over many years it was one of the first to implement the changes to meet the savings requirements that were coming in. I give credit to Martin Baker, Debbie Simpson’s predecessor, for implementing those changes, not least in the backroom areas, which have now been hugely civilianised. In addition, when we consider the ratio of council tax to central Government funding, we see that Dorset taxpayers are already paying a disproportionate amount of tax in comparison with other parts of the country However, Dorset police force is not a force that sits on its butt and whinges. Far from it: it faces the challenge—and is facing this challenge—as best it can. As the Minister knows—we have spoken about this on several occasions—Dorset police are forming a strategic alliance with Devon and Cornwall police. For example, they are now looking to merge their firearms teams and considering how best to collaborate further across the whole south-west. Based on what Dorset police know and the figures that we have been given, the projection for 2016-17 could be extremely serious. According to the PCC’s office, between £3 million and £5 million is needed for the force to stand still, but that is referendum territory. If year-on-year savings of 6% are implemented, as predicted, Dorset could see the number of police officers drop by 500, which is what it takes to police Bournemouth. I am not suggesting, of course, that Bournemouth will have no police force; I mention that just to give an idea of the scale if year-on-year savings of 6% continue. I hope that more money will become available as the economy recovers. I point out to the Opposition that when we inherited the financial mess, we faced a huge problem, and this country still does so. I pay tribute to the Policing Minister for doing all he can within a very tight remit to safeguard front-line services. I know that he, as a former firefighter and Grenadier Guard—I forgive him for that—has done all he can, along with his team, to protect the police front line. However, this country must learn to live within her means, because parties of all colours have overspent for years. We must now face the unpalatable truth that we have to live within a very tight budget and learn to do things differently. Sarah Newton - Hansard - Copy Link - - Excerpts I am very pleased that Devon and Cornwall police are working so well with the Dorset constabulary. My hon. Friend’s constituency is not dissimilar to those in Cornwall, so does he, like me, draw comfort from the remarks made today about a revised funding formula, which might help us get fairer funding in our part of the world? Richard Drax - Hansard - Copy Link - - Excerpts My hon. Friend pre-empts my speech, as I intend to end my remarks on future funding. The Policing Minister and I have spoken about that, as has our PCC—he is on the Minister’s board, which is excellent news. I seek reassurance from the Minister that year-on-year savings of 6% are not on the cards, for the reasons I have already expressed. As far as the PCC’s office is concerned, such savings would have an effect on community policing, on PCSOs and on the very nature of policing as we know it currently. That would be inevitable because the resources would be fewer and would have to be targeted in a very different way. Crime is falling, and for that I pay tribute once again to the Government and to our police officers, those brave men and women who are out there doing their best to reduce crime, and obviously succeeding. However, the nature of crime is changing. I have been told that Dorset police are now dealing far more with cybercrime, forced marriage, slavery, domestic abuse and child sexual exploitation— [ Interruption. ] The Minister jests from a sedentary position that it is all happening in Dorset, but Dorset is not the sleepy backwater that perhaps he thinks it is. Those sorts of crimes cost 25% more to investigate than old-style crimes. As the Minister has said, the number of burglaries has dropped, but one of my constituents recently lost £93,000 in a telephone scam. Someone pretending to be a policeman got him to move that sum from his bank account to another, and for reasons that I will not go into now he lost the lot. An investigation is now taking place. I imagine that the criminals are thoroughly well organised and probably have their fingers right across the cyber network, so it will take an awful lot of police time and effort to bring them to court. We in this place are making it clear, as of course are the police, that those sorts of crimes must be reported. Following the ghastly revelations in Rotherham and elsewhere, it is clear that it has never been more important for people to come forward and tell the police what is going on. I will end my remarks by talking about the funding formula. I have lobbied the Policing Minister hard on that on many occasions, and I know that he has listened to Martyn Underhill, our PCC. I am most grateful that Mr Underhill will be sitting on the Minister’s board when the funding formula is reviewed in the summer. I note that tourism, which of course affects Dorset and many other beautiful counties, including Cornwall, is not taken into account. I know that the Minister knows that, but with budgets tightening and savings having to be made, those sorts of considerations must be taken into account so that Dorset police and other forces in rural areas that attract vast numbers of visitors can continue to police their counties. Finally, the Minister and others talk about innovation. I have seen huge innovation in Dorset, not least the increased co-operation with other forces in the south-west. However, I suggest that rather than allowing police forces to go off on their own to try to find the best way forward, a more cohesive approach— Mike Penning - Hansard - Copy Link - - Excerpts My hon. Friend makes a really important point. They are not going off on their own. The Home Office testing laboratories, the Crown Prosecution Service and the Ministry of Justice, which I have the honour of working in, are working together on type approvals. We pilot them in certain areas so that we can then roll out best practice in other parts of the country. That is the best way to get the biggest bang for our buck, and I will make sure that we get it right. That is exactly what my hon. Friend is asking for. Richard Drax - Hansard - Copy Link - - Excerpts I am most grateful to the Minister, but perhaps I was talking about co-operation on a bigger scale. For example, Dorset police are now co-operating with Devon and Cornwall police, and there is also an area collaboration. Perhaps leadership is the wrong word to use. We need a more cohesive and co-ordinated approach between the Government and the police—if we are to go on facing these savings, and I quite understand why we will—rather than allowing individual county police forces to go off and experiment. We need a bigger debate on how to provide policing in this country so that we all move forward together in the most cost-effective way and, as the Minister said, get the best value for money. I will end my remarks by once again paying tribute to the brave men and women on our streets in Dorset. We are all totally indebted to those brave men and women who soldier on. I hope that in future we can take the politics—the bitterness and envy—out of debates on policing. Let us deal with the facts and then try to produce a police force in this country that does the job within the stretched resources that sadly we now face. 14:47 Steve McCabe (Birmingham, Selly Oak) (Lab) - Hansard - Copy Link - - Excerpts The Home Secretary told us yesterday that the measures she has taken to deal with bureaucracy have saved 4.5 million hours of police time. If I may say so, that is a classic volume measure; it would be fascinating to understand how her officials arrived at it. I wonder whether the Minister is familiar with the work of Professor John Seddon. In his book “The Whitehall Effect”, he describes the phenomenon of “failure demand”; how many cost-cutting initiatives, such as setting up single call centres and outsourcing back office activities, can lead to failure demand, a constant inability to recognise and respond to the real problem while encouraging a referral culture and repetition of largely useless actions. Those effects are rarely spotted by the consultants who advise on the changes, because they measure their work in terms of volume—the volume of calls made or answered within a specified time, and the estimated hours saved. Volume does not measure problems solved or the quality of engagement, but rising failure demand leads to decreasing police efficiency. Would the Minister care to look at that as he considers the measures that he is taking forward? As the Minister demonstrated earlier today, the Government are quick to tell us that crime is falling, and it is true that the most recent statistics show a continuing and welcome fall in many traditional crimes but, as we have heard, they also show a rise in violent crime, rape and sex offences, and an alarming and perhaps still under-recorded rise in fraud, identity crime and cybercrime. These serious crimes need to be tackled, and the changing face of crime needs to be considered. As the hon. Member for South Dorset (Richard Drax) told us, crime is changing, and when we look at the crime figures and contemplate police budgets, we need to bear in mind that crime is not a static phenomenon. Our police forces need to reconfigure some of their activities in order to respond to these new types of crime. That is much harder in an environment where the preoccupation is the constant search for cuts. As the largest force outside the Met, the responsibilities of the West Midlands force are enormous. I pay tribute to the amazing job that the force does, but I worry that it may be approaching the limits of what we can reasonably expect of it. It has seen £126 million cut from its budget over the past five years, with a further £100 million of cuts still to come if the Chancellor is able to make good his promise of another five years of austerity for vital public services. The west midlands is hit doubly hard because it has a very low council tax base and therefore a very low police precept—the second lowest in the country. That means that we are more reliant on central grant than some other areas, and consequently the policy of flat rates cuts has a disproportionate impact on us. For example, whereas central Government provide 86% of the West Midlands police budget, other areas are reliant on grant for only about 49%. John Healey (Wentworth and Dearne) (Lab) - Hansard - Copy Link - - Excerpts My hon. Friend is making a very interesting and important argument to the House. Does he accept that our position in south Yorkshire is similar to his in the west midlands, with exactly the same financial bind? Since 2010 the South Yorkshire police have faced cuts in excess of £30 million. In south Yorkshire, as in the west midlands, we are seeing the hollowing out of neighbourhood policing and the closure of local police stations such as Rawmarsh and Wath, and this is setting back a generation of progress over the previous decade. Steve McCabe - Hansard - Copy Link - - Excerpts Indeed. The effect of disproportionate cuts is that some areas, often areas with higher levels and different types of crime, are taking a much harder hit. As a result of what the Government are doing, we in the west midlands are losing about 22% of our funding, as opposed to about 12% in Surrey. Given that, as in my right hon. Friend’s area, we have higher crime rates and more complex policing needs, it is hard to see how anyone could regard that as fair or just. In the west midlands the position is made worse by the continued use of formula damping. If the west midlands was paid grant according to formula needs, we would receive a further £43 million. I recall attending a meeting with the then Policing Minister over three years ago—I think my hon. Friend the Member for Birmingham, Erdington (Jack Dromey) was also present—when the then Minister promised to take that factor into account. I know the Government are into re-announcements, but here we are, more than three years later, and the Minister tells us today that he is going to review the police formula. I think we have been here before. We want to know when we will see some action to address the unfairness. Of course, as the Minister was making that announcement, his hon. Friends were getting to their feet to say, “Don’t make any changes that will affect the situation that we are benefiting from.” Mike Penning - Hansard - Copy Link - - Excerpts To be fair, there is a cycle for reviews, as I am sure the hon. Gentleman knows. Changes to the review process were made under the previous Administration. They were not fundamental changes, merely tinkering, which is why we need such a fundamental review now, as the whole House would agree. Steve McCabe - Hansard - Copy Link - - Excerpts If the Minister’s fundamental review will give us some of the £43 million that we have been robbed of for the past few years, I welcome it. If we were just £10 million closer to our current entitlement in the west midlands, that would still mean that we were hit three times harder than any other force in the country. I hope that what the Minister is promising is good news, and I thank him for it. The current situation is not fair. The people of the west midlands are paying the price for protecting policing services in more prosperous low crime areas in other parts of the country. That is what the formula changes need to address. Not only do we have to contend with more crime, but we have to respond to terrorist threats and public order demands without additional funding, which is steadily eroding the police’s capacity to respond to more localised crime. The latest west midlands strategic policing requirement report to the policing and crime board, which the Minister is familiar with, states: “It has become increasingly challenging to maintain all local policing services during times of significant public order deployments…with the staffing reductions we have experienced in recent years…we are often compelled to delay non-emergency services beyond our normal service expectations.” The chief constable is attempting to manage all this demand with 300 fewer officers than he had this time last year. There has been a 23% reduction in the number of traffic police at a time when road deaths are on the increase, and there has been a 6% rise in child fatalities. Road accidents remain the largest single cause of child deaths in this country. I know that the Home Office cannot tell us how many hit-and-run incidents there are, or how many hit-and-run drivers are never caught and prosecuted, because it chooses not to collect those data, but I can tell the House that my constituent, young Phebe Hilliage, was knocked down while on her way to school by a hit-and-run driver who overtook and mowed her down on a pedestrian crossing. He shattered her foot and she may never walk properly again. I want to know, Phebe’s parents want to know and my constituents want to know that West Midlands police have the resources to track down that person and bring him to justice. Behind today’s announcement there is the reality of policing: fewer officers, squeezed budgets, unfair application of the existing grant formula, more consultants most likely feeding failure demand, new and changing forms of crime, terrorists and public order pressures, and victims such as Phebe who deserve justice. There is an awful lot more that the Government need to do before we can be satisfied that their approach to crime and policing is the right one. 14:59 Mike Kane (Wythenshawe and Sale East) (Lab) - Hansard - Copy Link - - Excerpts The Minister said that we have the greatest police force in the world, but the coalition has had a funny way of showing it, given the cuts made to the police up and down this land in the past five years. In a spirit of even-handedness, I also criticise my hon. Friend the Member for Birmingham, Erdington (Jack Dromey), who said that spending levels would be going back to those of the 1930s. I remind him of the famous Mancunian Robert Peel and the fact that there was no police force before the Metropolitan Police Act 1829—those are the levels we will be going back to. Our chief constable, Peter Fahy, and our police and crime commissioner, Tony Lloyd, have said that if policing cuts continue beyond 2017, Greater Manchester police will not be able to maintain its service to the public. That is a very serious accusation from two very senior people in the police force of this land. Cuts to GMP’s front-line services have been ongoing since the coalition Government came to power. GMP has lost 1,151 officers, with a further 226 expected to go this year alone. The service has already made considerable savings as it strives to deal with the £134 million hole in its budget this financial year, resulting in 1,000 fewer police staff posts and the loss of 1,138 police officers from our streets in Greater Manchester. Since 2010, the Government have slashed Greater Manchester’s police budget by a quarter, with an estimated £114 million of cuts still to come. This does not take into account the community fund, which in 2013 saw a further £6 million of cuts to GMP’s funding, to be redirected to London. In 2013, GMP had a further £6.4 million slashed from its budget to fund the Government’s own projects. That money, which could have paid for 145 police officers or 210 PCSOs, was clawed back by the Government to fund unpopular schemes such as the proposal to allow people to join the police service at a senior rank without ever having to walk the beat, and giving additional funding to the Independent Police Complaints Commission and to City of London police. At the beginning of 2014, the Chancellor announced that the Home Office budget, which includes policing, would be cut by another 6% in 2015-16. A 6% cut would see Greater Manchester police lose another £26.8 million—the equivalent of 1,200 student police officers. Most recently, the police and crime commissioner was asked to find £19 million to cut from GMP’s budget. This is on top of the £134 million that has already been taken from policing in the region, resulting, as I said, in the loss of 1,138 police officers. So much for the northern powerhouse and devolution in our great cities! Between 2010 and 2013, the service was losing on average 350 police officers each year as GMP struggled to cope with the ongoing programme of austerity. In order to meet the cuts required by central Government, GMP has undertaken a series of changes, including using office space that accommodates 1,100 admin and support staff in a building with space for just 500 desks. All employees can now work from home or in other GMP buildings. The closure and disposal of surplus estates has thus reduced operating costs by £3 million, with further year-on-year savings to come through associated reductions in business rates, energy and maintenance. GMP is playing its part. GMP and Manchester city council are sharing vehicle servicing with each other. The force has developed a simulation model to help it understand the effects of changes to demand and resources. It researched the length of time taken by officers to deal with certain types of crimes and then used this understanding to anticipate demand and allocate resources more efficiently. Through partnership working, GMP has taken part in a variety of schemes, including a pilot scheme in Oldham providing officers with access to mental health professionals, linking with Stockport’s psychiatric department to train response officers and concluding agreements with care homes on how they and the force can work together. GMP is clearing up more and more of the other problems that are being caused by this Government’s austerity programme. Much has been made of the need to preserve the numbers of PCSOs within GMP, in accordance with the neighbourhood policing strategy. Despite the best efforts of the police commissioner to preserve PSCO numbers, since 2010 there has been a reduction of just over 50. However, the service expects its numbers to be back up to full strength by next March. These reductions have been mitigated slightly by an increase in operational front-line staff, with an increase of 200 over the same period. Early in 2014, the commissioner outlined plans to raise the police precept element of council tax by 5%, which would have raised £3.3 million. The plan was to help to mitigate some of the cuts being made by central Government. It would have added £5 to the average annual council tax bill—about 10p a week. This money would have been invested in shoring up neighbourhood policing teams, including the recruitment of 50 new police officers to mitigate the annual loss of about 350 officers. Unfortunately, the referendum that would have been triggered as a result of the Government’s introduction of compulsory referendums on tax increases over 5% would have cost more money to implement than it would have raised. As a result, the commissioner was able to raise only £2 million towards the cost of GMP’s policing budget, and that has been used to support front-line policing. Most of the increases in crime rates from 2013 onwards are in what could loosely be defined as economic-type crimes such as theft, burglary, vehicle offences and shoplifting. This has come at the same time as the slashing of police numbers that we have seen in Greater Manchester. Let me make this very clear: the Government say that crime is going down, but crime in Greater Manchester is going up. Mike Penning - Hansard - Copy Link - - Excerpts No, it is not. Mike Kane - Hansard - Copy Link - - Excerpts The combination of all these measures is threatening the great work that has been done by Greater Manchester police, partner agencies and local communities to build safer neighbourhoods across our region. That work is being endangered. The Minister said from a sedentary position that crime in Greater Manchester is not going up. I suggest that he talk to the Manchester Evening News , which has proved— Mike Penning - Hansard - Copy Link - - Excerpts Crime in the Greater Manchester area since 2010 is down by 21%. The hon. Gentleman should not believe everything he reads in the local newspaper. I used to write for one, so I know just how they work. However, we have had an increase in reported crime in some areas, which I am really pleased about, particularly rape and serious assaults, which have seen a 3% increase this year. Three per cent. off 21%—there has been a 18% decrease since the election. Mike Kane - Hansard - Copy Link - - Excerpts When Robert Peel graced the Minister’s position, he introduced the police force and Catholic emancipation and got rid of the corn laws, and now we are arguing about whether crime is up or down. The position is clear. Statistics released this year show that crime in Greater Manchester is on the rise for the first time in 20 years. The areas that have seen the biggest increase are theft offences, including burglary, mobile phone theft and shoplifting. Detection rates across Greater Manchester are also falling, which could indicate the effect of the massive reduction in the number of police officers as a result of the cuts. Her Majesty’s inspectorate of constabulary has echoed the concerns of GMP and the commissioner that the ongoing programme of cuts could start to hit front-line services. An HMIC report “Policing in Austerity: Meeting the Challenge” has tracked how police have responded to budget cuts since summer 2011, using force data and inspections to analyse how they are making savings and how this is affecting the way they work and the service they provide to their communities. GMP is one of the forces to have received a “good” rating for the way it has managed the budget cuts so far, but HMIC also recognised that budget cuts disproportionately affect Greater Manchester. The chief constable has told me, “We are now standing at the edge of a cliff.” He says that if this programme of cuts goes beyond 2017, he cannot provide the levels of policing that Greater Manchester people expect and deserve, because there is simply not enough money in the pot. If policing cuts continue beyond 2017, GMP will not be able to maintain its service to the public. The police and crime commissioner, Tony Lloyd, has warned since before he was elected that the Government’s reckless programme of cuts is endangering community safety and threatening the work done by GMP over the past 20 years to reduce crime rates and restore Manchester’s reputation in the light of the “Gunchester” years. That is in addition to our counter-terrorism work. After I entered public life in the early 1990s, our city experienced two terrorist attacks by the IRA. In 1992, 65 people were injured, and in 1996 the biggest bomb in peacetime devastated our city. In 2003, PC Oake was murdered by fundamentalist Islamists when he visited a scene to arrest somebody. There are currently all sorts of pressures on how Greater Manchester deals with counter-terrorism. Sarah Newton - Hansard - Copy Link - - Excerpts I know the hon. Gentleman’s constituency very well because my in-laws are from that part of the world and I recognise the challenges he is describing, but has he actually costed his proposals and have they been cleared by the shadow Chancellor? Mike Kane - Hansard - Copy Link - - Excerpts Dear oh dear. My hon. Friend the Member for Birmingham, Erdington has clearly explained how we can mitigate some of the cuts. I say to the hon. Lady: how can we not do this when crime is going up in my community and where I live? Jack Dromey - Hansard - Copy Link - - Excerpts I am glad that point has been made, because all the costings for proposals by Opposition Front Benchers have been checked, including with the House of Commons Library. The simple reality is that the difference between the Government and the Opposition is that, in circumstances where sensible savings can be made which would save the 1,000 police officers under threat in 2015-16, the Government are choosing to go ahead with their proposals, irrespective of what has been said by the hon. Member for South Dorset (Richard Drax) and my hon. Friends the Members for Birmingham, Selly Oak (Steve McCabe) and for Wythenshawe and Sale East (Mike Kane). Mike Kane - Hansard - Copy Link - - Excerpts I could not agree more with my hon. Friend. Savings of £136.8 million are forecast to be required by my force alone by March 2018. Savings of £71.3 million have already been identified, with the majority coming from a net reduction in police numbers by 1,054 over that period. There is a choice at this general election: people can choose that type of austerity and see crime rise on their patch or they can choose a better way. In conclusion, I thank my police and crime commissioner, Tony Lloyd, for his hard work; the chief constable, Peter Fahy; my local officers in Wythenshawe and Sale East, and the fine network of home watch associations that I support, particularly Sale Homewatch, and Graham Roe, who helped me prepare this speech. 15:12 Mike Penning - Hansard - Copy Link - - Excerpts I thank the shadow Minister, the hon. Member for Birmingham, Erdington (Jack Dromey), for giving me early sight of his speech. I say that a little tongue in cheek because it was written by the shadow Home Secretary and issued this morning, and the hon. Gentleman would have read it out verbatim if I had not interrupted him. This has mostly been a sensible debate in which MPs have rightly stood up for their constituents and praised, as I did in my opening speech, the fantastic work done by police forces across England and Wales, which are the countries for which I have responsibility. I reiterate my earlier remarks that front-line policing is a vital component, but so much work is done behind the scenes that the public do not see. The hon. Member for Rochester and Strood (Mark Reckless) intervened on me on that issue. He should visit his chief constable. [ Interruption. ] I know he probably has already, but he should talk to him very carefully about the work done by non-uniformed police, including CID, the counter-terrorism and serious fraud units, and clerks and officers. Jack Dromey - Hansard - Copy Link - - Excerpts rose — Mike Penning - Hansard - Copy Link - - Excerpts The shadow Minister has had plenty of time to read someone else’s speech, so I am not going to give way to him. I know where the hon. Member for Rochester and Strood is coming from, but there is no way that I would say that front-line police are not important. I will touch on the shadow Minister’s comments later, but it is important that I first address some of the points raised by Back Benchers, because when I come on to some of his points I am afraid I will find it very difficult to keep a straight face. Jack Dromey - Hansard - Copy Link - - Excerpts Will the Minister give way? Mike Penning - Hansard - Copy Link - - Excerpts No, I am not taking interventions from the shadow Minister, because he made a complete fool of himself earlier and I am not going to help him make even more of a fool of himself. I say to my hon. and gallant Friend the Member for South Dorset (Richard Drax) that Dorset police do absolutely fantastic work. I think he thought that I might have said, “It all happens here,” or something like that, but that was my hon. Friend the Member for Bournemouth East (Mr Ellwood), who had come in to listen to his speech. I understand that about 20,000 people go to Bournemouth on a Friday and Saturday to enjoy the night-time entertainment. That shows how diverse police work can be in Dorset, and I praise the work done there. Martyn Underhill will be on the review board, which is important. My hon. and gallant Friend asked for a commitment until 2016-17, but that is difficult because there is going to be a review and his police and crime commissioner will be on the board. It would be wrong for me to pre-empt that review. As I said in my opening remarks, it is vital that everybody looks at the different types of policing needed, especially going into 2016-17, and at how the formula was formulated all those years ago. That will not be a tweak; we have to take a fundamental look at the changes needed. John Healey - Hansard - Copy Link - - Excerpts Will the Minister give way? Mike Penning - Hansard - Copy Link - - Excerpts I am not going to give way at the moment. I might give way later if I make some progress, but I have been given a time limit by Madam Deputy Speaker, which is why I do not want to give way too much. Let us not get into the semantics of the speech made by the hon. Member for Wythenshawe and Sale East (Mike Kane): he was doing exactly what I would expect him to do in standing up for his force. It will be really interesting to see what happens when Manchester gets a mayor. It has clearly worked brilliantly in London, but we will wait to see what the Home Secretary decides. That sort of localism is very important. The PCC for Greater Manchester police does a good job, even though the shadow Minister said today—or was it the shadow Home Secretary?—that Labour wants to abolish the position. The costings are very interesting. Several hon. Members talked about the number of police cut since the coalition came to power. Interestingly, the speech/article read out by the shadow Minister mentioned 100 new officers. The assumption is that Labour would make a saving of £100 million through procurement. I do not know where that figure comes from. There are always assumptions within procurement, but we are working very closely with forces on that; as I said earlier, it is absolutely fine for Governments to decide what should be done as long as we get it right. The shadow Minister talked about making huge savings on shotgun licences. That matter is currently under review, and an announcement will be made shortly. He said that the abolition of police and crime commissioners would save £50 million, even though I understand that Labour police and crime commissioners were told at the weekend that they were expected to be in place until at least 2017. That is another hand-brake turn following others. I am sure that Vera Baird and Paddy Tipping would love to know exactly what the policy is, because it appears to have changed since the conference. Even on such assumptions, including that the shadow Minister is right to say that this horrible Government would cut 1,000 police next year—that is complete and utter rubbish—and Labour would put in 100 police officers, that works out at an average of 24 per constabulary. That will make a difference, but not quite the difference that some Opposition Members think the shadow Minister has announced today. Jack Dromey - Hansard - Copy Link - - Excerpts Will the Minister give way? Mike Penning - Hansard - Copy Link - - Excerpts I have explained why I will not give way. The hon. Member for Birmingham, Selly Oak (Steve McCabe) made some important comments in his very measured and sensible speech. When he talked about centralised control and such things, my mind drifted back to the regional fire control centres introduced by the previous Administration. As an ex-fireman, I have followed the issue very closely. I was absolutely fascinated by the sheer waste of taxpayers’ money caused by the disastrous policy of regionalising fire control centres. When I was the Minister with responsibility for shipping, I was very lucky to be able to add the coastguard to the centre in Gosport, which saved the coastguard a huge amount of money; however, it also cost the Department for Communities and Local Government a huge amount. It is absolutely right to look very carefully wherever there is centralised control. That is why I have always said that forces should work together to make sure that they know exactly what is going on. Forces do not necessarily need to work with their natural partners on their boundary, because they do not have to be next to each other to do procurement, human resources or IT together, as is absolutely vital. The key to this debate is that although we as constituency MPs quite rightly want to stand up for our forces, we must be aware that ongoing savings are required within police budgets, as the shadow Minister said. We must make sure that the review does what it says on the tin and that we have a proper review. John Healey - Hansard - Copy Link - - Excerpts rose — Mike Penning - Hansard - Copy Link - - Excerpts The right hon. Gentleman was not in the Chamber for most of the debate, so I will not give way to him even if I had time to do so. We need to stand up for our forces, but we must also be realistic about them. Shadow Ministers should not make false accusations, build up promises or spread doom and gloom about the police who do such a fantastic job for us. They should not stand at the Dispatch Box and run down our police. [ Interruption. ] I am told that I am supposed to give way. You gave me 10 minutes, Madam Deputy Speaker, and I am now at that time limit, which is why I am not giving way. If the shadow Minister had not spoken for so long, reading out an article that the shadow Home Secretary wrote in a newspaper this morning, I would have been happy to give way. I hope that we can now conclude the debate on time, as you requested, Madam Deputy Speaker. I hope that the motion will go through, and that there will be no more scaremongering from the Opposition. 15:22 Division 150 Ayes: 285 Conservative: 240 Liberal Democrat: 45 Noes: 212 Labour: 200 UK Independence Party: 2 Plaid Cymru: 2 Independent: 2 Democratic Unionist Party: 2 Conservative: 1 Green Party: 1 Social Democratic & Labour Party: 1 Resolved , That the Police Grant Report (England and Wales) for 2015-16 (HC 930), which was laid before this House on 4 February, be approved. Return to start of debate - Return to top of page Local Government Finance Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Divisions during this debate: 19:13 - The House divided: - Ayes: 286 / Noes: 190 - Question accordingly agreed to. 15:37 Madam Deputy Speaker (Dame Dawn Primarolo) - Hansard - Copy Link - - Excerpts We now come to the two motions on local government finance, which are to be debated together. Before I call the Minister to move the first motion, I have to inform the House that there is an error on the Order Paper, in that the two reports relating to local government finance appearing in item 3 on the Order Paper have been considered by the Select Committee on Statutory Instruments. The Parliamentary Under-Secretary of State for Communities and Local Government (Kris Hopkins) - Hansard - Copy Link - - Excerpts I beg to move, That the Local Government Finance Report (England) 2015–16 (HC 1013), which was laid before this House on 3 February, be approved. Madam Deputy Speaker - Hansard - Copy Link - - Excerpts With this we will consider the following: That the Referendums Relating to Council Tax Increases (Principles) (England) Report 2015–16 (HC 1014), which was laid before this House on 3 February, be approved. Kris Hopkins - Hansard - Copy Link - - Excerpts On 18 December, I presented to the House a draft of the local government finance report, which set out our provisional settlement for local authorities in England for 2015-16, and began a period of consultation on our proposals. As I made clear to hon. Members then, we aim to deliver a settlement that is fair to all parts of the country, and that recognises the responsibility of local government to explore every opportunity for sensible savings. Every part of the public sector needs to do its bit to pay off the deficit left by the previous Administration. Local government, which accounts for a quarter of all public spending, must continue to play its part. Sir Greg Knight (East Yorkshire) (Con) - Hansard - Copy Link - - Excerpts During the Minister’s remarks, will he tell the House what the Government are doing to assist rural authorities? Will he also spell out what is being done to alleviate the burden generally of council tax? Kris Hopkins - Hansard - Copy Link - - Excerpts I assure my right hon. Friend that I will consider rural provision in my speech. Since coming to power in 2010, we have recognised that rural communities need additional support. I am sure he will see from the document I laid in the House on 3 February that we have responded appropriately. Mr Graham Stuart (Beverley and Holderness) (Con) - Hansard - Copy Link - - Excerpts The Minister says he wants a settlement that is fair to all communities. He has himself recognised that the current settlement, notwithstanding the Government’s efforts, is not fair to rural communities. The central Government grant is 50% higher for urban communities than it is for rural communities, even though rural communities are on average poorer and have fewer services. Kris Hopkins - Hansard - Copy Link - - Excerpts My hon. Friend always makes a robust challenge to the figures we lay before the House, because he is passionate about supporting rural communities. When I get to the section on rural communities I will elaborate further. Mr Clive Betts (Sheffield South East) (Lab) - Hansard - Copy Link - - Excerpts The Minister says that local government has to bear its fair share of the cuts. Does he accept that according to the Office for Budget Responsibility—the Local Government Association produced these figures for us—if we exclude spending on schools and public health, which local authorities cannot affect, in 2009-10 local authorities represented 19% of public expenditure? By 2015-16, it will represent 16%. In other words, local government has surely borne more than its fair share of cuts. It has had more cuts as a percentage than the rest of central Government services. Kris Hopkins - Hansard - Copy Link - - Excerpts I do not have those figures, but what I will say is that I recognise that local government has had to make a substantial contribution to driving down the deficit left by the previous Administration. It is important that we recognise that local government has responded in an extremely positive way to the challenge we have placed before it. During the consultation period, which closed on 15 January, my ministerial colleagues and I met a number of local authorities and representative groups. I also led a phone-in discussion, with more than 100 authorities participating. In addition, the consultation received numerous written responses. We considered very carefully the views of all those who commented on the provisional settlement. On 3 February, we laid before the House a local government finance report which confirmed our proposal for the settlement for 2015-16 as announced. We also confirmed our proposal that the council tax referendum principle for 2015-16 will be set at 2%. I recognise the time and effort that those responding to the consultation—councils, in particular—have given in submitting detailed and considered comments on our proposals. As I said, we listened to those views carefully. In doing so, we recognised that councils asked for additional support. As a result, our announcement on the final settlement for 2015-16 included provision for a further £74 million to support upper-tier authorities, including to help them to respond to local welfare needs and improve social care provision. Mrs Louise Ellman (Liverpool, Riverside) (Lab/Co-op) - Hansard - Copy Link - - Excerpts If the Minister listened carefully to representations and wanted to be fair, how can the outcome be that Liverpool, the most deprived local authority in the country, is suffering some of the harshest cuts? Kris Hopkins - Hansard - Copy Link - - Excerpts We need to recognise—I have said this before—that the 10% most deprived authorities receive on average 40% more than the most wealthy authorities. It is right that we create a formula to ensure the more vulnerable and deprived areas get that response, but we should not just measure on the basis of what moneys have been allocated. Local authorities now have the ability to raise money and are rewarded for building houses. I would also point out that the growth deals associated with Liverpool are significant and are led by local leaders. With the addition of these extra resources, the overall reduction in local authority spending power in 2015-16 is 1.7%. That is lower than that proposed in our provisional settlement. Taking into account the funds we are providing to support local transformation, the overall reduction is still lower, at 1.5%. Once again, the settlement ensures that councils facing the highest demand for services will continue to receive substantially more funding, and we continue to ensure that no council will face a loss of more than 6.4% in spending power in 2015-16. John Healey (Wentworth and Dearne) (Lab) - Hansard - Copy Link - - Excerpts Does the Minister accept that spending power disguises the real pressure on many councils, and that the money allocated does matter? Barnsley, which covers part of my constituency, is facing eye-watering cuts: a 26.9% cut in the revenue support grant next year, it tells me, and an overall cut in its settlement of 13.6%. It is absolutely nothing like the smaller figures he is giving the House. Kris Hopkins - Hansard - Copy Link - - Excerpts I hope, then, that the right hon. Gentleman has apologised to his constituents for the financial nightmare this country faced in 2010. The Government are not making these decisions out of a desire to reduce funding for the sake of it; we are responding to the appalling economy that Labour left. Mr John Redwood (Wokingham) (Con) - Hansard - Copy Link - - Excerpts Can the Minister comment on the balance in his settlement between the money that goes directly in the block grant and the money that goes for special purposes and as a reward for certain kinds of conduct? How is that developing, and what difference does it make to the percentage change? Kris Hopkins - Hansard - Copy Link - - Excerpts I hope my right hon. Friend will forgive me; I cannot give him the percentage change, but I can give him some clear figures. For example, business rate retention by local authorities alone is some £11 billion, and as the Prime Minister said this morning, should a Conservative Administration be returned at the forthcoming general election, we would hope to increase that to two thirds. Through consecutive settlements, we have ensured that these unavoidable changes to local authority funding have been applied in a fair and sustainable way, and through our reforms to local government finance we have established a basis for more self-reliant government—a sector less dependent on grant and increasingly confident about using the tools and incentives we are providing to grow their local economies. Dame Angela Watkinson (Hornchurch and Upminster) (Con) - Hansard - Copy Link - - Excerpts The low level of private rents in the London borough of Havering has given rise to a surge in demand, particularly for children’s services. The local population is already top heavy with older people and all the demands that come with that. How might the funding formula respond more to individual boroughs with particular difficulties? Kris Hopkins - Hansard - Copy Link - - Excerpts The key thing about the choices that we have placed before local government is just that—local authorities can determine where money is spent. We appreciate that there is less money to spend as a consequence of the previous Administration’s activities, but it is right that people can make choices, set their priorities and—in this case—choose to look after very vulnerable individuals. As well as growing their economies, the best authorities are transforming how they do business and demonstrating innovation, including in how they work with local partners. We are supporting them as they do that, helping them to achieve savings and, perhaps most importantly, improving outcomes for people who use local services. As I announced in December, we are developing proposals for a project to identify and disseminate good practice in transforming services, especially in rural areas. This work will involve rural authorities and the Rural Services Network, and is a clear commitment to our rural areas. Mr Jim Cunningham (Coventry South) (Lab) - Hansard - Copy Link - - Excerpts The hon. Member for Hornchurch and Upminster (Dame Angela Watkinson) mentioned demand for children’s services. In Coventry, we have to find an additional £7 million for children’s services. More importantly, we have to cut services across the board, because there has been a cut from the Government of £80 million, or 2,000 jobs, in general terms. What will the Minister do about that? He cannot go on blaming the previous Government. The coalition is in government now. There is no choice here, and that is being reflected in local government up and down the country. Local government is becoming a whipping boy for this Government, as it was for previous Conservative Governments. Kris Hopkins - Hansard - Copy Link - - Excerpts I am not moving away from the fact that there was a huge deficit in 2010, which this Government or whoever come to power after the May election will have to continue to address. The hon. Gentleman says that we keep on going back to local government. I have not seen anything from the Opposition to suggest that they will do anything but continue to bear down on spending on local government, because they will have to address the issues of concern. We have given local government the opportunity to grow resources by promoting and developing business, by securing planning permission and building the houses required for the local populace. That is the right thing to do. Several hon. Members - Hansard - Copy Link rose — Kris Hopkins - Hansard - Copy Link - - Excerpts I shall give way in a few moments. We continue to recognise the challenges faced by rural communities. Through consecutive settlements, we have helped address the gap in urban/rural spending power. We expect the gap to continue to close. In the meantime, the settlement confirms another year of additional resources for the most rural authorities to recognise the challenges they face in delivering services. For 2015-16, in direct response to Members of all parties, we have increased the grant to £15.5 million. Mr Andrew Love (Edmonton) (Lab/Co-op) - Hansard - Copy Link - - Excerpts Does the Minister recognise the challenges faced by London, whose population is on the increase? The population of my own borough, the London borough of Enfield, will increase by 10% up to 2020, putting enormous strain on services, not least on children’s school places. What recognition has the Minister given to that population increase, and will he include it in the baselines so that it is reflected in the grant settlement? Kris Hopkins - Hansard - Copy Link - - Excerpts What I recognise is that London is a great international city, which has thrived under this Administration, and will continue to deliver significant jobs, wealth and income to the individuals out there. That is the root issue. Many Labour Members stick their hands out and ask for more money; the reality is that this Government are setting about ensuring that we grow our economy, get people into work and give them the ability to stand on— [ Interruption .] Several hon. Members - Hansard - Copy Link rose — Kris Hopkins - Hansard - Copy Link - - Excerpts Let me make a bit more progress. The Government previously consulted on a range of options for how local welfare provisions for the upper-tier local authorities should be funded in 2015-16, following localisation. The Department for Work and Pensions carried out a review, and the Government concluded that local authorities should continue to be able to offer local welfare assistance from existing budgets in 2015-16, alongside a range of other services if they judge them to be a priority in their area. To assist in identifying how much of their existing funding is involved, an amount relating to local welfare provision was separately identified in each upper-tier authority general grant as part of the provisional settlement. This totalled about £130 million nationally, and was distributed in line with local welfare provision funding for 2014-15. The Government have always been clear that councils should choose how best to support local welfare needs, so this allocation cannot be ring-fenced and we will not place any new duties, expectations or monitoring requirements on its use. Sir Edward Garnier (Harborough) (Con) - Hansard - Copy Link - - Excerpts My hon. Friend is generous in giving way this afternoon. Harborough district council area covers about a quarter of the geographical area of the county of Leicestershire. It follows that it is a large rural area, with all the sparsity factors that go with it. The district council is Conservative run and it is doing its best to ensure that taxpayers’ money is wisely spent. If I may say so, it has behaved extremely well in ensuring that both the Government’s policies and its own policies are bearing fruit. However, will my hon. Friend bear in mind that there is a perception of a distinction being made between rural funding and city funding, particularly for the city of Leicester in comparison with my area, so will he do all he can to help me explain to my constituents that this Government mean what they say—that they have not forgotten their rural heartlands? Kris Hopkins - Hansard - Copy Link - - Excerpts Members have asked for a clear direction of travel in relation to our incremental increases in rural additional funding. I think it is clear that we have done our best to provide those increases during our time in office, given the limited resources that are available to us, but let me repeat an offer that I have already made: I shall be happy to meet my hon. and learned Friend and members of his council to discuss how we can communicate better what we are trying to do. In response to the representations that we received during the consultation, we have decided to allocate an additional £74 million to upper-tier authorities to help them to deal with pressures on local welfare, health and social care. That will help councils further as they develop localised arrangements. Caroline Lucas (Brighton, Pavilion) (Green) - Hansard - Copy Link - - Excerpts Will the Minister acknowledge the warnings issued by the Local Government Association about the cumulative impact of a 40% cut in local government funding? Does he accept that many authorities, including Brighton, are struggling to provide services? Is not the truth that this Government do not care about the future of local government as we know it? Kris Hopkins - Hansard - Copy Link - - Excerpts I suggest that one of the reasons Brighton council is struggling is its poor leadership. Moreover, the figure given by the hon. Lady clearly does not include significant amounts of public money, including money from the better care fund. Some £5.3 billion appears to be missing from the LGA’s calculation. That £74 million will be topped up with £37 million of additional funding for local authorities during the current year. That extra money will ensure that councils can step up their efforts to get people home as soon as they are ready to leave hospital, and avoid the need for people to go into hospital in the first place. It will help to promote joint working between our local public services, and will improve front-line services for some of the most vulnerable people in our communities. Mr Graham Stuart - Hansard - Copy Link - - Excerpts Will the money be distributed in a way that is proportionate to the number of over-65s in local populations? As my hon. Friend will know, rural communities typically contain older, more vulnerable residents than their urban counterparts. Kris Hopkins - Hansard - Copy Link - - Excerpts Although I live in a large metropolitan district, I also represent a significant rural area, and I know that many single elderly people live in large houses. That is another form of deprivation, in that they must sustain those houses on limited and fixed incomes. 1 urge all councils to protect taxpayers this year by taking the additional Government funding that is on offer for a freeze. That will enable them to help hard-working households and those on fixed incomes, such as pensioners, with their living costs. The tax-freeze grant will be embedded in councils’ baseline funding. Five successive years of freeze funding have seen council tax in England fall by 11% in real terms since 2010, after being doubled by the last Administration. Our actions will save for the average Band D household up to £1,075 over the course of this Parliament. Annette Brooke (Mid Dorset and North Poole) (LD) - Hansard - Copy Link - - Excerpts I welcome the extra funds that will help people to be moved from hospital into the community or to other forms of care, but what is the rationale for ring-fencing that pot of money and not ring-fencing the local welfare assistance money? Kris Hopkins - Hansard - Copy Link - - Excerpts The additional £37 million is specifically to address some of the winter pressures we face. We wanted to make sure that local councils work with authorities to address the particular needs of those individuals we wanted to help move into appropriate accommodation, and make sure there was sufficient and appropriate domiciliary care to look after them. That is why it is targeted around that group. Ms Gisela Stuart (Birmingham, Edgbaston) (Lab) - Hansard - Copy Link - - Excerpts The Minister asserted that the settlement was both fair and sustainable, and I want to address the word “sustainable.” On the current trajectory, by 2018 Birmingham will have lost, using 2010 as a baseline, £821 million. That is two thirds of its discretionary spending. By any definition, that is not sustainable. Kris Hopkins - Hansard - Copy Link - - Excerpts I have a lot of respect for the hon. Lady, but I am afraid that poor leadership in Birmingham and the fact that it has not collected some £100 million in council tax arrears may explain some of the issues it is facing. Stronger leadership and the ability to carry out the simple function of placing a charge on an individual and collecting it will assist it. Robert Neill (Bromley and Chislehurst) (Con) - Hansard - Copy Link - - Excerpts Does my hon. Friend agree that the real way to achieve proper sustainability for local government funding is to reward those councils who go for growth in their area and increase their tax bases—as we are seeing with the increase in business rates income anticipated this year—and make councils less dependent on central Government grant in the long term? Kris Hopkins - Hansard - Copy Link - - Excerpts My hon. Friend speaks very wisely and he knows from his own experience that local authorities appreciate these tools we have given them to grow their finance base, and there is an incentive for them to carry this out by improving those key services and increasing the resources to those services. For those who do not freeze the council tax, the referendums principles report laid before the House on 3 February confirms that any increase of 2% or more will require a binding referendum by the local electorate. Councils that want to increase their bills should have the courage of their convictions and seek a mandate from their electorate. It is already the case that a council tax referendum can be held at a reduced cost in 2015-16 when combined with the general election. We announced on 3 February that any savings to the Consolidated Fund as a result of a combination of a referendum with the general election will be redirected to councils, so the cost of the referendum to a local authority is low. This weakens the argument that some might make that holding a local referendum will result in excessive cost. Mr Andy Slaughter (Hammersmith) (Lab) - Hansard - Copy Link - - Excerpts I have no doubt the Minister will want to congratulate Hammersmith and Fulham council, which is one of eight to cut its council tax this year, but why is he rewarding it by cutting its discretionary housing payment not by 24%, which is the national average, or 35%, which is the figure for London, but by 52%? This is an area with the highest property prices and where there is family break-up with people being forced out of the area. DHP is absolutely vital. Will he look again at that cut? Kris Hopkins - Hansard - Copy Link - - Excerpts This Government continue to ensure there is a substantial welfare net to look after the most vulnerable individuals, and we have put additional funding into the budget. I applaud the council for reducing its council tax, however, and I would just note that it is following the trajectory given by the previous Conservative administration. That may be only a small glimmer of light, but somebody appears to have learned from the excellent previous Conservative administration. The local government finance report 2015-16 sets out a fair settlement, which ensures councils continue to have significant spending power. Even with the savings that have been made to date, local authorities in England were expected to spend over £115 billion in the current financial year. When we factor in councils’ new responsibilities for public health, the amount local government are expected to spend is higher than it was under the last Administration. Mr Love - Hansard - Copy Link - - Excerpts My local authority, the London borough of Enfield, is the 64th most deprived in the country, but its ability to deal with the problems of need is hampered by the long-term impact of the damping formula. I understand what the Minister said earlier about the need for floors, but can he offer any support to those local authorities struggling to address the needs of their boroughs because of capping over a long period? Kris Hopkins - Hansard - Copy Link - - Excerpts There are two things. First, there is not a cap; there is an opportunity for people to increase their council tax, and if councils believe that their public would support them, they may hold a referendum. Secondly, I go back to a point that I made earlier about the success of individuals. The route out of poverty and deprivation for an area such as my former council area of Bradford involves getting people skilled up, with local councils supporting them, and those individuals getting a job and being able to stand on their own feet. Breaking the cycle for an individual trapped in one has to be the responsibility of both central and local government. The referendum principles report sets a sensible threshold for council tax increases, unless local people are happy to approve something else through a referendum. It is more important than ever that councils can demonstrate to local taxpayers that they are using every pound of their money to best effect to deliver efficient and effective services and to achieve sensible savings. 16:06 Hilary Benn (Leeds Central) (Lab) - Hansard - Copy Link - - Excerpts That was an interesting speech. I pay tribute to the Minister for his generosity in giving way to Members, but councillors up and down the country listening to what we have just heard—in particular the part where he talked about giving authorities the ability to grow their resources—will look at their circumstances today and ask whether the Minister really understands what is going on in our authorities. I want to begin with the scale of what is happening, because the Minister queried the figure given by the hon. Member for Brighton, Pavilion (Caroline Lucas), which was the Local Government Association’s calculation of a 40% reduction in core Government funding to councils since 2010, as a result of which councils have had to make reductions or savings worth about £20 billion. Would the Minister argue, however, with the National Audit Office, which said in its report “Financial sustainability of local authorities 2014”: “The government will reduce its funding to local authorities by 37% in real terms between 2010-11 and 2015-16”? Kris Hopkins - Hansard - Copy Link - - Excerpts I would disagree, because neither the LGA nor the NAO includes the money for public health or the better care fund. Hilary Benn - Hansard - Copy Link - - Excerpts I shall come to that point directly, but the Minister did not actually contest the NAO figure. The reduction in resources of 1.7% that he has talked about today is a selective figure, because it does indeed include council tax, the better care fund and other ring-fenced funding, but if that is excluded the LGA says that the reduction is actually 8.5%. Whatever the statistics that the Minister wants to argue about, the truth is that local government has faced the biggest reductions in the whole of the public sector, as we heard in an intervention. We should first pay tribute to councils for the extraordinary job that they have done—councils up and down the country, of all political parties—in trying to deal with the consequences of the cuts, because their effort has been herculean. I pay tribute to the Minister for his tone, which is slightly different from that of his predecessors, but councils really resented the Secretary of State once famously describing the cuts as “modest”—which I bet he now regrets—and the LGA’s fears for the future of local government as “utterly ludicrous”. Mr Graham Stuart - Hansard - Copy Link - - Excerpts If we are talking about making admissions, will the right hon. Gentleman now accept that his Government, at what seemed to be a time of relative plenty, skewed funding to urban areas at the expense of rural ones? Now that we are in a period of austerity, which will continue whoever is in power, it is those poorer, more highly taxed and yet lower-serviced rural areas that are suffering most. Will his party pledge to do something about that, or will it carry on putting its own party interests ahead of fairness for the British people? Hilary Benn - Hansard - Copy Link - - Excerpts I have to say to the hon. Gentleman that I resent that suggestion. I make no apology for the fact that the last Labour Government provided funding on the basis of need and that local authorities saw an increase in resources under Labour. I do not recall hearing any complaints about that from the then Opposition when those decisions were being made. Mr Stuart - Hansard - Copy Link - - Excerpts rose — Hilary Benn - Hansard - Copy Link - - Excerpts I am going to make some more progress; the hon. Gentleman has had his answer. I accept the point he has made in a number of these debates about the particular challenges facing rural areas. I want to see a fairer funding formula, and I shall address that a little later. Ministers are in denial about the scale of the challenge that authorities face and are still claiming that the settlement is fair—this is my first and fundamental point. The Minister told the House in December that the settlement is “fair to all parts of the country, whether north or south, urban or rural.” —[ Official Report , 18 December 2014; Vol. 589, c. 1590.] He said that again today, but let me tell him that nobody else believes it because it clearly is not true. He does not need to take my word for it; all he has to do is listen to what others have had to say about what Ministers have done. The Audit Commission has said that “councils in the most deprived areas have seen substantially greater reductions in government funding as a share of revenue expenditure than councils in less deprived areas.” The Joseph Rowntree Foundation has said that “cuts in spending power and budgeted spend are systematically greater in more deprived local authorities than in more affluent ones”. The Public Accounts Committee report on the financial sustainability of local authorities said: “local authorities with the highest spending needs have been receiving the largest reductions.” The Chair of the PAC, my right hon. Friend the Member for Barking (Margaret Hodge), said: “These cuts have not hit all local authorities equally, with reductions ranging between 5% and 40%. Councils with the greatest spending needs—the most deprived authorities—have been receiving the largest reductions.” At least the former local government Minister, the hon. Member for Bromley and Chislehurst (Robert Neill), had the honesty some time ago to say: “Those in greatest need ultimately bear the burden of paying off the debt” —[ Official Report , 10 June 2010; Vol. 511, c. 450.] Today’s Minister mentioned council tax, but the one group of people who have not benefited from any freeze in council tax are those on the very lowest incomes, who have been affected by the changes to council tax benefit. There has been no freeze for them. Robert Neill - Hansard - Copy Link - - Excerpts It is a pity that the right hon. Gentleman quoted selectively, forgetting that I said that that would be because the Labour party would ruin the economy, and only by growing the economy would the poorest benefit. He has said there would be no new money for local government were Labour to come into office, so will he help us by coming clean as to which local authorities he will then penalise so he can distribute money to his political friends and on what basis? Hilary Benn - Hansard - Copy Link - - Excerpts Once again, I do not accept the charge that this is about distributing funds to friends; it is about having a fair funding formula. I remind the hon. Gentleman that when the coalition Government took office unemployment in this country was falling and the economy was growing —[Laughter.] It is no good Government Members laughing, because the evidence, the statistics, the facts will show that that was indeed the case. On council tax increases, Ministers have frequently made reference to what happened under the last Labour Government, so I have taken the trouble to look at what actually happened then. The truth is that the biggest increases in council tax between 1997 and 2010 were put in place by Conservative-controlled authorities and the smallest increases were under Labour. Indeed, 11 of the top 15 increases in council tax during that period came under Conservative-controlled authorities, two were under authorities with no overall control and one was under a Lib Dem-controlled authority. I suppose that was a coalition. Mr Stuart - Hansard - Copy Link - - Excerpts Will the right hon. Gentleman give way? Hilary Benn - Hansard - Copy Link - - Excerpts No. The hon. Gentleman may not like the fact, but the truth is that Conservative-controlled authorities were leading the way in raising council tax. What I am interested in, in this debate, is what the figures show. Why is it that by 2017, as we heard a moment ago, the city of Liverpool, with the most deprived local authority in the country, will have lost half its Government grant since 2010? I have nothing against Wokingham, but why is it on course to have higher spending power per household than Leeds or Newcastle, despite the greater needs of those two cities? Why is it that, having claimed that those with the broadest shoulders would bear the biggest burden, Ministers have done the very opposite to local government? Will the Minister explain why Elmbridge, Waverley and Surrey Heath have been given an increase in spending power over the past five years although they are among some of the very wealthiest parts of the country? They rank among the 10 least deprived local authorities in England. There is a lot of austerity elsewhere, but it does not appear to apply in those places. Seema Malhotra (Feltham and Heston) (Lab/Co-op) - Hansard - Copy Link - - Excerpts Does my right hon. Friend agree that the way the Government have approached local government finance is putting councils between a rock and a hard place? My own council in Hounslow will have to make cuts of around 40% on what it had in 2010. To raise council tax even by 2% would generate about £2 million. To go over that would cost between £300,000 and £400,000 in terms of running a referendum. The council is concerned about what will happen to services, which will have to be very deeply cut. Hilary Benn - Hansard - Copy Link - - Excerpts My hon. Friend makes an important point about the difficult choices faced by local authorities up and down the country. I know that councils will do their darnedest to try to minimise any increase in council tax because of the pressure on people’s finances and because of what has happened over the past five years. Tom Blenkinsop (Middlesbrough South and East Cleveland) (Lab) - Hansard - Copy Link - - Excerpts I wish to give one example to show that this is all about the political nature of an authority rather than the previous funding formula. In Redcar and Cleveland between 1999 and 2003, when the council was Labour-run, and 2007 and 2011—eight years—the council tax under Labour did not go up cumulatively by the amount it did under the Tories between 2003 and 2007, who raised it by 24% in four years. Hilary Benn - Hansard - Copy Link - - Excerpts I am grateful to my hon. Friend for putting the record straight, given the charge that has been laid against us by the Government. The fundamental question today is why the system has been moving away from one where funding properly reflected need to one where the principle is being lost. That question was put by my hon. Friend the Member for Sheffield South East (Mr Betts), who chairs the Select Committee, in this debate last year, but so far there has been no answer. John Healey - Hansard - Copy Link - - Excerpts My right hon. Friend is making a powerful and principled point about the way that funding has moved against those areas with greatest need. He is making that case with great clarity, but does he accept that using spending power, as he just did, disguises the depth of the cuts that many councils face? It really cannot be the case that we can accept £1.8 billion of a better care fund in next year’s budget as an increase in councils’ spending power when the power to approve the spending decisions lies not with councils but with the health service in those areas? Hilary Benn - Hansard - Copy Link - - Excerpts My right hon. Friend makes an extremely important point. That is why the attempt that the Minister made to include that spending power, when we know that a goodly portion of that money is not in the hands of local authorities, is not a fair reflection. The point I put to the Minister is simply this: the NAO said that the Government should publish figures detailing the change in individual local authority income in real terms since 2010-11 so that the cumulative impact of funding reductions could be plain for all to see. The question is why have the Government refused to do it, and why are we relying on the finance department of Newcastle city council to do the work of the Department for Communities and Local Government? Sir Oliver Heald (North East Hertfordshire) (Con) - Hansard - Copy Link - - Excerpts The right hon. Gentleman will appreciate that in a constituency such as mine in Hertfordshire we are facing a lot of new building of homes and we need infrastructure. If he deprives my council of the new homes bonus and its community infrastructure levy, how will we provide for all these people in our part of the world? It just does not add up. Hilary Benn - Hansard - Copy Link - - Excerpts I have no intention of depriving the hon. and learned Gentleman’s local authority of CIL income, but as he raises the new homes bonus, I shall be straight and direct with him. I shall come on to this in a moment—in fact, if he will bear with me, I shall come to that point about the new homes bonus and set out why it needs to change. Mr Jim Cunningham - Hansard - Copy Link - - Excerpts A good illustration of what is happening in local government can be seen in Coventry, at University hospital. Cuts in the care budget have led to bed blocking, and now there are also cuts in the welfare budget. The Government say that they are trying to be gentle with local government, but does my right hon. Friend not agree that they are actually putting the boot in? Hilary Benn - Hansard - Copy Link - - Excerpts I agree and I shall come to that point, too, when I talk about the consequences of what has happened for health and social care more generally. Mr Redwood - Hansard - Copy Link - - Excerpts The shadow Secretary of State is usually very fair-minded, so does he agree that the largest local authority service is education, which has over the past five years had cash increases and small real increases in spending, and that the biggest local public service is the NHS, as administered locally, which has had real increases as well? Were they not the right priorities and would not his party have shared exactly that priority of protecting health and education? Hilary Benn - Hansard - Copy Link - - Excerpts Indeed. If one looks back at the record of the previous Labour Government, one can see that that is precisely what we did. In fact, we increased investment in those two things as that reflects public priorities. Of course, Government life is about the choices one has to make and one of the choices the Government have not made is to publish the figures that the NAO has asked them to publish. I suspect that Ministers know what the figures are and know that they will damage their argument that this is a settlement that is fair to all, north and south, and therefore do not want to reveal what is happening. We also know that the NAO has criticised the Department and Ministers for not paying close enough attention to what is going on. Again, those are not my words but those of the National Audit Office, which said: “The Department has a limited understanding of the financial sustainability of local authorities and the extent to which they may be at risk of financial failure.” That is why the Public Accounts Committee said: “The Department does not understand the impact over time of reductions in funding to local authorities, and the potential risks of individual authorities becoming financially unsustainable if reductions continue.” On current trends, the revenue support grant will disappear entirely by 2019-20. When the Minister replies, will he confirm that that is the case? What assessment have the Government made of the impact of that on the viability of local authority services, particularly in the areas most reliant on Government support? Indeed, I ask Members to pause for a moment and contemplate their local authority’s budget without any revenue support grant whatsoever. The Chair of the Public Accounts Committee was very clear when she said recently: “Further cuts could not just undermine the entire viability of most optional services, but might threaten some statutory services in these areas.” Dame Angela Watkinson - Hansard - Copy Link - - Excerpts I am sure that the shadow Secretary of State is aware that the 12 inner London boroughs hold more in reserves collectively than the 20 outer London boroughs. Does he think that that indicates that funding is going where the greatest need is or does he agree with me that the balance of funding between inner and outer London needs to be reviewed? Hilary Benn - Hansard - Copy Link - - Excerpts The size of the reserves held by authorities across the country—they have been criticised by Ministers for doing that—shows the scale of the challenge they face. Councils are doing exactly what families do if they have any money to put by when times are hard, as they do not know what is around the corner or what difficulties they will face. That is my first point. Secondly, a lot of those reserves are earmarked for capital investment, including invest-to-save projects to help deliver savings further down the line. Thirdly, if councils decided today just to spend all of their reserves, that would pay for local government services for about a month and then they would all be gone. Then what should they do? It is no good criticising local councils for having reserves when they are trying to manage their money prudently. I want to come to the point raised by my hon. Friend the Member for Coventry South (Mr Cunningham) about social care, which is under particular strain because of the growing number of older people. Will the Minister, in replying, tell us what percentage of the better care fund, about which we have heard today, is flowing into local authorities to support social care as opposed to going to the health service? He will be well aware of the pressures faced by local authorities and, as we have just heard and as all hon. Members know, part of the reason for the rising pressure in A and E departments, and for the growing number of elderly people in hospital beds when there is no medical need for them still to be there, is the reductions, in some cases, that have had to be made by local authorities, despite their best endeavours, in entitlement to social care. The Local Government Association estimates that adult social care faces a funding gap of £1.6 billion in 2015-16 and that that is expected to rise to £4.3 billion in 2019-20. Is that a figure that Ministers accept? If so, what do they intend to do about it? Will the Minister confirm that the new homes bonus takes money away from the most disadvantaged communities and gives it to areas where, in all probability, the new homes would have been built anyway? What does he have to say about the NAO’s conclusion that there is little evidence that the new homes bonus has yet made significant changes to local authorities’ behaviour towards increasing housing supply? Even two of the Ministers on the Front Bench are not wildly keen on it. The Under-Secretary of State for Communities and Local Government, the hon. Member for Bristol West (Stephen Williams), has admitted that he is “not a fan”, and the Under-Secretary of State for Communities and Local Government, the hon. Member for Keighley (Kris Hopkins), was even more frank because he told the House back in November 2013: “I am afraid the new homes bonus is not about encouraging people to build homes.” —[ Official Report , 25 November 2013; Vol. 571, c. 11.] Given that, why are Ministers so opposed to funding being allocated on a fairer basis, based on need, as we are proposing? We are lectured frequently about the need to take tough decisions in tough times. If one accepts the argument—those on the Government Benches do not—that the way in which the cuts have been applied is fundamentally unfair to some authorities, one of the things one can do is to redistribute, and the new homes bonus provides an opportunity to do that. Sir Oliver Heald - Hansard - Copy Link - - Excerpts So what the right hon. Gentleman is saying is that we have to take the homes and he gets the bonus. What is fair about that? Hilary Benn - Hansard - Copy Link - - Excerpts There is section 106 and there is CIL in order to raise financing. There are also the changes that we are proposing in order to give local authorities, such as the hon. and learned Gentleman’s, greater power over the construction of new homes so that communities can determine where homes are built, but when it comes to the new homes bonus, if one accepts the argument that it is regressive in its impact because it is top-sliced from revenue support grant which is supposed to reflect need and therefore goes towards areas where people want to build homes which tend to be less disadvantaged than others, it is a tough choice. But when people say, “What are you going to do to redress the unfairness of what the coalition has done?”, that is part of my answer. I know that other Members want to speak so I shall make progress. In these difficult times, what councils want is, first, fairer funding, which we are committed to; secondly, help with longer-term funding settlements so that they can plan ahead; and thirdly, more devolution of power so that they can work with other public services to get the most out of every pound of public funding. We have heard Ministers argue in the past that the relationship of old was based on a begging bowl mentality. A former local government Minister used to talk about that. That is pretty insulting to local authorities which, over the years, have worked hard to grow their economies and create jobs. One cannot look at the growth and success of the city of Leeds over the past 30 years and say that that is the result of a begging bowl mentality. It is because the council, businesses and local people have worked hard to grow the economy, create jobs and improve people’s lives. It was a question of leadership. That brings me to what is absent from the statement today—devolution of funding to local authorities. I support the city deals that the Government have put in place and I welcome them. I have said that before, but progress has been slow and timid. We had been promised a further deal for the Leeds and Sheffield city regions, following the recently agreed deal with Greater Manchester, but there is no sign of it. Who is running that policy? Is it the Secretary of State, the Chancellor of the Exchequer or the Deputy Prime Minister? Everyone in the House knows that the reason why the deals are being held up is that the Chancellor wants to impose a metro mayor as part of the deal and the Deputy Prime Minister does not. I am not sure what the Secretary of State’s view is, but he is clearly no particular fan of combined authorities because he said not long ago that he is afraid that they “will suck power upwards away from local councils”. In case the Secretary of State has not noticed, combined authorities are local councils coming together freely, voluntarily, in the interests of co-operation, because they see the benefit for their residents. When the Minister replies, will he tell us when Leeds and Sheffield are going to get the same deal as Manchester? The last point that I want to come on to is about the counties of England. We have heard some voices in the contributions today. It was noticeable that at the recent county councils network conference, for some reason not one of the Department for Communities and Local Government House of Commons Ministers was able to turn up to address the representatives of the county councils. It was extraordinary. I suspect the reason is that county leaders feel wholly ignored by this coalition Government because they see the devolution that has been offered to cities. Where is the devolution to counties and county regions? There is none. If we get the opportunity, we will change that. We would offer economic devolution to every part of England—county regions as well as city regions—to give them greater control over their economic future. On that, I am in agreement with the Minister. We would devolve decision making on transport investment and on bus regulation. If that is good enough for London, it is good enough for the rest of the country. We would offer funding for post-19 skills, working with businesses and co-commissioning a replacement for the Government’s Work programme to help the long-term unemployed back into a job. We would offer new powers over housing so that communities can build the houses they want in the places they want, and the houses go to the people who need them. By devolving £30 billion-worth of funding—much more than the Government are offering—we would give combined authorities the ability to retain 100% of business rate income growth. The Prime Minister has said that he wants to move towards two thirds, so if he hurries up a bit, he will finally catch up with Labour policy. Mr Graham Stuart - Hansard - Copy Link - - Excerpts The right hon. Gentleman said that he would bring in a new, fairer funding formula for local government. Does he accept that in the formula introduced by the previous Government, weighting was put in for density—four times that for sparsity—which has absolutely no link to need, and that is partly why certain parts of the country, even under this Government, have unfairly benefited? Will he unpick that so that sparsity is given greater weight than density, which has nothing to do with need? Hilary Benn - Hansard - Copy Link - - Excerpts If we get the opportunity after a certain event on 7 May, I would be very happy to receive representations from the hon. Gentleman and everyone else, because when I say that we want to achieve a fairer funding mechanism, that is what I mean. In return for this economic devolution deal, all we ask is that local government comes together to form combined authorities across England. Their shape will vary from place to place, because economic geography and travel-to-work areas vary. This is a challenge to local government. Local government says to all politicians, “Trust us more.” Well, we would trust local government more. We would say, “Get organised, and significant devolution of funding is on offer in return.” Mr Redwood - Hansard - Copy Link - - Excerpts rose — Sarah Newton (Truro and Falmouth) (Con) - Hansard - Copy Link - - Excerpts Will the right hon. Gentleman give way? Hilary Benn - Hansard - Copy Link - - Excerpts I have been generous in giving way, but I am going to bring my remarks to a close because many other Members want to speak. Councils want fairer funding, longer-term settlements, and devolution of power. They have worked really hard to reduce the impact of funding reductions on their residents, but they are now saying that this settlement could mark a turning point where the things they have worked hard to protect will be more difficult to protect in future. If the loss of services that we have seen—in the case of social care, that is largely hidden, because someone has no idea what they would have got before, as they only discover what they will get at the time when they need social care—is only part of what the Chancellor, the Secretary of State and the Prime Minister have in mind for local government in the years ahead, I say to the Minister that Labour Members will certainly not be joining him in a headlong rush back to the 1930s. Hard-working councillors want a Government who acknowledge that they have had a tough time and face stark choices, and Ministers who give an appearance of knowing what is going on. Labour Members recognise that local government has to make a contribution to tackling the deficit—tough times do indeed require tough decisions—but there is no justification whatsoever for taking the most from those who have least. However many “Fair to all, north and south” speeches we may hear from Ministers, they can no longer pretend that that is the case. For that reason, while we do not oppose the referendum report, we will vote against the local government finance report. 16:33 Robert Neill (Bromley and Chislehurst) (Con) - Hansard - Copy Link - - Excerpts In one respect, it is a pleasure to follow the right hon. Member for Leeds Central (Hilary Benn), because he always speaks with courtesy and care. On the other hand, it is regrettable that, yet again, we have seen a classic piece of sleight of hand from Opposition Front Benchers. Labour Members have remarkably selective memories. I give him credit, though, for doing rather better than his party leader in at least managing to mention the deficit. The right hon. Gentleman talked about localism, but then made it clear that Labour Members’ version of devolution and decentralisation, which one might think at first was one of the great damascene conversions of our time—not so much a road to Damascus as a bypass, given where they started from—is totally hedged in with centralised control, saying, “We’ll devolve if you go along with our imposed regional template.” Basically, he is a more subtle version of the noble Lord Prescott. He wants to re-impose regional straitjackets on local authorities through the back door. That is the reality of Labour’s supposed devolution agenda. Sarah Newton - Hansard - Copy Link - - Excerpts I share my hon. Friend’s concern, because what I have just heard is a proposal to reverse what this Government are doing through their regional growth funds: devolving real power and responsibility to Cornwall council. The Opposition are saying that we cannot have that unless we join up with Plymouth or Devon or who knows where. Robert Neill - Hansard - Copy Link - - Excerpts It is a little like the classic Henry Ford approach of telling people that they can have any colour car they like so long as it is black. The Opposition are saying that people can have any type of devolution they like so long as they sign up to their version of what they now call a county region—that’s a new one! Calling it the north-east or east of England did not work; they are calling them county regions now, but only so long as people sign up to their imposed template. Local government has not forgotten that this is the same team that introduced capping without giving it the chance to ask for the views of local voters; that introduced comprehensive area assessments; that interfered through the Standards Board and tried to micromanage the behaviour of councillors; and that did nothing to deal with predetermination, which stifled democratic debate. It is the same old Labour. They have not changed at all; they have just reworked the language. This is the same team that, at the end of the day, created the financial ruin of this country which, slowly, the coalition has had to put right. They are the people who damaged the hardest pressed in this country through their economic management, but there has been no apology or word of recantation. Mr Redwood - Hansard - Copy Link - - Excerpts Did my hon. Friend notice the continued insult to England? The Opposition say absolutely nothing about allowing England to settle her income tax levels, but they want Scotland to settle theirs. They want Scottish MPs to come down here and help dictate to England our income tax while they Balkanise England and pretend that breaking it up into mock European areas is some substitute for proper devolution. Madam Deputy Speaker (Dame Dawn Primarolo) - Hansard - Copy Link - - Excerpts Order. The right hon. Gentleman has got his point on the record, but you will stick to local government finance, won’t you, Mr Neill? Robert Neill - Hansard - Copy Link - - Excerpts Indeed I will, Madam Deputy Speaker. As we consider the future shape of the United Kingdom, I hope we will have a genuine debate about serious devolution of financial responsibility to local authorities, but that is certainly not what the Labour party’s proposals will achieve. Mr Mike Hancock (Portsmouth South) (Ind) - Hansard - Copy Link - - Excerpts The hon. Gentleman, like me, has had a long career in local government. Over 40 years, I have heard successive Labour Members say that they will find a fairer system to help local government survive, but the first thing they do when they come into office is find ways to reduce the amount of money going to local government while at the same time increasing its responsibilities. How can we take seriously what the right hon. Member for Leeds Central (Hilary Benn) has said if he is following that same pattern? Robert Neill - Hansard - Copy Link - - Excerpts That is certainly true of Labour Governments when they have come into office. I would gently add that when this coalition Government came into office we said that we would abolish capping and get rid of the Standards Board and the comprehensive area assessments, and we did so. We actually delivered on what we said. That is the difference between the two. Mr Graham Stuart - Hansard - Copy Link - - Excerpts My hon. Friend is rightly dissecting the speech given by the shadow Secretary of State, who failed to say, despite having repeated opportunities to do so, that he would seek to redress the imbalance between rural and urban areas. Is it not clear that every rural community in this country should recognise that a Labour Government will put its own political interests ahead of a fair and equitable settlement? They should not be fooled by the words that have come from the shadow Secretary of State’s mouth today, because he refused to commit to a change that would make the situation fairer. Robert Neill - Hansard - Copy Link - - Excerpts At the end of the day, it is implicit that a Labour Government would carry out a redistribution. We know from experience that the clever—and sometimes surreptitious—tweaking of the weightings in those 270-odd elements that go into the formula grants through the regression analysis was deliberately manufactured to move money away from parts of this country to those that historically tended to vote Labour. There is no getting away from that reality and the same thing will be done again. My hon. and learned Friend the Member for North East Hertfordshire (Sir Oliver Heald) made a serious point about what would happen to those authorities dealing with housing need, which I thought both parties recognised. The current Government have said, sensibly, that the money should follow the population growth, because that results in the costs of services being given to local authorities. The Labour party wants to scrap that entirely. It is abject nonsense to go down that route. Sir Oliver Heald - Hansard - Copy Link - - Excerpts If we have to build all these homes in Hertfordshire without the new homes bonus, and if our CIL is cut as the shadow Secretary of State suggested, we will end up with absolute traffic chaos and the whole county becoming a car park. Does my hon. Friend agree that this just does not add up? Robert Neill - Hansard - Copy Link - - Excerpts I have no doubt that we would also see the imposition of regional planning through the right hon. Gentleman’s delicately termed “county region authorities”. That would be another imposition on local authorities. The new homes bonus has enabled authorities that want to provide homes for their populations to deliver those homes and to pay for the services that such populations rightly demand. There is an inherent contradiction in the Opposition’s argument. It is significant that Opposition Members are talking about greater devolution. I, too, hope that there will be an increase in the retained element of business rates. Interestingly, that never happened throughout the whole of the Labour party’s watch. They only started to move towards a devolutionary stance after my right hon. Friend the Secretary of State introduced the retention of some of the additional business rate. We have a track record of delivering policies, but they are simply saying that they would do the reverse of whatever they did in the past, which seems fairly normal for the Labour party at the moment. Mr Betts - Hansard - Copy Link - - Excerpts Will the hon. Gentleman give way? Robert Neill - Hansard - Copy Link - - Excerpts I will of course give way to the Chair of the Select Committee. Mr Betts - Hansard - Copy Link - - Excerpts I agree with the hon. Gentleman on the business rate—the direction of travel is right, and it is sensible to move towards total retention—but is there any evidence that the new homes bonus has led to the building of one additional home? Robert Neill - Hansard - Copy Link - - Excerpts Yes, it is very clear that more new homes are being built. The right hon. Member for Leeds Central talked about need. One of the biggest recipients of the new homes bonus has been the inner-London borough of Tower Hamlets. It has built homes in a needy area, and it has been one of the biggest beneficiaries of the new homes bonus. There is therefore a direct correlation, and that correlation also relates to need. With respect to the hon. Member for Sheffield South East (Mr Betts), his point was not the best he has made in debates in the Chamber. It is worth observing that local authorities have calculated that they will see an increase in business rate income in 2014-15, thanks to the Government’s economic policies. Some 91% of local authorities anticipate that their business rate income will grow during 2014-15, because we are starting to get the economy back on track. Having record levels of jobs and economic activity would be prejudiced by the Labour party, but that is the real way to create sustainable funding for local government, not a culture dependent on tweaking handouts. My hon. Friend the Member for Hornchurch and Upminster (Dame Angela Watkinson) made an important point about why we need to move away from the culture of dependency. Historically, there were disparate levels of resourcing between inner and outer-London boroughs. Once upon a time, that to some degree reflected the demography of London, but that demography has changed significantly. As I know from the experience of my London borough of Bromley, the pressures facing outer-London boroughs are now much closer to those of inner-London boroughs. As my hon. Friend the Member for Beverley and Holderness (Mr Stuart) observed, the artificial inflation of the weight given to density has made the problem worse in some cases. Throughout this Parliament, my right hon. Friend the Secretary of State and his ministerial team have gradually sought to rectify such wrongs, and I hope that in the next Parliament we can build on the very solid foundations built so far. At the end of the day, I hope that we can move away from the artificial argument about dependence on the central Government grant. We should give local government the tools to invest, which is why the new homes bonus and the retention of business rates are so important. A fairer and more transparent basis for funding is critical, and that is what the coalition Government have delivered. There is still more to do, although none of us would disagree that local government is probably the most efficient part of the public sector. That is why I was pleased to see the excellent work done through the better care fund. I represent a top-tier authority, and most such authorities regard adult social care as one of their principal funding pressures. Once the better care fund is established, I hope that much more work will be done to align adult social care with health services. Local authorities can often deliver many of the health-related aspects of services for elderly people more efficiently than the traditional health service model. Again, my right hon. Friend the Secretary of State is to be congratulated on opening up that new opportunity, which sensible authorities, such as mine in Bromley, have already seized. We must ensure that health authorities and commissioning groups understand that too, and that they fully co-operate and do not seek artificially to hang on to money—often, their local government colleagues may be best placed to get the best bang for local residents from the available buck. I hope we will see more of that important development. Although not directly part of the grant settlement, I hope my right hon. Friend will continue to point out to colleagues in the Department for Education that we could look for greater flexibility in the operation of the dedicated schools grant. That is a good thing in itself, but some types of educational spending currently fall outside its parameters, and we could consider that issue for the future. None of that takes away from the fact that every local government Minister has to do a balancing act when they set out the local government finance settlement. I believe that the DCLG ministerial team has done a good job, and above all we must keep bearing down on the deficit and keep public finances under control. Equally, we should continue to reward councils that do the right thing. In due course, as my right hon. Friend the Member for Wokingham (Mr Redwood) was hinting—I will say this in a way that does not make me out of order, Madam Deputy Speaker—I hope that as we consider future funding arrangements for the whole United Kingdom, we will be able to give more weight to councils such as Bromley that have historically shown high levels of efficiency. Bromley delivers its services at the lowest unit cost per head of any London borough, and it also happens to have the second lowest level of central Government grant. The more we remove local authorities from the need to depend on that ratio of central government grant the better, and the more likely it is that they will profit from their own efficiency. That is the way forward. I hope that in the short term we will look again at some elements of the way the grant is calculated and give greater weight to efficiency. It is probably right that there should be a greater relationship in local government between behaviour and out-turns, and between behaviour and consequences. The best thing would be to ensure that a higher percentage of local government spend is raised locally, and the Government are on course for that. They have made a good start but can always continue to do further work in future. At least we are able to offer local government a realistic programme as we go into the general election, building on achievements that have been delivered, rather than on the inherently contradictory flights of fancy from Opposition Members. We respect local government—I spent many years of my life in local government, and there are good people and authorities of all colours. For all the words of the right hon. Member for Leeds Central, imposed centralism is not the answer, and we must build incrementally—as the Secretary of State rightly has done—to return powers increasingly to local government. This finance report is consistent with that path, and I hope the House will support it. 16:47 Mr Clive Betts (Sheffield South East) (Lab) - Hansard - Copy Link - - Excerpts This Parliament will clearly go down as the Parliament of austerity, but let us go back to 2010 and look at the situation when we began this journey. At the general election in 2010 the economy was growing— [ Interruption. ] I know Conservative Members do not like to hear that, but it was growing. The Government made a commitment in the coalition agreement to removing the deficit over the course of this Parliament, but that has not happened, has it? That is because the economy stopped growing because of the immediate severity of the cuts. As a result, not only did that happen, but real wages have not grown, the tax take has been less than anticipated, and the increase in housing benefit paid to people in work has grown substantially. That is why the deficit has been cut to only a third or a half—depending on the definition —of its original level. Mr Graham Stuart - Hansard - Copy Link - - Excerpts The hon. Gentleman is the only senior commentator I have heard suggest that the economy stalled primarily because of a reduction in Government spending. Surely he should accept that it was to do with the general economic dislocation across the continent of Europe. While the rest of Europe is flatlining, and while this Government have tried to wrestle down the deficit, Britain has returned to growth. We have higher growth this year than any other major economy in the world, and that should be celebrated. Mr Betts - Hansard - Copy Link - - Excerpts That is interesting. If the hon. Gentleman is saying that the fundamental problem was a major dislocation in Europe and the world because of the banking crisis and collapse, it is difficult to blame it solely on the Labour Government. After the major dislocation and the recession, the economy had started growing by the time of the election in 2010. It then went back into recession. That is what happened. We are where we are. Through all the austerity and the pain of service cuts, the deficit is at least half of what it was. In other words, the Government have missed their target by at least 50%. That is the position. Nobody will dispute that, will they? It is fairly clear that the Government missed their target by at least 50%. We have had all that austerity, but has it been fair? Has it been fair to local government as a whole, to Conservative councils as well as Labour councils, because they will make that point strongly? Why has local government been asked to bear the biggest burden? There is another way of putting that: why do Ministers believe that the services our communities receive from their local councils are less important than other public services? That is important. Mr Stuart - Hansard - Copy Link - - Excerpts We were protecting the health service. You can’t have it both ways. Mr Betts - Hansard - Copy Link - - Excerpts The hon. Gentleman shouts, “We were protecting the health service,” but social care provided by local councils is as important. Of course, that is not protected from the reductions. The figures I quoted earlier were from the Local Government Association and the Office for Budget Responsibility, so they are clearly right—perhaps hon. Members want to challenge them. The spending that local authorities can control—which excludes schools, public health, which is ring-fenced, and housing benefit—has fallen from 19% of total public sector current expenditure in 2009-10 to 16% in 2015-16. That is a disproportionate cut in local government spending compared with public spending as a whole. There is another way of looking at it: local government spending as a percentage of GDP has fallen from 4% to 2.9%. That is a significant fall. The Government have tried to spin the 2015-16 cut as a 1.7% cut in spending power, but we should again look at the figures produced by the LGA, which are based on OBR figures. The real figures that local authorities can control, on a like-for-like basis over the years, excluding the better care fund, council tax and the public health grant, which is ring-fenced, show that the cut is 8.5% in real terms. That is the figure. Ministers like including spending power and they like the better care fund. Hon. Members should read the exchange that the Communities and Local Government Committee had with the permanent secretary recently. He accepted that the better care fund was not part of the grant from central Government to local authorities. That money is included in the budget of the national health service, in the Department of Health. That is where it is accounted for. Ministers cannot count it in both the Department of Health budget and the Department for Communities and Local Government budget. That would be double counting. Ministers count the better care fund in the Department of Health budget, and say, “Ah. We do not talk about the actual grant and money for local authorities. We talk about spending power.” Although the better care fund is in the Department of Health budget, they say that it is part of local government spending power. That is how they get their calculation down to 1.7%. That is how they do it—by sleight of hand. We cannot have that double counting. That is not to decry or demean the better care fund. The concept of trying to join up health service and local authority social care is obviously a good one. Mr Stuart - Hansard - Copy Link - - Excerpts Will the hon. Gentleman give way? Mr Betts - Hansard - Copy Link - - Excerpts I will make a little progress and come back to the hon. Gentleman. There are major issues. Why are local authorities singled out for bigger cuts? Within local government, why have the deprived communities had the largest cuts? Ministers could make a logical, rational argument. They could say that the authorities with the biggest grant might lose the most grant in cash terms. I might not agree with the argument, but I can see a logic to an argument that says because authorities have so much more money given to them historically, they are likely to lose more when cuts are made. Can Ministers sustain an argument that says authorities historically receiving the most grant, the most needy authorities, should therefore have the biggest percentage cuts? What is the logic for that? It is one thing to argue the biggest amount, in cash terms, should come from authorities with the most cash given to them, but why should they have the biggest percentage cuts? What is the logical argument for that? How can it possibly be right that over the period of this Parliament, between 2010-11 to 2015-16, Sheffield’s spending power—I will use the Minister’s own definitions —has fallen by £230.60 per head and Wokingham’s has fallen by £2.29 per head, only 1% of Sheffield’s fall? How can there be any rational, reasonable justification to explain that cut? How can there be? Mr Gordon Marsden (Blackpool South) (Lab) - Hansard - Copy Link - - Excerpts My hon. Friend is making a powerful and incisive point. Does he agree that this bears down particularly badly on those unitary authorities, such as my own in Blackpool, which have above-average needs in big spending areas such as education and social services, but find themselves subject to precisely the phenomenon he describes? Mr Betts - Hansard - Copy Link - - Excerpts Absolutely. As I say, Ministers can make an argument that those who have had the most grant might lose the most cash, but not that they should have bigger percentage cuts. They are the areas in greatest need. In two years’ time, we will have the ridiculous situation where Sheffield and most of the northern cities, such as Liverpool and Manchester, will have a lower spending power per head than Wokingham. Can anyone on the Government Benches justify that? It is simply not reasonable. The hon. Member for Bromley and Chislehurst (Robert Neill), an ex-Minister, said he suspects a future Labour Government would find surreptitious ways to redistribute money back to Labour authorities. I think we can be open about this: this Government have not been surreptitious. They have done it blatantly. They have taken money away from the most needy and given it to the most privileged. That is what they have done, to the point where the spending power of Wokingham in two years’ time will be greater than the spending power of Sheffield on a per-head basis. Sorry, but that is just not reasonable and no one can justify it. The impact is there for all to see. I went around my constituency last weekend and met people. We talk about the need to join up social care and the health service—of course we need to. Sheffield had a wonderful in-house care service provision called “Care for you”, which dealt with some of the most needy people who were in their own homes and required extensive support. Sheffield ended that service because it was cheaper to go to a private supplier that had lower overheads, mainly because it does not train as well and pays the minimum wage at best. I then met a constituent on Saturday whose elderly father’s carer missed four appointments. After 36 hours his father was found collapsed on his bedroom floor and, of course, was admitted to hospital. Why was he admitted? The care package had failed. Why had it failed? The authority was having to make cuts because of the budget cuts. That is the reality of how things are in local government at present. That is not a bad authority trying to do it on the cheap, but an authority trying to reduce spending, because of the massive cuts it is facing, by another £60 million next year. In the end, much of that will have to fall on social care, the biggest budget. Mr Graham Stuart - Hansard - Copy Link - - Excerpts The hon. Gentleman talks about double counting. He accepted that the Government had protected the schools budget and the health budget, and that therefore, given the size of those budgets in overall Government expenditure, there would be disproportionate cuts elsewhere. Will he put it on the record that his party would, as it did in Wales, cut the health service to protect local government funding? Tough choices means being clear about what one protects and what one will cut. His party seems to want to have it every which way without telling people the truth. Mr Betts - Hansard - Copy Link - - Excerpts I think we should also deal with the myth that somehow the NHS has been protected. If we look at the King’s Fund and other commentators—the British Medical Association, certainly, or go to the GPs in my constituency—its spending has gone up in line with general inflation. Unfortunately, though, it has not been sufficient to cope with the increased demand, particularly from elderly people wanting ever more support from community GPs and hospitals. If we have dealt with half the budget deficit this Parliament, is the Tory party saying that, if it is returned to power, this scale of local government cuts will continue? Can we really contemplate reducing local government spending as a percentage of GDP from 4% to 2.9% and below? If so, we will not be back to 1930s levels of service provision; we will have gone back even further. The graph of doom is coming. Tory councils as well as Labour councils are talking about it. Figures from the Office for Budget Responsibility show that by the end of the next Parliament, if the cuts continue on the same trajectory, we will reach the point where statutory responsibilities take up the whole local government budget, and nothing will be left for discretionary services. But I do not expect Ministers to respond, because, as the damning report from the National Audit Office said: “The Department does not understand the impact over time of reductions in funding to local authorities, and the potential risks of individual authorities becoming financially unsustainable if reductions continue.” That is what the NAO said, and that is the reality we are facing up to. I do not have time to go into all the issues of decentralisation. I am a decentralist, and I speak on behalf of the Select Committee. We would decentralise not merely spending responsibilities, but tax-raising responsibilities, which the Labour Front-Bench team is beginning to move towards, with full responsibility for retaining business rates locally. I hope we can go further, but so far the Government are not prepared to move in that direction. In conclusion, there are three big questions that the Government have not answered. Why have local authorities had to face more than their fair share of cuts, compared with other Government services, in this Parliament? Why have the poorest authorities faced the largest cuts—far larger than is proportionate? In the end, do Ministers seriously believe that in the next Parliament we can continue with the same level of local cuts and maintain the financial sustainability of local councils and the services they deliver? 17:02 John Pugh (Southport) (LD) - Hansard - Copy Link - - Excerpts It is a pleasure to follow the hon. Member for Sheffield South East (Mr Betts). It would be churlish not to welcome the new money announced—it is welcome and needed—but I want to make a few brief observations. It is indisputable that during the attack on the deficit local government has been hit first and hardest, as it often is by all Governments—because local government is not us. We set the budget and they, the councillors, have to make the cuts. In fact, however, it is the only public service budget that has to reach a black line every year, no matter what we throw at it—and we have thrown an awful lot at it, which makes things tough and constrained. It is widely admitted, however, that in very difficult circumstances local government has coped quite admirably—somehow—but in varied ways and with greater or lesser difficulty. If the NAO is to be believed, the Government do not realise how much that has varied and cannot be sure that local government can continue to cope in the future. The hon. Member for Sheffield South East made that point very effectively. We cannot be sure that local government is sustainable in its current form, particularly because no party is offering it any kind of reprieve, so far as I can see. It is indisputable—I would not disagree with the hon. Gentleman—that by and large the metropolitan and urban areas have lost most in proportional and real terms. We can, as the Government do, call that fair, because they had the most per capita in the first place—and they still have—or unfair because they have the greatest need. We can stand in argument either way, and most of our argument concerns just that point. I personally regard a 40% overall reduction in the DCLG’s account during this Parliament as too severe to be well managed and as unnecessarily damaging. I say that as a supporter of the Government’s deficit reduction ambitions. I have voted unflinchingly so far on most financial issues. On this occasion, however, one thing sticks in the craw—the dishonesty and disingenuousness of the presentation of the facts. It was bad enough when we had the sophistry of spending power replacing the clear grant support figures in hard cash terms. When we started to include money actually in the NHS budget in council spending power—and then went on to deny double counting—the truth started to recede for me. It was very depressing. As the hon. Member for Sheffield South East has explained, the last straw came last week when I and other members of the Communities and Local Government Committee, some of whom are present, saw the permanent secretary and head of the civil service, Bob Kerslake, attempting to describe double counting as something else. It was almost comical—there were contortions that could have appeared in a TV sketch for “Yes Minister”. It was a genuinely class act of a civil servant defending the indefensible. I urge hon. Members to try to download it or find it on Parliament Live, where they will see it is a work of considerable ingenuity! My point is simple. To make cuts and defend them is honest and tough; to make cuts and disguise them is, as I think most would accept, cowardly and weak; but to make cuts and deny them and absurdly twist language to do so is dishonest and dangerous. 17:06 Chris Williamson (Derby North) (Lab) - Hansard - Copy Link - - Excerpts I congratulate my right hon. Friend the Member for Leeds Central (Hilary Benn), the shadow Secretary of State, on his excellent exposition, setting out Labour’s alternative to what the Government have put forward today. We are meeting at an apposite time. Hon. Members have referred to the reports of the National Audit Office and the Public Accounts Committee. I have with me a copy of the PAC report. To summarise it in respect of the Government’s record on local government, let me say that the Government have failed to provide leadership on local government finance; failed to understand the impact of the cuts they are making; failed to apply the cuts fairly, as we have heard today; and failed to recognise the effect that the cuts are having on councils’ ability to deliver their statutory services. Many of us here will be familiar with the “graph of doom” produced by the Local Government Association, which has pointed out that in a very short time local authorities will be capable of delivering only their statutory services, and that if the funding arrangements continue on their present trajectory, many authorities will be struggling to deliver even their statutory obligations. It was my privilege a couple of weeks ago to re-launch the “Fair Deal for Derby” campaign. Derby has been crucified by this Administration, and the Secretary of State is acting like a giant wrecking ball on local government services in the city. We have seen a reduction in funding for the local authority of some £379 per household in the city of Derby. The cuts that the council has already had to make amount to some £96 million with a further £69 million to find—unless the Government change tack or unless, as we hope, we see the election of a Labour Government on 7 May. Mr Graham Stuart - Hansard - Copy Link - - Excerpts Is it the hon. Gentleman’s understanding, as it is mine, that the Labour party has not pledged to increase the overall funding envelope for local government? Will he spell out—in a way that the right hon. Member for Leeds Central (Hilary Benn) failed to do—exactly who would be the losers in a process where there will be no winners except at the expense of others? Chris Williamson - Hansard - Copy Link - - Excerpts My right hon. Friend the Member for Leeds Central was absolutely clear about the funding. He said there would be a fairer funding settlement. I cannot see how my right hon. Friend could have been any clearer than that. What we have seen over the past four and a half years is anything but a fair settlement. What we have seen is the neediest and most deprived parts of the country shouldering the biggest burden. What did we hear from the Prime Minister and the Chancellor? We heard that they would not balance the books on the backs of the poorest people, yet that is precisely what they have done, as we heard from my right hon. Friend. My local authority in Derby will have lost half its budget. Just imagine the impact of that on council services for vulnerable children and elderly and disabled people in our city! Social care has been decimated, and facilities such as street cleaning, street lighting and leisure services are also under threat as a result of the Government’s cuts. Last week saw the ridiculous scenario, the ridiculous spectacle, of the Secretary of State coming to Derby and suggesting that the council should use its reserves. “The council has £81 million in reserves,” said the Secretary of State. “Why does it not use that money?” Well, as my right hon. Friend pointed out, we can only use the reserves once, and, furthermore, they have already been earmarked. They have been earmarked for new schools, for instance, and for the cost of the redundancy payments that must be made to the public sector workers who have had to be sacked because of the unprecedented cuts that the Government have imposed on Derby. It is ludicrous for the Secretary of State to come to Derby and say that the council should simply use its £81 million worth of reserves, as if they were not earmarked, which they are, and as if it could keep on using them, which it cannot. It is crazy for him to do that. To add insult to injury, not only did the Secretary of State turn up unannounced, but when the leader of the council, Ranjit Banwait, politely asked if the Secretary of State would meet him, the Secretary of State snubbed him. He said, “No, no, I haven’t got time to meet the leader of the council.” The leader wanted to report some of the concerns felt by councillors and some of the problems that the council was facing, and to put the case for a fair deal for Derby, but the Secretary of State was not interested. He was only interested in making political capital and in speaking to the leader’s political opponents, his own Conservative friends on Derby city council. As if that were not bad enough, the Prime Minister then weighed in. He appeared on Radio Derby, and he too referred to the reserves. He then made the ludicrous assertion that West Oxfordshire district council, his local authority, had been worse affected than Derby. I do not know whether the Prime Minister has been paying a visit to planet Zog or has been living in cloud cuckoo land for the past four and a half years, but the suggestion that West Oxfordshire has been worse affected than Derby flies in the face of the facts. The facts are very clear. The cut in West Oxfordshire amounts to some £90-odd per household, whereas the cut in Derby is almost £400 per household, which is four times as much. I know that the Prime Minister went to a very good school. He went to Eton, I understand. I left school at 15, and I was not great at arithmetic, but it seems to me that the Prime Minister could have done with spending some time in Labour’s former “numeracy hour” to work out basic arithmetic, because he clearly got that very badly wrong. As Labour Members have already pointed out, the cuts have caused the economy to struggle and to go into a downturn. We have experienced the longest recession for more than 300 years, and the slowest recovery for more than 100. Why is that? When this Government came to power, they inherited a growing economy and falling unemployment, We had started to turn the corner, but what did the Government do? Owing to their ideological zeal, their determination to smash the state, and their obsession with neo-liberal economics, they sent the economy into a tailspin. It is important to bear in mind the symbiotic relationship that exists between the public and private sectors. Where does the Minister think public sector workers spend their money? Where do the almost 1,500 redundant council workers in Derby spend their money? They spend it in the local economy; they spend it on goods and services provided by the private sector. That is why it is important to recognise this symbiotic relationship between the public and private sectors. Members on the Government Benches clearly do not understand that or why the economy has struggled so much and continues to struggle. They claim it is doing incredibly well now—well, you could have fooled me and many millions of people who are still struggling with the cost of living crisis. It is obvious that their obsession with austerity and market-led economics and their hostility to the public sector have been an utter disaster in terms of the impact on the people who rely on those services and on the economy. What is desperately needed is a Labour Government on 7 May, with my right hon. Friend the Member for Leeds Central as Secretary of State for Communities and Local Government, because he has made it very clear that there will be a fairer funding settlement within the financial envelope. We have also made it very clear that a Labour Government would grow the economy, which this lot have been singularly unsuccessful in achieving. We would then be able to use the fruits of economic growth to sustain our public services, to continue to grow our economy and to create that economic virtuous circle. Today we saw the ludicrous spectacle and the political stunt of the Prime Minister pleading with the captains industry: “Britain needs a pay rise.” I thought for a moment when I saw that that he had converted to the TUC because it has been calling for this for a long time. Yes, Britain does need a pay rise—a pay rise for ordinary people, not the oligarchs and the hedge fund managers who fund the Conservative party, and whom Conservative Members were hobnobbing with last night at their black-and-white ball. What we need is a Labour Government, and a Labour Secretary of State—my right hon. Friend—with a fairer funding settlement so we can get this country back on its feet, and get our public services delivering the services people in our country desperately need. 17:17 Anne Marie Morris (Newton Abbot) (Con) - Hansard - Copy Link - - Excerpts This Government have done a tremendous job in rectifying some of the wrongs the previous Administration inflicted on local government. Local authorities provide key services for all of us—care for the elderly, care for the disabled, care for children, the highways, street-lighting, libraries, youth services, economic development and so on. In that context, there is a real challenge for local authorities that service the rural community, and my community is very rural and is in the heart of Devon. One challenge we face, in common with many rural communities, is that we have an ageing population. We also have significant infrastructure challenges given the amount of road there is in Devon. Devon has, I believe, more roads than Denmark, and that gives rise to a huge number of challenges, never the mind the challenge of the pothole. The Government’s comprehensive spending review of 2010 changed the system for funding local authorities and, rightly, looked at a programme of significant funding reductions. It did not take account of the particular needs of rural communities, however. Consequently, in Devon funding has fallen by £80 million and it has had to look at saving £128 million in total, so it has reduced staffing, introduced pay freezes, rationalised the estate and reduced management costs, and by all accounts has done all that a responsible local authority could do. Therefore, in the context of the funding settlement for 2015-16, looking at what further it can do is a real challenge. Devon’s core funding has been reduced by £29 million, a significant sum given the work that has already been done. There is also significant concern about the implications of the Care Act 2014, which implemented the Dilnot findings and introduced a cap on lifetime cost of care. The authority therefore has concerns about what additional funds it is going to have to find. The Care Act also changed the threshold at which people contribute. All of those uncertainties add to the challenge, and the Care Act is particularly significant for us given the ageing profile of Devon’s population. That said, Devon is grateful for those chunks of money that it has received: the £16 million schools funding—the minimum funding level for school block units—is welcome, as is the £871,000 sum for welfare and social care, which we badly need. None the less, that does not deal with replacing the old grant of £1.3 million to support the vulnerable, which is now gone. What can we do now? Where can we move forward? How can we rectify that imbalance between the urban community and the rural community? As has been said, the Government recognise the challenge and that something must be done. Indeed, they have already begun to deal with it. The challenge was that the changes in the sparsity weighting were lost in damping, and the reality is that rural areas on average still receive £153 per head less in Government grants than urban areas. The rural services delivery grant was, again, a welcome help, but £15.5 million equates to £1.20 per head. Realistically, that is a drop in the proverbial ocean, and that amount fills about 1% of the gap in the settlement funding assessment. We need £30 million each year, on a cumulative basis, to begin to right that wrong. My concern, on top of the lack of funding, is that our rural communities are also being penalised by having to pay a greater level of council tax—indeed, £81 more than the average urban constituent. Locally, if we compare Teignbridge district council with the nearest city, which is Plymouth, the residents of Plymouth will get £93.84 more under the latest Government funding settlement. That simply cannot be justified. There are huge pressures on local authorities, which are really challenged. Whatever they do with council tax, they are still struggling. It is not surprising that the new homes bonus has in effect come to their rescue, to fill the gap, or that, equally, communities feel deeply frustrated and concerned that that is leading to overdevelopment. In our communities, including my Devon community, there is real pressure on care, day care centres, children’s centres and libraries. We are getting to the point at which we will be squeezing the pips and they will be squeaking. The Government must act to rectify the imbalance and they need to set a new formula. I want to see something set out in the upcoming and final Budget, with real recognition of the real need of rural communities. Even more, I would love to see a manifesto commitment. We need recognition that, for rural communities, social care is a huge cost and a real issue and that infrastructure is a real challenge. 17:22 Mrs Louise Ellman (Liverpool, Riverside) (Lab/Co-op) - Hansard - Copy Link - - Excerpts Whatever the Government’s protestations, it is absolutely clear that the settlement is grossly unfair to Liverpool, the most deprived local authority in the country. The settlement can only be construed as part of an ongoing attack on public services. This year, individual residents of Liverpool will in effect each receive a cut to their local services of more than £391. By 2017, Liverpool city council will have suffered an astounding real-terms cut of 58% to its funding from central Government. That is devastating. The city’s deprivation is mirrored in its tax base, and 77% of homes in Liverpool are in the lower council tax bands, A and B, which means that only 9% of the city council’s budget can be raised through the council tax. In West Oxfordshire, 49% of the budget can be raised through the council tax, because of the wealth of the area. Mayor Anderson and his council are doing a valiant job in difficult circumstances. They are building new homes, and more than 2,500 have come on stream this year, which has produced more than £3.5 million in additional revenue, but that cannot match the massive cuts by central Government. The council has set a three-year budget to bring stability and has carefully examined threatened services. By looking at new ways to fund libraries it has managed to save the city’s libraries. When the Government withdrew funding for schools under the Building Schools for the Future programme, the council found a way of building the most essential schools. It has also protected Sure Start and children’s centres, although some cuts have been made and, sadly, those services are again being reviewed because of the new cuts being imposed by this Government. Reserves have been spent as far as it is prudent to do so —by 2017 the city’s reserves will be down to £17.6 million —and they cannot be reduced further if the council is to act prudently. Despite all those measures the council has taken in becoming increasingly efficient and looking for innovative ways of funding public services and creating new revenue streams, vital services are being attacked. The most important and concerning crisis being faced currently is on vital packages of social care. Social care is support to enable people who are ill, elderly or disabled to live in their own home in dignity. When this Government came into power, 15,000 people in Liverpool had support through social care packages, enabling them to live a dignified life, whereas now, as a direct result of Government cuts, that is down to 9,000 people—6,000 people have been deprived of care, despite rising needs. Unless something dramatic happens, the figure will reduce even further. That puts people’s lives at risk and robs them of their dignity. It also affects hospital admissions, because it means that, increasingly, people who are well are not able to leave hospital because appropriate care is not available for them. Liverpool’s council is enterprising. I was horrified last year when the Minister in charge of local funding at the time said from the Treasury Bench that he thought Liverpool was a city where people wanted to doff their caps. That was an horrendous statement to make; Liverpool is a proud city. It deserves support, it acts enterprisingly and it helps itself. Increasing numbers of jobs have been brought to Liverpool, and in two months’ time Cunard, in celebrating its 175th anniversary, will bring three major, spectacular liners to Liverpool. Their return is a symbol of the city’s renaissance, which has been brought about by the efforts of the city council. But whatever the city council does in supporting jobs and working with the private sector, it cannot provide the public services that the Government are so savagely cutting away. All I can ask for today is for the Government to be fair to local authorities in general, to be fair to the most deprived local authorities and to recognise that in Liverpool city council they have an enterprising, positive local authority, which is there to serve its people, bringing jobs and working with the private sector. Surely it deserves a better deal for public services to serve our local communities. 17:28 Annette Brooke (Mid Dorset and North Poole) (LD) - Hansard - Copy Link - - Excerpts As a vice-president of the Local Government Association, I wish to start by discussing the LGA figures. They point out clearly that there has been a 40% reduction in core Government funding since 2010, and that today’s settlement will require councils to make a further £2.5 billion in budget cuts. We must all be concerned about the financial sustainability of local government, and I concur with some of the points made by Labour Members and by my hon. Friend the Member for Southport (John Pugh). We must praise councils and councillors across the country for the way in which most have responded to the challenges, finding new ways of working, finding efficiency savings and protecting front-line services—and we find that satisfaction in council services has increased. That is remarkable. I am proud that this Government introduced the Localism Act 2011 and of the emphasis on local decision making, with some notable exceptions such as top-down pronouncements or when local authorities have to implement local schemes with inadequate funds under constraints set by central Government such as the council tax reduction scheme. On that issue, more transparency on central support—or lack of support as the case may be—would be welcome. Looking ahead, to deliver services more efficiently and effectively and to drive economic growth we must have devolution within and across England and on demand, building on what has been achieved so far. I do not exclude counties, as it is right that we have bottom-up devolution, through which areas outside the cities have opportunities to have more power. Tax-raising powers should be given to such areas. My right hon. Friend the Chief Secretary to the Treasury discussed that very point this week. Westminster has to let go. It would be good to see published work on the implications of increasing the proportion of business rates retained by local authorities. I welcome the Government’s inclusion in the final settlement of an additional £74 million for local welfare assistance. I could criticise it and say that it is not enough, but to be honest, I am greatly relieved that all the many representations were listened to, including my own and that of the Liberal Democrat communities and local government committee, of which I am a co-chair. I feel so strongly that local authorities are a place of last resort for people who are destitute and who must be able to access immediate support when some unforeseen crisis has occurred. Mr Graham Stuart - Hansard - Copy Link - - Excerpts Can my right hon. Friend explain why her party believes that the local government settlement should and can be determined by the votes of Scottish MPs, when Scotland decides on the distribution of its local government formula itself? That is fundamentally unfair to the English voter whose will at the ballot box should hold in the way that local government funding is distributed. Annette Brooke - Hansard - Copy Link - - Excerpts I think I will stick to the issue under discussion this afternoon. I am very much speaking from a personal viewpoint. Let me continue with comments on the local welfare assistance fund. I wish to address some of the brilliant schemes that the fund has been used to support. I hope that they will be able to continue and that the £74 million will continue—or even be increased—in the future. On behalf of town and parish councils I wish to make a few general points. It is to be welcomed that no town or parish councils will be subject to the referendum threshold. That has concerned me greatly, because parish councils have taken on more responsibilities as services have been cut from higher level councils. I feel that that is a great deterrent to the taking on of some really important services, such as a community library in my constituency, but concerns remain on the short-changing by some principal councils of Government funding for council tax support. The National Association of Local Councils identified more than 30 such councils this financial year, and its research shows that the number of principal councils not passing on any council tax support funding to town and parish councils will increase in 2015-16. I have just received a holding answer to some questions that I tabled. I was told that my question on what further action the Minister will take on this issue will take a little more work. I hope that the Minister will be able to give me an answer today. Will he tell me what more can be done to ensure that principal councils pass on this funding, which is intended to be passed on? I represent parts of both rural and urban authorities, and I support the Rural Fair Share Campaign. We have had some welcome steps in the right direction, but there is a central unfairness to rural residents, which is that they receive less in services and pay more. We need much more done in that area. I welcome the reconsideration by the Government of Christchurch and East Dorset councils’ bid for the transformation challenge award and the allocation now of £867,500. The two councils have been working on service sharing for some time now, following a line suggested by the Government. That process has been hard for staff and a recent survey showed that staff morale is very low. I hope that this fund will mean a smoother process and some reassurances that residents in Corfe Mullen, Wimborne and Colehill in my constituency will not feel that they are on the fringes and left out. I was very pleased when the three principal councils in Dorset were named as the first winners of the Government’s transformation challenge award in October 2013. With other partners, they are working together to transform how health and social services are delivered across Dorset over the coming years, but despite the excellent work that is taking place, funding for social care remains of enormous concern in my constituency. I decided to look at my first speech in this House on local government finance and I found that in October 2002 I said that “in the south-west, a recent analysis shows that there is a £70 million care gap. Local authorities are warning that the social care safety net is not adequate for children, the elderly and the vulnerable.” —[ Official Report , 24 October 2002; Vol. 391, c. 452.] Of course, I was addressing a Labour Government. The needs are rising and the problem is becoming worse, but we should acknowledge that it is this Government who have made moves to bring health and social care funding together to make services work better together and to get more for our money. Those are moves in the right direction, although of course I would like some transparency and clarity about the extra funding available through the better care fund for local authorities. I recently met the leader of Poole borough council, Councillor Elaine Atkinson, and the Under-Secretary of State for Communities and Local Government, my hon. Friend the Member for Bristol West (Stephen Williams). The council leader’s concerns centred around the ranking of Poole, which is the third lowest funded unitary authority in England, and local needs. The greatest concerns were about social care, and I must praise the council leader, who is not a member of my party, for her passion for social care and for producing and providing the best possible services. In Poole, the over-65s—that includes me—make up 21.61% of the population. That is a very hefty proportion indeed. For the rest of Dorset, the figure is 26.95%, and, interestingly, the figure is lower in Bournemouth. The demands are great and, of course, following the High Court ruling, we have extra expenditure on the deprivation of liberty safeguards. That judgment obviously affects the statutory requirements for all councils, and I am quite sure that it is important, but there is a shortage of funding. Additionally, as many Members have mentioned, there are even more pressures across children’s social care. That is happening for the saddest possible reasons, but at least we are alert to what is happening out there. With Poole always having such a low ranking, there is very little room for manoeuvre with the extra demands placed on it. There is great concern that not as much money is coming out of the better care fund locally from the Dorset clinical commissioning group as was initially expected. I welcome the fact that Poole is to receive extra funding to help with the winter pressures of people being stuck in hospital when they are sick but do not necessarily need a hospital bed. A point that the council leader was very anxious to make concerned the difference between Poole and Bournemouth. It is very difficult to make comparisons between different places to argue a case, but her point was that Poole is allowed to retain 25.49% of its business rates whereas Bournemouth is allowed to retain 42.46%. Obviously, that is worked out according to the existing formula. I do not doubt that the figures are correct, but I am beginning to doubt the mechanism, because on the face of it, looking at Poole and Bournemouth, I cannot understand it. I can understand it on the formula, but I think that it will be really sad if we have to wait until 2020 for the make-up of that percentage to be looked at. I would like that to be reviewed earlier. In conclusion, I have said a lot today about social care, because I think that local government’s greatest concern is that day of doom, as we have heard. The Care Act 2014 is introducing new and welcome responsibilities, but with them come great uncertainty about the scale of the costs. I think that local government has done us proud. It is important that central Government give local government the tools and resources it needs. 17:40 Jonathan Ashworth (Leicester South) (Lab) - Hansard - Copy Link - - Excerpts I rise to make a few remarks on behalf of the city of Leicester, which I am fortunate enough to represent. In common with my hon. Friends the Members for Liverpool, Riverside (Mrs Ellman), for Derby North (Chris Williamson) and for Sheffield South East (Mr Betts)—he is no longer in his place—I represent a city that sadly often scores far too highly in the deprivation league tables, yet it has had to cope with significant budget cuts under this Government. That is why I wholeheartedly endorse the vision laid out by my right hon. Friend the shadow Secretary of State in his opening speech on the need for a fairer funding settlement. I also endorse the shadow Secretary of State’s vision for devolving more powers to local government, because although our city has huge levels of deprivation, we have tremendous potential. We are an exciting and vibrant city, with 9,000 businesses in our city centre and two first-class universities producing graduates who go on to work in the east midlands’ manufacturing base and computing base. Our mayor, Sir Peter Soulsby, has been integral to our city deal and central to getting a deal that will see IBM bring 300 jobs to the city. Indeed, IBM praised the work of the city council when it announced that it was coming to our city. Leicester’s cultural life is rich. Next month we will reinter King Richard III at Leicester cathedral. While we will be putting on a celebration that is literally fit for a king, 2 miles down the road in Spinney Hills a third of children are growing up in poverty—half the children if we include housing costs. Later this year we will host rugby world cup games, which many will enjoy coming to Leicester to watch, yet 2 miles down the road from the King Power stadium, on the Saffron Lane estate a quarter of the children are growing up in poverty. Some 3,000 families across Leicester are trying to cope with the bedroom tax. Food banks have doubled across our city over the past two years. Our Sikh gurdwaras report that the number of people turning up for free food has increased over the past two years. However, by 2015-16 Leicester city council will have seen a real-terms cut of 45%—£95 million cut from its budget—for a city that ranks in the league tables as the 25th most deprived in the country. On the Government’s own figures for revenue spending per head, it is losing £205 per person. As my hon. Friend the Member for Derby North and others have said, what a contrast that is with the losses in some of the wealthier and more well-heeled parts of the country, such as in the Prime Minister’s backyard. We are seeing the ending of crisis loans and community care grants and the ceasing of funding for welfare support. In a city where there is such reliance on food banks and other providers of that ilk, I dread to think what that will mean. Mr Graham Stuart - Hansard - Copy Link - - Excerpts I wonder whether the hon. Gentleman can tell us what the unemployment rate is now in his constituency, including that for young people, compared with 2010. Jonathan Ashworth - Hansard - Copy Link - - Excerpts The unemployment rate increased quite significantly under this Government, and it has now begun to come down, but in my constituency it is still above average. Is that okay for the hon. Gentleman? I concede that unemployment has come down, but in Leicester it is too high and we need to get it down further. Chris Williamson - Hansard - Copy Link - - Excerpts Would it not be true to point out also that many of my hon. Friend’s constituents are on zero-hours contracts, in part-time work and in low-paid occupations? As the Prime Minister himself has said, Britain needs a pay rise. We also need to get rid of those exploitative zero-hours contracts, which the Labour party is committed to doing. Jonathan Ashworth - Hansard - Copy Link - - Excerpts In his contribution a few moments ago, my hon. Friend spoke eloquently about the need for Britain to have a pay rise and poked fun at the Prime Minister’s late conversion to the need to deal with the fact that wages have been squeezed considerably under this Government. Indeed, by the end of this Parliament people will be worse off than they were at the start of the Parliament, which is unusual by historical standards. I want to concentrate on Leicester where, like other cities, we are seeing increasing demands on our children’s services. Luckily, our local authority has managed to keep our Sure Start centres open, but some services have had to be cut. We are seeing growing demand on adult social care, like other cities, yet we are trying to cope with deep cuts. We are a city with a proud, vibrant voluntary sector. Perhaps it could be argued that the big society was invented in Leicester, yet all voluntary sector organisations are seeing their grants cut and they are struggling to provide the level of services to the community that they have been able to provide for the past few years. The Government’s rhetoric on the big society rather sticks in the throat when we see what is happening on the ground. As to how the Government present the figures, my right hon. Friend the Member for Wentworth and Dearne (John Healey) and my hon. Friend the Member for Sheffield South East did extremely well in exposing the fact that when the Government talk about spending power calculations, they are trying to disguise the cuts facing councils. The hon. Member for Southport (John Pugh), who is not in his place, made a brutal contribution referring to that as sophistry. The Government tell us that, on their spending power calculations, Leicester sees a 5.4% reduction. However, as many have pointed out, these figures are distorted by including the totality of the better care fund, a significant proportion of which is not available for local authorities to spend. With that element removed, the year-on-year reduction in spending power for Leicester is 9.4%, so what we need is not sophistry, in the words of the hon. Member for Southport, but a fairer funding settlement for cities such as Leicester. We need a funding settlement that truly recognises the deprivation in cities such as Leicester. In Leicester—which, by the way, did what the Government want; we have a directly elected mayor—what the city mayor and the local authority need is a funding settlement that allows them to budget for the longer term. We need the devolution of genuine powers to our cities, because a city such as Leicester, with its vibrant, dynamic population, can take full advantage of those powers and make a real difference. 17:44 Mr Graham Stuart (Beverley and Holderness) (Con) - Hansard - Copy Link - - Excerpts It is a pleasure to take part in this debate. We have heard a number of excellent speeches from both sides of the House, none more brilliantly delivered than that of the shadow Secretary of State, the right hon. Member for Leeds Central (Hilary Benn), who in the most lucid way presented a picture of a much fairer settlement for local government, if only the Labour party came to power. No one in the House has such a pleasant and agreeable manner as the right hon. Gentleman, yet beneath that surface we heard nothing to tell us about what the Labour party would do if it got into power. Despite all the protestations from Labour Members about the dreadfulness of spending reductions for local government, we know that the Labour party is not committed to spending any more at all. So if anyone is to win, by the sound of it, it will be the local authorities that already have the largest and most generous settlements from central Government, whereas those local authorities in rural areas with an ageing population which, on average, is poorer and has a lower average income will lose out. People in rural areas already pay a significantly higher level of tax and have weaker access to services, yet they will lose out if Labour comes to power. That has not been stated categorically. Members have asked for greater transparency. We got no transparency from the Labour party today. Tonight our job is to vote. The House decides this evening on the settlement—the distribution of funding to local government across England. It is Labour policy that in a year’s time 35 or perhaps—in the Labour party’s worst nightmares, and it is not that unlikely— 40 Scottish National party Members of Parliament will be able to dictate the distribution of local government funding in England, despite the fact that at the general election people expressed a preference for an entirely different vision. That is possible. When there is greater devolution to Scotland, it is quite wrong that we are unable to distribute our own funds within England in a way that does not allow that to be dictated by those who represent people whom it does not affect. I would like to put that on the record. As we discuss this subject, I am disappointed that I must again highlight the unfairness that my rural constituents and others across this country face in the settlement. I do not accept the Government line that this is a fair settlement for all. I recognise, though, that they inherited from Labour a funding system so skewed, so indefensible and so politically rigged that it was a shameful scandal. It was one in which, when the numbers could not be made to work out to the political preference of the then Labour Ministers, officials were asked to invent new technicalities in the system—new ways of ensuring that the money went where those Ministers wanted it to go. What did they come up with? They decided that they would use density as the weighting to drive the money where they wanted it. The new formula had all sorts of perverse outcomes. For the most part, it delivered the additional funds to Labour seats that Ministers were aiming for, but it was totally wrong, because density, which does not link to need in any way, was set at four times the weighting given to sparsity, which does link to need. Although it served the party political purposes of Labour at the time, it also led to perverse outcomes in distribution across seats in areas represented predominantly by Liberal Democrats or Conservatives. It was fundamentally unfair, and areas of the country that are rural and have lower incomes have lost out ever since. This Government inherited a deeply skewed, morally unjustifiable funding settlement from Labour, and nothing we have heard from Labour Members today suggests that they do not plan to return to precisely the same methodologies if they get back into power. I welcome this year’s announcement of an additional £4 million for rural authorities through an increase in the rural services delivery grant, which did not exist until this coalition Government came to power and recognised the need to do something to address the inequalities in rural areas. In meetings with Ministers this year, colleagues from multiple parties have received the clearest recognition yet that the Government accept the principle that the funding system is biased against rural areas. I am grateful to Ministers who have begun to right the historical injustice brought about by the previous Government. My right hon. Friend the Member for East Yorkshire (Sir Greg Knight) wished to be present when I was speaking but was unable to be here. However, he fully supports the points that I am making on behalf of all the people in east Yorkshire. On average, as has been said—it is worth repeating after the excellent speech by my hon. Friend the Member for Newton Abbot (Anne Marie Morris)—that rural residents pay £81 more in council tax than their urban counterparts and earn less, on average. Over time, it has been good to see Labour Members slowly taking in this fact; it has been dripping in. People in rural areas are not living in some prosperous idyll—far from it. On average, they have lower earnings than people in urban areas and face greater costs in accessing services. Yet rural residents, who pay more council tax and are poorer, on average, receive £153 less per head in central Government grant than do those, on average, living in cities. Chris Williamson - Hansard - Copy Link - - Excerpts Will the hon. Gentleman give way? Mr Stuart - Hansard - Copy Link - - Excerpts In a moment. This is not about Toxteth or areas of the most concentrated deprivation; it is about a broader picture in which it would be perfectly possible to protect the most deprived areas of, say, the hon. Gentleman’s constituency while seeking to address an imbalance in the funding formula. Chris Williamson - Hansard - Copy Link - - Excerpts The hon. Gentleman talks about the income profile of rural residents being somewhat lower. Would he therefore support me in encouraging those living in rural areas to join a trade union to try to improve their living standards and incomes? Mr Stuart - Hansard - Copy Link - - Excerpts I appreciate the hon. Gentleman’s point, but that would mean a further bill for a left-wing organisation and we know where that leads. He will be aware that in the past couple of years the wages of non-unionised workers have eclipsed those of unionised workers and that the TUC is, for the most part—as, indeed, is the hon. Gentleman’s party—a front organisation for those who receive money from the public purse. Trade union membership does not have a great deal of relevance to those who work in the private sector, which exports across the world and generates the wealth that pays for those of us, including MPs, who are paid from the public purse. However, I would always welcome and support anyone who wished to join a trade union, if they saw fit to do so. Although there is a smaller gap of £73 per person between rural and urban spending power, it is smaller only because it takes into account the higher council tax that rural residents have to pay. Poorer rural residents are subsidising richer urban authorities. That is worth repeating, because anyone listening to the impassioned protestations of Labour Members would think that was not true: poorer rural residents are subsidising richer urban authorities. There is no acceptable justification for that status quo. The fact that the Government have introduced the rural services delivery grant during this Parliament and increased it every year is welcome recognition of the rural penalty. This year its value has been set at £15.5 million, or £1.20 per head. At just 1% of the shortfall in the main central Government grant, that additional money does not by itself deliver a fair deal for rural areas. Jonathan Ashworth - Hansard - Copy Link - - Excerpts Will the hon. Gentleman give way? Mr Stuart - Hansard - Copy Link - - Excerpts I will happily give way to the hon. Gentleman. Perhaps he will be able to provide us with more honesty than those on the Labour Front Bench and give the House the honest account of who the losers will be if Labour comes to power. I suspect there would be further injustice for rural residents across England. Jonathan Ashworth - Hansard - Copy Link - - Excerpts The hon. Gentleman was very keen to intervene on virtually everybody else who has spoken, so I am pleased he has eventually given way to me. If I follow his argument correctly, is he saying that the funding settlement for cities such as mine is too generous? Mr Stuart - Hansard - Copy Link - - Excerpts I am grateful to the hon. Gentleman for making that point. I had hoped that he would talk about the fact that his party would not invest any more money in the local government funding settlement. If his reading of what his Front-Bench colleagues have said is that his area will receive more money—I think that is the case—that means that the injustice for poorer rural residents will increase. It is not the case that urban authorities in general are unfairly funded or have had disproportionate levels of cuts, because that funding was skewed in the direction of urban areas in the first place. The Labour party refuses to explain how it would have dealt with local government funding in this Parliament. Justin Tomlinson (North Swindon) (Con) - Hansard - Copy Link - - Excerpts My hon. Friend is making an excellent speech. Labour has said that it would raid the new homes bonus, which is worth £6 million to my local authority and which we are getting to fund infrastructure as a reward for taking development and building the new houses we need. Frankly, it is disgraceful that Labour wishes to raid that and redistribute it to other areas. My residents will certainly not support that. Mr Stuart - Hansard - Copy Link - - Excerpts My hon. Friend is absolutely right. The hon. Member for Liverpool, Riverside (Mrs Ellman) said how deprived Liverpool is, but what she did not mention was what has happened to unemployment there, which, as in Leicester and Derby, is down under this Government. That is not because Labour has suddenly become enterprise friendly or is the result of decades of failure to promote enterprise, prosperity and wealth creation; it is because this Government have created the conditions that have helped drive down unemployment. By putting in place incentives such as the new homes bonus and understanding that incentives drive behaviour, this Government have tried to create a response in councils that will lead to the right outcomes for people. In that way, in 20 years’ time, the successors of Labour Members representing urban areas will not be shroud-waving proudly in the Chamber about how deprived their communities are; they will be celebrating the fact that their communities have been transformed and made more prosperous. That is the coalition Government’s vision, but through all the years of false boom presided over by the Labour party, so many people in urban centres represented by Labour Members were left to fester. Too many people were left on dole queues, from which they are now being removed by precisely those policies, such as the new homes bonus, that encourage the right behaviour. As my hon. Friends have said, there is a risk. Areas doing the right thing and challenging the nimbys—saying, “Look, we need housing, and we want it to be affordable; we want affordable housing and market housing; and we want housing to accommodate our young people and give them hope for the future”—need to be rewarded with the funding to put in place the infrastructure to make such developments saleable to their residents. However, Labour Members want to strip away the new homes bonus. Yet again, they just do not understand. They want everyone to take the money from the central public purse. They talk about devolution, but that in fact means more central control. They talk about improving incentives to do the right thing, but they want to strip away the new homes bonus. Their approach to local government finance is incoherent and damaging, and it will lead to a raid on the already poorly funded and inequitable settlement for people in rural areas. The discussion today has covered social care. Like the right hon. Member for Mid Dorset and North Poole (Annette Brooke), I attended debates about care during the last Parliament. I cannot say they were massively attended, but time and again she and I faced Labour Ministers who said they were sympathetic to bringing social care and the NHS together. What did they do? Absolutely nothing. I remember, as she will, that after they had been particularly sympathetic to the direction of travel, they gave a 4% increase to the NHS and a 1% increase to social care in their next financial announcement —and they wonder why we have not created a more co-ordinated system. This Government are working to bring the NHS and social care together so that there is seamless support for an ageing population. The ageing population is disproportionately located in rural areas, such as the East Riding of Yorkshire—including my constituency of Beverley and Holderness—which have had the largest increases in the numbers of over-65s and over-80s in the country. That drives cost, but the Labour party would allow the money to be skewed to their core areas, which on average have much younger populations and no such needs. To look at the NHS settlement as a parallel, at the end of Labour’s time in office, Tower Hamlets, with its peculiarly young population, spent four times more on each cancer patient than Dorset, with a very aged population. That is gross inequity, but the first time we hear anything from Labour Members is when a Government who inherited appalling public finances seek, inch by inch, to create a little more fairness. I want to finish in the same way as my hon. Friend the Member for Newton Abbot. I am sad that no Conservative Ministers are on the Front Bench at the moment, but I know they are assiduous readers of Hansard . I say to the Under-Secretary of State for Communities and Local Government, the hon. Member for Bristol West (Stephen Williams), that I hope the Liberal Democrats and the Conservative party—I would like to say this of the Labour party, but I am not holding my breath—will make a manifesto commitment to bringing in a truly fair funding formula based on need. The right hon. Member for Leeds Central talked about that, but he would not in fact implement it. As my hon. Friend the Member for Newton Abbot said, I hope that a commitment will be made in the Budget before the election to increase the grant to at least £30 million a year. In that way, we can close the gap between urban and rural areas by 2020, recognising that people in rural communities are older, have lower average incomes and pay higher council tax, and recognising the fact that they deserve justice—at last—from whoever is in power on 8 May. 11:30 Mr Gordon Marsden (Blackpool South) (Lab) - Hansard - Copy Link - - Excerpts Some of us might well wish the hon. Member for Beverley and Holderness (Mr Stuart) would hold his breath, but I would like to move on and talk about the impact of the cuts on my constituency. We should focus on the human issues—the lost council workers’ jobs, the lost opportunities for young people, the impact on street cleaning, and the impact on those who are hit by benefit sanctions or the bedroom tax—but we must also hold the Government to account for their totally inadequate formula and calculations that have informed this year’s cuts. They have disguised the completely unjust treatment of our most deprived areas and failed to take into account the pressures with which our most vulnerable areas already contend. The Department for Communities and Local Government says that, on its minimalist spending power criteria, Blackpool’s funding has been cut by £114 per person, or 4.7%. According to those formulas, even that is two and half times the average cut in England. That is bad enough, but it does not reflect the real damage that is inflicted by cumulative cuts to a small unitary authority that has special factors in terms of demographics, transience and health, which have borne down further on it, not least when we include a large percentage of care and health issues. The Government are imposing those damaging cuts when there is an ever-increasing pressure in Blackpool and an ever-rising bill to maintain services. The annual grant provided to Blackpool, the sixth most deprived council on the Government index of multiple deprivation, has fallen by about £50 million since 2010. That is about 35% of the 2010 budget. Blackpool has also had to cope with rising demands in areas such as children’s services, whether because of increased numbers of referrals from high-profile child welfare investigations, or because of transience both from outside and within Blackpool as some families have to move several times because of poverty or family break-up. To meet those demands, the council has had to cut more than £90 million, which it would normally have spent on services, to balance the budget. The human price of that has been 759 council workers losing their jobs since 2010, with a further 200 to 300 facing that threat from this year’s settlement. Incidentally, all those council workers have already made significant sacrifices, this year taking five more days’ unpaid leave. It is no wonder that the leader of Blackpool council, Councillor Simon Blackburn, has said that we are entering uncharted territory, and that my residents speak at packed meetings and healthwatch panels of the thinning of the fabric that has kept Blackpool a vibrant and cohesive town even when there were major realignments in tourism and visitor numbers. The money is not shared out fairly between the regions, as the Government claim. The LGA was quick to point out that the Government’s supposed average of 1.8% cuts would be more like 8.8% in effect. Newcastle council estimates that Blackpool’s official cut of 4.7% is nearer 9%. The Chartered Institute of Public Finance and Accountancy says that Blackpool’s real loss of spending power has been 9.7%, double what the Government claim. It is the 11th worst-hit area of 383 in the country. No wonder CIPFA described the Government’s figures as disingenuous and as underplaying the size and scope of the cuts. Why are there discrepancies? Pooling budgets between the NHS and the council can be a valuable way of improving local services, but the Government are wrong to use that to mask the full nature of local cuts. As has already been said, money that has been spent by the NHS and placed in pooled budgets should not be counted in local budget figures. That money is not available to plug the gaps in council services. That serves only to disguise the full stress that vital local services have been put under. When we add to that the vagaries of revenue raising from income from visitors on a year-by-year basis, as is the case in all seaside and coastal towns, and when we take into account the fact that in Blackpool, given our larger than average percentage of disabled and older people, which means that issues around morbidity as well as mortality are extremely challenging, there is something almost obscene about a sleight of hand that means the change from 2010-11 to 2015-16, when we include public health and the better care fund, is £260 per head compared with that of leafy Surrey, where there is an actual gain of £3. We have also seen in Blackpool some perverse implications from the blunt mechanisms that determine the grant. Laudable local initiatives to replace high rise housing estates, which have struggled to provide residents with safe and secure housing, with new spread out family building have left us with the fifth lowest new homes bonus in the country. This blinkered focus on simply counting the numbers of dwellings disregards the quality of the houses. I shall not hold my breath, but perhaps the Minister can provide us with a coherent reason why Blackpool and other more deprived areas are so much harder hit than Tory shire areas. The other issues that need to be considered are the specifics of how an authority such as Blackpool is affected. The early intervention grant has been almost entirely scrapped, with a 93% cut. There is almost a standstill because of the pressures on public health funding—this in a borough where alcohol and substance misuse problems are extremely significant. Payments for discretionary housing are down from £581,000 to £370,000, and housing benefit has been squeezed even further. The cuts are having a double whammy effect on the voluntary sector. First, they are putting more and more pressure on the voluntary sector to fill the gap. At the same time, the funding that the sector has historically received from local authorities like Blackpool has been drastically cut. While we are on this issue, let us look at the deforming effect of the so-called reforms of welfare on budgets. The Secretary of State, on a visit to Blackpool last Friday, tried to pacify people and said that no one should be suffering, because there was a hardship fund. Well, they are suffering. My casework is full of people who are suffering. They are suffering because the voluntary sector and local authorities do not have the capacity to come to their aid. It is not surprising, therefore, that more than 12,500 respondents said no to the original local welfare provision findings from the Government, with only 17 in favour. The Government have been forced by this outcry to make last minute judgments. I have said in this House many times that I am a firm believer in the ability of properly empowered local authorities. The Minister, in his speech, has underlined that point conclusively. As a former shadow skills and regional growth Minister, I believe that co-operation, collaboration and multi-agency agreements, and the devolution proposals that are now at the heart of Labour’s policy in this area, can secure transformative change. Real localism requires respect shared between all parties. The Government who fail to understand the practical pressures being faced by local councils, who disguise the full extent of the cuts being imposed on them, and who show political favouritism to some areas over others could never be part of the creation of a bold new locally led system. Ultimately, it is the people in communities such as Blackpool who have suffered. We would welcome more powers to stop rogue payday lenders, to limit the number of gambling outlets in high streets, to stop our pubs being driven to the wall, and to control and provide public transport that is tailored to community needs and not simply to a cartel of operators. Blackpool is an enterprising council. We have shown that in the way in which we have used, in a very positive fashion, lottery funding for our visitor, illumination and heritage initiatives. Ultimately, objections to the unsustainable withdrawal of local funding for core council services, which we have seen again in this settlement, are treated as inconvenient obstacles to the political decisions of the Government. That cannot be satisfactory; that cannot be the way forward; and that cannot be the mantra of the new Labour Government we all hope for in May. 18:15 Richard Burden (Birmingham, Northfield) (Lab) - Hansard - Copy Link - - Excerpts From a seaside town, we move to an inland city that also has great needs that are not being met by the settlement and the policies of the Government. I wish to say a few words about a specific issue affected by the settlement imposed on local authorities like mine, and then to make a few points of more general significance, particularly as regards Birmingham. I was in Birmingham this morning, and for once there was some good news. For many months, school crossing patrols—lollipop men and women—have been under threat, as a result of the huge cuts being passed down to our city. It has caused massive concern among parents, schools and everybody who worries about children’s safety, and I pay tribute to the unions in the city for spearheading the campaign and to our local paper, the Birmingham Mail , for highlighting the issue. The good news is that the campaign has borne fruit. We are not out of the woods—there will still be fewer school crossing patrols, and there needs to be a discussion between schools and the council about what their respective responsibilities should be—but today the Labour city council confirmed that it would maintain school crossing patrols on the busiest roads where there were no other controlled crossing points and where the only other crossing point was a zebra crossing. The council has listened. In a meeting I had with it yesterday, it said it would redouble its efforts to integrate school crossing patrols in an effective overall strategy for providing safe school routes, whether that be 20 mph zones or by encouraging safe walking and cycling to schools. That is the good news, and I pay tribute to all those I have mentioned, as well as my fellow Labour MPs from the area, for spearheading that campaign. The less good news was the response from the Secretary of State. I too am sorry that he is not in his place. Indeed, I am sorry that the Under-Secretary of State for Communities and Local Government, the hon. Member for Bristol West (Stephen Williams), has been left entirely on his own by his coalition partners—oh, he has now been joined. Anyway, perhaps he will pass on a few sentiments to the Secretary of State, who, as my hon. Friend the Member for Derby North (Chris Williamson) mentioned, made a sweeping visit to the midlands last week. When confronted with the issue of school crossing patrols in Birmingham, he said: “We had to send someone in to look at Birmingham because it’s been so badly run for quite a long time.” In fact, his party ran it for quite a long time! He continued: “We’ve made a number of recommendations and it really does need to start looking at the more important things that will bring in quite a lot of money, than start messing around with people who take kiddies across the street and keep them safe.” How dare he? This is from the Minister who railed against the use of CCTV outside schools to deter drivers from parking where they should not—something that parents know is a problem in front of many schools. To grab a headline, he wanted to get rid of one of the tools that could keep those children safe, and he tried to force it through in his deregulation Bill, but was forced into a U-turn when his colleagues said it was important to exempt schools from his ban on CCTV. How dare he imply that cuts to school crossing patrols are simply a Birmingham problem, when we know, from research we have done, that two thirds—66%—of local authorities have cut the number of school crossing patrols since 2010? That means 1,000 fewer lollipop men and women than when the Prime Minister took office. In 2013, the shadow Transport team obtained through freedom of information requests the following figures on road safety budgets and staffing levels in 133 local authorities. It found 92% reported having to cut their budgets from 2010-11 to 2013-14. Of those, there was an average budget reduction of over a third—42%—while two thirds of all local authorities responded by cutting staff working on road safety in the same period, and nearly half of all respondents—49%—had cut budgets for walking and cycling. A recent survey by Brake revealed that two thirds of the parents of primary school children think roads are unsafe for walking and cycling, while Sustrans has reported that about the same number of parents say their child has experienced a “near miss” on the school run. The latest figures show that in 2014 the number of children killed or seriously injured rose for the first time in 20 years. Progress on reducing casualty rates is stalling under this Government, with three consecutive increases in road deaths last year. So how dare the Secretary of State make those comments about school crossing patrols in my city? How dare he do so when our city has lost a third of its budget since 2010—the equivalent of £161 per household compared to a national average of £47, which is far more than places such as Surrey that have seen their spending power increase? A number of hon. Members have raised that point. For the 2015-16 financial year, we in Birmingham are facing the largest cut in history, of £100 million, at the same time as we need to spend more money on child protection and social care. More than £250 million-worth of savings are required by 2017-18, and the total between 2010 and 2018 will have been £821 million, as my hon. Friend the Member for Birmingham, Edgbaston (Ms Stuart) pointed out a little while ago. We have been urged to spend more—and rightly so—on child protection and safeguarding, but we face a Government who will the end while cutting the means to achieve precisely that. Birmingham is facing yet another above-average cash cut in spending power to 2015-16—as I say, about £161 per dwelling, which is 6%. That is more than three times the national average cut of £47 per dwelling. Mr Graham Stuart - Hansard - Copy Link - - Excerpts Will the hon. Gentleman give way? Richard Burden - Hansard - Copy Link - - Excerpts Yes, I will, but this will have to be the only time. Mr Stuart - Hansard - Copy Link - - Excerpts I am grateful. Because the hon. Gentleman’s speech is so gloomy, I thought he might like to hear something more positive, which is that the unemployment rate in his constituency has seen a bigger cut still. It has halved since 2010. Is it not true that every Labour Government leave more people on the dole than when they came in, and that it is the Conservatives who put the country back together, put people back to work and put money in their pockets? Richard Burden - Hansard - Copy Link - - Excerpts I said I would give way only once to the hon. Gentleman, but I will give way again. He has looked at the figures for my constituency, so let me ask him what has happened to long-term unemployment? Mr Stuart - Hansard - Copy Link - - Excerpts The hon. Gentleman will be aware— [Interruption.] I will tell him. Between 2009 and 2010, the number of people who were long-term unemployed in his constituency went up from 460 to 1,090—more than doubling in the final year that Labour was in power. That was a perfect encapsulation of Labour’s impact on ordinary working people: they get disadvantaged. Richard Burden - Hansard - Copy Link - - Excerpts The hon. Gentleman has perhaps missed the fact that there was a worldwide recession at that time, as a number of my hon. Friends have had to remind Conservative Members. Another theme in the hon. Gentleman’s statistics is that when Labour was power before the worldwide recession, there were 25 young people in my constituency out of work for more than a year. There are now five times that number. If people are out of the labour market, they find it very difficult to get back in. Frankly, this Government’s policies are doing nothing to address that problem. Judging by what we have just heard and what we heard from the Minister who opened the debate—who knows whether the Minister now on the Front Bench will say the same when he winds up the debate?—it is clear that they still do not get it. They simply do not get it. Whether in a city, or in a town on the coast or inland, or in a rural or urban area, if needs are greater but areas face percentage cuts similar to those of more affluent areas—or, as my hon. Friend the Member for Sheffield South East (Mr Betts) who I am pleased to see just back in his place said, if the percentage cut is even greater—the former will be hit harder. Services suffer more, and real people suffer more. That is the reality that Birmingham faces. We have heard a few times from Government Members that urban areas such as Birmingham were favoured or featherbedded in the past. Government Members are fond of claiming that anything that is not right today is somehow the fault of the Government who were in power before 2010. Birmingham was a Conservative council from 2004 until 2012, when the Conservatives lost power. I do not remember a single Conservative councillor, a single Liberal Democrat councillor or, indeed, a single Conservative Member of Parliament in Birmingham claiming during that time that their city—our city—received too much from the Labour Government. I do not remember any of them saying that we could easily afford to lose another third of our budget, and up to two thirds in the future. I do not remember any of them saying any of that while they themselves were trebling Birmingham’s debt, so let us have no more buck-passing from Ministers now. We need a funding formula that is fairer—a funding formula that is based on the principle that those in the greatest need receive the most support. My right hon. Friend the shadow Secretary of State has outlined some of the ways in which that could start to happen, but at present we do not have a fair deal. Unfairness is at the heart of the Government’s local government policies, and I am convinced that that will not change in the next few months. It will require a Labour Government after 7 May to ensure that change happens. 18:27 Ms Gisela Stuart (Birmingham, Edgbaston) (Lab) - Hansard - Copy Link - - Excerpts It a great pleasure to follow my hon. Friend the Member for Birmingham, Northfield (Richard Burden). Not only do we have adjoining constituencies, but when I became a Member of Parliament in 1997 I took over part of his constituency, so our work has always overlapped. I want to talk about cities, and the future of cities. Cities do not reflect the national economy; they are the national economy, and that has never been more true than it is today. Whether we are talking about Birmingham, greater Birmingham or a combination of authorities, those big conurbations and their populations are a driving force. In the 19th century, Birmingham exploded in size. Formerly an insignificant village, it became the fourth largest urban centre in the United Kingdom, and few of the 175,000 men and women who lived there had been born locally. Birmingham was also the most divided city in the country in the context of religion: no one Church was predominant, and the tone was set by various Protestant nonconformist denominations. It was also an aspirational community, which was proud of its innovation and enterprise, its skills and its people. The late Joe Chamberlain made Birmingham the best-governed city in the empire, and he did so in important ways. He wanted clean water, because it was a public health good. He wanted a gas supply to modernise the city’s infrastructure and raise revenue to support business rates. He wanted better housing for the people, and he wanted free primary school education, because skills were the foundation for future prosperity and well-being. This is not just some pointless history lesson; it is about the “civic gospel” that was Chamberlain’s vision of cities. Every generation must rediscover its own civic gospel according to its circumstances. These are the questions that I really want to ask Ministers. What is their vision of cities? What is their civic gospel? How do they see the future? I can tell them what my vision is. The city of Birmingham contains 1.1 million people, of whom 238,000 were not born in the United Kingdom, of whom 53% are white British—compared with a national average of 80%—150,000 are Pakistani, 65,000 are Indian, and 50,000 are black Caribbean. Of those people, 46% say that they are Christian, 22% say that they are Muslim, and 20% say that they have no religion at all. Regardless of where those people come from and regardless of where they were born, however, 86% say that they are British. It is a very young city, too, with 40% of the population under the age of 25 and 30% under 15. It also has pockets of the most persistent unemployment, and they are very often in the very areas where we have the increase in the birth rates. The city also trains 40,000 graduates every year, but we do not as yet hold on to the graduates we are creating. So I say: let us define the responsibilities of the city. They include education, linking schools with employers, providing public health, looking after the vulnerable, whether young or old, and providing decent infrastructure. That takes me to the settlement, because this settlement will not allow us to do that. If the Secretary of State’s vision of the town hall is that it is no more than a call centre, let us talk about that. Let us use that as the basis of saying that the Conservative Government vision of local government is so minimalist that it has statutory duties and beyond that very little extra. Let us have a debate about that. I do not think the Secretary of State is making that case, however. He is saying he has a much greater vision, including to do with wealth creation, but the funding structure simply will not allow us to do that. I am also going to be frank now. Not all is well in Birmingham. We must acknowledge that. There have been some deep systemic structural failures in that city going back over several administrations. We have had three major reviews—Kerslake, Warner and Tomlinson. They have shown us a way forward. The city must grasp that and say, “This is our chance to come to terms with some of the problems of the past and put them right.” While I do not want to be party political, I do want to make one point. Lord Whitby built a magnificent library which will cost £1 million every month for the next 40 years before we even put in the first book or the first people of Birmingham go through the door. Interest payments on that library are costing us £1 million a month, which is more than the city of Birmingham spends in the entire year on traffic wardens outside our schools. In respect of his £188 million project, he said he was “saddened” that the city council was cutting the services and the hours. I am not just saddened; I am very disappointed. He says he is sad and he tells us through the newspapers that he could find solutions to this by involving local business. As he does not seem to be overtaxed by making speeches in the other place, perhaps he would like to broker such agreements and talk to local businesses and bring them in. The problems of Birmingham are the responsibility of all of us, not just of that city. It is a city that is more dependent on Government grants and therefore requires high levels of expenditure, yet it has had reductions in funding year on year, the last one being 18.6%. It is growing consistently, too, which creates its own specific responsibilities. We are not just facing cuts; as my hon. Friend the Member for Birmingham, Northfield said, we are also having to increase spending on child protection services—an extra £21.5 million—and on older people and younger adults by £6.5 million. As I said in an intervention, on the current trajectory by 2018 we will have lost two thirds of our discretionary spending. Where is the long-term structural solution coming from? I want to make a further point. The ethnic diversity of Birmingham is also one of its strengths. Ethnic cohesion in that city is far stronger than people realise or acknowledge. I was in Manchester when the Moss Side riots flared up. I never want to see anything like that happening in our cities again. When Haroon Jahan died in Birmingham in 2011, his father called for calm and asked the community to stand together. I am proud of the fact that our only Jewish primary school in Birmingham has got more Muslim than Jewish children. It is a very Jewish school, but the Muslim population sends its children there. Our Catholic schools also have large numbers from the Muslim communities. We need to foster that diversity and ambition, because part of what I see as our civic future is for Birmingham to succeed in life sciences, manufacturing and technology. Our population, our young population, our location and institutions could help us to achieve that. If we do not, and if our cities fall back to the difficulties that we had in the 1980s—frankly, the kind of funding structures being offered to us are on the road to such difficulties—it will not be only a Labour city council’s problem, or even a Conservative city council’s problem, it will be a problem for all of us. Our cities are the lifeblood that provides everything. Where do we go with this? Whitehall is not minded to give more money to our cities, so I do not think there is any other way but to look at independent funding streams, which give reliability and certainty that the areas generating the wealth will keep it. I am agnostic as to whether we go for land tax, stamp duty, business rates or whatever the streams are, but all the talk of devolution and returning responsibility to our cities and city leaders will go nowhere unless we make our cities our opportunities. Our cities are our strength. I heard all that discussion about rural areas, and as a Bavarian farmer’s daughter, no one needs to tell me what the countryside is like, I remember it well, thank you very much— Mr Graham Stuart - Hansard - Copy Link - - Excerpts A long time ago! Ms Stuart - Hansard - Copy Link - - Excerpts It is a long time ago, but I can still milk a cow—if the hon. Gentleman wants to take me up on that challenge, I can show him who the more rural creature is, him or me. Mr Geoffrey Cox (Torridge and West Devon) (Con) - Hansard - Copy Link - - Excerpts Done! Ms Stuart - Hansard - Copy Link - - Excerpts Name the time, name the place, I am there. However, cities such as Birmingham, ethnically diverse, young and growing, are our future. It will be to the Government’s lasting shame if they do not come up with a structure that will allow us to realise a new vision for our big cities. If we do not, we will all pay the price. My ambition for Birmingham is clearly higher than the ambitions of the Government Members. 18:37 Mr Andy Slaughter (Hammersmith) (Lab) - Hansard - Copy Link - - Excerpts What a difference a year makes. At the time of the previous debate on the local government finance settlement, Hammersmith and Fulham had a council that after eight years was increasingly at war with its own residents on housing, planning, health, education and social care. Its decisions seemed designed not only to alienate the electorate, but, perhaps because of that, to seek to change it by socially engineering the borough so that the resident population or large parts of it were encouraged to move out, to be replaced either by the very wealthy or, in the case of the council template of buy-to-leave or safety-deposit box flats, by no one at all. There are tall, empty buildings where offshore money is simply dumped in west London and other places. We are still dealing with the consequences, but it seems extraordinary that a park was being sold off in the most deprived area of my constituency. Where there had been free football pitches, people would now be charged £90 an hour. The Earls Court exhibition centre is, sadly, still being knocked down, despite the chronic lack of exhibition space in this country. It was going to be replaced by 1,300 luxury flats, with no affordable flats at all. Shepherds Bush market is still, I am afraid, under threat, but we are working hard to save that iconic, 100-year-old market that serves my constituents, which again was to be replaced by luxury flats. Charing Cross hospital was designated for demolition, also to be replaced by luxury flats, and a whole council estate, with thousands of council tenants and leaseholders having their homes demolished, was to make way for high-rise developments. I do not know whether it was because of or in spite of that, Hammersmith and Fulham council was described by the Prime Minister as his favourite council and by the Secretary of State as the apple of his eye for its hard-line Thatcherite policies, whereby everything socially useful seemed to be on the demolition list and everything that gave the area identity was to be replaced by faceless blocks. The electorate, however, did not agree, and they evicted the council last May and replaced it with a Labour council. Had that new council done nothing and sat on its hands for four years, it would still have been a blessed relief for my constituents, but it has not been doing that—far from it. In preparation for the debate, I asked the Labour leader of the council, Councillor Stephen Cowan, to give me a short list of the council’s achievements in the past nine months. The list is too long for me to read out, even in the time I have left, but I will give some examples, because it illustrates how a council takes over from the car crash that preceded it, having not only to remedy and ameliorate the policies I talked about, but to introduce positive and progressive policies of its own, in a climate of the cuts that many right hon. and hon. Members have eloquently spoken about this afternoon. The council set up a hospitals unit to try to save Charing Cross hospital. People may ask how a council can affect that, but we have an effective hospitals campaign which is now welcomed into the town hall and supported by the council, and we are confident that, using the powers we have, we will be able to save that hospital. One of the first things the councillors did was vote through a 10% cut in their own special responsibility allowance. The second thing they did was to save Sulivan primary school, which had become a national cause célèbre. It is one of the best primary schools in the country, according to its results, and one of the most inclusive. I have a soft spot for it because I went to a school just next door to it. It was designated for demolition and closure solely to provide a site for a secondary free school. That school has been found another site, but Sulivan survived and is thriving. Millions of pounds in new affordable housing have been negotiated; an additional £26 million has been negotiated on extant planning consents. That is not about new planning consents, where, obviously, and contrary to the previous council, we are asking for significant amounts of social and affordable housing; it is on deals that were already done. One of the most shocking things about the previous council was that it was such a poor negotiator. Whether that is because it did not really want to take money off private developers, it could not care less or it did not want, for reasons of gerrymandering, to have social housing, I do not know, but that is an extraordinary figure. It says that we can negotiate tens of millions of pounds simply by going back to the developers, even though we have, in effect, no bargaining power other than to say, “If you want to work with us in the future, you need to show you are responsible.” It is ironic that property developers are more responsible than Conservative politicians in that respect. We also now have the largest ever number of local police funded by the council, at 44 police constables funded, which, to take up the theme of this afternoon’s previous debate, makes up in some way for the cuts Boris Johnson has made in the Met; we have had a 25% increase in voluntary sector funding, with an emphasis on homelessness and social inclusion; and we have begun the programme of turning the residential streets into 20 mph safe zones. Visitors to Hammersmith a year or so ago would have seen what we described as “North Korean-style” banners hanging from every lamppost, with pictures of smiling Conservative councillors and messages like, “Grain production up 2,000%”. By cutting those and the glossy magazines the Tories produced, we saved, at a stroke, £600,000 a year, which we can spend on essential services. We did not get rid of the tri-borough, with the two neighbouring Tory councils, because there were some economies of scale there—so that is not an ideological point—but we did take back the decision-making powers from the tri-borough to ensure that Labour values would prevail in Hammersmith, unlike with the repeated cuts made in Kensington and in Westminster. We established an independent health commission chaired by Michael Mansfield, which is taking evidence now because the Health Secretary has refused consistently either to meet west London MPs or to review the appalling decision to close the four accident and emergency departments in west London. We cut the proposed rent rise for council tenants from 4.5% to 2.89%. We have started the process of buying back Hammersmith park, which had been sold. We have given support to local food banks and taken action to tackle food poverty. We are challenging the Mayor of London’s right to nationalise the northern part of the borough and turn it into a development corporation for the construction of luxury housing—I will not dwell on this matter further because I have secured a debate on it on Thursday. We have saved the Lyric theatre after the Tories disastrously mismanaged the regeneration scheme, started to introduce safer and better cycling provision, given new support to the Royal British Legion, and reduced the use of management consultants. We have introduced, for the first time, speaking rights for residents at planning committees and involved residents, through commissions on issues such as the third runway at Heathrow, in leading policy decisions. We have taken action against the disastrous special educational needs provision, particularly the transport contract, that the Tories introduced. We have introduced housing benefit advice workers in citizens advice bureaux. There is a new openness in the way in which the council does business. Nine children’s centres have been saved from planned closure. There has been action to support start-up businesses. We have trialled pedestrianisation of the North End road market, which attracted 10,000 shoppers on the day. We have blocked the Tories’ proposals to reduce trade union representation, cut meals on wheels charges by 33% and cut 15 other charges. We have halted the Tories’ plans—they did not reveal them before the election—to increase parking charges by 15% and we have frozen charges for school meals and 138 other charges. We have abolished charges for home care for elderly and disabled people—we are only the second local authority in the country to do that. Last but not least on my list is that foster carers have been exempted from paying council tax, and we are, I think, the only council in London, and only one of eight in the country, to cut council tax. All of those things were done in the first nine months of a Labour council in Hammersmith, and they were done against a background of cuts in our budget. Ostensibly, there is a 4.7% cut in the financial settlement, but when ring-fenced budgets are taken into account, that is actually a cut of 10%. Hammersmith has received a cut of £286.16p per head, and that is despite being the 55th most deprived local authority in the country. That is the background against which these decisions are being made. I am proud of the record that a Labour council is establishing, and I know from the correspondence from my constituents that they also appreciate what is being done. We are not out of the woods by any means. The baton, which was dropped by the previous Conservative council, has simply been picked up by the Mayor and the Government. Some very brave and courageous shopkeepers around Shepherds Bush market took three legal actions to try to save their livelihoods and their businesses. When they won the public inquiry against the compulsory purchase that the previous Conservative council had instituted, they thought—and we all thought—that we had saved the market and the shops. But then, giving no reason at all, the Secretary of State intervened and overturned the decision and said that the development should go ahead. Similarly, he agreed to the demolition of the exhibition centre at Earls Court and the 750 council homes on the site and allowed that premium land to be sold off at a substantial under-value. Worst of all, a mayoral development corporation is to be set up—as I have said before I will not dwell on this matter as it is the subject of a Westminster Hall debate on Thursday—taking in the whole of the north of my constituency, where the Mayor of London intends to build 25,000 homes. As far as we are aware, none of those homes will be genuinely affordable or for local use. The Mayor has described it as a mini Manhattan. Is that the Conservative view of localism, so that where Conservative councils are rejected firmly and clearly by electorates they will simply find ways of pursuing their policies by other means, by taking over the land and overriding local decisions through the powers of the Secretary of State? In my intervention earlier, I gave an example and I am sorry that the Minister was unable to answer the question that I was genuinely asking, and if the Minister who is winding up cannot deal with it I would like him to get back to me on it. The discretionary housing payment is a vital lifeline in many authorities, but in none more than in London authorities, where the combined effect of the bedroom tax, the cap on local housing allowance and the cap on benefits means that many hundreds of families now cannot afford their rent. The consequence will be that they will be forced out of London, losing their jobs, being separated from their families and having to take their kids out of school. The one lifeline they had was DHP and yet for this coming year the cut for Hammersmith and Fulham is 52%, more than double the national average of 24% and substantially above the average for the rest of London, which is 35%. How can the Minister justify that as regards that lifeline, which keeps families and communities together? It is little enough on its own but, as I say, it is just another way in which the process of social cleansing continues across west London. It is great that we have a Labour council now and it will be great to have a Labour Mayor as well next year, but my constituents are living in the worst housing conditions I have seen for 30 years in terms of overcrowding and a lack of affordability for everybody from Generation Rent through to families in council and housing association homes. The only thing that will change that situation and build the houses they need is the election of a Labour Government in May. I pay tribute again to the Labour council for doing everything it possibly can to assure the welfare of the people of Hammersmith and Fulham. It needs that additional assistance and to work in partnership with a Government who genuinely care about everybody who lives in our inner cities, not only those who can afford to buy the tower blocks of £2 million flats that are the only answer the Conservative party seems to have to the regeneration of London. 18:52 Andy Sawford (Corby) (Lab/Co-op) - Hansard - Copy Link - - Excerpts The debate has illustrated just how clueless the Government are about the impact of the cuts imposed on local government. As we have heard, the Government have been criticised by the National Audit Office and the Public Accounts Committee for not understanding the real impact of the cuts. What is worse is that they are deliberately trying to hide how the cuts have been distributed unfairly. We have heard how the areas of the country with highest need have received cuts up to 16 times greater than those with the lowest levels of need. Places such as Elmbridge, Waverley and Epsom and Ewell have had a funding increase at a time when local government’s grant overall has been reduced by 40%. We have heard from Members such as my hon. Friend the Member for Derby North (Chris Williamson) about their authorities facing cuts of up to £50 million. The figure is even more in larger authorities such as Birmingham. In those areas, times are extremely tough and I echo the remarks made by my right hon. Friend the Member for Leeds Central (Hilary Benn) in paying tribute to the great work of councils of all parties up and down the country. In particular, I acknowledge the great work of Labour councils who, on the whole, have faced much larger cuts. The National Audit Office found that the Government will have reduced funding to local authorities by 37% in real terms over this Parliament. The Local Government Association says that it is a 40% reduction and the Government tell us that it is a 1.7% reduction. Nobody, but nobody, believes their figure. Even if we attempted to massage the figures by including council tax and other ring-fenced funding, as we have heard, the LGA says that that would mean an 8.5% reduction. Within that, there is double counting. My hon. Friend the Member for Sheffield South East (Mr Betts), speaking from his experience as Chair of the Select Committee on Communities and Local Government, forensically took apart the Government’s claims, highlighting the double counting and the money sitting on the NHS books that DCLG Ministers claim is available for councils. The hon. Member for Southport (John Pugh) called it sophistry. In a damning turn of phrase for a coalition MP, he said that sophistry to disguise the cuts would be cowardly, but to deny them is dishonest and dangerous. That is what is happening. Will the Minister commit to publishing the cumulative impact of funding reductions on individual councils? The National Audit Office has requested that, and I have tabled written questions to that effect, although I received a very disappointing response today telling me that the information will not be made available. As the hon. Member for Southport quite rightly said, that is an attempt to disguise what is really happening, because those figures would expose the deep unfairness of the cuts. My right hon. Friend the Member for Leeds Central referred to the comments of the Public Accounts Committee, the Audit Commission and the Joseph Rowntree Foundation, which has stated: “Cuts in spending power and budgeted spend are systematically greater in more deprived local authorities than in more affluent ones”. My hon. Friend the Member for Blackpool South (Mr Marsden), who represents the sixth most deprived area in the country, talked about the cost pressures in his area, with the rising demands on children’s services, the growing elderly population, the challenge of implementing £90 million of cuts and the loss of 759 council workers. We do not denigrate those people as town hall bureaucrats in the way coalition Ministers do; they were providing a valuable public service in their communities. My hon. Friend talked about the thinning of the very fabric that has kept that community together. I recognise those remarks, as I am sure do hon. Members on both sides of the House. We have heard today that by 2017 the city of Liverpool, the most deprived local authority in the country, will have lost over half its Government grant compared with 2010. In fact, my hon. Friend the Member for Liverpool, Riverside (Mrs Ellman) told us that the latest estimate is 58%. That, in her words, is “devastating”. The council has taken measures to become more efficient, to generate new revenue streams and to reduce and use reserves as effectively as possible while maintaining a reasonable level of reserves, but it is also having to make cuts that are damaging people’s lives. The truth is that no councillor wants to talk about that. Her great city mayor, Joe Anderson, and the councillors serving the city do not want to talk about the incredibly difficult decisions they are having to make, because they are doing their very best to keep the show on the road. However, as my hon. Friend said, older people in her city are being deprived of care despite their growing needs. She said that at the start of this Parliament 15,000 people were receiving care and help, but now the figure is 9,000, so there is a real unmet need. That is the human cost of the cuts. That is the real tragedy. My hon. Friend the Member for Birmingham, Edgbaston (Ms Stuart) talked passionately, as she always does, about the great city she represents. It is a diverse and young city that trains 40,000 graduates a year. She talked of her vision for the city and all the opportunities to exploit its great strengths in sectors such as life sciences, and she talked honestly about the challenges it faces, but by 2018 the council will have lost two thirds of its discretionary spend. That is a very real threat to the city’s ability to make the most of the opportunities it has. Mr Graham Stuart - Hansard - Copy Link - - Excerpts Will the hon. Gentleman give way? Andy Sawford - Hansard - Copy Link - - Excerpts The hon. Gentleman has virtually made two speeches, given his 20 interventions, so I am sure that he will understand if I reply to the points that have been made rather than giving way. My hon. Friend the Member for Birmingham, Edgbaston said—I paraphrase—that it would be to the Government’s lasting shame if they do not do what they can to create the conditions in which Birmingham can succeed. It is our intention to create the conditions in which all our great cities, and all our great counties and metropolitan unitary areas of our country, can succeed. We want a devolution deal that will give opportunities to all areas of our country. My hon. Friend the Member for Birmingham, Northfield (Richard Burden) talked about a particular issue in his constituency: school crossing patrols. I congratulate him on his campaign. I will not run down his campaign in the way that we heard the Secretary of State disappointingly has done. My hon. Friend has found a positive way forward to try to keep children in his constituency safe, and he should be congratulated on that, as should Birmingham city council. My hon. Friend the Member for Hammersmith (Mr Slaughter) told us that in just nine months the council has set up a hospital unit to defend hospital services, saved Sulivan primary school, invested in affordable housing, funded police officers, backed the voluntary sector, cut the proposed Tory rent rise, taken action on food poverty, saved the local theatre and backed cycling—I have to say that it could soon be my favourite council, second only to Corby borough council. My hon. Friend made a powerful case for the great things that Labour councils are doing against a background of higher cuts than in Conservative and coalition areas across the country. Having claimed that those with the broadest shoulders should bear the greatest burden, why have Ministers done the very opposite in local government? Since 1948 local government has been funded largely through a grant according to need, a principle that existed through successive Labour and Tory Governments. The idea behind it is very simple: not all areas of the country are the same; they have different needs; and it is good for our economy and our society to give the people of every area a fair chance of a good life. Decent local services provide the basis of that, so that whether a looked-after child is growing up in Newham, Newcastle or Northamptonshire, their needs will be met. The Government have argued that the old way of doing that, which strove for fairness, lacked incentives. The Labour Government introduced the local authority business growth incentive scheme. The next Labour Government will let combined authority areas keep 100% of business rate growth. Incentives have a role to play, but it was wrong to freeze the grant at 2013 levels and engineer a complete shift away from redistribution. The ability of areas to take up the incentives and to replace lost grant with income from them varies enormously. We know that for all sorts of reasons, in the short term, from one year to the next, the chances of generating growth in some areas is much greater than in others. To compound the unfairness, the incentives being funded are from top-slicing the grant—a further raid on the resources of councils with the greatest needs. So when the Minister replies, will he say why he thinks it is right that the spending power of Wokingham will soon overtake that of Newcastle and Leeds, which have much greater needs? On current trends, revenue support grant will disappear entirely by 2019-20. There is a real question about the future viability of local authority services, including statutory services. We can already see the impact of the cuts—for example, the impact of the cuts to social care on the national health service. A Labour Government will end the bias against areas with the greatest needs by ensuring that the funding we have is distributed more fairly. That means a settlement that works for all authorities in all areas of the country. That will include the new homes bonus, which was criticised by hon. Members, including the hon. Member for Newton Abbot (Anne Marie Morris). It takes money away from the most disadvantaged communities and gives it to areas where new homes would have been built anyway. That is the point. The new homes bonus is top-sliced from one year to the next. It is no basis for planning ahead. We say to every area that a fair long-term approach will be best for every local council. That is why we are committed to longer-term funding settlements and multi-year budgets, so that local authorities can plan ahead, push ahead with reform and shift from high-cost ways of doing things towards investment in preventing problems, rather than paying for them later. There has to be a better way forward than taking a huge amount of resources from the poorest areas of our country. At the same time, we will devolve significant powers and resources to all areas of our country—not just small-time agreements with a small number of cities, but large-scale devolution across our country. We will introduce a new model of decision making and new local accountability structures, like the local public accounts committee. Labour will put devolution at the very heart of the next Labour Government, with a new English regional cabinet committee. Today we affirm our commitment that a Labour Government will move quickly towards fair funding. We reject the deeply unfair funding changes that this Government have imposed on local councils. Taking most from the areas with the greatest need is wrong and we will vote against the motion. 19:02 The Parliamentary Under-Secretary of State for Communities and Local Government (Stephen Williams) - Hansard - Copy Link - - Excerpts We have had 13 Back-Bench contributions to the debate. Most of them have been thoughtful and reasonable, with Members standing up for their constituents, as our electors would expect. We have heard a lot about different areas, including the reinterment of Richard III in Leicester and the lollipop people, if I may put it that way, in Birmingham. We heard about cities and counties. The speech I found most enjoyable was that of the hon. Member for Birmingham, Edgbaston (Ms Stuart), who addressed not only the history of her great city, but the future vision. There may be a face-off between her and my hon. Friend the Member for Beverley and Holderness (Mr Stuart) as to who can milk the cow most productively. As someone who grew up in a Welsh village surrounded by sheep, I will not offer any rural contribution. What we heard from the Opposition Benches was long on what problems there are and how awful the position is, but had very little recognition of the fact that one of the reasons for the current difficulties is the situation that we inherited in 2010. A couple of Members looked through that rear-view mirror and were in almost complete denial about that legacy. That might have been understandable in 2011 or 2012, but at this point in the political cycle, 90 days before the country goes to the polls, we expected to hear more of the vision that the hon. Member for Birmingham, Edgbaston spoke about—the solutions to funding local government in the future. Thanks to this Government’s policies of stabilising the economy, getting the public finances under control and rebalancing the economy, we are now seeing a better future for this country. Local government, like every part of the public sector, has made a significant contribution to getting to where we are. As my right hon. Friend the Member for Mid Dorset and North Poole (Annette Brooke) said, councillors from all parties should be congratulated on that. The Government continue to need to make difficult decisions to put the public finances on to a sustainable path. In that context, it is inevitable that councils, which account for a quarter of all public spending—this year they will spend about £115 billion-worth of taxpayers’ money—will have to operate with reduced budgets. Let me assure the House that, contrary to claims that have been made, in this settlement, like those before it, councils with the greatest needs and the highest demand for services still get the most funding. Indeed, the 10% most deprived local authorities in England receive 40% more spending power per head than the 10% least deprived. Several questions were asked about different authorities. Let me take the top and the bottom as examples. Hackney is the most deprived local authority area in England, and its spending power per dwelling will be £3,706.89, while Hart—I am putting together the district and county services and comparing like with like—will receive £1,854.57. At the top and the bottom, we can see that need is still reflected within the system. Mr Betts - Hansard - Copy Link - - Excerpts Under the Government’s projections, in two years’ time, Sheffield, Liverpool, Manchester and Newcastle will have lower spending power per head than Wokingham. Is that fair? Stephen Williams - Hansard - Copy Link - - Excerpts That would indeed seem rather odd on the face of it, but we are talking about the settlement now, not making projections about the future. What happens in future will be a matter for the next Government, in whatever configuration they are, and we will have to see where we are at that point. Several hon. Members talked about additional resources for rural authorities. We recognise the challenges that those authorities may face in delivering services to their communities. My right hon. Friend the Member for Mid Dorset and North Poole and my hon. Friends the Members for Beverley and Holderness and for Newton Abbot (Anne Marie Morris) made a powerful case. We have listened, and that is why, for the ongoing settlement, we are adding £15.5 million for the most sparsely populated rural areas. My hon. Friend the Member for Beverley and Holderness said that poverty is found in rural areas as well as in urban areas. Indeed, the only area of the country that still has objective 1 funding from the European Union is Cornwall—not one of our big cities. Mr Graham Stuart - Hansard - Copy Link - - Excerpts I am grateful to my hon. Friend for his comments about rural areas. Labour Members have not said anything about unemployment. In the shadow Minister’s constituency, there has been a drop in unemployment of more than 60%. In Liverpool, Riverside, the figure is more than 45%. Contrary to what the hon. Member for Birmingham, Northfield (Richard Burden) said, long-term unemployment is also down in his patch. That is the reality that underlies this debate. That is what the Government are doing, though Labour Members said that there would be 1 million more unemployed. We have had to fix the mess that the previous Government left behind. Stephen Williams - Hansard - Copy Link - - Excerpts That is absolutely right. Contrary to the predictions made by the shadow Chancellor, in particular, that unemployment would sail to over 3 million and we would have disorder in the streets, it has in fact fallen dramatically, certainly in my constituency of Bristol West, where it is dramatically down on the 2010 figures. We are providing an additional £74 million to support upper-tier authorities to help them to respond to local welfare needs and to improve social care provision. We have deliberately shifted the emphasis from keeping councils dependent on grant to providing them with the tools they need to grow and shape their local economies. For Britain to prosper, every part of the country needs to fulfil its potential. That will not happen if councils remain entirely dependent on Whitehall. We have set up a system that rewards councils that go for growth: those that are supporting businesses, attracting investment, and helping to create jobs. Councils that are open to new business will see the benefits of that growth through a retention of their business rates. Those that support new house building are rewarded through the new homes bonus. Many councils, of all parties, agree that these measures are having a positive impact on their ability to deliver better outcomes in their areas. That is not all. Contrary to the impression that we are somehow drawing the heart out of local communities through this funding settlement, we have to see it in the context of resources that have been given to local areas. For instance, £12 billon is being given to local enterprise partnerships in England to spend on local economic priorities. Those growth deals will help to train young people, create thousands of new jobs, build thousands of new homes and start hundreds of infrastructure projects. We will have had six rounds of the regional growth fund, spending £2 billion helping innovative businesses to grow, and through the £90 million coastal communities fund, which also helps rural authorities, we are investing in jobs and growth in our coastal towns. As well as growing their economies, the best authorities are transforming the way they do business. We are supporting them as they do so, achieving real savings and, importantly, improving outcomes for the people who use local services. In November, we announced the latest round of successful bids to the transformation challenge award. We will provide about £90 million to support 73 projects that will improve services and ultimately save the public sector more than £900 million. Councils must demonstrate a readiness to learn from each other and from projects proven to develop change elsewhere. We are committed to helping local places deliver more integrated local public services that improve outcomes for everyone. A good example of that is the better care fund in relation to health and social care. Initially we had hoped that £3 billion would be pooled locally, but we were pleased to see the figure increased to £5 billion. Several Members said that that was double counting, but that £5 billion, spent by the NHS and local government, is overseen by health and wellbeing boards, with local councillors taking the lead in shaping integration between social care and the national health service. There can be no doubt that councils are rising to the challenge. Every council has issued a balanced budget this year. The majority of residents remain satisfied with the way their council runs things, which is testament to the great skill that authorities have shown; I pay tribute to them for all their efforts. Councils continue to have significant spending powers—as I have said, they have more than £112 billion this year—but they must satisfy local taxpayers that they are using every pound of their money to best effect to deliver efficient public services. Finally, to rise to the challenge put down by the hon. Member for Birmingham, Edgbaston, I think that all three main parties in England are moving at different paces. My party probably got there first, in coalition, and our coalition colleagues have also embraced localism and regional growth. We see a strong future for local government—with cities driving their local economies and counties having the opportunity to do so, too—with more powers, more responsibility and an end to the situation where England is the most centralised state in Europe. Question put. 19:13 Division 151 Ayes: 286 Conservative: 244 Liberal Democrat: 41 UK Independence Party: 1 Noes: 190 Labour: 183 Plaid Cymru: 2 Independent: 2 Green Party: 1 Democratic Unionist Party: 1 Resolved, That the Local Government Finance Report (England) 2015-16 (HC 1013), which was laid before this House on 3 February, be approved. Local government finance Resolved, That the Referendums Relating to Council Tax Increases (Principles) (England) Report 2015–16 (HC 1014), which was laid before this House on 3 February, be approved . —( Kris Hopkins .) Return to start of debate - Return to top of page deferred divisions Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Motion made, and Question put forthwith (Standing Order No. 41A(3)), That, at this day’s sitting, Standing Order No. 41A (Deferred divisions) shall not apply to the Motion in the name of Mr David Gauke relating to the Counter-Terrorism and Security Bill: Money (No. 2) .—(Damian Hinds.) Question agreed to Counter-terrorism and Security Bill: Money (NO.2) Queen ’s recommendation signified. Resolved , That, for the purposes of any Act resulting from the Counter-Terrorism and Security Bill, it is expedient to authorise the payment out of money provided by Parliament of expenditure incurred under or by virtue of the Act by any Minister of the Crown in connection with any proceedings relating to temporary exclusion orders . —(Stephen Williams.) Counter-terrorism and Security Bill: programme (NO.3) Motion made, and Question put forthwith (Standing Order No. 83A(7)), That the following provisions shall apply to the Counter-Terrorism and Security Bill for the purpose of supplementing the Orders of 2 December 2014 (Counter-Terrorism and Security Bill (Programme)) and 6 January 2015 (Counter-Terrorism and Security Bill (Programme) (No. 2)): Consideration of Lords Amendments (1) Proceedings on consideration of Lords Amendments shall (so far as not previously concluded) be brought to a conclusion one hour after their commencement at today’s sitting. Subsequent stages (2) Any further Message from the Lords may be considered forthwith without any Question being put. (3) The proceedings on any further Message from the Lords shall (so far as not previously concluded) be brought to a conclusion one hour after their commencement . —(Mrs May.) Question agreed to. Return to start of debate - Return to top of page Counter-terrorism and Security Bill Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Read Debate Ministerial Extracts Consideration of Lords amendments Mr Deputy Speaker (Mr Lindsay Hoyle) - Hansard - Copy Link - - Excerpts I must draw the House’s attention to the fact that financial privilege is involved in Lords amendments 1, 2, 9, 21 and 32. If the House agrees with them, I shall ensure that the appropriate entry is made in the Journal . Clause 1 Seizure of passports etc from persons suspected of involvement in terrorism 19:27 The Secretary of State for the Home Department (Mrs Theresa May) - Hansard - Copy Link - - Excerpts I beg to move, that this House agrees with Lords amendment 1. Mr Deputy Speaker - Hansard - Copy Link - - Excerpts With this it will be convenient to take Lords amendments 2 to 39. Mrs May - Hansard - Copy Link - - Excerpts On the day the Counter-Terrorism and Security Bill was last considered by this House, news of the appalling events in Paris and the brutal murders at the office of Charlie Hebdo were still unfolding. What followed was a two-day manhunt for those responsible, a horrific attack on a Jewish supermarket and further murders of innocent people. Those attacks were yet another reminder of the very grave threat we face from terrorism, a threat that we have discussed in this House on many occasions. I am certain that everyone in this House is committed to ensuring that the police, MI5 and others have the powers and capabilities they need to keep the public safe. That is why we brought forward the Bill and sought its swift progress through Parliament. Since the Bill was sent to another place, it has been the subject of robust scrutiny. A number of substantial amendments have been made to ensure that these new powers will deliver the optimum capability for our agencies, and to reassure the public that they will be used appropriately and proportionately. They were all Government amendments, which were broadly welcomed by their lordships, and I hope and expect that they will find similar favour in this House. I will now turn to the amendments themselves. Two amendments were tabled by the Government to part 1 chapter 1 of the Bill, which concerns the temporary seizure of travel documents from individuals reasonably suspected of wishing to travel overseas to engage in terrorism-related activity. Amendments 1 and 2 make provision for civil legal aid to be made available where appropriate at the hearings of applications in England, Wales and Northern Ireland to extend the 14-day time period in which an individual’s travel documents may be retained. This is an issue in which the Joint Committee on Human Rights took considerable interest. Legal aid is already available for judicial review proceedings in England and Wales, and in Northern Ireland, subject to individuals’ meeting the statutory means and merits tests. Turning to temporary exclusion, as I have made clear to this House at earlier stages, the Government are absolutely committed to the appropriate and proportionate use of this power. As my hon. Friend the Minister for Security and Immigration indicated on Report, we carefully considered the constructive suggestions from David Anderson, the independent reviewer of terrorism legislation, on the matter of judicial oversight, and following that consideration, we tabled amendments to introduce oversight of the power in line with his recommendations. Specifically, the amendments propose the creation of a permission stage, before the imposition of a temporary exclusion order, and a statutory judicial review mechanism to consider the imposition of the order and any specific in-country requirements. Pete Wishart (Perth and North Perthshire) (SNP) - Hansard - Copy Link - - Excerpts I thank the Secretary of State for giving way so early, but is not consideration of these issues the job of elected Members—those who bothered to go to the electorate—not that affront to democracy down the corridor whose Members have taken it upon themselves to form Government business? Mrs May - Hansard - Copy Link - - Excerpts The very reason we are debating the amendments is that the House has an opportunity to consider them, so the hon. Gentleman’s argument is completely false. During the permission stage, the court would have the power to refuse permission for the order where prior permission was being sought, and in retrospective review cases, it would have the power to quash the order. During the statutory judicial review, the court would have the power not only to consider in detail and quash the specific in-country requirements placed on an individual, but to consider whether the relevant conditions for imposing the temporary exclusion order were and continued to be met. It could quash the whole order or direct that the Secretary of State revoke it. The amendments will ensure effective judicial scrutiny of the power, and I trust they provide sufficient reassurance to the House on this important issue. Mr Dominic Grieve (Beaconsfield) (Con) - Hansard - Copy Link - - Excerpts That does provide me with the reassurance I sought at an earlier stage, and I am grateful to my right hon. Friend for having listened carefully to the representations made here and in another place. They are most welcome and I believe will add considerably to the Bill’s legitimacy. Mrs May - Hansard - Copy Link - - Excerpts I thank my right hon. and learned Friend for his comments and recognise that he raised these issues and questioned the original proposals when they were debated in this place. Richard Fuller (Bedford) (Con) - Hansard - Copy Link - - Excerpts Alas, I am not quite at the same stage of happy reassurance as my right hon. and learned Friend the Member for Beaconsfield (Mr Grieve). Will my right hon. Friend reassure me that the additional judicial step will not mean that, in the time we understand it will take for a return to be made, people can get back into the country while legal proceedings are ongoing? The purpose was to say to those with a family member subject to terrorist infiltration that if they went abroad it would be a one-way ticket. My concern is that this additional legal step might stop that in some cases. Mrs May - Hansard - Copy Link - - Excerpts As my hon. Friend will recall, we have retained the initial decision by the Secretary of State, but, as with the legal process for terrorism prevention and investigation measures, it would then be for the court to consider whether it was right for the Secretary of State to have taken that decision. That process would be followed and then the order would be served, so I do not think that the timing issue, which he is concerned about, would arise. Jeremy Corbyn (Islington North) (Lab) - Hansard - Copy Link - - Excerpts If the person against whom the order is sought is outside UK jurisdiction, how would they appeal and what recompense would there be if the appeal is successful and the conviction quashed? Mrs May - Hansard - Copy Link - - Excerpts The whole point is that such people will be outside the country. The aim of a temporary exclusion order is to ensure that when they return to the UK, they do so on our terms, which is why their passport would not be available to them and they would have to be issued with temporary travel documents. As I indicated to my hon. Friend the Member for Bedford (Richard Fuller), the process of judicial oversight would have to be followed before the order is placed on the individual. As I said, these are important additions to the Bill reflecting the concerns expressed by right hon. and hon. Members at an earlier stage. I now come to amendments 10 and 11, the aviation, shipping and rail security amendments, which provide for direct parliamentary scrutiny of an authority-to-carry or no-fly scheme made or revised by the Secretary of State. Any such scheme would be subject to the affirmative procedure. These amendments act on a recommendation made by the Delegated Powers and Regulatory Reform Committee. Amendments 28 and 29 bring the aviation security powers in the relevant schedule into force on Royal Assent rather than at a later date by order. This includes strengthened powers to request information from the aviation industry and issue security directions, with a penalty regime to enforce them. The threat to aviation from terrorist groups is well documented and continues to evolve. We already work closely with foreign Governments and airlines, as well as UK operators, to make sure that the necessary security measures are in place and are being implemented effectively. These measures will enhance our ability to do so. I therefore hope the House will agree that it is right for these strengthened powers to be available at the earliest opportunity. There was an extensive debate in the other place on the Prevent duty set out in chapter 1 of part 5. Most notably, debate took place on the potential impact on freedom of speech and academic freedom in universities. The Government listened to those concerns, and amendment 16 ensures that further and higher education institutions must, when carrying out the Prevent duty, have particular regard to the duty contained in section 43(1) of Education (No. 2) Act 1986 to secure freedom of speech. Mr David Heath (Somerton and Frome) (LD) - Hansard - Copy Link - - Excerpts I hope to say a few words on this subject later if I get the opportunity to do so, but will the Home Secretary tell me whether subsection (3) of the new clause proposed by amendment 16, which applies the duty to ensure freedom of speech and academic freedom to the Secretary of State herself in drawing up the guidance, will have a material effect on the draft guidance she has already issued? Mrs May - Hansard - Copy Link - - Excerpts As my hon. Friend knows, the draft guidance has been subject to consultation. We received a significant number of responses to the draft guidance, and we are going through those responses in order to make changes as appropriate. The point of building this directly into the Bill is that it makes it very clear to those exercising this duty that we are introducing for universities under Prevent that they must have “particular regard”, as it says, to the issues of freedom of speech and academic freedom. This makes it absolutely clear that the Prevent duty is not overriding, to put it that way, the academic freedom that we all accept our universities should have. Robert Neill (Bromley and Chislehurst) (Con) - Hansard - Copy Link - - Excerpts Can the Home Secretary assure me that when she considers the responses to the consultation, the final document will be so cast that it does not, albeit inadvertently, impede the work of genuine, benign and well-intentioned student bodies such as Christian unions and other groups that are active within our universities? Mrs May - Hansard - Copy Link - - Excerpts I can give my hon. Friend that assurance. There is no intention to make any impact on the sort of benign organisation to which he refers. Nicola Blackwood (Oxford West and Abingdon) (Con) - Hansard - Copy Link - - Excerpts The Home Secretary is generous in giving way on this point. I am sure she can understand the concerns raised locally with me, a university MP, and I welcome the renewed emphasis on freedom of speech and on the stronger scrutiny for Parliament in amendment 16. Can she assure me that the guidance will be sufficiently clear for universities to have no uncertainty about their responsibilities under the new legislation? Mrs May - Hansard - Copy Link - - Excerpts I thank my hon. Friend for giving me an opportunity to make it absolutely clear that we intend the guidance to be clear. We have produced the guidance for consultation; as I said, we are considering the responses to it; and we are looking at areas where we need to clarify the guidance. It is important for universities, notwithstanding academic freedom and the need to secure freedom of speech, also to recognise the duty of care they have to students. That is why I believe it absolutely right for universities to be within this legislation and within the Prevent duty that is being put into statute. We will, of course, make the guidance clear, so that universities can operate appropriately. Mark Field (Cities of London and Westminster) (Con) - Hansard - Copy Link - - Excerpts I very much agree with my right hon. Friend’s view on the issue of freedom of speech. Vice-chancellors and others who are in control of our universities are worried about their ongoing duties, so can we ensure that the guidance will not fall into place and further duties will not be placed on our universities until such time as the clarity of the guidance is manifest, even if that means waiting for a further academic year? Mrs May - Hansard - Copy Link - - Excerpts There is a reason why we are putting the Prevent duty on a statutory basis, and there is a reason why the Bill has gone through Parliament slightly more quickly than would normally be the case. We have made it clear that we have issued guidance for consultation, and that we will respond to the consultation and revise the guidance. We have also made it clear, in the amendments, the particular regard that universities must have to freedom of speech and academic freedom. However, as I have said, I think that universities must also recognise their duty of care to students. I hope that, if students are being radicalised on their campuses, universities will get to know about it and take some action. Several hon. Members - Hansard - Copy Link rose — Mrs May - Hansard - Copy Link - - Excerpts I have been very generous in giving way, and I should now like to make a little more progress. Let me simply say to my hon. Friend the Member for Cities of London and Westminster (Mark Field) that the duty is that which is in the legislation, and that the guidance will be revised in accordance with our response to the consultation. The Secretary of State will also be required to have particular regard to freedom of speech and academic freedom when issuing guidance, or when giving a direction to an educational body that has failed to discharge the duty. Lords amendment 17 allows the Secretary of State to nominate suitable monitoring authorities for further and higher education institutions, and obliges relevant bodies to provide them with such information as they require, including information about the steps being taken to improve performance. We fully expect institutions to co-operate with the authorities, but there may be rare cases in which institutions do not co-operate. Lords amendment 18 provides for the Secretary of State to give directions to relevant further and higher education bodies when they have failed to supply information, and the Secretary of State can, if necessary, seek a mandatory order from the court to enforce any such directions. Lords amendments 14 and 15 provide that the guidance underpinning the duty will be subject to the affirmative procedure, which will ensure further scrutiny of it before it takes effect. There are a number of more minor amendments to this part of the Bill and the corresponding schedules. Lords amendments 12 and 13 would ensure that, if further bodies are made subject to the Prevent duty in the future, there will be greater flexibility to make it possible to focus on particular functions of the authorities, while Lords amendment 19 makes it clear that functions exercised outside Great Britain are not subject to the duty. Lords amendments 34 to 39 tidy up entries in the schedules listing the Prevent specified authorities and the Channel panel partners. Lords amendments 26 and 30 allow the Government to amend those schedules by order at any time after Royal Assent, subject to Parliament’s approval of the changes. The amendments to part 7 relate to the remit of the independent reviewer of terrorism legislation and his relationship with the proposed privacy and civil liberties board. They reflect the extensive debate that has taken place in both Houses, and the views that have been expressed by David Anderson QC. Lords amendments 21, 22, 25 and 27 make changes to the statutory remit of the independent reviewer to include areas of counter-terrorism legislation that are currently not subject to independent oversight. They also allow for a greater degree of flexibility in the reporting arrangements relating to the Acts that are within his purview. Lords amendments 23 and 24 make it clear that the independent reviewer will chair the privacy and civil liberties board, which in turn will operate under his direction and control. Dr Matthew Offord (Hendon) (Con) - Hansard - Copy Link - - Excerpts I have received several e-mails from constituents who are worried about the speed with which the Bill will be implemented. The Home Secretary has allayed some of my fears, which will enable me to support the Bill, but will she tell us more about the policy and civil liberties board, and about when it will come into effect? Mrs May - Hansard - Copy Link - - Excerpts I will say a little more about the board later in my speech, but I can tell my hon. Friend that, as certain matters will have to be dealt with, it will not come into effect in the immediate future. As for the amount of time that has been given to the Bill, it has indeed had a faster track through Parliament than a normal Bill, with the agreement of the Opposition. There has, however, been considerable debate both in the House of Commons—and the Committee stage was taken on the Floor of the House—and in another place. Yesterday, during the final debate in another place, a number of their lordships expressed their gratitude for the amount of time that had been made available and the amount of scrutiny that had taken place. So I think there has been sufficient scrutiny. 19:45 While I recognise that concerns have been expressed about the privacy and civil liberties board, it is worth reflecting on David Anderson’s most recent comments on these matters: “if skilled and practical people are appointed to the Board, content to work under the Reviewer’s direction, the capacity for independent review will be improved.” I should also draw the attention of hon. Members to his acknowledgement published on his website and dated 31 January that “the Government has listened to what I have been saying, and put forward changes which should significantly improve the ability of the Independent Reviewer to do an effective job.” Julian Smith (Skipton and Ripon) (Con) - Hansard - Copy Link - - Excerpts On the point of people’s concerns about privacy, we now have a Select Committee, which has done a detailed report on Lee Rigby and has shown it is scrutinising Parliament and the intelligence services, and we now have the civil liberties board. We have tremendous oversight in this country, and is it not now time that we say we have got good control of our intelligence services and we need to let them get on and do the job? Mrs May - Hansard - Copy Link - - Excerpts My hon. Friend makes an important point. Our country has one of the strictest legal structures for dealing with these kinds of matters. We also have significant oversight through the role of the various commissioners and the independent reviewer of terrorism legislation and through the enhanced capabilities of Parliament’s Intelligence and Security Committee, which has, through its Woolwich report, shown how it can use those powers to scrutinise in detail what has taken place and report to the public. Our intelligence agencies do a very good job for us every day of the week, and we need to ensure they can carry on doing that job with appropriate oversight, which I think we have in place. On the privacy and civil liberties board, as I said in response to my hon. Friend the Member for Hendon (Dr Offord), there is further work to be done because we have to consider the responses to the recent consultation on it before bringing forward regulations to establish the board, but I trust the amendments we have made will reassure the House about the Government’s approach to these important issues. The range and significant nature of these amendments demonstrates the approach that the Government have taken on this Bill. With the support of the official Opposition, we have agreed a timetable to ensure that it will be enacted at the earliest opportunity, but we have also ensured that our proposals have been subjected to robust analysis, and we have listened to the full range of views from all sides of both Houses. The Bill has certainly benefited from that scrutiny. I welcome the fact that these measures have broad cross-party support, and I am grateful to all hon. Members, and particularly the Opposition Front Bench, for the constructive approach that they have taken throughout our consideration of this Bill. As I have made clear previously, we are in the middle of a generational struggle against a deadly terrorist ideology. The first duty of Government is to keep the people of Britain safe and this Bill will help us to do so. The amendments made in the Lords will improve the provisions, and strike the right balance between our rights to privacy and security. I invite the House to agree them, so that we can enact this legislation without any further delay. Mr David Hanson (Delyn) (Lab) - Hansard - Copy Link - - Excerpts We, too, welcome the Lords amendments. The Home Secretary was right to commence her remarks by reminding the House of the events in Paris and the ever-present threat of terrorist activity on these shores. It is for that reason that we took a constructive approach to the Bill; we believe there is a threat, and it needs to be effectively managed, and we in Her Majesty’s Opposition give the Home Secretary the support she needs for the work of the police, MI5 and others, which she has sought to give extra powers to in this Bill. We are also keen to respond to the positive comments made last year by David Anderson, the reviewer of terrorism of legislation. We are grateful that the Home Secretary has listened to the comments made by Mr Anderson, and indeed by the other place. The Bill was introduced into this House at the end of November. There was no pre-legislative scrutiny or public consultation on most of its provisions and it finished its Commons stages on 7 January. I understand why the Home Secretary has moved quickly on these matters, but the fact that 39 amendments were made in another place and have come to this Chamber shows that some serious issues have had to be reflected on during the passage of the Bill. We welcome the thrust of the amendments made by the Government, because they are a series of concessions to points made not only in another place—I take the point made by the hon. Member for Perth and North Perthshire (Pete Wishart) about that—but in this House. Julian Smith - Hansard - Copy Link - - Excerpts Does the right hon. Gentleman regret, as I do, that the amendments tabled by the noble Lord King that sought to bring back the draft Communications Data Bill, or all the elements of it, did not make it back to this House? Does he agree that we need to move forward with that as soon as possible? Mr Hanson - Hansard - Copy Link - - Excerpts We need to look at and deal with that issue. Five years ago, in my last year as a Minister in the Home Office, I was briefed as the Minister for Policing, Crime and Counter-Terrorism on the need for such a Bill, so we do need to examine the matter. Whoever wins the election in some weeks’ time, the next Parliament will have to return to that issue. In fact, I think it would have returned to it in this Parliament had it not been for the Liberal Democrats—but let us not find division where there is none this evening. We welcome the measures agreed to by the Home Secretary. We need strong terrorism powers and to accept that the rise of ISIL and associated groups represents an exceptional threat, but we also need to look at how we manage such powers within the confines of ensuring that we uphold the principles of democracy in this country. On the temporary exclusion orders, therefore, we welcome the principle of judicial oversight being accepted following amendments in another place. In this House on 2 December the shadow Home Secretary, my right hon. Friend the Member for Normanton, Pontefract and Castleford (Yvette Cooper), rightly pointed out that there was such judicial oversight for terrorism prevention and investigation measures, and stated that we would be tabling amendments on that very principle. The Home Secretary said to me in Committee on 15 December that such oversight was not necessary and that for her to have the power to make that decision should suffice. Not only Opposition Members but Government ones, such as the right hon. and learned Member for Beaconsfield (Mr Grieve), the hon. Member for Cities of London and Westminster (Mark Field) and others, made the point that we need to uphold democracy and the right of appeal and oversight at the same time as tackling the threat head on. The debate continued on Report and, indeed, the Opposition tabled an amendment to achieve the objectives that the Government are now accepting following amendments in another place. Both Government parties voted against the earlier Labour amendment, but now support proposals that, broadly speaking, do exactly the same thing. It is a significant U-turn by the Government, but welcome all the same. The case for judicial oversight has been clear all along, and the conditions now in place are welcome. Her Majesty’s Opposition also fully support the Prevent strategy changes made by the Home Secretary this evening. Labour developed Prevent when in government, and my right hon. Friend the Member for Salford and Eccles (Hazel Blears) was key to that at the time. It is important for us to have a statutory basis for Prevent. The Bill introduces the obligation on public bodies to implement Prevent and to follow statutory guidance. We supported that in principle, but, again, we made it clear that we wanted to press strongly on the guidance, on the nature and drafting of which my hon. Friend the Member for Kingston upon Hull North (Diana Johnson) made some key comments. We tabled some amendments, which the Government have now accepted, on the guidance being subject to parliamentary approval. That amendment was drafted by the Labour party and supported by Universities UK. We also supported in another place specific protection for universities’ obligation to uphold freedom of belief. I welcome the fact that my hon. Friend made those points, that Labour Members have made the points in another place, that the House of Lords has agreed the amendments and that the Government have now accepted them. We support the creation of the privacy and civil liberties board, but there was significant confusion about its role as introduced in the Commons. Yet again, we raised that issue in this place and in another place, and the Government have now accepted some of the points made and have clarified, particularly, the interaction of the board and the independent reviewer. That will address some of the capacity problems faced by the independent reviewer. It is also important that we have accepted the amendments on the authority-to- carry scheme. That is a vital power but most of the detail and how it will impact carriers has been left to secondary legislation. The Government have now accepted that these detailed regulations will need to have proper parliamentary scrutiny, and, again, that is welcome. There was not a great deal of division between the Government and us on the principles of the Bill before it left this place, but we did want to see some strengthening, and those strengthening measures have been put in place. I wish not only to pay tribute to my hon. Friend the Member for Kingston upon Hull North and my right hon. Friend the Member for Normanton, Pontefract and Castleford for raising those issues here, but to thank Lord Rosser and Baroness Smith of Basildon for raising and dealing with those issues in another place. Serious consideration has been given in the House of Lords and this Bill is the better for it. I am pleased that the Home Secretary has accepted those amendments, and she will have our support on them tonight and on the implementation of the Bill in due course. Several hon. Members - Hansard - Copy Link rose— Mr Deputy Speaker (Mr Lindsay Hoyle) - Hansard - Copy Link - - Excerpts May I just say to Members that we do not have much time, but if we can be brief, we will get every Member in? Mr Heath - Hansard - Copy Link - - Excerpts As I said on Report, it is extraordinarily difficult to get the balance exactly right between the security of the citizen and of the realm and the accretion of powers by the state. I pay tribute to the Home Secretary and her colleagues in the Department for listening carefully to the things said about this Bill by Members on both sides of the House. All the amendments we have received from the other place, many of them stimulated by our discussions in this House and now back before us, improve the Bill rather than make it worse. That is not to say that there are not areas where I might have gone a little further than the Government amendments in the Lords, but let us recognise that it has been improved. I particularly welcome—this was the deal breaker—the introduction of judicial oversight of the temporary exclusion orders. I honestly do not understand why the right hon. Member for Delyn (Mr Hanson) believes it would be better for the House to have supported an Opposition amendment that was inadequate to the task rather than the Home Office’s own amendment, which we were promised on Report and which has now been produced in the Lords. Mr Hanson - Hansard - Copy Link - - Excerpts The reason I made a point of that was not about the amendment, but about the principle of the amendment initially, which is important. Mr Heath - Hansard - Copy Link - - Excerpts That is not the way Third Reading and Report work; what we put into the Bill then is the Bill—it is not a question of principle at that stage. The principle was that the Home Secretary accepted our arguments, she has brought this back and I am grateful to her. I am also grateful to her for the changes to the privacy and civil liberties board. The one area where we still have a mess, despite the welcome improvements, is on the draft guidance on places of higher education. Of course I welcome the explicit references now in the Bill to “freedom of speech” and “academic freedom”, but introducing those as something to which both the universities and the Home Secretary need to have particular regard means that we have an incomplete hierarchy of priorities between that and the guidance in the draft guidance. That makes it difficult for vice-chancellors and others to assess exactly where their duties lie. The saving grace lies in amendment 14, which means that the guidance will come before this House for consideration. The reason I specifically asked the Home Secretary what changes she would make to the draft guidance as a consequence of subsection (3) of the new clause in amendment 16 is that there is a clear implication, if that means anything at all, that there will be changes made on that basis. It cannot simply be done in response to the consultation process; there needs to be something that emerges from that process. I look forward to seeing the draft guidance revisited, reissued and then coming before this House for final decision. However, I make a plea to the Home Secretary not to have something that is too bureaucratic or to have hurdles that are impossible for large universities to jump. I have to say that I would be quite incapable of telling a university at which I was speaking what I was going to say two weeks in advance—I do not know what I am going to say when I stand up to make a speech. Dr Julian Lewis (New Forest East) (Con) - Hansard - Copy Link - - Excerpts Or even afterwards. Mr Heath - Hansard - Copy Link - - Excerpts Indeed. I really do hope that we have something that is workable, that addresses specifically, and on a risk basis, the issues that the Home Secretary seeks to address, and that does not introduce a duty that is inaccessible. Mrs May - Hansard - Copy Link - - Excerpts Perhaps I can give my hon. Friend a little further reassurance. My noble Friend Lord Bates made it clear in the other place that we would be amending the guidance, and I have made that clear, too. This issue of speakers providing two weeks’ notice of what they are going to say is precisely something that we will clarify as not necessary. Mr Heath - Hansard - Copy Link - - Excerpts That is a very helpful reassurance from the Home Secretary. I am grateful to her for what she has said. On that basis, I shall now sit down. 20:00 Hazel Blears (Salford and Eccles) (Lab) - Hansard - Copy Link - - Excerpts First, I should like to place on the record my thanks to the Minister for Security and Immigration, the hon. Member for Old Bexley and Sidcup (James Brokenshire), who is not in his place this evening, for his conduct of the debate on this Bill; he has been open, inclusive and generous. Very often, he has listened and genuinely responded to the points that all Members have made. I also wish to thank him for coming to a roundtable discussion that I organised two weeks ago. He made an excellent contribution among a group of academics, practitioners and people from think-tanks about how we can do some practical work around tackling extremism and radicalisation. I will let him have a report of that discussion this week, and I look forward to continuing the dialogue with Government about what we can do in practical terms to make this situation better than it is at the moment. I wish to comment briefly on amendments 14 and 16, which relate to part 5 of the Bill and the Prevent programme. Like every other Member, I welcome amendment 14, which provides for parliamentary scrutiny of the guidance. I am delighted that the Government have now accepted that. It will be through the affirmative resolution procedure, and it will enable proper detailed scrutiny and debate of the matters that are in the guidance. I have now had the opportunity to read the guidance. On Second Reading and in Committee, I kept saying to the Minister, “When will we see the guidance?” He implored me to be patient, saying that the issues I was raising would be addressed in that guidance. Well, I have been as patient as I can be, but I remain concerned about two issues that the guidance seeks to address. The first matter I raised in debate was that much of the Bill is couched in terms of dealing with individuals who are in danger of being radicalised and drawn into terrorism. There was very little, if anything, about the need to work on a broader basis with communities to build the resilience of communities to the extremist message and to galvanise communities into being actively engaged on this agenda. I am afraid that the guidance, as I have read it, is still completely focused on individuals. This afternoon, I read the guidance in great detail, even to the point where I did a word search on it. It is 39 pages long and has 178 paragraphs and—I hesitate to say this to the House—the words “parent” and “family” do not appear once in that guidance. I would that thought that families and parents are absolutely on the front line of trying to prevent our young people from being drawn into extremism. I know that the Home Secretary will know that mothers, sisters and women in those communities can play a life-changing role in safeguarding the future of our young people, and yet nowhere in the guidance is there any mention of families and parents. Nicola Blackwood - Hansard - Copy Link - - Excerpts The right hon. Lady is making a very important argument about increasing community resilience. Does she agree that one of the most important ways that we can do that is by improving critical engagement with online content, which is one of the most pervasive forms of radicalisation? Hazel Blears - Hansard - Copy Link - - Excerpts I absolutely agree with the hon. Lady that online radicalisation has become increasingly important as technology has developed. Many young people are drawn into the most horrific websites and see the most horrendous content, which inevitably affects how they view these issues. I personally believe that the service providers have a great responsibility on this agenda and would like them to be much more active. Google, for example, has done some excellent work on gangs and I would like to see it replicate that work for the counter-terrorism agenda. We need a more inclusive conversation with the service providers on all these issues. Richard Fuller - Hansard - Copy Link - - Excerpts Does the right hon. Lady agree that we should not focus too much on the individual, as it is that individual who is at risk and who cannot put the circumstances into context in making decisions? Secondly, does she agree that communities are dispersing around the country and if we do not equip families to have those conversations, the strategy will not be as effective as it could possibly be, given those changes? Hazel Blears - Hansard - Copy Link - - Excerpts I agree, and I do not think that the two are mutually exclusive. We need to tackle individuals and we need action plans for individuals, but individuals live in families and in communities. We therefore need a much more holistic engagement programme. Dr Julian Lewis - Hansard - Copy Link - - Excerpts Unfortunately, the right hon. Lady is stepping down as a Member of this House very soon and I only hope that her voice will not be stilled on such topics in other arenas. Does she agree that although there has been a welcome change in that Ministers from the Prime Minister downwards are now talking about the underlying perverted ideology at the root of radicalisation, we need to back up that new rhetoric with arrangements to counter that perverted ideology? Hazel Blears - Hansard - Copy Link - - Excerpts The hon. Gentleman has a proud record of having pursued these issues with such determination and tenacity that he has, perhaps, had no small influence on the Home Secretary and the Prime Minister in talking about the long-term generational struggle and the need to deal with ideology. I want to return to the point made by the hon. Member for Oxford West and Abingdon (Nicola Blackwood) about resilience, as that is the second issue that I am concerned about. I have read the guidance very carefully and the first mention of building community resilience is in paragraph 175 of 178, on page 39. It is about the police and it states: “The success of Prevent work relies on communities supporting efforts to prevent people being drawn into terrorism and challenging the extremist ideas that are also part of terrorist ideology. The police have a critical role in helping communities do this. To comply with the duty, we would expect the police, working with others, to build community resilience”. There is no objection to community resilience in principle in the guidance, yet it takes us 175 paragraphs before we talk about the need to do that. The Home Secretary is looking at me quizzically, but this is the guidance as we see it now and when it is revised, as I hope it will be, I hope that there will be a stronger emphasis on families, parents and communities. I have made those points consistently and I asked the Home Secretary to reflect carefully on that. Fiona Mactaggart (Slough) (Lab) - Hansard - Copy Link - - Excerpts Within those communities, there is a hunger to be engaged and a worry that at the moment the terms of engagement seem to be determined completely by the police and not sufficiently by families. I had a meeting with a group of Muslim mums in my constituency who asked for better education on how they could understand what was going on on the internet. We need a non-police-led element to this Prevent work as well. Hazel Blears - Hansard - Copy Link - - Excerpts My hon. Friend makes a point that is based on experience and it is all the more authentic and powerful for that. These issues are not mutually exclusive. The police have a role to play and have an important security role, but other agencies and people in the community can equally make a big contribution. The second point that I have raised consistently is about ideology. I am more reassured about ideology and paragraph 4 of the guidance, right at the front of the document, states that one of the objectives is to respond to the ideological challenge. Paragraph 17 talks about the need to train front-line staff so they are aware of the ideology and what they can do to push it back. I have asked again during the passage of the Bill how much resource will go into the area. We have £120 million to deal with the increased threat, but how much will go into the Prevent agenda? It is very important for people out there to know that. There is a hunger for training, support and capacity building among all the agencies that will have to carry out that duty. We need to offer some reassurance that that capacity and guidance will be in place. My final point is about freedom of speech. I know that many Members have made their points on that already. The noble Lord Bates made a neat attempt to try to make the division between having due regard to and having particular regard to. I am not sure that I would envy him the prospect of litigating on that basis, because it seems to me to be a bit of a philosophical exam question. I know that the Home Secretary will look at that guidance again and make it as practical as possible, but reconciling those two formulations seems to me to be intrinsically difficult. I do not think for one moment that I am capable of reconciling that; that would require a greater philosophical brain than mine. Perhaps it will eventually come to judges. If the Home Secretary could say a little more about that, that would be very welcome. Finally, will the Home Secretary publish all the responses to the consultation? That would help us all significantly in seeing the direction of travel. She has said that this is an ongoing generational struggle, as indeed has the Prime Minister. He said last week that the shadow will hang over our generation for many years to come. We are all engaged in trying to ensure that we tackle the problems we face. I will certainly seek to make whatever contribution I can to this agenda now and in future. Yasmin Qureshi (Bolton South East) (Lab) - Hansard - Copy Link - - Excerpts On Second Reading, I and a number of other Members talked about the need for judicial or legal oversight of temporary exclusion orders and of the removal of passports and documents. I am pleased that some judicial or legal oversight has now been provided, but I am still a little disappointed about the number of days that a person’s passport can be held before that can effectively be challenged in the courts. I am also concerned that temporary exclusion orders are still closed proceedings, which means a person will not necessarily know what is being said against them. The ex parte nature of these proceedings is fundamentally wrong. It has been said that any application for an exclusion order or to take someone’s documents will be intelligence-led and based on proper evidence. If that is the case, why is everybody frightened of proper judicial or legal oversight? That would not be by the method of judicial review, but in a proper, straightforward way, for example by going to the High Court to argue why a person should be excluded, or why they should not be on the managed programme, or why their documents should be taken. Proper legal aid should be provided for all those purposes as a matter of right, not as a matter of discretion. On Prevent, I have to say that I disagree not only with the Home Secretary, but with my party and with what has happened previously. Prevent was brought in on a voluntary basis in 2007. I am afraid that some people think that they can introduce these kinds of things and then sit back and say, “Right, that’s going to deal with the whole issue of radicalisation.” That view is based on a fundamental flaw in the argument, which is that somehow this is all based on ideology. It is not based on ideology, or on a perverted ideology; there are other reasons why these things happen. It is completely wrong to think that simply by monitoring people in nurseries, schools, colleges, universities, hospitals and doctors’ surgeries we will be able to identify who might make the big leap from having a socially conservative view of something to going out to commit suicide and injure and maim other people. I am very disappointed that that has not been looked at critically in this House. There seems to be universal acceptance here that Prevent is some kind of panacea; it is not. A number of organisations have said the same. A Demos report from 2010 recommended that the Government should dismantle the preventing violent extremism programme. The Intelligence and Security Committee’s report following the murder of Fusilier Lee Rigby in 2013 said that the Government’s counter-radicalisation programmes are not working. 20:15 Baroness Eliza Manningham-Buller, the former director of MI5, who should know what she is talking about, said recently when the Bill was debated in the House of Lords: “However, it seems to me that Prevent is clearly not working. . . It also follows, therefore, that I am not convinced of the value of putting Prevent on a statutory footing. I am out of date. The Government may be able to convince me but I cannot see how legislation can really govern hearts, minds and free speech.” —[ Official Report, House of Lords, 13 January 2015; Vol. 758, c. 752.] Other researchers have reached similar conclusions. Mark Sageman, who was a CIA counter-terrorist officer, looked at 500 so-called radicalised persons and concluded that programmes such as Prevent had no effect on them and that religious ideology was not the motivation for those people to go on to commit serious criminal offences. Studies in this country by MI5 also conclude that such offences are not to do with ideology and result from other things. I know I am going to be lynched, because whenever somebody expresses such opinions, everybody else has a go at them. What is happening internationally, what is happening in the political world out there has a bearing on some of that behaviour. That is not the total explanation, but it is part of the equation. To ignore that and concentrate on ideology is to look at the problem through a prism. We know what we are talking about. We are talking about the Muslim community and it is thought that people commit an offence because of ideology. Putting Prevent on a statutory basis is one of the worst things that could happen. Even the voluntary scheme was not a good idea. I have spoken to some of the people who have been taken away to the so-called radicalisation unit. What sort of questions were they asked? Questions such as, “Were you against the Iraq war? What do you think of the middle east situation? Did you go to the Iraq war demonstration?” Millions of people in this country would answer yes to those questions. Does that mean that we should all be subjected to a programme to deradicalise us? No. We are heading towards a McCarthyite state, where everybody will be spying on everybody else, where nursery teachers, school teachers, hospital nurses, doctors and everybody else will say, “My friend said something that may be critical of someone or something. That means I have to report them to the local authority or the police.” That person will then be arrested, taken away and questioned. I shall give an example of a woman who worked in a hospital. She went off to do umrah—hajj—in Saudi Arabia. When she came back, she was wearing a headscarf and she started praying a bit more. What happened? Her manager apparently reported her to the Prevent people and suggested they have a chat with her. It turned out that, in her opinion, she had become a little more religious. That kind of thing will happen, and it has been happening in recent years. All it has done is cause people to feel angry and to feel that they are being spied on. That is not a British value. It is not how we do things in Britain. British values do not entail spying on our next-door neighbour or the person next to us and reporting them. With the regulations being put on a statutory footing, there will be more and more picking on people, which will not help anyone. It will not make anyone safer. If Members think that holding a socially conservative view about particular issues means that people are going to commit suicide and kill everybody around them, Members do not understand the real situation out there. I mean that very respectfully. We are going to have a McCarthyite state where people spy on each other, and that is not right. People who commit such offences are criminals and should be dealt with. Anybody who saw the two criminals who killed Fusilier Rigby would have seen that they were frothing at the mouth. It is clear that they were mental. Many educational psychologists and others who have studied people who become radicalised and commit criminal offences say that those people are often educationally deprived, economically deprived and have mental health issues. It is those issues that we should address. Concentrating on Prevent will not stop all the problems. Whatever is happening internationally and what those people are doing will continue. Dr Lewis - Hansard - Copy Link - - Excerpts I appreciate the passion with which the hon. Lady is making her point and I agree with a lot of what she says about the fact that the people who commit those terrible crimes are unbalanced and unstable. That was true of the criminals who killed Lee Rigby, but it is precisely because they were unbalanced and unstable that they were susceptible to a particular extreme interpretation of a religious ideology. Therefore the two things interact. It is not quite as simple as she says. Yasmin Qureshi - Hansard - Copy Link - - Excerpts I do not agree with that. One of the murderers of Fusilier Rigby quoted, “An eye for an eye and a tooth for a tooth.” That comes from the Old Testament, not from the Koran. We cannot start saying that this is somehow linked with religious ideology. These are just confused, mentally disturbed people. Dr Lewis - Hansard - Copy Link - - Excerpts rose— Yasmin Qureshi - Hansard - Copy Link - - Excerpts I am sorry, but I have only a little time, and I have something to say that is different from what everybody else has said, so I would like to be able to take the opportunity to say it. People do not seem to appreciate that a lot of these people are mentally unbalanced and have other issues. The Prevent programme has shown that spying on young people, taking them in and questioning them incessantly simply traumatises them—I have spoken to some of them. It does not help them in any way, shape or form, and it makes them even more frightened to say anything. Programmes like Prevent, in channelling people’s thoughts or what they say, are effectively stopping them discussing things. If I come across somebody who has a certain view and take the law enforcement agencies or the local authorities to them, they will clam up and we will not hear anything that they have to say. These things are completely counter-productive. The former director general of MI5, the noble Baroness Eliza Manningham-Buller, is not somebody who does not know what she is talking about. She and a number of people like her have said that Prevent does not work and we do not need it. If people do not want to listen to me, why cannot they listen to people like her and intelligence officers who have been involved in these kinds of things and say that ideology is not the reason behind them? Finally, I want to talk about an aspect of the Bill that I hope the Home Secretary will reassure me about—part 4, on ships and aviation. I hope that these provisions will not end up stopping people from a particular country being able to travel to this country. Some of my constituents have expressed the fear that if certain parts of part 4 are applied, the way that the law is currently worded could allow people to say that because people from one particular country are coming here with some issues and challenges— Madam Deputy Speaker (Mrs Eleanor Laing) - Hansard - Copy Link - - Excerpts Order. I hesitate to interrupt the hon. Lady, but perhaps she does not realise that this is a very short debate. I trust that she will soon be coming to a conclusion. Yasmin Qureshi - Hansard - Copy Link - - Excerpts I thank you for your indulgence, Madam Deputy Speaker. I hope that the way the provisions in part 4 are put together will not lead to airlines or countries saying, “We will not allow people from this particular country to travel here.” I hope that reassurance will be provided in the guidelines that are produced later on. I know that what I am saying may be different from the conventional view of some people in this House. However, as somebody who talks to young people all the time and deals with people who commit criminal offences, defending and prosecuting, I have a very good knowledge of the criminal justice system and the people who often come into it. Most of them are unhinged and most have problems. Prevent is the worst possible thing to put on to a statutory footing. It will criminalise people. I do not often agree with Peter Hitchens of the Daily Mail , but I agreed with his article of 15 January where he said that these kinds of things are going to lead to people being banged up, and in 10 years time we will ask how that happened. It happened, I am sorry to say, because not enough people in this House got up and said that Prevent is a bad idea and the whole process of looking at these things is wrong. John McDonnell (Hayes and Harlington) (Lab) - Hansard - Copy Link - - Excerpts My local mosque is extremely progressive, but I was invited to visit it on Monday because it has concerns about the Bill. Perception is sometimes as effective as reality and they feel that the Muslim community is under suspicion and that this Bill is targeted at them. I understand what has been said about the speed at which the Bill has gone through, but I do not think that the wider community has caught up with the debate or why there is a sense of urgency. On the Bill’s implementation, it is absolutely critical that we engage at local level and allow the community to lead, rather than just the police. I completely agree with the argument about the involvement of families and mothers in particular, but that involvement has to be resourced as well. There is a real feeling in my community that these measures are targeted at Muslims in a way that will infringe on their religious freedoms and divide the community rather than unite it. I agree with my hon. Friend the Member for Bolton South East (Yasmin Qureshi): real care needs to be taken in how the Bill is implemented at the local level. In my area, we are bringing all the mosques and agencies together to talk through the detail of the Bill, not only so that people can be brought up to speed, but, more importantly, so that we as a local community can drive the initiative, rather than its being seen as something that is being done to the Muslim community by the state. Jeremy Corbyn - Hansard - Copy Link - - Excerpts My hon. Friend the Member for Bolton South East (Yasmin Qureshi) made some very important points. I have two concerns about the Bill, which unleashes worries about civil liberties in this country. The first relates to the effective banning of people from either travelling from or returning to this country. That will open a can of worms, the effects of which we will suffer for many years to come. Surely the principle of holding nationality is that a person should be free to return to the country of which they are a national. My second concern relates to freedom of speech. I recognise that the House of Lords has tried to improve the question of freedom of speech in universities, but I draw this House’s attention to the letter signed by 500 professors in The Guardian on 2 February. It pointed out that the issue is fraught with enormous difficulties. On the one hand, the Prevent strategy is being imposed on universities, but at the same time it is being insisted that they have freedom of speech. Racism, anti-Semitism and Islamophobia are all awful things— 20:26 One hour having elapsed since the commencement of proceedings on consideration of Lords amendments, the proceedings were interrupted (Programme Order, this day ). The Deputy Speaker put forthwith the Question already proposed from the Chair (Standing Order No. 83F), That this House agrees with Lords amendment 1. Question agreed to . Lords amendment 1 accordingly agreed to , with Commons financial privileges waived . The Deputy Speaker then put forthwith the Question necessary for the disposal of the business to be concluded at that time (Standing Order No. 83F ). Lor ds amendments 2 to 39 agreed to, with Commons financial privileges waived in respect of Lords amendments 2, 9, 21 and 32. Return to start of debate - Return to top of page Business without Debate Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text European Union Documents Motion made, and Question put forthwith (Standing Order No. 119(11)), Financial Management That this House takes note of European Union Documents No. 12213/14 and Addenda 1-6, a Commission Report: Protection of the European Union’s financial interests–Fight against fraud 2013 Annual Report, and unnumbered Document, the European Court of Auditors’ 2013 Annual Reports on the implementation of the budget and on the activities funded by the Eighth, Ninth and Tenth European Development Funds; agrees that budgetary discipline and robust financial management at all levels remains crucial, including to support domestic efforts to tackle the deficit and debt, especially given the continuing fiscal constraints and fragile economic recovery across the EU; believes that it is unacceptable that EU budget expenditure has not been granted an unqualified Statement of Assurance by the European Court of Auditors for the twentieth year; supports the Government’s efforts to press the Commission for a clear action plan to address the European Court of Auditors’ recommendations relating to the European Development Fund; and urges the Government to continue to engage with other Member States and the Commission to drive for urgent improvements designed to facilitate an error rate below the European Court of Auditors’ materiality threshold. —(Damian Hinds.) Question agreed to. Delegated Legislation Madam Deputy Speaker (Mrs Eleanor Laing) - Hansard - Copy Link - - Excerpts With the leave of the House, we shall take motions 8 to 12 together. Motion made, and Question put forthwith (Standing Order No. 118(6)), Police That the draft Protection of Freedoms Act 2012 (Code of Practice for Powers of Entry and Description of Relevant Persons) Order 2015, which was laid before this House on 8 December 2014, be approved. Northern Ireland That the draft Northern Ireland Assembly (Elections) (Forms) Order 2015, which was laid before this House on 8 January, be approved. That the draft Local Elections (Forms) (Northern Ireland) Order 2015, which was laid before this House on 8 January, be approved. That the draft European Parliamentary Elections (Forms) (Northern Ireland) Regulations 2015, which were laid before this House on 8 January, be approved. Representation of the People, Northern Ireland That the draft Parliamentary Elections (Forms) (Northern Ireland) Regulations 2015, which were laid before this House on 8 January, be approved. —(Damian Hinds.) Question agreed to. Madam Deputy Speaker - Hansard - Copy Link - - Excerpts With the leave of the House, we shall take motions 13 to 18 together. Motion made, and Question put forthwith (Standing Order No. 118(6)), Electricity That the draft Electricity Supplier Obligations (Amendment & Excluded Electricity) Regulations 2015, which were laid before this House on 19 January, be approved. That the draft Electricity Market Reform (General) (Amendment) Regulations 2015, which were laid before this House on 19 January, be approved. That the draft Electricity Capacity (Amendment) Regulations 2015, which were laid before this House on 19 January, be approved. Legal Services That the draft Legal Services Act 2007 (The Law Society) (Modification of Functions) Order 2015, which was laid before this House on 8 December 2014, be approved. Police That the draft Police and Criminal Evidence Act 1984 (Codes of Practice) (Revision of Code A) Order 2015, which was laid before this House on 5 December 2014, be approved. Investigatory Powers That the draft Regulation of Investigatory Powers (Communications Data) (Amendment) Order 2015, which was laid before this House on 10 December 2014, be approved. —(Damian Hinds.) Question agreed to. Motion made, and Question put forthwith (Standing Order No. 118(6)), Public Health That the draft Smoke-free (Private Vehicles) Regulations 2015, which were laid before this House on 17 December 2014, be approved. —(Damian Hinds .) The Deputy Speaker’s opinion as to the decision of the Question being challenged, the Division was deferred until tomorrow (Standing Order No. 41A). Madam Deputy Speaker - Hansard - Copy Link - - Excerpts With the leave of the House, we shall take motions 20 to 26 together. Motion made, and Question put forthwith (Standing Order No. 118(6)), Public Service Pensions That the draft Firefighters’ Pension Scheme (England) (Consequential Provisions) Regulations 2015, which were laid before this House on 17 December 2014, be approved. That the draft Teachers’ Pension Scheme (Consequential Provisions) Regulations 2015, which were laid before this House on 17 December 2014, be approved. That the draft Police Pensions (Consequential Provisions) Regulations 2015, which were laid before this House on 17 December 2014, be approved. That the draft Armed Forces Pension (Consequential Provisions) Regulations 2015, which were laid before this House on 17 December 2014, be approved. That the draft Public Service (Civil Servants and Others) Pensions (Consequential and Amendment) Regulations 2015, which were laid before this House on 17 December 2014, be approved. That the draft National Health Service Pension Scheme (Consequential Provisions) Regulations 2015, which were laid before this House on 17 December 2014, be approved. Road Traffic That the draft Passenger and Goods Vehicles (Recording Equipment) (Downloading of Data) Regulations 2015, which were laid before this House on 8 January, be approved. —(Damian Hinds.) Question agreed to. Return to start of debate - Return to top of page Petitions Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text 20:29 Mr Lee Scott (Ilford North) (Con) - Hansard - Copy Link - - Excerpts I have a petition signed by 676 people declaring that they are extremely concerned, as I am, at the high level of reported accidents—averaging one per week—as well as the potential for fatal accidents at the Redbridge roundabout, which is a major junction of the M11, the north circular and the A12. There needs to be urgent action to stop what has become a nightmare for residents of the area and anyone travelling through it. The petition states: The Petitioners therefore request that the House of Commons urges the Government to direct Transport for London to install traffic lights at the Redbridge Lane East junction or to at least put measures in place (such as adjusting the existing traffic light timings) so that at least 6 or 8 cars can safely get onto the roundabout on each traffic light cycle. Following is the full text of the petition: [ The Petition of residents of Ilford North , Declares that the Petitioners are extremely concerned at the high level of reported accidents (which averages at one accident per week) as well as the potential for more fatal accidents on the Redbridge roundabout (LBR); further that this is a major road junction on the east of London which carries heavy traffic from the M11, North Circular Road and the A12; further that it is reputed to be one of the busiest and most dangerous road junctions in Europe; further that all connecting roads on the gyratory have traffic lights apart from one road, Redbridge Lane East; further that traffic from Redbridge Lane East is unable to safely join this constantly busy roundabout and only two or three cars can enter the roundabout on each cycle of the lights; further that this causes up to 45 minute delays on reaching the roundabout, generates pollution levels above safe limits, causes inconsiderate driving by frustrated drivers and results in stress and anxiety experienced by drivers contemplating taking the high-risk strategy of attempting to get across the roundabout without having an accident; and further that a local petition on this matter in the Ilford North constituency and the surrounding area was signed by 2187 individuals . The Petitioners therefore request that the House of Commons urges the Government to direct Transport for London to install traffic lights at the Redbridge Lane East junction or to at least put measures in place (such as adjusting the existing traffic light timings) so that at least 6 or 8 cars can safely get onto the roundabout on each traffic light cycle . And the Petitioners remain, etc. ] [P001432] 20:30 Mr Lee Scott (Ilford North) (Con) - Hansard - Copy Link - - Excerpts I have a petition signed by 4,864 people to save the Oakfield site, which covers playing fields and a sports area on green-belt land. Sadly, the London borough of Redbridge has put out to consultation a proposal to build homes on the site. There are brownfield sites in the area that have not yet been built on and should perhaps be looked at as a matter of urgency before the proposal is even considered. The proposal must be thrown out: it is a rape of our countryside and our green-belt land, and it is a misuse of land needed by children and adults for recreational purposes. The Petitioners therefore request that the House of Commons urges the London borough of Redbridge to reconsider any proposal to develop the Oakfield site for housing, and further request that the House of Commons urges the Government to reject any requests to remove green-belt status from Oakfield. Following is the full text of the petition: [ The Petition of the Save Oakfield Site (SOS) campaign group, Declares that the precious, high quality sports field known as Oakfield has twelve full size and nine junior size grass football pitches and four cricket grounds as well as two large pavilions which together act as an inclusive social hub contributing to community cohesion; further that the Petitioners believe that there are proposals to concrete over this irreplaceable green belt land and to destroy the pavilions; further that this would be a massive and irreversible loss to the residents of the Borough of Redbridge, to the many sportsmen and sportswomen in the surrounding London Boroughs and in the County of Essex and beyond, and to the many voluntary and other organisations that provide services to local schools and the wider public; further that the London Borough of Redbridge has planned to seek de-classification of green belt status for Oakfield; further that the Petitioners believe that these plans have occurred without good reason following a flawed process; further that at a time when sport is seen as the Olympic Legacy and as the solution to ever-increasing obesity in the nation, removal of such facilities represents a loss of opportunity for exercise for the existing and growing number of potential users and increases the risk of ill health and will also put further strain on NHS resources; further that the Borough Council would be failing to supply conveniently located, good quality playing fields to satisfy the current demand and the likely future demand in line with the policy of Sport England; further that the proposed development of the stated 800 units of housing on the site will increase already chaotic traffic congestion to intolerable levels and will increase the local pollution level which currently exceeds the rate that is identified as acceptable by the EU and the WHO and will reduce safety without contributing anything significant to social and key-worker homes; and further that all this is based on long-term population projections for the Borough that extrapolate from past trend analysis to produce unrealistic, and unfounded housing demands on the Borough that ignore the needs and rights of the existing population for a sustainable quality of life and are unfair in relation to other London Boroughs and national Government demographic policies. The Petitioners therefore request that the House of Commons urges Redbridge Borough Council to reconsider the proposal to develop the Oakfield site for housing and further request that the House of Commons urges the Government to reject any requests to remove green belt status from Oakfield. And the Petitioners remain, etc.] [P001433] Return to start of debate - Return to top of page Transport (Tees Valley) Tuesday 10th February 2015 (8 years, 4 months ago) Commons Chamber Share Debate Copy Link Read Full debate Read Hansard Text Read Debate Ministerial Extracts Motion made, and Question proposed, That this House do now adjourn. —(Damian Hinds .) 20:31 Andy McDonald (Middlesbrough) (Lab) - Hansard - Copy Link - - Excerpts I sought this debate on transport in Tees Valley to voice my concerns about how the discussion is developing on the need for greater investment in our transport infrastructure, and on the need for rebalancing our economy both in geographical terms and in terms of a greater focus on our manufacturing industries. By way of introduction, Tees Valley may be more than 200 miles away from Westminster, but that is no excuse for the concerns of our region being as far away from the considerations of Downing street and Whitehall as they are at present. Last year, I asked the Prime Minister about the huge disparity in spending on transport infrastructure between the north-east and the south-east, and how the needs of the Tees Valley were neglected. In his response, he talked about the Tyne and Wear metro, the Tyne crossing and the A1 between Newcastle and Gateshead, but said not a single word about Tees Valley. I hope this evening to fix the location of Tees Valley better in the Government’s collective memory. Much attention has been paid recently, and quite rightly, to the One North initiative of our great northern core cities of Manchester, Liverpool, Leeds, Sheffield and Newcastle, and to the transport for the north announcement made just a few weeks ago, which involves the same players, while the Chancellor has talked of an HS3 rail link between Manchester and Leeds, all of which has been set against the backdrop of the northern powerhouse. All that is to be welcomed, but in this debate I want to explore the current limitations placed on such discussions, and ask whether these matters should be the sole prevail of the self-named core cities. I want to dispel the myth perpetuated by some that the north ceases at the M62. There is a great deal more to the north than that, and I submit that if we are truly to talk of a northern powerhouse and the interconnectivity of our economic engine rooms, it is essential to consider all of the north. In doing so, it is imperative that the role of Tees Valley should be properly considered. I will concentrate in the main on rail infrastructure. It is telling that modern Middlesbrough came into being as a direct result of the creation of the railways and the founding of the Stockton and Darlington Railway Company to serve as the river access point for receiving coal from the Durham coalfields on the banks of the River Tees for onward shipping. Middlesbrough was subsequently propelled into the industrial revolution by becoming the site of the explosive iron and steel industry. It was described by Gladstone as the “Infant Hercules”, and it soon became the fastest-growing town in European history. Despite that railway heritage, Middlesbrough, which is now at the heart of a conurbation of some 660,000 people, is the largest conurbation in the UK without a direct service to the capital. There are far too many aspects of the economic powerhouse of Tees Valley for me to cover in the time available, but the sub-regional transport needs must be seen in the context of the Tees Valley’s industrial and commercial might. Alex Cunningham (Stockton North) (Lab) - Hansard - Copy Link - - Excerpts I congratulate my hon. Friend on securing the debate, which is crucial to Teesside and the wider Tees area. I appreciate that he is concentrating on rail, but the Tees Valley local enterprise partnership reminded us today that we have no major road network and are forced to rely on secondary roads such as the A19 and the A66, which impacts on our ability to attract jobs. Does he agree that, as well as direct rail routes to London with electrification on the lines, we need 21st-century roads, including another Tees crossing, if we are to serve Teesside properly? Andy McDonald - Hansard - Copy Link - - Excerpts I wholeheartedly agree with my hon. Friend, who is absolutely right. One glance at a road atlas will show the complete absence of blue roads—motorways. We need one or two of them in our region. The industrial might of the Tees Valley is a key component of the north-east of England’s manufacturing prowess. London apart, our region is the only one in the UK that consistently makes a positive contribution to our balance of payments. We lead the way in advanced manufacturing and export-led growth. Tees Valley’s integrated chemical complex at Wilton, Billingham and Seal Sands is the biggest in the UK and second-largest in Europe. It sits alongside the steel industry—two vital foundation industries side by side. The Tees Valley economy contributes significantly to the north. It contributes some £11.5 billion of gross value added to the national economy every year. We have a thriving digital and creative industries cluster, which grew faster than that in any other LEP area in 2014. We have a 280,000-strong highly skilled work force, and a small businesses base of more than 14,500 firms. We also have the UK’s third largest port, Teesport, which provides an international gateway, distributing products across the country and abroad. As a contemporary sign of its vitality and importance, PD Ports has just signed a seven-year contract with Sahaviriya Steel Industries for the continued shipping of its steel products. Our leading colleges, our universities and national knowledge centres are at the forefront of skills development and innovation. Tees Valley also has an international airport, albeit one that is crying out for investment and redevelopment—we look to Peel airports to better develop the airport services—and we have direct road and rail routes to key locations across the north. There is a consensus on the importance of reducing the UK’s trade deficit and rebalancing the economy. If that is to be achieved, it is important that Tees Valley and its mighty industries play their full role. Exciting developments in the energy-intensive industries hold great potential for our region and our country. Strictly subject to the science being right and there being verifiable safeguards, hydraulic fracturing and coal gasification have enormous potential for our future energy and industrial requirements. There is not time this evening to go into the detail, but subject to those safeguards, the future could be truly exciting. The major beneficiaries from the syngas so derived are the energy-intensive industries, and none more so than those on Teesside. I must mention the Teesside Collective, a pioneering infrastructure project comprised of a cluster of leading industrial players—BOC, Lotte Chemical UK, SSI and GrowHow—which offers a compelling opportunity for the UK to progress its industrial and environmental interests at the same time. Work is already under way for the development of a business case for deploying industrial carbon capture and storage in the Teesside cluster. It will be completed later this year. Tees Valley is in the right place at the right time to become the industrial carbon capture storage leader in Europe. It is therefore essential that the Government provide the necessary support that such key foundation industries need, which in turn will allow our manufacturing industries to compete on a global stage. Good rail and road infrastructure for freight and passengers is essential to all of that. On 17 January, the Secretary of State for Transport attended the launch in Leeds of Transport in the North, a body of regional leaders tasked with drawing up and delivering a comprehensive programme of strategic investment to transform the north’s infrastructure, and helping to maximise growth. I argue that, if that particular body is to properly speak on the transport needs of the north, it is wholly inappropriate if Tees Valley does not sit alongside the five cities on the board. James Wharton (Stockton South) (Con) - Hansard - Copy Link - - Excerpts I congratulate the hon. Gentleman on securing what is a very important debate. I think across the House we can all agree that it is in the interests of the areas we represent to talk up Teesside and the great things happening there: steelmaking is back, train-making is coming and investment is coming in. This is a very important cross-party point: Tees Valley LEP needs to be represented, as those other bodies are, to give our area the strong voice it needs. I want to voice my support and to make it very clear that this is something that unites MPs from different parties, and council leaders and groups, in support. We need to ensure our voice is strong and heard. Andy McDonald - Hansard - Copy Link - - Excerpts I thank the hon. Gentleman for that intervention. I think we are speaking with one voice for Tees Valley and I am grateful to him for his support. Quite simply, the Tees Valley transport infrastructure, opposite the existing and future needs of businesses and communities, is lacking in key areas, and those deficits need to be addressed if we are to capitalise on the terrific potential of our region. Undoubtedly, Tees Valley is not configured like the self-styled core cities, but it has its own unique configuration and status that warrants a seat at the table. The Minister will be aware of the excellent inclusive outcomes that have been achieved in the governance arrangements for Rail North, and I hope he will agree with me that it would be entirely sensible to take that sort of inclusive approach in terms of the board of Transport for the North. I urge the Minister to take the necessary steps to ensure that Tees Valley has a seat. It is regrettable that the state cannot currently compete alongside private companies for rail franchises, but putting that argument to one side for another day I am nevertheless pleased that on the awarding of the new franchise the business case has been won for the reintroduction of a direct Middlesbrough to London rail service, so I need not repeat it. Clearly, the economic growth that this will deliver is unarguable. The disappointment is that the service will come into being only in five years’ time in 2020. I wish to place on record my thanks to the Under-Secretary of State for Transport, the hon. Member for Devizes (Claire Perry) for meeting me to discuss this matter last week. I would like to think that she was persuaded by the veracity of the case for accelerating the start of the service. I hope that Virgin East Coast can find ways and seize whatever opportunities present to bring forward the start date of the service. Turning to a matter that concerns Network Rail, just over a year ago the main entrance to Middlesbrough station was closed because of structural difficulties with the Victorian cloister buildings that sit underneath the station main car park. This means there is now no vehicular or indeed pedestrian access to the station from the main southerly aspect, because of the inherent dangers. A year on, plans are now being progressed to board up the frontage, install signage and prepare alternative parking arrangements while architects and engineers go about preparing plans for reconstruction and development. All well and good, but this is all simply far too slow. The people of Middlesbrough deserve better than this. They pay their taxes, unlike some HSBC super wealthy customers. I can only look on with envy at the £895 million redevelopment of Reading station. It looks fantastic and is entirely fit for purpose in the modern railway age. Back in Middlesbrough, however, progress is painfully slow. The town’s people are incredibly patient—they’ve had practice. Indeed, while Dresden, Frankfurt and Berlin were all rebuilt in the aftermath of the second world war, Middlesbrough railway station’s beautiful glass and steel-domed roof was destroyed by the bombs dropped by the Luftwaffe in 1942 and we are still waiting for it to be put back. I urge the Minister in turn to press home the need with Network Rail for much greater urgency and I plead for better communication. It surely cannot be too much to ask for there to be a dedicated website to explain directly to the public what the problem is, what they are doing about it and how long it will all take to put right. Turning to Darlington railway station, which is the sub-region’s east coast mainline hub, there are significant encumbrances, but their resolution will facilitate significant developmental opportunities. I am confident that my hon. Friend the Member for Darlington (Jenny Chapman) will not mind me trespassing, but the entrapment of the local west-east line out of Darlington station, between the north and southbound lines of the east coast, causes immense difficulties in terms of managing the competing traffic demands. It is also a source of congestion and delay for the east coast service itself. The accepted solution is to move the local line from its current configuration and relocate it free of the mainline crossover. Not only will that improve both local and long-haul services, it will free up a major commercial developmental opportunity within the station itself. All that was brought into stark reality for me just two weeks ago, when changing trains from the King’s Cross Darlington train for the Darlington-Middlesbrough train. The local train was a Pacer train—perhaps one of the worst in the fleet with the metal-framed bus seats. There was a problem with the points, and there were no trains in or out of Darlington for more than an hour. On a bitterly cold evening, the choice facing passengers was to step out on the freezing platform or to wait in their seats and suffer the dreadful poisonous diesel fumes coming into the carriages. That these are our travelling conditions some 200 years after George Stephenson created the first passenger railway in the very town of Darlington simply beggars belief. My plea to the Minister is that we get rid of these cattle trucks as quickly as possible and replace them with some decent forms of transportation. David Higgins, the CEO of HS2, has himself said that if the good people of the south of England were asked to tolerate such appalling rolling stock, there would be riots. The time for change is long past. I know that the Secretary of State has been pressed on this, but they need to go, and to go quickly. With more than 70% of major local businesses internationally owned, we remain globally competitive by offering effective transport links and resilient infrastructure. Undoubtedly, rail connectivity needs to be improved, and electrification across the north of England is crucial to this objective. While the TransPennine and Northern franchises have yet to be awarded, it is absolutely essential for the vitality of Tees Valley, the entire northern region and the UK as a whole that good and direct links be preserved and developed right across the north to include direct services from Middlesbrough to Leeds, Manchester and Liverpool. The argument for electrification has long since been won. I shall not recite the environmental and economic justifications, but the benefits to Tees Valley would be enormous. Much is said about the interconnectivity of our core cities, and rightly so. We have to address that issue, but the same principle applies to interconnectivity within regions such as the north-east and sub-regions such as Tees Valley. It currently takes up to one hour and 36 minutes to travel between Middlesbrough on the Tees and Newcastle on the Tyne—a distance of 40 miles by road between the two major conurbations; and it takes 53 minutes to travel from Saltburn to Darlington by way of a bone-shaking Pacer that has no part in modern-day transport in one of the richest countries on the planet. Mo Farah would give it a good run for its money! I know that the electrification taskforce will report imminently, but I trust that the Minister will agree that the case has been more than made that electrification from the east coast main line from Northallerton through to Teesport is a top priority. The concept of the Tees Valley metro has been on the stocks for some considerable time, but only electrification of the existing sub-regional network could make it feasible. A light rail or tram system would be trans- formational for Tees Valley. The way in which bus services are currently delivered is encapsulated in the stories I hear when I speak to Avanta, which is charged with delivering the Work programme. It tells me that far too often it can source entry level work at places such as Teesport and elsewhere across Tees Valley, only for it to prove impossible for the client physically to travel to such places of work at the times the businesses need them and/or to get home again. Quite frankly, we do not have a public transport system worthy of the name. My constituents in places such as Berwick Hills tell me of the lack of buses to get to the hospital. It is essential that when powers are devolved to combined authorities they include the re-regulation of buses, in the way that benefits London, and mandatory comprehensive transport coverage for accessing health services and other key destinations. A truly integrated transport system must be one where bus, road and rail services coalesce around the needs of our businesses and communities. Tom Blenkinsop (Middlesbrough South and East Cleveland) (Lab) - Hansard - Copy Link - - Excerpts My hon. Friend makes an excellent point about the bus service through Park End. This follows the recent news of the closure of the medical clinic in Park End, which also served his constituents in Berwick Hills. Not only are primary health care services being cut, but access to secondary health care services is being reduced as a result of the bus service terminations. Andy McDonald - Hansard - Copy Link - - Excerpts My hon. Friend makes a good point. People need to get to hospital when they are ill or visiting relatives, and they need to get to work at the time their businesses need them and then get home again. Almost finally, roads warrant an entire debate of their own, but as my hon. Friend the Member for Stockton North (Alex Cunningham) said, Tees Valley is crying out for an additional road crossing over the Tees. Several plans have been prepared over the years, and I would urge the Minister to have his officials consider them. In conclusion, Tees Valley has a proud history of major contribution to the economic vitality of this country, and not only does it continue to make that contribution, but the capacity for even greater achievement is immense. However, that vast potential can only be realised if the Government understand and respond in appropriate terms. In addition, I ask that the core cities realise that the northern powerhouse story is not just about creating a London of the north, but about building interconnected communities and economies that provide inclusive prosperity for all. 20:49 Mr Iain Wright (Hartlepool) (Lab) - Hansard - Copy Link - - Excerpts I thank my hon. Friend the Member for Middlesbrough (Andy McDonald) for giving up some of his time to allow me to make a number of very brief points. I wholly agree with what he said about the governance of the transport board, which penalises, excludes and isolates our region from the rest of northern transport policy and procedures. I also agree fully about the importance of proper investment in our rolling stock. The Pacer trains to which he referred are unacceptable and no longer used in the rest of the country, so they should be considered unacceptable and unusable in Middlesbrough, Hartlepool and on to Newcastle, as well. I shall concentrate, as I have on many occasions, on the inadequacy of our bus service. As my hon. Friend said, only re-regulation will provide a co-ordinated proper bus service for our region. In the past week, I have received correspondence from the principal of Hartlepool college, who said that inadequate transport provision meant that potential students from Teesside, North Yorkshire and South Durham were not able or could not afford to get to the college. Apprentices aged 16 or 17 from Hartlepool might not be able to take up the opportunities in Wilton or elsewhere. Ensuring that the transport system, particularly the bus network, matches the routes to learning and employment, as well as ensuring that we can avoid social exclusion, are crucial. At the moment, that does not happen on Teesside. I therefore ask the Minister what he will do to ensure that we can provide a cheap, reliable and co-ordinated bus and transport network across Teesside so that people in our area have the opportunity to achieve their potential and make sure that the population and industrial potential are matched. 20:51 The Minister of State, Department for Transport (Mr John Hayes) - Hansard - Copy Link - - Excerpts I congratulate the hon. Member for Middlesbrough (Andy McDonald) on introducing this debate. He reminded me, as I am sure he will have reminded you, Madam Deputy Speaker, of Hegel. It was Hegel who said: “Nothing great in the world has ever been accomplished without passion.” The hon. Gentleman’s passionate advocacy of the interests of his constituents and indeed of Teesside more generally certainly made an impression on me—and, I am sure, on other Members. I do not disregard the significance of Teesside. I could hardly do so, given that when I was a Minister at the Department for Business, Innovation and Skills, the hon. Member for Hartlepool (Mr Wright), who has contributed to this debate, brought a group of business men from Tees Valley, who themselves illustrated, indeed personified, the very range of innovative industries that the hon. Member for Middlesbrough has described tonight. I am well aware of the character of the innovation taking place there and of the need to provide the right kind of transport infrastructure to support it. I have a very long and impressive speech, but I shall not have time to deliver it. I know that that is a disappointment to you, Madam Deputy Speaker, and to the whole House. I shall, however, make a commitment to include anything I cannot cover in a letter that I will send to the hon. Members who have contributed to this evening’s proceedings. However, I would like to deal now with some of the specific points that the hon. Gentleman raised. As I say, we recognise that effective transport plays a key role in stimulating growth across the country, creating a more balanced economy, connecting communities and enabling people to access jobs, services and leisure in the way described in the contributions we have heard. That is why we have determined to reverse the effect of some of the neglect in respect of infrastructural development that has characterised previous regimes. Members will be pleased to know that I am not going to be more partisan than that, but I wanted to make that point at the outset. I know that the hon. Member for Middlesbrough will recognise and, I hope, acknowledge the importance of the road investment strategy that we have put in place. This is a long-term funded commitment, looking at the national road network in an innovative way, based on empirical analysis of the benefits we get from the money we spend. It secures both plans and money through to 2021. It is a £15 billion investment—probably the biggest road investment programme since the 1970s—and the north, including the north-east, will benefit from it, as the hon. Gentleman will know. The hon. Gentleman mentioned Tees Valley in connection with logistics, environment interests, the creative industries and so forth, and I am aware that the connectivity he described is vital. A major new scheme will be taken forward on the A19. My hon. Friend the Member for Stockton South (James Wharton) has campaigned on this for some time, and I was pleased to see his parliamentary neighbour, the hon. Member for Stockton North (Alex Cunningham), joining his campaign to make those improvements. Major new schemes, the Norton to Wynyard schemes, will be implemented on the A19. Along with two previously announced schemes on Tyneside—the A19 coast road and A19 Testos schemes—they will raise the A19 to expressway standard from Yorkshire to north of Newcastle. The widening of the A19 Billingham bypass in Teesside to three lanes between the A139 and the A689 will also include replacement of the concrete surface with low-noise surfacing. These investments will complement the Highways Agency’s pinch point schemes, which are already under way at two key junctions on the A19, and will smooth the way along the entire route, delivering more reliable journey times and reducing congestion and pollution. Alex Cunningham - Hansard - Copy Link - - Excerpts Will the Minister give way? Mr Hayes - Hansard - Copy Link - - Excerpts I will happily give way. Alex Cunningham - Hansard - Copy Link - - Excerpts Those who travel from the junction at Norton, where I live, on the A19 at 8.30 in the morning just join a queue for the next half hour. The real question is this: can we look forward to another crossing over the River Tees in the next programme that the Government plan? Mr Hayes - Hansard - Copy Link - - Excerpts I suggest that the hon. Gentleman apply for an Adjournment debate on just that issue, so that we can explore it in the depth that it deserves. As the Minister responsible, I should be delighted to respond to such a debate. The roads investment plan also reflects the conclusions of the six feasibility studies announced in June 2013, which examined the case for improvements on the A1 and in other key national corridors. In the time available to me, I shall depart from my script in order to deal specifically with some of the points made by the hon. Member for Middlesbrough, and, hopefully, give him good news. I share his view of the work that is being done on the Victorian cloisters at Middlesbrough station, and I will ensure that we pursue Network Rail so that the matter is dealt with speedily. Indeed, I will go further than that. The hon. Gentleman spoke about the roof which was destroyed in 1942. I wonder if we might consider the feasibility of doing something about that too, in the longer term. I agree with the hon. Gentleman that a seat at the “Transport for the North” table for his area would be appropriate. He makes a persuasive case. I shall need to take it up with the Secretary of State, but I know that he is sympathetic to it, and I think that we should go ahead with it speedily. I also think that the hon. Gentleman is right about direct services to Middlesbrough, and I do not see why we should not consider the further improvements that he suggests as soon as the Government’s improvements to the east coast main line—on which I enjoy the privilege of travelling very frequently—have been completed. Phil Wilson (Sedgefield) (Lab) - Hansard - Copy Link - - Excerpts Will the Minister give way? Mr Hayes - Hansard - Copy Link - - Excerpts I hope that the hon. Gentleman will forgive me if I do not. I am very short of time. The hon. Member for Middlesbrough also made a persuasive case about rolling stock, and I shall be happy to look at that as well. As he will appreciate, such matters need to be considered in the round, but I agree with him that people deserve a chance to travel on trains that are fit for purpose. Generosity has taken hold of me. I will give way to the hon. Member for Sedgefield (Phil Wilson) after all. Phil Wilson - Hansard - Copy Link - - Excerpts I am grateful to the Minister. I wonder whether he will raise with his Treasury colleagues an aspect of air passenger duty which affects Durham Tees Valley airport and the other airport in the north-east, namely its devolution to Edinburgh. It would be very beneficial if the Government gave some thought to what could be done to ensure that there is no loss to the regional airports in the north-east. Mr Hayes - Hansard - Copy Link - - Excerpts As you know, Madam Deputy Speaker, the breadth of my grasp and the length of my vision know few bounds, but we have no time to explore that issue in detail this evening. The hon. Member for Middlesbrough made some important points about buses. As he will know, bus travel is dear to my heart. He advanced the interesting argument that no adequate public transport was available to provide access to health services, and to hospitals in particular. Again, I share his view. The situation is similar in my own constituency, where bus services serving the new Johnson community hospital have been restricted. I am fighting a similar campaign in my constituency, and I think we should look closely at this. It seems to me to be important that particularly the sick and vulnerable should be able to get to those services readily and easily and affordably, and the relatives and people who care for them and want to visit them, too. Those are all areas where I think we can make progress. We can do so on the basis that the hon. Gentleman brought these matters to the attention of the House this evening and, as he will know, we can only do so because this Government have created an economic turnaround. Through our long-term economic plan, we are creating sufficient resource to be able to look at all these matters. Were it not for the determination shown by the Government not only to think strategically about transport in respect of rail, buses and roads in the ways I have outlined, but to do so on the basis of a credible, rational long-term economic plan, none of what the hon. Gentleman has asked for, or I—I hope reasonably, moderately, in a non-partisan way—have agreed would be possible. Question put and agreed to. 21:01 House adjourned. Return to start of debate - Return to top of page Create Alert for Receive Alerts for: Parliamentary Debates Written Questions Early Day Motions Tweets Select Committee Publications View Sample Alert Choose Alert Frequency If no alert frequency is chosen, an Immediate alert is created by default Immediate Daily Alert Weekly Alert Enter time for alert: Select Day for alert: ---- Monday Tuesday Wednesday Thursday Friday Saturday Sunday Enter Time for alert: A Parallel Parliament Subscription is required to receive alerts, you can view more details by clicking on the button below. Subscription Options Close
https://www.parallelparliament.co.uk/debate/2015-02-10/commons/commons-chamber
Haplogroup I resulted in the Great Height of South Slavs [Archive] - Eupedia Forum Found this interesting article: https://phys.org/news/2017-04-tallness-herzegovinian-men-linked-gene.html Summed up it says how certain hunter gatherers would have eaten meat from large prey animals, rich in protein etc, and grown to great size, and have stayed as such for long enough that it stuck to the gene pool. From what I've heard from various sources, such a thing exists in nature where a population can have gigantism or dwarfism, depending on food supply/quality in their habitable Haplogroup I resulted in the Great Height of South Slavs then why not Romanians that have as many i2 people as the whole Yougoslavia combined? Macedonians, Bulgarians? Why not I2 Hungarians, Ukrainians, Moldovans, Russians,NORTH eUROPEANS,? If you pause a second and see the map, south slavs are tall only in areas where they mixed with Illyrians. Illyrains are documented as being tall, and still are. GEG Albanians are not far behind of being tall compared to Slavs,. Every other hypothesis does not stand the proof of reality. WHO HAS A HEAD AND USES IT PROPERLY SEE THAT ASLAVS WHO MIXED WITH non Illyrians aRE NOT EXEPTIONALLY TALL It can not be I2 cause the women are tall too in that region. then why not Romanians that have as many i2 people as the whole Yougoslavia combined? Macedonians, Bulgarians? Why not I2 Hungarians, Ukrainians, Moldovans, Russians,NORTH eUROPEANS,? If you pause a second and see the map, south slavs are tall only in areas where they mixed with Illyrians. Illyrains are documented as being tall, and still are. GEG Albanians are not far behind of being tall compared to Slavs,. Every other hypothesis does not stand the proof of reality. WHO HAS A HEAD AND USES IT PROPERLY SEE THAT ASLAVS WHO MIXED WITH non Illyrians aRE NOT EXEPTIONALLY TALL According to the Wikipedia World Height page; Slovaks and Czechs (North Europeans) are taller on average than Albanians, and other neighboring Southern Europeans (Italians, Greeks). And yeah Romanians are majority I2 as well, but the article is saying that western South Slavs descent from a particular group of I2 hunter gatherers who solely hunted large game (mammoth etc), not that all the people who were I2 did so back then. This large game is what resulted in larger size, to improve combating such animals. It can not be I2 cause the women are tall too in that region. But their dads are often haplogroup I2 According to the Wikipedia World Height page; Slovaks and Czechs (North Europeans) are taller on average than Albanians, and other neighboring Southern Europeans (Italians, Greeks) The source that Wikipedia uses for the average height of Albanians is questionable, for starters it is outdated and, as far as I know, doesn't outright mention the average male height. Studies from 2017 and 2019 showed that the average height of Kosovar Albanian males was ~179-180cm. And so, the average male height of Albanians from Albania should be pretty similar, if not the same. Also, Slovaks and Czechs aren't "North Europeans". https://bib.irb.hr/datoteka/984054.MJSSM_March_2019_Masanovic_69-76.pdf https://www.researchgate.net/profile/Fitim_Arifi2/publication/317278480_Body_Height_and_Its_Estimation_Utilizing _Arm_Span_Measurements_of_both_Gender_Adolescents_ from_Central_Region_in_Kosovo/links/592fdef845851553b67edd22/Body-Height-and-Its-Estimation-Utilizing-Arm-Span-Measurements-of-both-Gender-Adolescents-from-Central-Region-in-Kosovo.pdf Anyways, it is pretty clear that there is no real connection between Y-DNA and height, only coincidences. If the presence of I2 in the South Slavs was truly the reason as to why they are taller than the average European, then they should have consistently been the tallest populations in Europe. But that isn't the case. For example, in the 1880s the average height of Croats from Dalmatia was around 165cm, shorter than many Western European averages. Whilst right now it is over 180cm. https://www.researchgate.net/figure/Relationship-between-average-male-height-at-the-end-of-the-19th-century-and-the-most_fig6_264624478. The world's 10 tallest countries Netherlands - 1.838m. Montenegro - 1.832m. Denmark - 1.826m. Norway - 1.824m. Serbia - 1.82m. Germany - 1.81m. Croatia - 1.805m. Czech Republic - 1.8031m. I2-PH908 from Serbia here, 182cm tall. This isn't considered very tall here at all. But their dads are often haplogroup I2 But they aren't, so the I2 logic is not valid. i think that the missing link To south slavs height could be e-v13🤔 i think that the missing link To south slavs height could be e-v13[emoji848]Hehe, a Y haplo again. :) I myself am E-V13 and I'm 198 cm tall...but my sister is 181 cm and she certainly isn't E-V13. :) It could be something about dairy farming - milk and cheese. Balkan has the longest continuity in Europe. Dutch consume also a lot of these but so do the Swiss but they aren' especially tall. It's probably a mixture of factors but it's not Y chromosome for sure. Your sister is higher than me I am a shorty 1.78 😂 But i am not european my direct paternal line Was born in syria And i think my height for middle eastern is Ok averege🤔 Yes agree could be few factors not only y haplogroup.... Your sister is higher than me I am a shorty 1.78 [emoji23] But i am not european my direct paternal line Was born in syria And i think my height for middle eastern is Ok averege[emoji848] Yes agree could be few factors not only y haplogroup....That's a normal hight. It's less stress. Buying clothes is a traumatic experience for me. I hope you don't have these problems. [emoji16]
https://www.eupedia.com/forum/archive/index.php/t-39738.html?s=87af3278f175528c1e8ea815edbf53c7
Re-engineered blood vessels show promise for bypass surgery, grafts, UMHS researchers find | EurekAlert! Science News Surgeons at the University of Michigan Health System report that they have been able to strip tiny blood vessels from rats and re-engineer them to be more effective when implanted in a new animal. The findings could benefit people who have already had vascular bypass surgery and need new blood vessels for subsequent procedures. Re-engineered blood vessels show promise for bypass surgery, grafts, UMHS researchers find ANN ARBOR, Mich. - Surgeons at the University of Michigan Health System report that they have been able to strip tiny blood vessels from rats and re-engineer them to be more effective when implanted in a new animal. The findings could benefit people who have already had vascular bypass surgery and need new blood vessels for subsequent procedures. Essentially, the researchers take these hair-width arterial grafts from a donor rat, remove all living cells from the rest of the tissue, insert vascular cells from the new host and then reimplant the graft. Using the host's own cells increases the likelihood of success by reducing the chance of rejection. "Small blood vessels are needed all the time for grafts to use in heart bypass surgery, lower extremity bypasses and tissue transfer. The biggest problem is finding a source for these vessels. A typical source is some other blood vessel in the patient's body. To be able to have something that we can manufacture ahead of time or be able to take off the shelf, would be advantageous to many patients," says lead researcher David L. Brown, M.D., assistant professor in the Division of Plastic Surgery at the U-M Medical School. Previous research has used similar techniques with larger blood vessels, like those used in cardiac bypass surgery. This is the first study to look at these very small blood vessels. "You'd expect that the smaller the vessel is, the greater the chance that it would clot. But in our study, the blood vessels stayed open, despite being only 1 millimeter in diameter," says Gregory Borschel, M.D., a resident surgeon in the Division of Plastic Surgery at the U-M Medical School. Clotting becomes a problem when reattaching the vessels. "Tissue engineered blood vessels may provide further options for patients who need vascular bypass procedures yet have no suitable donor vessels of their own," says Borschel, who will present his findings Wednesday, Oct. 22, at the American College of Surgeons 89th Annual Clinical Congress in Chicago. Though Borschel and Brown are plastic surgeons, perhaps the widest applications for this technique are in cardiac surgery. For example, patients undergoing coronary artery bypass might benefit from tissue engineered donor vessels. For people receiving bypass surgery or a tissue transfer after an injury, surgeons often harvest blood vessels from the leg, sternum or arm. But taking tissue from these areas can cause problems in that location. Donor tissue is not an option because the body would reject the foreign cells. The engineered tissue would be injected with the host's own cells, reducing the risk of rejection. In this study, researchers harvested the iliac (groin) grafts from rats. They then stripped this tissue of its cells using a detergent solution. The acellular tissue was injected with endothelial cells from genetically identical rats before being grafted into the rat's femoral artery. A control group of rats received grafts of acellular tissue not re-engineered with the new rat's cells. The resulting blood vessels were monitored every 48 hours and examined closely after four weeks and again at three months. At four weeks, eight of the nine recellularized grafts remained open and functioning, while three of the five acellularized control grafts had clotted. One group of recellularized grafts was viable at three months. The recellularized grafts also demonstrated structural characteristics similar to normal vessels. "This is a very close collaboration between three areas: clinical, engineering and basic biology," says study co-author Robert G. Dennis, Ph.D., assistant professor of biomedical engineering at U-M. Researchers are now looking at ways to use this technology. In one application, researchers have created a biochamber that contracts like a heart. The pressure stimulates the endothelial cells into the chamber, helping new cells to grow and take root. U-M is applying for a patent for this technique and is in negotiations with a company that wishes to use the technology commercially. The study was funded by the Plastic Surgery Educational Foundation, the U.S. Department of Defense's Defense Advanced Research Projects Agency (DARPA), and the Ethel C. Coller Fellowship in the UMHS Department of Surgery. In addition to Brown, Borschel and Dennis, study authors include U-M researchers Yen-Chih Huang, Douglas E. Dow, J.B. Lynch and William M. Kuzon. Keywords
https://archive.eurekalert.org/pub_releases/2003-10/uomh-rbv102103.php
Guests urged to be vaccinated for party at anti-vax Kennedy’s home: report | The Hill Guests of a holiday party thrown at Robert F. Kennedy Jr.’s home were urged to be vaccinated in order to attend, according to a report by Politico. Kennedy, the nephew of former President John F. Kennedy, is a longtime, prominent anti-vaccine advocate. Because of his history speaking against vaccination, guests were surprised when they received an invitation for a… Guests urged to be vaccinated for party at anti-vax Kennedy’s home: report Guests of a holiday party thrown at Robert F. Kennedy Jr.’shome were urged to be vaccinated in order to attend, according to a report byPolitico. Kennedy, the nephew of former President John F. Kennedy, is a longtime, prominent anti-vaccine advocate. Because of his history speaking against vaccination, guests were surprised when they received an invitation for a party at his California home that asked those attending to be vaccinated against the coronavirus and to take COVID-19 tests beforehand, Politico reported. Kennedy, however, told Politico that it was the doing of his wife, “Curb Your Enthusiasm” actress Cheryl Hines, as he said the party was held for Hines’s friends in the entertainment industry. Kennedy stated that he had not been aware of the contents of the invitation prior to the day of the party. Kennedy said to Politico, “I guess I’m not always the boss at my own house.” He said that guests’ test results and vaccination status were not verified upon arrival to the party at his home, per Politico. Children’s Health Defense media relations Director Rita Schreffler shared a statement from Kennedy with The Hill claiming that he did not require vaccinations in order to attend. “Politico and other news outlets have written near-identical stories regarding a recent holiday party at my home. The angle of these stories is that I required guests to be vaccinated in order to attend.  I did not,” he said, according to the spokesperson. “I believe that every person has the right to make health decisions free from coercion, threats or force by governments, employers, and fellow citizens.  I don’t always agree with the decisions of others, of course, but I always support their liberty to decide for themselves.  I extend this respect to everyone including colleagues, friends, and family members.” This news comes after Kennedy was the focus ofan article published by The Associated PressWednesday that outlined his long history of pushing anti-vaccine disinformation. The article discussed Kennedy’s recent book release, “The Real Anthony Fauci: Bill Gates, Big Pharma, and the Global War on Democracy and Public Health,” which remains a best-seller on Amazon. “It is criminal medical malpractice to give a child one of these vaccines,” Kennedy stated at a far-right conference, according to the AP, going against the consensus of medical experts. Kennedy said at the same conference that profits from his book would go to his charity Children’s Health Defense, which has fueled misinformation against COVID-19 vaccines while drawing credibility from Kennedy’s family name, per to the AP. Other members of Kennedy’s family, however, have called his anti-vaccine work “dangerous,” the AP reported. Kennedy’s sister Kerry Kennedy has spoken out against his use of the former president’s name to promote his anti-vaccine disinformation, according to the AP. “Anyone who believes this does not know their history. Vaccinations were a major effort of John F. Kennedy, both as a senator and later as president,” she said, per the AP. “I love Bobby, I think he’s just completely wrong on this issue and very dangerous,” added Kerry. “Failure to take vaccines puts people’s lives at risk. It not only impacts the person who refuses the jab but imperils the community at large.” Kennedy has been named one of the internet’s “Disinformation Dozen” — the top disseminators of disinformation about vaccines online — by the Center for Digital Hate, per the AP, in part because of the false information spread through the website for his charity. Kennedy himself wasbannedfrom Instagram earlier this year for spreading disinformation about vaccines on the platform. Tags Anthony Fauci California COVID-19 vaccine misinformation and hesitancy Disinformation Kennedy family Robert F. Kennedy Jr. Robert F. Kennedy Jr. Vaccine hesitancy
https://thehill.com/briefingroom-blogroll/586308-guests-urged-to-be-vaccinated-for-party-at-anti-vax-kennedys-home/?fbclid=IwAR2JmKU724w_JSv3noRh839q0eH1cW0ZS6w1s4VxaOITtDQtEEVy4sESXUY
Photo-Biocatalysis: Biotransformations in the Presence of Light | Request PDF Request PDF | Photo-Biocatalysis: Biotransformations in the Presence of Light | Light has received increased attention for various chemical reactions but also in combination with biocatalytic reactions. Because currently only... | Find, read and cite all the research you need on ResearchGate Article Photo-Biocatalysis: Biotransformations in the Presence of Light April 2019 ACS Catalysis 9(5):4115-4144 DOI: 10.1021/acscatal.9b00656 Abstract Light has received increased attention for various chemical reactions but also in combination with biocatalytic reactions. Because currently only a few enzymatic reactions are known, which per se require light, most transformations involving light and a biocatalyst exploit light either for providing the cosubstrate or cofactor in an appropriate redox state for the biotransformation. In selected cases, a promiscuous activity of known enzymes in the presence of light could be induced. In other approaches, light-induced chemical reactions have been combined with a biocatalytic step, or light-induced biocatalytic reactions were combined with chemical reactions in a linear cascade. Finally, enzymes with a light switchable moiety have been investigated to turn off/on or tune the actual reaction. This Review gives an overview of the various approaches for using light in biocatalysis. ... Photoenzymes simply require a continuous flux of photons to remain catalytically active and offer huge experimental advantages over thermally activated enzymes [1,2]. Apart from the photoenzymes involved in photosynthesis, only three families of proteins bear light-driven activity in nature [3] . One is DNA photolyases with functions in repairing UV-damaged DNA [4]. ... ... Because of the highly specific substrates of DNA photolyases or protochlorophyllide oxidoreductases, their practical application as in vitro biocatalysts is limited [3, 4,6,7]. This is in contrast to CvFAP, which converts various fatty acids [8,9] and dicarboxylic acids [10] into the desired C1-shortened/C2-shortened alkanes with excellent regioselectivity. ... ... Beisson et al. suggested that CvFAP is a member of the glucosemethanol-choline (GMC) oxidoreductases, and, there is likely to be a group among GMC oxidoreductases with a conserved FAP function [1, 3] . Unfortunately, CvFAP is the only enzyme that has been characterized as having in vitro fatty acid decarboxylation activity, although its Chlamydomonas reinhardtii homolog, CrFAP and the predicted ancestral of the CvFAP clade [18] have shown decarboxylation activities as well. ... Comparative characterization and physiological function of putative fatty acid photodecarboxylases Light-driven fatty acid photodecarboxylases (FAPs) are unique and promising biocatalysts for chemical synthesis and biomanufacturing. However, the exploitation of FAP enzymes is still in its early stage. To date, although it has been proposed that FAPs are conserved in a group of the glucose-methanol-choline (GMC) oxidoreductases, the prior studies have been limited to CvFAP (from Chlorella variabilis NC64A) and CrFAP (from Chlamydomonas reinhardtii 137C). In this study, a comparative characterization of several enzymes classified in the FAPs clade was performed to elucidate their physiological functions. A library of recombinant enzymes including 15 putative FAPs, CvFAP, and CrFAP were prepared. Their catalytic performance was investigated by the photoenzymatic decarboxylation of six fatty acids and seven dicarboxylic acids yielding C1- and C2-shortening alkanes, respectively. In addition, identification of the flavin prosthetic group provided experimental evidence that the cofactor flavin adenine dinucleotide (FAD) was present in FAPs. Five new enzymes with superior FAP photochemical activity to CvFAP/CrFAP in terms of overproduction in Escherichia coli, activity/substrate specificity and thermostability were obtained. This work expands the state-of-the-art of photodecarboxylases in sustainable fuel production and organic synthesis. ... Photobiocatalysis adopts natural or artificial light for exploiting the advantages of photocatalyst reactivity and enzyme selectivity ( Figure 1) [13] [14][15][16][17]. In the search for efficient strategies that exploit the potential of light in biocatalysis, promising basic concepts have emerged that are fundamental to the meaningful implementation of both whole-cell and in vitro photobiocatalytic applications [15,18,19]. ... ... The construction of these so-called artificial photoenzymes typically exploits two strategies: (1) the covalent linking of a photocatalysts via an (unnatural) amino acid and using the photocatalyst for direct single-electron transfer; and (2) the conjugation of a photosensitizer nearby an immobilized organometallic complex within a protein scaffold [10,12,22]. While artificial enzymes also have been constructed to supply electrons to naturally occurring enzyme cofactors to increase native activity [13, 15,93], we herein focus on artificial enzymes that have been constructed for non-natural reactivities. Already in 2015, Lewis et al. used a click chemistry approach to conjugate a modified acridinium 9-mesityl-10-methyl (Acr + -Mes) cofactor to an unnatural amino acid within a prolyl oligopeptidase to construct an artificial photoenzyme for the sulfoxidation of thioanisoles [94,95]. ... Light-driven bioprocesses Article Full-text available Enzyme catalysis and photocatalysis are two research areas that have become of major interest in organic synthesis. This is mainly because both represent attractive strategies for making chemical synthesis more efficient and sustainable. Because enzyme catalysis offers several inherent advantages, such as high substrate specificity, regio-, and stereoselectivity, and activity under environmentally benign reaction conditions, biocatalysts are increasingly being adopted by the pharmaceutical and chemical industries. In addition, photocatalysis has proven to be a powerful approach for accessing unique reactivities upon light irradiation and performing reactions with an extended substrate range under milder conditions compared to light-independent alternatives. It is therefore not surprising that bio- and photocatalytic approaches are now often combined to exploit the exquisite selectivity of enzymes and the unique chemical transformations accessible to photocatalysis. In this chapter, we provide an overview of the wide variety of light-driven bioprocesses, ranging from photochemical delivery of reducing equivalents to redox enzymes, photochemical cofactor regeneration, to direct photoactivation of enzymes. We also highlight the possibility of catalyzing non-natural reactions via photoinduced enzyme promiscuity and the combination of photo- and biocatalytic reactions used to create new synthetic methodologies. ... It is evident from the literature that photocatalytic NADH regeneration and organic transformation consuming solar light illumination are a rising research zone, which provides various possibilities for future work. In this addition, NAD + is a bio-enzyme that needs a steady flux of solar light to photocatalyze a solar chemical synthesis [24] . Thus, solar light is essential in the chemical transformation reaction catalyzed by the enzyme. ... ... To date, various types of photo enzymes have been investigated, which are used as a photosystem for organic transformation and solar chemical regeneration [25]. It is supposed that most of the possible formerly existing solar light active enzyme derivatives were sorted out by progression and that nowadays, solar light active coenzymes are only the past survivors of this pathway [24] . The use of many metal-based compounds for solar chemical regeneration and environmental remediation has achieved the utmost attention in current times due to the active utilization of naturally existing solar energy and an effective solar light active system to terminate various types of unwanted materials [26,27]. ... Highly Efficient Self-Assembled Activated Carbon Cloth-Templated Photocatalyst for NADH Regeneration and Photocatalytic Reduction of 4-Nitro Benzyl Alcohol This manuscript emphasizes how structural assembling can facilitate the generation of solar chemicals and the synthesis of fine chemicals under solar light, which is a challenging task via a photocatalytic pathway. Solar energy utilization for pollution prevention through the reduction of organic chemicals is one of the most challenging tasks. In this field, a metal-based photocatalyst is an optional technique but has some drawbacks, such as low efficiency, a toxic nature, poor yield of photocatalytic products, and it is expensive. A metal-free activated carbon cloth (ACC)–templated photocatalyst is an alternative path to minimize these drawbacks. Herein, we design the synthesis and development of a metal-free self-assembled eriochrome cyanine R (EC-R) based ACC photocatalyst (EC-R@ACC), which has a higher molar extinction coefficient and an appropriate optical band gap in the visible region. The EC-R@ACC photocatalyst functions in a highly effective manner for the photocatalytic reduction of 4-nitro benzyl alcohol (4-NBA) into 4-amino benzyl alcohol (4-ABA) with a yield of 96% in 12 h. The synthesized EC-R@ACC photocatalyst also regenerates reduced forms of nicotinamide adenine dinucleotide (NADH) cofactor with a yield of 76.9% in 2 h. The calculated turnover number (TON) of the EC-R@ACC photocatalyst for the reduction of 4-nitrobenzyl alcohol is 1.769 × 1019 molecules. The present research sets a new benchmark example in the area of organic transformation and artificial photocatalysis. View ... The natural existing photosynthetic centers influence the development of lightdriven enzymatic catalysis. The potentialities of using light together with biocatalysis have gained a lot of attention to enhance the activity of the catalyst in different sustainable synthetic reactions as well [175] . In general, there are two different ways that a photo-biocatalytic reaction can occur. ... ... Photo-biocatalysis is still challenging because of its restricted relevance to naturally existing reactions [187]. Photo-enzymatic reaction optimization becomes complicated due to the absence of standardized light sources and photo-reactors, leading to problems like up-scaling the reactor to higher concentrations, diameter, length, etc. [175, 188]. The photo-generated oxygen quickly degrades the biomaterials by deactivating and denaturing the enzyme structure. ... Design and Applications of Enzyme-Linked Nanostructured Materials for Efficient Bio-catalysis Article Full-text available The current advancements in nanotechnology had exquisite impacts on biocatalysis. Enzymes are exceptional biocatalysts because of their excellent substrate selectivity, regio- and stereo-specificity, and capacity to accelerate the reaction rate up to several orders of magnitude. One of the significant challenges in biotechnology is the utilization and development of enzymes as reliable biocatalysts. Applications of enzymes have drawn a lot of attention as demand for environmentally friendly and sustainable operations increases. Enzymes are promising biocatalysts with a wide range of uses, including as a biosensor, in food, agricultural, and pharmaceutical industries. The distinctive catalytic chemistry of enzyme-linked compatible nanostructures put forward many applications, including biocatalysis. The most recent advancements in enzyme immobilization organic/inorganic supports—including carbon-based, polymeric or hybrid, metal–organic framework—as well as various nanomaterials comprised of metals and metal oxides are discussed. The methods for immobilizing enzymes onto carriers and their stability and catalytic properties are also highlighted. The synergistic coupling of nanotechnology with biotechnology covers a broad range of tremendous applications. Nanostructures have specific characteristics that can balance parameters like effective encapsulation of enzymes, porosity, etc., which present peculiar prospects for designing an ideal biocatalyst. For synthetic chemistry and bio-manufacturing, photo-enzymes are potentially attractive biocatalysts. This review highlights that efforts are underway to bring the benefits of combining two research-intensive fields, biocatalysis and photo-biocatalysis, in a meaningful way. Graphical Abstract ... [5,6] Especially in recent years, great advances have been achieved to study light-driven biotransformations and discover new photoenzymes. [7] [8][9] While the study of the photoactive enzymes is still in its early stages, great interest has been devoted to study the photocatalytic regeneration of cofactors or cosubstrates, especially for biocatalytic redox reactions. [7,9] Oxidoreductases, which catalyze a wide plethora of redox reactions, have been very attractive for industrial applications due to their high versatility and importance for organic synthesis. ... ... [7][8][9] While the study of the photoactive enzymes is still in its early stages, great interest has been devoted to study the photocatalytic regeneration of cofactors or cosubstrates, especially for biocatalytic redox reactions. [7, 9] Oxidoreductases, which catalyze a wide plethora of redox reactions, have been very attractive for industrial applications due to their high versatility and importance for organic synthesis. [10,11] Despite their high selectivity and activity under mild conditions, oxidoreductases have the disadvantage of depending on expensive cofactors [e. ... Design and Investigation of a Photocatalytic Setup for Efficient Biotransformations Within Recombinant Cyanobacteria in Continuous Flow Article Full-text available Photo‐ and biocatalysis show many advantages as more sustainable solutions for the production of fine chemicals. In an effort to combine the benefits and the knowledge of both these areas, we present a continuous photobiocatalytic setup designed and optimized to carry out whole‐cell biotransformations within cells of the cyanobacterium Synechocystis sp. PCC 6803 expressing the gene of the ene‐reductase YqjM from B. subtilis. The effect of the light intensity and flow rate on the specific activity in the stereoselective reduction of 2‐methyl maleimide was investigated via a design of experiments (DoE) approach. The cell density in the setup was further increased at the optimal operating conditions without loss in specific activity, demonstrating that the higher surface area/volume ratio in the coil reactor improves the illumination efficiency of the process. Furthermore, different reactor designs were compared, proving that the presented approach is the most cost‐ and time‐effective solution for intensifying photobiotransformations within cyanobacterial cells. ... CvFAP engineering has diverse applications in various laboratories, including the synthesis of chiral amines, α-hydroxy acids, and alkenes [55,72,[78] [79] [80][81][82]. Additionally, it has important uses in the degradation of trans fatty acids, plastics [38], and other fields. ... Photoenzymatic Decarboxylation to Produce Hydrocarbon Fuels: A Critical Review Article Full-text available MOL BIOTECHNOL Xiaobo Guo Rui Zhou Photoenzymatic decarboxylation shows great promise as a pathway for the generation of hydrocarbon fuels. CvFAP, which is derived from Chlorella variabilis NC64A, is a photodecarboxylase capable of converting fatty acids into hydrocarbons. CvFAP is an example of coupling biocatalysis and photocatalysis to produce alkanes. The catalytic process is mild, and it does not yield toxic substances or excess by-products. However, the activity of CvFAP can be readily inhibited by several factors, and further enhancement is required to improve the enzyme yield and stability. In this article, we will examine the latest advancements in CvFAP research, with a particular focus on the enzyme’s structural and catalytic mechanism, summarized some limitations in the application of CvFAP, and laboratory-level methods for enhancing enzyme activity and stability. This review can serve as a reference for future large-scale industrial production of hydrocarbon fuels. ... Light represents an abundant and cheap source of energy that can be harvested by a photoredox catalyst to tailor H 2 O 2 levels to enzymatic reactions 30, 31 . Light-driven LPMO reactions were first described in 2016. ... Visible light-exposed lignin facilitates cellulose solubilization by lytic polysaccharide monooxygenases Article Full-text available Lytic polysaccharide monooxygenases (LPMOs) catalyze oxidative cleavage of crystalline polysaccharides such as cellulose and are crucial for the conversion of plant biomass in Nature and in industrial applications. Sunlight promotes microbial conversion of plant litter; this effect has been attributed to photochemical degradation of lignin, a major redox-active component of secondary plant cell walls that limits enzyme access to the cell wall carbohydrates. Here, we show that exposing lignin to visible light facilitates cellulose solubilization by promoting formation of H2O2 that fuels LPMO catalysis. Light-driven H2O2 formation is accompanied by oxidation of ring-conjugated olefins in the lignin, while LPMO-catalyzed oxidation of phenolic hydroxyls leads to the required priming reduction of the enzyme. The discovery that light-driven abiotic reactions in Nature can fuel H2O2-dependent redox enzymes involved in deconstructing lignocellulose may offer opportunities for bioprocessing and provides an enzymatic explanation for the known effect of visible light on biomass conversion. ... 54,135,136 Photon inducible enzyme research has been observed as a new area because of the on-off concept of photo enzymes. 137, 138 Biocatalysts are environmentally friendly, inexpensive, and sustainable and have high enantioselectivity. These features make them more preferable in the pharmaceutical industry. ... Fundamentals of chirality, resolution, and enantiopure molecule synthesis methods Article The chirality of molecules is a concept that explains the interactions in nature. We may observe the same formula but different organizations revolving around the chiral center. Since Pasteur's meticulous observation of sodium ammonium tartrate crystals' structure, scientists have discovered many features of chiral molecules. The number of newly approved single enantiomeric drugs increases every year and takes place in the market. Thus, separation or resolution methods of racemic mixtures are of continued importance in the efficacy of drugs, installation of affordable production processes, and convenient synthetic chemistry practice. This article presents the asymmetric synthesis approaches and the classification of direct resolution methods of chiral molecules. ... Moreover, photoenzymes are enzymes that require a constant flow of light to catalyze a chemical reaction; consequently, light is directly required in the process catalyzed by the enzyme. Photoenzymes are catalytically inert in the absence of light [121] . In 2017 [122], researchers identified the fatty acid photodecarboxylase (FAP), which is light-activated. ... Microalgae biorefinery: An integrated route for the sustainable production of high-value-added products Article Full-text available Microalgae are pervasive organisms regarded as conservative alternatives for the sustainable synthesis of various high-value-added bio-products to replace depleting fossil fuels and reduce CO2 emissions. However, microalgae biorefinery is still very far from being commercially viable due to high costs, intensive energy requirements, and low availability of biomass and biomolecules. In this review, the current status of microalgae biorefinery is discussed by establishing the efficiency of green biotechnology in producing microalgae from wastewater and the diverse bio-products derived from the biotechnology of microalgae biorefinery. In addition, various aspects involved in the sustainable production of bulk chemicals and value-added bio-products from microalgae biorefinery, including their roles in environmental protection and the promotion of an integrated green circular bio-economy are elucidated. Lastly, the challenges facing microalgae biorefinery and recommendations to guide future research toward cost-effective, more efficient, and sustainable microalgae biorefinery are presented. ... Therefore, a deep study is required to understand the role of the water-water cycle and CEF-PSI in photosynthesis for genetic manipulation studies. Apart from the various studies on the ETC modification, it is observed that Cyt b6 and plastocyanin provide excellent opportunities for enhancing its efficiency but still more focused research is required to improve the conversion rate of solar energy to biomass and to develop the photosystem with less sensitivity to photodamage or should produce lesser reactive oxygen species (Schmermund et al. 2019 ). ... Genetic manipulation of photosynthesis to enhance crop productivity under changing environmental conditions Article Full-text available Nov 2022 PHOTOSYNTH RES Abhishek Kumar Shiv shanker Pandey Dhananjay Kumar Bhumi Nath Tripathi Current global agricultural production needs to be increased to feed the unconstrained growing population. The changing climatic condition due to anthropogenic activities also makes the conditions more challenging to meet the required crop productivity in the future. The increase in crop productivity in the post green revolution era most likely became stagnant, or no major enhancement in crop productivity observed. In this review article, we discuss the emerging approaches for the enhancement of crop production along with dealing to the future climate changes like rise in temperature, increase in precipitation and decrease in snow and ice level, etc. At first, we discuss the efforts made for the genetic manipulation of chlorophyll metabolism, antenna engineering, electron transport chain, carbon fixation, and photorespiratory processes to enhance the photosynthesis of plants and to develop tolerance in plants to cope with changing environmental conditions. The application of CRISPR to enhance the crop productivity and develop abiotic stress-tolerant plants to face the current changing climatic conditions is also discussed. ... Due to the high reactivity of open-shell intermediates, asymmetric photochemical transformations under visible light 4 are believed to be challenging. Even so, stereocontrol strategies including asymmetric organocatalysis 5 , organometallic catalysis 6 and enzyme catalysis 7 have been gradually applied to this area. As highlighted in Fig. 1a, the emerging dual catalysis strategy has achieved considerable success in construction of chiral carbon stereocenters [8][9][10][11][12][13][14][15][16][17] ; however, its application in construction of axially chiral molecules is in its infancy 18 . ... Construction of axial chirality via asymmetric radical trapping by cobalt under visible light Article Full-text available Sep 2022 Xuan Jiang Wei Xiong Shuang Deng Wen-Jing Xiao The 3d metals have been identified as economic and sustainable alternatives to palladium, the frequently used metal in transition-metal-catalysed cross-couplings. However, cobalt has long stood behind its neighbouring elements, nickel and copper, in asymmetric radical couplings owing to its high catalytic activity in the absence of ligands resulting in unfavourable un-asymmetric background reactions. Here we disclose an asymmetric metallaphotoredox catalysis (AMPC) strategy for the dynamic kinetic asymmetric transformation of racemic heterobiaryls, which represents a visible-light-induced, asymmetric radical coupling for the construction of axial chirality. This success can also be extended to the reductive cross-coupling variant featuring the use of more easily available organic halide feedstocks. The keys to these achievements are the rational design of a sustainable AMPC system that merges asymmetric cobalt catalysis with organic photoredox catalysis in combination with the identification of an efficient chiral polydentate ligand. ... These two approaches harvest clean and abundant solar energy to generate photoexcited charge carriers for driving enzymatic reactions (Supplementary Table 8). BPC systems, using molecular [46][47][48] or semiconducting photocatalysts 49, 50 , can have the advantage that catalytic reactions take place throughout the reaction medium without mass-transfer limitations. However, compared with BPEC approaches, many BPC systems suffer from the recombination 14,45 of photoexcited charge carriers and cannot use the merits that originate from the separation of oxidation and reduction sites (such as the preservation of redox enzymes from reactive oxidized electron donors 45 ). ... Photoelectrocatalytic biosynthesis fuelled by microplastics Article Sep 2022 Jinhyun Kim Jinha Jang Thomas Hilberath Chan Beum Park Biocatalytic artificial photosynthesis integrates photocatalysis and redox biocatalysis to synthesize value-added chemicals using solar energy. However, this nature-inspired approach suffers from sluggish rates of reaction because of challenging water oxidation kinetics. Here we report photoelectrochemical biosynthetic reactions that use non-recyclable real-world poly(ethylene terephthalate) (PET) microplastics as an electron feedstock. A Zr-doped haematite photoanode extracts electrons from hydrolysed PET solutions obtained from post-consumer PET waste, such as drinks bottles, and transfers the electrons to the bioelectrocatalytic site. Carbon-based cathodes receive the electrons to activate redox enzymes (for example, unspecific peroxygenase, L-glutamate dehydrogenase and ene-reductase from the old yellow enzyme family) that drive various organic synthetic reactions. These reactions include oxyfunctionalization of C–H bonds, amination of C=O bonds and asymmetric hydrogenation of C=C bonds. These photoelectrocatalytic–biocatalytic hybrid reactions achieve total turnover numbers of 362,000 (unspecific peroxygenase), 144,000 (L-glutamate dehydrogenase) and 1,300 (old yellow enzyme). This work presents a photoelectrocatalytic approach for integrating environmental remediation and biocatalytic photosynthesis towards sustainable solar-to-chemical synthesis. Plastic waste poses a serious economic, ecological and environmental threat. Here, non-recyclable, post-consumer microplastics are used as an electron feedstock for biosynthetic reactions in a photoelectrocatalytic system. The microplastics are simultaneously broken down into organic fuels, meaning that this system provides valuable chemicals at both the anodic and cathodic sites. ... The impact of LPMOs on polysaccharide conversion and the notion that these enzymes act on redox-active copolymeric substrates, raise the questions of whether and how light affects LPMO activity and thus biomass turnover. Light is an abundant and cheap source of energy that, in the presence of a photoredox catalyst and O 2 , can fuel H 2 O 2 -dependent enzyme reactions (23)(24) (25) . It has been demonstrated that lignin, a major aromatic component of plant cell walls, can act as a photocatalyst for solar-powered H 2 O 2 -dependent enzyme reactions (26). ... Natural photoredox catalysts promote light-driven lytic polysaccharide monooxygenase reactions and enzymatic turnover of biomass Article Full-text available Aug 2022 Eirik Kommedal Fredrikke Sæther Thomas Hahn Vincent G H Eijsink Lytic polysaccharide monooxygenases (LPMOs) catalyze oxidative cleavage of crystalline polysaccharides such as cellulose and chitin and are important for biomass conversion in the biosphere as well as in biorefineries. The target polysaccharides of LPMOs naturally occur in copolymeric structures such as plant cell walls and insect cuticles that are rich in phenolic compounds, which contribute rigidity and stiffness to these materials. Since these phenolics may be photoactive and since LPMO action depends on reducing equivalents, we hypothesized that LPMOs may enable light-driven biomass conversion. Here, we show that redox compounds naturally present in shed insect exoskeletons enable harvesting of light energy to drive LPMO reactions and thus biomass conversion. The primary underlying mechanism is that irradiation of exoskeletons with visible light leads to the generation of H 2 O 2 , which fuels LPMO peroxygenase reactions. Experiments with a cellulose model substrate show that the impact of light depends on both light and exoskeleton dosage and that light-driven LPMO activity is inhibited by a competing H 2 O 2 -consuming enzyme. Degradation experiments with the chitin-rich exoskeletons themselves show that solubilization of chitin by a chitin-active LPMO is promoted by light. The fact that LPMO reactions, and likely reactions catalyzed by other biomass-converting redox enzymes, are fueled by light-driven abiotic reactions in nature provides an enzyme-based explanation for the known impact of visible light on biomass conversion. Photocatalytic Transformation of Biomass and Biomass Derived Compounds—Application to Organic Synthesis Article Full-text available Jun 2023 MOLECULES Mario Andrés Gomez Fernandez Norbert Hoffmann Biomass and biomass-derived compounds have become an important alternative feedstock for chemical industry. They may replace fossil feedstocks such as mineral oil and related platform chemicals. These compounds may also be transformed conveniently into new innovative products for the medicinal or the agrochemical domain. The production of cosmetics or surfactants as well as materials for different applications are examples for other domains where new platform chemicals obtained from biomass can be used. Photochemical and especially photocatalytic reactions have recently been recognized as being important tools of organic chemistry as they make compounds or compound families available that cannot be or are difficultly synthesized with conventional methods of organic synthesis. The present review gives a short overview with selected examples on photocatalytic reactions of biopolymers, carbohydrates, fatty acids and some biomass-derived platform chemicals such as furans or levoglucosenone. In this article, the focus is on application to organic synthesis. Biocatalysis for Lead Discovery and Optimization Chapter Jan 2022 Corey Jones Manjinder S. Lall Scott P. France Chemoenzymatic Dynamic Kinetic Resolution of Secondary Alcohols and Amines Employing Copper-Based Photocatalysis Article Jun 2023 Clémentine Minozzi Nicolas Dowe Noémie Beaucage Shawn K. Collins Mechanism and Dynamics of Photodecarboxylation Catalyzed by Lactate Monooxygenase Article Jun 2023 J AM CHEM SOC Xiankun Li Claire G Page Laura Zanetti-Polzi Gregory D. Scholes Photoenzymes are a rare class of biocatalysts that use light to facilitate chemical reactions. Many of these catalysts utilize a flavin cofactor to absorb light, suggesting that other flavoproteins might have latent photochemical functions. Lactate monooxygenase is a flavin-dependent oxidoreductase previously reported to mediate the photodecarboxylation of carboxylates to afford alkylated flavin adducts. While this reaction holds a potential synthetic value, the mechanism and synthetic utility of this process are unknown. Here, we combine femtosecond spectroscopy, site-directed mutagenesis, and a hybrid quantum-classical computational approach to reveal the active site photochemistry and the role the active site amino acid residues play in facilitating this decarboxylation. Light-induced electron transfer from histidine to flavin was revealed, which has not been reported in other proteins. These mechanistic insights enable the development of catalytic oxidative photodecarboxylation of mandelic acid to produce benzaldehyde, a previously unknown reaction for photoenzymes. Our findings suggest that a much wider range of enzymes have the potential for photoenzymatic catalysis than has been realized to date. Metallaphotoredox catalysis for sp3 C-H functionalizations through hydrogen atom transfer (HAT) Article CHEM SOC REV In recent years, the integration of photocatalytic hydrogen atom transfer (HAT) with transition metal catalysis has emerged as a formidable strategy for the construction of C(sp3)-carbon and C(sp3)-hetero bonds. The fusion of these two methodologies has been utilized widely in organic synthesis, leading to new transformations in chemical synthesis. In this review, we aim to summarize the recent advances made in sp3 C-H functionalizations through photocatalytic HAT followed by transition metal catalysis. Our focus will be on the diverse strategies and their synthetic applications, in addition to detailed mechanisms involved in these reactions. An in-depth understanding of these mechanisms is crucial for the rational design of new catalysts and reaction conditions to further enhance the efficiency of these transformations. We hope that this review will serve as a valuable resource for researchers in the area of metallaphotoredox catalysis, and will inspire the further development of this application in green chemistry, drug synthesis, material science, and other related fields. From Diazonium Salts to Optically Active 1‐Arylpropan‐2‐ols Through a Sequential Photobiocatalytic Approach Laura Rodríguez-Fernández Jesus Albarran Velo Iván Lavandera Exciting Enzymes: Current State and Future Perspective of Photobiocatalysis May 2023 Véronique Alphand Willem J. H. van Berkel Valentina Jurkaš Solar-powered P450 catalysis: Engineering electron transfer pathways from photosynthesis to P450s With the increasing focus on green chemistry, biocatalysis is becoming more widely used in the pharmaceutical and other chemical industries for sustainable production of high value and structurally complex chemicals. Cytochrome P450 monooxygenases (P450s) are attractive biocatalysts for industrial application due to their ability to transform a huge range of substrates in a stereo- and regiospecific manner. However, despite their appeal, the industrial application of P450s is limited by their dependence on costly reduced nicotinamide adenine dinucleotide phosphate (NADPH) and one or more auxiliary redox partner proteins. Coupling P450s to the photosynthetic machinery of a plant allows photosynthetically-generated electrons to be used to drive catalysis, overcoming this cofactor dependency. Thus, photosynthetic organisms could serve as photobioreactors with the capability to produce value-added chemicals using only light, water, CO2 and an appropriate chemical as substrate for the reaction/s of choice, yielding new opportunities for producing commodity and high-value chemicals in a carbon-negative and sustainable manner. This review will discuss recent progress in using photosynthesis for light-driven P450 biocatalysis and explore the potential for further development of such systems. Photobiocatalytic Strategies for Organic Synthesis CHEM REV Biocatalysis has revolutionized chemical synthesis, providing sustainable methods for preparing various organic molecules. In enzyme-mediated organic synthesis, most reactions involve molecules operating from their ground states. Over the past 25 years, there has been an increased interest in enzymatic processes that utilize electronically excited states accessed through photoexcitation. These photobiocatalytic processes involve a diverse array of reaction mechanisms that are complementary to one another. This comprehensive review will describe the state-of-the-art strategies in photobiocatalysis for organic synthesis until December 2022. Apart from reviewing the relevant literature, a central goal of this review is to delineate the mechanistic differences between the general strategies employed in the field. We will organize this review based on the relationship between the photochemical step and the enzymatic transformations. The review will include mechanistic studies, substrate scopes, and protein optimization strategies. By clearly defining mechanistically-distinct strategies in photobiocatalytic chemistry, we hope to illuminate future synthetic opportunities in the area. Advances in One-Pot Chiral Amine Synthesis Enabled by Amine Transaminase Cascades: Pushing the Boundaries of Complexity Adenine Fine-Tunes DNA Photolyase's Repair Mechanism The comparative study of DNA repair by mesophilic and extremophilic photolyases helps us understand the evolution of these enzymes and their role in preserving life on our changing planet. The mechanism of repair of cyclobutane pyrimidine dimer lesions in DNA by electron transfer from the flavin adenine dinucleotide cofactor is the subject of intense interest. The role of adenine in mediating this process remains unresolved. Using microsecond molecular dynamics simulations, we find that adenine mediates the electron transfer in both mesophile and extremophile DNA photolyases through a similar mechanism. In fact, in all photolyases studied, the molecular conformations with the largest electronic couplings between the enzyme cofactor and DNA show the presence of adenine in 10-20% of the strongest-coupling tunneling pathways between the atoms of the electron donor and acceptor. Our theoretical analysis finds that adenine serves the critical role of fine-tuning rather than maximizing the donor-acceptor coupling within the range appropriate for the repair function. Light-responsive biodegradation of wastewater pollutants: New developments and potential perspectives Switching Type I/Type II Reactions by Turning a Photoredox Catalyst into a Photo-Driven Artificial Metalloenzyme Ethyl Acetoacetate and Acetylacetone Appended Hexabromo Porphyrins: Synthesis, Spectral, Electrochemical, and Femtosecond Third-Order Nonlinear Optical Studies Asymmetrically substituted porphyrins possessing ethyl acetoacetate or acetylacetone (EAA or acac) with six bromine atoms at β-positions were synthesized and then characterized by various spectroscopic techniques, such as UV-Vis, fluorescence and NMR, and also by CV, DFT, MALDI-TOF-MS and elemental analysis. The mechanistic pathway followed the nucleophilic substitution reaction (nucleophile: EAA and acac) with MTPP(NO2)Br6 (M = 2H, Cu(II), and Ni(II)), and the resultant β-heptasubstituted porphyrins exhibited keto-enol tautomerism, as supported by 1H NMR spectroscopy. The six bulky bromo and EAA/acac groups made the macrocyclic ring highly electron deficient and nonplanar such that the quantum yield and fluorescence intensity for H2TPP[EAA]Br6 and H2TPP[acac]Br6 were severely reduced in contrast to those values for H2TPP. The poor electron density and nonplanarity over the porphyrin ring shifted the first oxidation potential from 11 to 521 mV anodically for MTPP[X]Br6 [M = 2H, Cu(II), and Ni(II); X = EAA or acac] as compared to corresponding MTPPs. Notably, density functional theory proved the nonplanarity of the synthesized porphyrins as Δ24 spans from ±0.546 to ± 0.559 Å while ΔCβ stretches from ±0.973 to ±1.162 Å. The third-order nonlinear optical measurements were performed using the femtosecond pulsed laser Z-scan technique at 800 nm and 1 kHz repetition rate to acquire insights into nonlinear absorption and nonlinear refraction of the porphyrins. The three-photon absorption coefficients (γ) are in the range of 2.2 × 10-23-2.8 × 10-23 cm3 W-2 and the nonlinear refractive index values were in the range of 3.7 × 10-16-5.1 × 10-16 cm2 W-1. The higher-order nonlinear absorption exhibited by porphyrins helps improve resolution at depth for various photonic and optoelectronic applications. The Evolving Nature of Biocatalysis in Pharmaceutical Research and Development Photocatalytic Regeneration of a Nicotinamide Adenine Nucleotide Mimic with Water-Soluble Iridium(III) Complexes Nicotinamide adenine nucleotide (NADH) is involved in many biologically relevant redox reactions, and the photochemical regeneration of its oxidized form (NAD+) under physiological conditions is of interest for combined photo- and biocatalysis. Here, we demonstrate that tri-anionic, water-soluble variants of typically very lipophilic iridium(III) complexes can photo-catalyze the reduction of an NAD+ mimic in a comparatively efficient manner. In combination with a well-known rhodium co-catalyst to facilitate regioselective reactions, these iridium(III) photo-reductants outcompete the commonly used [Ru(bpy)3]2+ (bpy = 2,2'-bipyridine) photosensitizer in water by up to 1 order of magnitude in turnover frequency. This improved reactivity is attributable to the strong excited-state electron donor properties and the good chemical robustness of the tri-anionic iridium(III) sensitizers, combined with their favorable Coulombic interaction with the di-cationic rhodium co-catalyst. Our findings seem relevant in the greater context of photobiocatalysis, for which access to strong, efficient, and robust photoreductants with good water solubility can be essential. Emerging Strategies for Asymmetric Synthesis: Combining Enzyme Promiscuity and Photo‐/Electro‐redox Catalysis As an emerging opportunity to expand the reactivity repertoire of enzymes to achieve unnatural transformations of enzymes in organic synthesis, enzyme promiscuity has attracted great interest in recent years. The combination of enzyme catalysis and photo‐/electro‐redox catalysis which can benefit from both the exquisite selectivity of enzymes and unique chemical transformations accessible to photo‐/electro‐chemistry has many advantages, such as new reactivity, high enantioselectivity, green synthesis, and high yields. In the past decades, most photoenzymatic catalysis and enzymatic electrosynthesis mainly focused on exploiting regenerated cofactors to function in native enzymatic activity. However, recent developments have demonstrated that combining enzyme promiscuity and photo‐/electro‐redox catalysis can unlock new asymmetric reactions. This minireview highlights these emerging strategies and covers the literature from 2016 to date. Furthermore, the future development direction of this field is prospected. Advances of asymmetric synthesis by combining enzyme promiscuity and photocatalysis or electrosynthesis are highlighted in this Review. The substrate scopes and proposed mechanisms were discussed. Moreover, the development potential of these featured approaches in organic synthesis has also been prospected. Genetically Encoded Photosensitizer Protein Reduces Iron–Sulfur Clusters of Radical SAM Enzymes Jan 2023 Rongrong Huang Ning Zhi Lu Yu Min Dong Radical S-adenosylmethionine (SAM) enzymes are a family of proteins with hundreds of thousands of members that all contain an essential [4Fe-4S] cluster. The [4Fe-4S] cluster needs to be reduced to cleave SAM and generate a 5′-deoxyadenosyl or 3-amino-3-carboxypropyl radical. Due to the low reduction potential of the [4Fe-4S] cluster, dithionite has been widely used in studies on the activity of radical SAM enzymes in vitro. Inspired by the efficient photoreduction of the [4Fe-4S] cluster in natural photosystem I, we applied the 27 kDa photosensitizer protein PSP2, which we reported previously, to reduce the [4Fe-4S] cluster of radical SAM enzymes. Herein, we demonstrate that light-activated PSP2 generates a PSP2 radical, which is capable of reducing the catalytic [4Fe-4S] cluster of the radical SAM enzyme BtrN. PSP2-reduced BtrN cleaves SAM to generate 5′-deoxyadenosine and converts the substrate 2-deoxy-scyllo-inosamine to 3-amino-2,3-dideoxy-scyllo-inosose. Remarkably, our study shows that PSP2 can reduce the auxiliary [4Fe-4S] cluster of BtrN that has the lowest reduction potential among the known radical SAM enzymes and cannot be reduced by dithionite. The reduction of this auxiliary cluster experimentally proves its function in product formation. In addition, we show that PSP2 can reduce the [4Fe-4S] cluster of Dph2, a noncanonical radical SAM enzyme involved in diphthamide biosynthesis, and help the modification of the substrate protein elongation factor 2. Therefore, PSP2 is a powerful photoreductant for radical SAM enzymes and a useful tool for studying clusters with low reduction potential. Enhancing the compatibility of the amyloid-dye hybrid nanostructure for improved photo-biocatalysis Mar 2023 Zhen Dong Yanying Wang Qin Yang Peng Wu Development of an Integrated System for Highly Selective Photoenzymatic Synthesis of Formic Acid from CO 2 Dec 2022 A Zr‐based dual‐ligand MOFs with pre‐installed Rh complex was employed for NADH regeneration in situand also used for immobilization of FDH in order to realize a highly efficient CO2 fixation system. Then, based on the detailed investigations into the photochemical and electrochemical properties, it is demonstrated that the introduction of the photosensitive ligands TCPP increased the catalytic active sites and improved photoelectric properties. Furthermore, the electron mediator Rh complex, anchored on the zirconium‐based dual‐ligand MOFs, enhanced the efficiency of electron transfer efficiency and facilitated the separation of photogenerated electrons and holes. Compared with UiO‐66‐NH2, Rh‐H2TCPP‐UiO‐66‐NH2 exhibits an optimized valence band structure and significantly improved photocatalytic activity for NAD+ reduction, resulting the synthesis of formic acid from CO2 increased from 150 µg/mL (UiO‐66‐NH2) to 254 µg/mL (Rh‐H2TCPP‐UiO‐66‐NH2). Moreover, the assembled photocatalyst‐enzyme coupled system also allows facile recycling of expensive electron mediator, enzyme, and photocatalyst. Coding Synthetic Chemistry Strategies for Furan Valorization into Bacterial Designer Cells Following a synthetic chemistry blueprint for the valorization of lignocellulosic platform chemicals, this study showcases a so far unprecedented approach to implement non‐natural enzyme modules in vivo. For the design of a novel functional whole cell tool, two purely abiotic transformations, a styrene monooxygenase‐catalysed Achmatowicz rearrangement and an alcohol dehydrogenase‐mediated borrowing hydrogen redox isomerisation, were incorporated into a recombinant bacterial host. Introducing this type of chemistry that is otherwise unknown in biosynthesis, the cellular factories were enabled to produce complex lactone building blocks in good yield from bio‐based furan substrates. This whole cell system streamlines the synthetic cascade, eliminates isolation and purification steps, and provides a high degree of stereoselectivity that has so far been elusive in the chemical methodology. Light-Driven Oxidative Demethylation Reaction Catalyzed by a Rieske-Type Non-heme Iron Enzyme Stc2 Kelin Li Rieske-type non-heme iron oxygenases/oxidases catalyze a wide range of transformations. Their applications in bioremediation or biocatalysis face two key barriers: the need of expensive NAD(P)H as a reductant and a proper reductase to mediate the electron transfer from NAD(P)H to the oxygenases. To bypass the need of both the reductase and NAD(P)H, using Rieske-type oxygenase (Stc2)-catalyzed oxidative demethylation as the model system, we report Stc2 photocatalysis using eosin Y/sulfite as the photosensitizer/sacrificial reagent pair. In a flow-chemistry setting to separate the photo-reduction half-reaction and oxidation half-reaction, Stc2 photo-biocatalysis outperforms the Stc2-NAD(P)H-reductase (GbcB) system. In addition, in a few other selected Rieske enzymes (NdmA, CntA, and GbcA) and a flavin-dependent enzyme (iodotyrosine deiodinase, IYD), the eosin Y/sodium sulfite photo-reduction pair could also serve as the NAD(P)H-reductase surrogate to support catalysis, which implies the potential applicability of this photo-reduction system to other redox enzymes. Combined Photoredox/Engineered P450 Enzymatic Direct Dioxygen-functionalization of Arylalkanes to Chiral Acyloins To date, the examples of difunctionalization of alkanes to directly incorporate two functional groups are very limited. In this study, we combined photoorgano redox catalysis and P450 biocatalysts to obtain dioxygen-functionalization of α/β-C-H bonds of arylalkanes in a straightforward manner. The synthesis of enantiomerically chiral acyloins through a one-pot two-step photoredox/P450-catalyzed cascade reaction is described. Two P450 mutants with stereocomplementary bio-oxidation were obtained using mutagenesis technology and were able to asymmetrically hydroxylate ketones to acyloins with excellent ee values, which were further proved to be efficient on a wide range of substrates. Moreover, a photoredox synthesis of ketones in situ was developed by the direct carbonylation of aromatic methyl C-H bonds and subsequently combined with the aerobic P450-biocatalytic enantioselective hydroxylation of intermediate ketones, thus providing a green and sustainable approach towards optically pure acyloins. Engineering cyanobacterial chassis for improved electron supply toward a heterologous ene-reductase Cyanobacteria are noteworthy hosts for industrially relevant redox reactions, owing to a light-driven cofactor recycling system using water as electron donor. Customizing Synechocystis sp. PCC 6803 chassis by redirecting electron flow offers a particularly interesting approach to further improve light-driven biotransformations. Therefore, different chassis expressing the heterologous ene-reductase YqjM (namely ΔhoxYH, Δflv3, ΔndhD2 and ΔhoxYHΔflv3) were generated/evaluated. The results showed the robustness of the chassis, that exhibited growth and oxygen evolution rates similar to Synechocystis wild-type, even when expressing YqjM. By engineering the electron flow, the YqjM light-driven stereoselective reduction of 2-methylmaleimide to 2-methylsuccinimide was significantly enhanced in all chassis. In the best performing chassis (ΔhoxYH, lacking an active bidirectional hydrogenase) a 39% increase was observed, reaching an in vivo specific activity of 116 U gDCW⁻¹ and an initial reaction rate of 16.7 mM h⁻¹. In addition, the presence of the heterologous YqjM mitigated substrate toxicity, and the conversion of 2-methylmaleimide increased oxygen evolution rates, in particular at higher light intensity. In conclusion, this work demonstrates that rational engineering of electron transfer pathways is a valid strategy to increase in vivo specific activities and initial reaction rates in cyanobacterial chassis harboring oxidoreductases. Strategies for Transferring Photobiocatalysis to Continuous Flow Exemplified by Photodecarboxylation of Fatty Acids Full-text available Oct 2022 Stefan Simić Miglė Jakštaitė Wilhelm T. S. Huck Wolfgang Kroutil The challenges of light-dependent biocatalytic transformations of lipophilic substrates in aqueous media are manifold. For instance, photolability of the catalyst as well as insufficient light penetration into the reaction vessel may be further exacerbated by a heterogeneously dispersed substrate. Light penetration may be addressed by performing the reaction in continuous flow, which allows two modes of applying the catalyst: (i) heterogeneously, immobilized on a carrier, which requires light-permeable supports, or (ii) homogeneously, dissolved in the reaction mixture. Taking the light-dependent photodecarboxylation of palmitic acid catalyzed by fatty-acid photodecarboxylase from Chlorella variabilis (CvFAP) as a showcase, strategies for the transfer of a photoenzyme-catalyzed reaction into continuous flow were identified. A range of different supports were evaluated for the immobilization of CvFAP, whereby Eupergit C250 L was the carrier of choice. As the photostability of the catalyst was a limiting factor, a homogeneous system was preferred instead of employing the heterogenized enzyme. This implied that photolabile enzymes may preferably be applied in solution if repair mechanisms cannot be provided. Furthermore, when comparing different wavelengths and light intensities, extinction coefficients may be considered to ensure comparable absorption at each wavelength. Employing homogeneous conditions in the CvFAP-catalyzed photodecarboxylation of palmitic acid afforded a space-time yield unsurpassed by any reported batch process (5.7 g·L-1·h-1, 26.9 mmol·L-1·h-1) for this reaction, demonstrating the advantage of continuous flow in attaining higher productivity of photobiocatalytic processes. Catalysis by Nature's photoenzymes Article Dec 2022 CURR OPIN STRUC BIOL Aoife Taylor Derren J. Heyes Nigel S Scrutton Photoenzymes use light to initiate biochemical reactions. Although rarely found in nature, their study has advanced understanding of how light energy can be harnessed to facilitate enzyme catalysis, which is also of importance to the design and engineering of man-made photocatalysts. Natural photoenzymes can be assigned to one of two families, based broadly on the nature of the light-sensing chromophores used, those being chlorophyll-like tetrapyrroles or flavins. In all cases, light absorption leads to excited state electron transfer, which in turn initiates photocatalysis. Reviewed here are recent findings relating to the structures and mechanisms of known photoenzymes. We highlight recent advances that have deepened understanding of mechanisms in biological photocatalysis. Photobiocatalytic Cascades for Acylating N‐Heterocycles with Natural Amino Acids via the 2‐Keto Acids Article Oct 2022 Xuexian Cui Wenchao Geng Huifeng Jiang Bian Wu Photobiocatalysis fully utilizing the unique reactivity of photocatalysis and efficient transforming biobased feedstocks of biocatalysis represents a promising approach for future green synthesis. However, photobiocatalytic cascade with biobased starting substrates has been rarely reported. Here, we present photobiocatalytic cascades that modify the N‐heterocycle with keto acids biocatalytically synthesized from natural amino acids. The types of aliphatic, aromatic, and polar natural amino acids are compatible with the photobiocatalytic cascades system. In addition, the cascade is compatible with a range of N‐heterocycles with moderate to good yield (up to 82%). Furthermore, the cascade system can reach gram scale (0.91 g) with a good separation yield, demonstrating the potential for scaling up production to practical application. This photobiocatalytic cascade can synthesize a range of important N‐heterocyclic derivatives from natural amino acids in a green fashion and paves the way for greener synthesis by combining biocatalysis and photocatalysis. Immobilization and Application of Fatty Acid Photodecarboxylase in Deep Eutectic Solvents Oct 2022 CHEMBIOCHEM Santiago Nahuel Chanquia Frederik Vig Benfeldt Noémi Petrovai Selin Kara Since its discovery in 2017, the fatty acid decarboxylase (FAP) photoenzyme has been the focus of extensive research, given its ability to convert fatty acids into alka(e)nes using merely visible blue light. Unfortunately, there are still some drawbacks that limit the applicability of this biocatalyst, such as poor solubility of the substrates in aqueous media, poor photostability, and the impossibility of reusing the catalyst for several cycles. In this work, we demonstrated the use of FAP in non-conventional media as a free enzyme and an immobilized preparation. Namely, its applicability in deep eutectic solvents (DESs) and a proof-of-concept immobilization using a commercial His-tag selective carrier, performing a thorough study of reaction and immobilization conditions in each case, as well as reusability studies were shown. We observed an almost complete selectivity of the enzyme towards C18 decarboxylation over C16 when used in a DES, with a product analytical yield up to 81% when using whole cells. Furthermore, when applying the immobilized enzyme in DES, we obtained yields >10-fold higher than the ones obtained in aqueous media. Light-driven biocatalytic oxidation Full-text available Sep 2022 Chul-Ho Yun Frank Hollmann Jinhyun Kim Chan Beum Park Enzymes are the catalyst of choice for highly selective reactions, offering nature-inspired approaches for sustainable chemical synthesis. Oxidative enzymes (e.g., monooxygenases, peroxygenases, oxidases, or dehydrogenases) catalyze a variety of enantioselective oxyfunctionalization and dehydrogenation reactions under mild conditions. To sustain the catalytic cycles of these enzymes, constant supply with or withdrawal of reducing equivalents (electrons) is required. Being redox by nature, photocatalysis appears a 'natural choice' to accomplish the electron-relay role, and many photoenzymatic oxidation reactions have been developed in the past years. In this contribution, we critically summarize the current developments in photoredoxbiocatalysis, highlight some promising concepts but also discuss the current limitations. Enantiocomplementary Synthesis of Vicinal Fluoro Alcohols through Photo-bio Cascade Reactions Article Jan 2022 Yu Zhang Huizhong Liu Qing-Shan Shi Xiaobao Xie The combination of the catalytic power of photocatalysis and biocatalysis has greatly boosted the development of novel synthetic strategies due to its functional diversity and stereoselective specificity. Herein, we described... Recent Advances in Cyanobacterial Biotransformations Article Sep 2022 Hanna Christiane Grimm Robert Kourist Lenny Malihan-Yap Light‐driven biotransformations in recombinant cyanobacteria have been explored in recent years for the production of chiral compounds and platform chemicals. In particular, cyanobacteria harboring oxidoreductases proved to be sustainable hosts providing and recycling reducing equivalents and improving the atom economy of the reactions. However, the provision of light in photobioreactors is considered to be the major bottleneck for up‐scaling. In this review, genetic tools for generating recombinant cyanobacterial strains and up to date cyanobacterial biotransformations including redesigning of the photosynthetic electron transport chain to increase specific activities are presented. Finally, several photobioreactor geometries to circumvent the light limitation are discussed and some future perspectives are presented. The generation of recombinant cyanobacteria is performed using genetic tools and their activities are increased by enzyme discovery as well as redesigning of the photosynthetic electron transport chain. Various photobioreactors are utilized to upscale the reaction and overcome light limitation. Characterization of Pt/g-C 3 N 4 -Catalyzed Methanol Oxidation to Drive Peroxygenase-Catalyzed Oxyfunctionalization of Hydrocarbons Article Sep 2022 Qianqian Shen Chen Zhang Lei Chen Wuyuan Zhang Light-Driven [FeFe] Hydrogenase Based H 2 Production in E. coli : A Model Reaction for Exploring E. coli Based Semiartificial Photosynthetic Systems Full-text available Aug 2022 Marco Lorenzi Mira Theresa Gamache Holly J Redman Gustav Berggren Biohybrid technologies like semiartificial photosynthesis are attracting increased attention, as they enable the combination of highly efficient synthetic light-harvesters with the self-healing and outstanding performance of biocatalysis. However, such systems are intrinsically complex, with multiple interacting components. Herein, we explore a whole-cell photocatalytic system for hydrogen (H2) gas production as a model system for semiartificial photosynthesis. The employed whole-cell photocatalytic system is based on Escherichia coli cells heterologously expressing a highly efficient, but oxygen-sensitive, [FeFe] hydrogenase. The system is driven by the organic photosensitizer eosin Y under broad-spectrum white light illumination. The direct involvement of the [FeFe] hydrogenase in the catalytic reaction is verified spectroscopically. We also observe that E. coli provides protection against O2 damage, underscoring the suitability of this host organism for oxygen-sensitive enzymes in the development of (photo) catalytic biohybrid systems. Moreover, the study shows how factorial experimental design combined with analysis of variance (ANOVA) can be employed to identify relevant variables, as well as their interconnectivity, on both overall catalytic performance and O2 tolerance. Biomacromolecule-Assisted Screening for Reaction Discovery and Catalyst Optimization Stephany M. Ramos De Dios Virendra Kumar Tiwari Christopher Mccune David B Berkowitz Reaction discovery and catalyst screening lie at the heart of synthetic organic chemistry. While there are efforts at de novo catalyst design using computation/artificial intelligence, at its core, synthetic chemistry is an experimental science. This review overviews biomacromolecule-assisted screening methods and the follow-on elaboration of chemistry so discovered. All three types of biomacromolecules discussed─enzymes, antibodies, and nucleic acids─have been used as "sensors" to provide a readout on product chirality exploiting their native chirality. Enzymatic sensing methods yield both UV-spectrophotometric and visible, colorimetric readouts. Antibody sensors provide direct fluorescent readout upon analyte binding in some cases or provide for cat-ELISA (Enzyme-Linked ImmunoSorbent Assay)-type readouts. DNA biomacromolecule-assisted screening allows for templation to facilitate reaction discovery, driving bimolecular reactions into a pseudo-unimolecular format. In addition, the ability to use DNA-encoded libraries permits the barcoding of reactants. All three types of biomacromolecule-based screens afford high sensitivity and selectivity. Among the chemical transformations discovered by enzymatic screening methods are the first Ni(0)-mediated asymmetric allylic amination and a new thiocyanopalladation/carbocyclization transformation in which both C-SCN and C-C bonds are fashioned sequentially. Cat-ELISA screening has identified new classes of sydnone-alkyne cycloadditions, and DNA-encoded screening has been exploited to uncover interesting oxidative Pd-mediated amido-alkyne/alkene coupling reactions. Artificial photosynthesis systems for solar energy conversion and storage: platforms and their realities Zhenfu Wang Yang Hu Songping Zhang In natural photosynthesis, photosynthetic organisms such as green plants realize efficient solar energy conversion and storage by integrating photosynthetic components on the thylakoid membrane of chloroplasts. Inspired by natural photosynthesis, researchers have developed many artificial photosynthesis systems (APS's) that integrate various photocatalysts and biocatalysts to convert and store solar energy in the fields of resource, environment, food, and energy. To improve the system efficiency and reduce the operation cost, reaction platforms are introduced in APS's since they allow for great stability and continuous processing. A systematic understanding of how a reaction platform affects the performance of artificial photosynthesis is conducive for designing an APS with superb solar energy utilization. In this review, we discuss the recent APS's researches, especially those confined on/in platforms. The importance of different platforms and their influences on APS's performance are emphasized. Generally, confined platforms can enhance the stability and repeatability of both photocatalysts and biocatalysts in APS's as well as improve the photosynthetic performance due to the proximity effect. For functional platforms that can participate in the artificial photosynthesis reactions as active parts, a high integration of APS's components on/in these platforms can lead to efficient electron transfer, enhanced light-harvesting, or synergistic catalysis, resulting in superior photosynthesis performance. Therefore, the integration of APS's components is beneficial for the transfer of substrates and photoexcited electrons in artificial photosynthesis. We finally summarize the current challenges of APS's development and further efforts on the improvement of APS's. A photonanozyme with light-empowered specific peroxidase-mimicking activity Wenlong Tan Pengfei Han Kun Li Although nanozymes have been widely developed, directly utilizing light to drive catalytic reactions like natural photoenzymes still remains challenging. Herein, we propose that photonanozymes (PNZs), as a novel kind of nanozyme, exclusively possess enzyme-mimicking activity under illumination. Only in the presence of visible light, the as-synthesized TiO2 proposed in this contribution shows excellent specificity of peroxidase-like without any oxidase- or catalase-like activity. The driving force of the light-empowered peroxidase-like photonanozymatic activity is explicated in terms of the photogenerated hot charge carriers in TiO2 PNZs and the accompanied reactive oxygen species. The co-substrates for photonanozymatic reaction over TiO2 PNZs facilitate the formation of the precarious and reactive peroxo-oxygen bridge between TiO2 and H2O2, enabling the catalytic specificity. With the TiO2 PNZ-based biosensing platform for visual glucose detection exemplifying the concept of the application of PNZs, this work may evoke more inspirations to explore strategies for enlarging the scope of photoenzyme mimics. Visible-Light Photoredox Catalysis in Water Camilla Russo Francesca Brunelli Gian Cesare Tron Mariateresa Giustiniano The use of water in organic synthesis draws attention to its green chemistry features and its unique ability to unveil unconventional reactivities. Herein, literature about the use of water as a reaction medium under visible-light photocatalytic conditions is summarized in order to highlight challenges and opportunities. Accordingly, this Synopsis has been divided into four different sections focused on (1) the unconventional role of water in photocatalytic reactions, (2) in-/on-water reactions, (3) water-soluble photocatalysts, and (4) photomicellar catalytic systems. Peroxygenases require controlled supply of H2O2 to operate efficiently. Here, we propose a photocatalytic system for the reductive activation of ambient O2 to produce H2O2 which uses the energy provided by visible light more efficiently based on the combination of wavelength-complementary photosensitizers. This approach was coupled to an enzymatic system to make formate available as sacrificial electron donor. The scope and current limitations of this approach are reported and discussed. In this study, we combined photo‐organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photocatalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light‐driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α‐chiral ketones with up to 99% ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering such as, applying a two‐phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo‐organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile >97% ee at gram scale. Unbiased biocatalytic solar-to-chemical conversion by FeOOH/BiVO4/perovskite tandem structure Redox enzymes catalyze fascinating chemical reactions with excellent regio- and stereo-specificity. Nicotinamide adenine dinucleotide cofactor is essential in numerous redox biocatalytic reactions and needs to be regenerated because it is consumed as an equivalent during the enzymatic turnover. Here we report on unbiased photoelectrochemical tandem assembly of a photoanode (FeOOH/BiVO4) and a perovskite photovoltaic to provide sufficient potential for cofactor-dependent biocatalytic reactions. We obtain a high faradaic efficiency of 96.2% and an initial conversion rate of 2.4 mM h−1 without an external applied bias for the photoelectrochemical enzymatic conversion of α-ketoglutarate to L-glutamate via L-glutamate dehydrogenase. In addition, we achieve a total turnover number and a turnover frequency of the enzyme of 108,800 and 6200 h−1, respectively, demonstrating that the tandem configuration facilitates redox biocatalysis using light as the only energy source. Generation of a functional, semisynthetic [FeFe]-hydrogenase in a photosynthetic microorganism
https://www.researchgate.net/publication/332307497_Photo-Biocatalysis_Biotransformations_in_the_Presence_of_Light
Kiwifruit and Human Platelet Function | Request PDF Request PDF | Kiwifruit and Human Platelet Function | Fruits and vegetables have long been thought to be beneficial in cardiovascular disease. The beneficial effects of fruits and vegetables may be... | Find, read and cite all the research you need on ResearchGate Chapter Kiwifruit and Human Platelet Function March 2018 DOI: 10.1002/9781119375913.ch8 In book: Nutraceuticals and Human Blood Platelet Function (pp.139-154) Authors: <here is a image 8df9702cb64ec4a8-cc0fcea1a4afd9b2> Asim K Duttaroy University of Oslo Abstract Fruits and vegetables have long been thought to be beneficial in cardiovascular disease. The beneficial effects of fruits and vegetables may be explained by the antioxidants and other components contained therein. These nutrients may function individually, or in concert, to protect lipoproteins and vascular cells from oxidation, or by other mechanisms such as reducing plasma lipid levels and platelet aggregation response. Platelets are involved in atherosclerotic disease development, and the reduction of platelet activity reduces the incidence and severity of cardiovascular disease. Consuming kiwifruits is beneficial as a preventive in cardiovascular disease (CVD). Kiwifruit extract has also shown anti‐platelet activity in vitro and ex vivo. Consuming kiwifruits reduces platelet aggregation response to collagen and ADP, but the nature of the responsible compounds are yet to be determined. Kiwi fruit consumption may be beneficial for the cardiovascular system. <here is a image 175d1bd4b7439d95-754927124da715c1> Discover the world's research 25+ million members 160+ million publication pages 2.3+ billion citations Effects of kiwifruit consumption on serum lipid profiles and antioxidative status in hyperlipidemic subjects Article Full-text available Feb 2009 INT J FOOD SCI NUTR <here is a image 015f012c4ccfd73c-e3c9d039c1baa888> Wen-Hsin Chang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jen-Fang Liu Cardiovascular disease (CVD) is the most important adult health problem in the world. Epidemiological studies and laboratory experiments have shown that fruit and vegetable consumption has protective effects against CVD. The purpose of the study was to investigate the effects of consumption of two kiwifruit per day on the lipid profile, antioxidants and markers of lipid peroxidation in hyperlipidemic adult men and women in Taiwan. Forty-three subjects who had hyperlipidemia, including 13 males and 30 females, participated in this study. They were asked to consume two kiwifruit per day for 8 weeks. Anthropometric measurements were made. Before the intervention and at 4 and 8 weeks of the intervention, fasting blood samples were analyzed for total cholesterol, triacylglycerol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol (HDL-C). Additionally vitamin E and vitamin C, the malondialdehyde + 4-hydroxy-2(E)-nonenal concentration, and the lag time of LDL oxidation were determined. No significant differences from baseline to 8 weeks of the intervention were detected for triacylglycerol, total cholesterol, or LDL cholesterol. However, after 8 weeks of consumption of kiwifruit, the HDL-C concentration was significantly increased and the LDL cholesterol/HDL-C ratio and total cholesterol/HDL-C ratio were significantly decreased. Vitamin C and vitamin E also increased significantly. In addition, the lag time of LDL oxidation and malondialdehyde + 4-hydroxy-2(E)-nonenal had significantly changed at 4 and 8 weeks during the kiwifruit intervention. Regular consumption of kiwifruit might exert beneficial effects on the antioxidative status and the risk factors for CVD in hyperlipidemic subjects. Inhibitory effects of kiwifruit extract on human platelet aggregation and plasma angiotensin-converting enzyme activity Article Full-text available Nov 2013 PLATELETS <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Lili L Dizdarevic <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Dipankar Biswas <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Main Uddin <here is a image 8df9702cb64ec4a8-cc0fcea1a4afd9b2> Asim K Duttaroy Abstract Previous human studies suggest that supplementation with kiwifruits lowers several cardiovascular risk factors such as platelet hyperactivity, blood pressure and plasma lipids. The cardiovascular health benefit of fruit and vegetables is usually attributed to the complex mixture of phytochemicals therein; however, kiwifruit's cardioprotective factors are not well studied. In this study, we investigated the effects of kiwifruit extract on human blood platelet aggregation and plasma angiotensin-converting enzyme (ACE) activity. A sugar-free, heat-stable aqueous extract with molecular mass less than 1000 Da was prepared from kiwifruits. Typically, 100 g kiwifruits produced 66.3 ± 5.8 mg (1.2 ± 0.1 mg CE) of sugar-free kiwifruit extract (KFE). KFE inhibited both human platelet aggregation and plasma ACE activity in a dose-dependent manner. KFE inhibited platelet aggregation in response to ADP, collagen and arachidonic acid, and inhibitory action was mediated in part by reducing TxA2 synthesis. The IC50 for ADP-induced platelet aggregation was 1.6 ± 0.2 mg/ml (29.0 ± 3.0 μg CE/ml), whereas IC50 for serum ACE was 0.6 ± 0.1 mg/ml (11.0 ± 1.2 μg CE/ml). Consuming 500 mg of KFE (9.0 mg CE) in 10 g margarine inhibited ex vivo platelet aggregation by 12.7%, 2 h after consumption by healthy volunteers (n = 9). All these data indicate that kiwifruit contains very potent antiplatelet and anti-ACE components. Consuming kiwifruits might be beneficial as both preventive and therapeutic regime in cardiovascular disease. Fruit and Vegetable Intake in Relation to Risk of Ischemic Stroke Article Full-text available Oct 1999 <here is a image 8ef919319e5ceaf1-a23889febcc95651> Kaumudi J Joshipura Alberto Ascherio JoAnn E. Manson <here is a image 695960370ec64d7f-ccb622bb8203138a> Walter C Willett Few studies have evaluated the relationship between fruit and vegetable intake and cardiovascular disease. To examine the associations between fruit and vegetable intake and ischemic stroke. Prospective cohort studies, including 75 596 women aged 34 to 59 years in the Nurses' Health Study with 14 years of follow-up (1980-1994), and 38683 men aged 40 to 75 years in the Health Professionals' Follow-up Study with 8 years of follow-up (1986-1994). All individuals were free of cardiovascular disease, cancer, and diabetes at baseline. Incidence of ischemic stroke by quintile of fruit and vegetable intake. A total of 366 women and 204 men had an ischemic stroke. After controlling for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake (median of 5.1 servings per day among men and 5.8 servings per day among women) had a relative risk (RR) of 0.69 (95% confidence interval [CI], 0.52-0.92) compared with those in the lowest quintile. An increment of 1 serving per day of fruits or vegetables was associated with a 6% lower risk of ischemic stroke (RR, 0.94; 95 % CI, 0.90-0.99; P =.01, test for trend). Cruciferous vegetables (RR, 0.68 for an increment of 1 serving per day; 95% CI, 0.49-0.94), green leafy vegetables (RR, 0.79; 95% CI, 0.62-0.99), citrus fruit including juice (RR, 0.81; 95% CI, 0.68-0.96), and citrus fruit juice (RR, 0.75; 95% CI, 0.61-0.93) contributed most to the apparent protective effect of total fruits and vegetables. Legumes or potatoes were not associated with lower ischemic stroke risk. The multivariate pooled RR for total stroke was 0.96 (95% CI, 0.93-1.00) for each increment of 2 servings per day. These data support a protective relationship between consumption of fruit and vegetables-particularly cruciferous and green leafy vegetables and citrus fruit and juice-and ischemic stroke risk. Correlation between mean platelet volume and fasting plasma glucose levels in prediabetic and normoglycemic individuals Article Full-text available Jan 2013 CARDIOVASC DIABETOL Masanori Shimodaira Tomohiro Niwa Koji Nakajima <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Tomohiro Nakayama Background Prediabetes is an independent risk factor for cardiovascular diseases. Mean platelet volume (MPV) can reflect platelet activity, and high MPV is associated with thrombogenic activation and an increased risk of cardiovascular disease. In diabetic patients, MPV is higher when compared with normal subjects. However, the relationship between MPV and prediabetes is poorly understood. The purpose of the present study was to compare MPV in prediabetic and normoglycemic subjects, and to evaluate the relationship between MPV and fasting plasma glucose (FPG) levels in these two groups. Methods We retrospectively studied 1876 Japanese subjects who had undergone health checks at Iida Municipal Hospital. Age, sex, body mass index (BMI), blood pressure, medical history, smoking habits, alcohol intake, lipid profiles, FPG levels, and MPV were evaluated. Subjects were categorized into four groups according to FPG: Q1 (70 mg/dL ≤ FPG < 90 mg/dL, n = 467), Q2 (90 mg/dL ≤ FPG < 95 mg/dl, n = 457), Q3 (95 mg/dL ≤ FPG < 100 mg/dL, n = 442), and Q4 (100 mg/dL ≤ FPG < 126 mg/dL, n = 512). Q1, Q2, and Q3 were defined as normal FPG groups and Q4 was defined as prediabetic group. Results The MPV increased with the increasing FPG levels, in the following order: Q1 (9.89 ± 0.68 fl), Q2 (9.97 ± 0.69 fl), Q3 (10.02 ± 0.72 fl), and Q4 (10.12 ± 0.69 fl). After adjusting for the confounding parameters, MPV of the prediabetic group was higher than that in other groups (P < 0.001 for Q4 vs. Q1 and Q2, and P < 0.05 for Q4 vs. Q3). MPV in the high-normal glucose group (Q3) was significantly higher than in the low-normal glucose group (Q1). MPV was independently and positively associated with FPG, not only in prediabetic subjects but also in normal FPG subjects (β = 0.020 and β = 0.006, respectively). Conclusions MPV in patients with prediabetes was higher than that in normal subjects, and was positively associated with FPG levels in prediabetic and normal subjects. Bioassay-Guided Isolation and HPLC Determination of Bioactive Compound That Relate to the Antiplatelet Activity (Adhesion, Secretion, and Aggregation) from Solanum lycopersicum Article Full-text available Nov 2012 Ricardo I. Castro Luis Astudillo Eduardo Fuentes <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Iván Palomo In seeking the functionality of foodstuff applicable to medicine, ripe tomato fruits were found to show an antiplatelet activity. Therefore, the bioactive compound was isolated, structurally identified, and studied for an inhibitory effects on platelet adhesion, secretion, and aggregation. The concentration of adenosine in ripe tomato fruits (pulp and skin extracts) and its processing by-products (paste and pomace) was determined by reversed-phase high-performance liquid chromatography (HPLC). According to platelet aggregation inhibition induced by ADP, the total extract residual was fractionated by liquid-liquid separation, obtaining aqueous, ethyl acetate and petroleum ether extracts. The aqueous extract was subjected to repeated permeation over sephadex LH-20 and semipreparative TLC. The isolate finally obtained was identified as adenosine on the basis of ESI-MS, (1)H NMR, HPLC, and UV spectra. Adenosine concentration dependently (2.3-457 μM) platelet aggregation inhibited induced by ADP. Also, adenosine present inhibition of platelet secretion and thrombus formation under flow conditions. The quantitative HPLC analysis revealed significant amounts of adenosine in ripe tomato fruits and its processing by-products. From these results, extracts/fractions of ripe tomato fruits and their processing by-products may be referred to as functional food and functional ingredients containing a compound that inhibits platelet function with a potent preventive effect on thrombus formation, as those that occur in stroke. Health Benefits of Fruits and Vegetables Article Full-text available Beate Lloyd Fruits and vegetables are universally promoted as healthy. The Dietary Guidelines for Americans 2010 recommend you make one-half of your plate fruits and vegetables. Myplate.gov also supports that one-half the plate should be fruits and vegetables. Fruits and vegetables include a diverse group of plant foods that vary greatly in content of energy and nutrients. Additionally, fruits and vegetables supply dietary fiber, and fiber intake is linked to lower incidence of cardiovascular disease and obesity. Fruits and vegetables also supply vitamins and minerals to the diet and are sources of phytochemicals that function as antioxidants, phytoestrogens, and antiinflammatory agents and through other protective mechanisms. In this review, we describe the existing dietary guidance on intake of fruits and vegetables. We also review attempts to characterize fruits and vegetables into groups based on similar chemical structures and functions. Differences among fruits and vegetables in nutrient composition are detailed. We summarize the epidemiological and clinical studies on the health benefits of fruits and vegetables. Finally, we discuss the role of fiber in fruits and vegetables in disease prevention. Lipocalin-2, glucose metabolism and chronic low-grade systemic inflammation in Chinese people CARDIOVASC DIABETOL <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ying Huang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Zhen Yang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Zi Ye <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Renming Hu Lipocalin-2 is a novel adipokine with connection to insulin resistance. In this study, we aimed to investigate the association of serum lipocalin-2 with glucose metabolism and other metabolic phenotype in a large-scale Chinese population. We evaluated serum lipocalin-2 in a cross-sectional sample of 2519 Chinese aged from 50 to 82 year in a Shanghai downtown district by ELISA. Glucose, insulin, lipid profile, inflammatory markers, and adipokines were also measured. Serum lipocalin-2 was significantly higher in subjects with isolated impaired fasting glucose, isolated impaired glucose tolerance, combined impaired fasting glucose/impaired glucose tolerance and newly-diagnosed type 2 diabetes than in those with normal glucose regulation. Lipocalin-2 elevation was clearly associated with a higher risk for impaired glucose regulation (OR 1.30 for each 10 ng/ml increase in serum lipocalin-2, 95% CI 1.23-1.62, p = 0.009) after adjustment of age, gender, smoking, alcohol drinking, family history of diabetes, serum CRP, serum adiponectin, serum CXCL5, HOMA-IR, BMI, and waist/hip ratio. The OR for participants with impaired glucose regulation and type 2 diabetes was 1.31 (95% CI 1.21-1.69, p < 0.001). Our findings suggest that elevated serum lipocalin-2 is closely and independently associated with impaired glucose regulation and type 2 diabetes. Kiwifruit decreases blood pressure and whole-blood platelet aggregation in male smokers Full-text available <here is a image 36fbd57f910d3214-475cb04fe6ed2fc1> Anette Solli Karlsen <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mette Svendsen Ingebjørg Seljeflot <here is a image 533beeb55af98377-eee0963f844dfd77> Rune Blomhoff Lifestyle modifications to reduce risk factors for cardiovascular diseases such as blood pressure (BP) and smoking have been emphasized. Fruits and vegetables may modify such risk factors. The major aim of this randomized, controlled trial was to investigate the effects of (1) kiwifruits and (2) an antioxidant-rich diet compared with (3) a control group on BP and platelet aggregation (that is, whole-blood platelet aggregation) after 8 weeks in male smokers (age 44-74 years, n=102). The kiwifruit group received 3 kiwifruits per day, whereas the antioxidant-rich diet group received a comprehensive combination of antioxidant-rich foods. In the kiwifruit group, reductions of 10 mm Hg in systolic BP and 9 mm Hg in diastolic BP were observed (P=0.019 and P=0.016 (change from baseline in the kiwifruit group compared with change from baseline in the control group)). In the antioxidant-rich diet group, a reduction of 10 mm Hg in systolic BP was observed among hypertensives (P=0.045). Additionally, a 15% reduction in platelet aggregation and an 11% reduction in angiotensin-converting enzyme activity was observed in the kiwifruit group (P=0.009 and P=0.034). No effects on these parameters were observed in the antioxidant-rich diet group. This study suggest that intake of kiwifruit may have beneficial effects on BP and platelet aggregation in male smokers.Journal of Human Hypertension advance online publication, 19 January 2012; doi:10.1038/jhh.2011.116. The Role of Platelets in Atherothrombosis Hematology <here is a image 5d5bcfab6acebf33-038131ec8391e441> Zane S Kaplan Shaun P Jackson Platelets have evolved highly specialized adhesion mechanisms that enable cell-matrix and cell-cell interactions throughout the entire vasculature irrespective of the prevailing hemodynamic conditions. This unique property of platelets is critical for their ability to arrest bleeding and promote vessel repair. Platelet adhesion under conditions of high shear stress, as occurs in stenotic atherosclerotic arteries, is central to the development of arterial thrombosis; therefore, precise control of platelet adhesion must occur to maintain blood fluidity and to prevent thrombotic or hemorrhagic complications. Whereas the central role of platelets in hemostasis and thrombosis has long been recognized and well defined, there is now a major body of evidence supporting an important proinflammatory function for platelets that is linked to host defense and a variety of autoimmune and inflammatory diseases. In the context of the vasculature, experimental evidence indicates that the proinflammatory function of platelets can regulate various aspects of the atherosclerotic process, including its initiation and propagation. The mechanisms underlying the proatherogenic function of platelets are increasingly well defined and involve specific adhesive interactions between platelets and endothelial cells at atherosclerotic-prone sites, leading to the enhanced recruitment and activation of leukocytes. Through the release of chemokines, proinflammatory molecules, and other biological response modulators, the interaction among platelets, endothelial cells, and leukocytes establishes a localized inflammatory response that accelerates atherosclerosis. These inflammatory processes typically occur in regions of the vasculature experiencing low shear and perturbed blood flow, a permissive environment for leukocyte-platelet and leukocyte-endothelial interactions. Therefore, the concept has emerged that platelets are a central element of the atherothrombotic process and that future therapeutic strategies to combat this disease need to take into consideration both the prothrombotic and proinflammatory function of platelets. Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection Nutr J <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Asgeir Brevik <here is a image c274c9578ef57b58-ed6687a34be06e35> Isabel Gaivão <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Tirill Medin Andrew R Collins The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products. We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair. Plasma vitamin C increased after supplementation as did resistance towards H₂O₂-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation. Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage. Effects of kiwifruit consumption on serum lipid profiles and antioxidative status in hyperlipidemic subjects INT J FOOD SCI NUTR <here is a image 015f012c4ccfd73c-e3c9d039c1baa888> Wen-Hsin Chang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jen-Fang Liu Cardiovascular disease (CVD) is the most important adult health problem in the world. Epidemiological studies and laboratory experiments have shown that fruit and vegetable consumption has protective effects against CVD. The purpose of the study was to investigate the effects of consumption of two kiwifruit per day on the lipid profile, antioxidants and markers of lipid peroxidation in hyperlipidemic adult men and women in Taiwan. Forty-three subjects who had hyperlipidemia, including 13 males and 30 females, participated in this study. They were asked to consume two kiwifruit per day for 8 weeks. Anthropometric measurements were made. Before the intervention and at 4 and 8 weeks of the intervention, fasting blood samples were analyzed for total cholesterol, triacylglycerol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol (HDL-C). Additionally vitamin E and vitamin C, the malondialdehyde + 4-hydroxy-2(E)-nonenal concentration, and the lag time of LDL oxidation were determined. No significant differences from baseline to 8 weeks of the intervention were detected for triacylglycerol, total cholesterol, or LDL cholesterol. However, after 8 weeks of consumption of kiwifruit, the HDL-C concentration was significantly increased and the LDL cholesterol/HDL-C ratio and total cholesterol/HDL-C ratio were significantly decreased. Vitamin C and vitamin E also increased significantly. In addition, the lag time of LDL oxidation and malondialdehyde + 4-hydroxy-2(E)-nonenal had significantly changed at 4 and 8 weeks during the kiwifruit intervention. Regular consumption of kiwifruit might exert beneficial effects on the antioxidative status and the risk factors for CVD in hyperlipidemic subjects. Effects of tomato extract on platelet aggregation in-vitro <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Lynn Crosbie <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> M-J Gordon <here is a image 8df9702cb64ec4a8-cc0fcea1a4afd9b2> Asim K Duttaroy Among all fruits tested in vitro for their anti-platelet property, tomato had the highest activity followed by grapefruit, melon, and strawberry, whereas pear and apple had little or no activity. Tomato extract (20-50 microl of 100% juice) inhibited both ADP- and collagen-induced aggregation by up to 70% but could not inhibit arachidonic acid-induced platelet aggregation and concomitant thromboxane synthesis under similar experimental conditions. The anti-platelet components (MW <1000 Da) in tomatoes are water soluble, heat stable and are concentrated in the yellow fluid around the seeds. The active fractions were separated using gel filtration and HPLC. The aqueous fraction (110 000 xg supernatant) of tomatoes containing anti-platelet activity was subjected to gel filtration column chromatography (Biogel P2 column). The activity was fractionated into two peaks, peak-3 and peak-4 (major peak). Subsequently, peak-4 was further purified by HPLC using a reversed-phase column. NMR and mass spectroscopy studies indicated that peak F2 (obtained from peak 4) contained adenosine and cytidine. Deamination of peak F2 with adenosine deaminase almost completely abolished its anti-platelet activity, confirming the presence of adenosine in this fraction. In comparison, deamination of peak-4 resulted in only partial loss of inhibitory activity while the activity of peak-3 remained unaffected. These results indicate that tomatoes contain anti-platelet compounds in addition to adenosine. Unlike aspirin, the tomato-derived compounds inhibit thrombin-induced platelet aggregation. All these data indicate that tomato contains very potent anti-platelet components, and consuming tomatoes might be beneficial both as a preventive and therapeutic regime for cardiovascular disease. Dietary components and human platelet activity <here is a image 8df9702cb64ec4a8-cc0fcea1a4afd9b2> Asim K Duttaroy Platelet hyperactivity is one of the most important factors responsible for the incidence of cardiovascular disease. There are many nutritive and non-nutritive compounds present in the diet which may affect platelet function in various ways. Recent discovery of anti-platelet factors in plants, vegetables and fruits provides a new dietary means for a long-term strategy to favorably modify human blood platelet activity. This review summarises the effects of these dietary components on human platelet function both in vitro and in vivo. Effects of kiwi fruit consumption on platelet aggregation and plasma lipids in healthy human volunteers Full-text available <here is a image 8df9702cb64ec4a8-cc0fcea1a4afd9b2> Asim K Duttaroy Fruits and vegetables have been thought to be beneficial in cardiovascular disease. The beneficial effects of fruits and vegetables may be explained by the antioxidants and other components contained therein. These nutrients may function individually or in concert to protect lipoproteins and vascular cells from oxidation, or by other mechanisms such as reducing plasma lipid levels (LDL cholesterol, triglycerides), and platelet aggregation response. Kiwi fruit which contains high amounts of vitamin C, vitamin E and polyphenols may be beneficial in cardiovascular disease; however very little is known about its cardioprotective effects. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. To this end, we evaluated whether consuming kiwi fruit modulated platelet activity and plasma lipids in human volunteers in a randomized cross-over study. We report that consuming two or three kiwi fruit per day for 28 days reduced platelet aggregation response to collagen and ADP by 18% compared with the controls (P < 0.05). In addition, consumption of kiwi fruit lowered blood triglycerides levels by 15% compared with control (P < 0.05), whereas no such effects were observed in the case of cholesterol levels. All these data indicate that consuming kiwi fruit may be beneficial in cardiovascular disease. Biochemical mechanisms of platelet activation <here is a image 912e01159607050c-b602909f388af635> Andrew Schafer Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement Jan 2005 B.A. Franklin Scott M. Grundy <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> James I. Cleeman Stephen R Daniels Fractions of aqueous and methanolic extracts from tomato (Solanum lycopersicum L.) present platelet antiaggregant activity Jan 2012 M.I. Gutierrez Pia I Rubio Eduardo Fuentes Luis A Astudillo Aspirin resistance Jan 2007 <here is a image b4f5221d274c1602-20881eb84f2d51bd> Huyen Tran S. S. Anand <here is a image 1a286792e19069b6-2adfad96715465d3> Graeme J Hankey <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> John Eikelboom Aspirin resistance refers to less than expected suppression of thromboxane A(2) production by aspirin and has been reported to be independently associated with an increased risk of adverse cardiovascular events. Possible causes of aspirin resistance include poor compliance, drug interaction, inadequate aspirin dose, increase turnover of platelets, genetic polymorphisms of cyclo-oxygenase-1, and upregulation of alternate (non-platelet) pathways of thromboxane production. Laboratory methods used to detect aspirin resistance include those that measure thromboxane A(2) production and thromboxane A(2)-dependent platelet function. However, since there is currently no standardised approach to the diagnosis and there are no proven effective treatments for aspirin resistance that improve outcome, patients with cardiovascular disease receiving aspirin should not be routinely tested for aspirin resistance. Instead physicians should be aware of the factors that may impair aspirin function, ensure that they use an appropriate dose of aspirin and optimise compliance with aspirin therapy. Further research exploring the mechanisms of aspirin resistance is needed in order to better define and develop a standardised test for aspirin resistance that is specific, reliable, can be readily applied in routine laboratories and correlate with an increased risk of cardiovascular events. Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement Article Jan 2006 CURR OPIN CARDIOL Scott M. Grundy <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> James I. Cleeman Stephen R Daniels Executive Summary An abstract is unavailable. This article is available as HTML full text and PDF. Evaluation of the extraction efficiency for polyphenol extracts from by‐products of green kiwifruit juicing Article Dec 2009 INT J FOOD SCI TECH <here is a image a259b870afa33d4f-69805f4373f3cb08> Dongxiao Sun-Waterhouse <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ivy Wen Reginald Wibisono Sandhya S. Wadhwa The health benefits of fruits are attributable in part to their bioactive components such as phenolics and pectic polysaccharides. By-products derived from kiwifruit processing can be a good source of such bioactive compounds. Extracts were produced using different concentrations of ethanol in water (0%, 30%, 50%, 74% and 96% v/v) from by-products (skin, residue and pulp) of the green-fleshed kiwifruit (Actinidia deliciosa‘Hayward’) juicing process. The amounts of phenolic compounds and uronic acid (UA) as well as the phenolic composition in each extract were determined. Results show that different by-products contained different concentrations of phenolics and pectic polysaccharides. Based on total phenolic contents, 96% v/v ethanol appeared to be the best extraction medium. The 30% or 74% ethanolic dilution was the second best medium for phenolic extraction from skin and pulp/residue, respectively. Water was a good medium for extracting satisfactory quantities of phenolics as well as the highest concentration of pectic polysaccharides. Phenolic profiling by high-performance liquid chromatography (HPLC) was used to detect individual phenolic compounds in an extract. Results using HPLC showed that alkali pre-treatment has improved the extraction efficiency of phenolics as a function of alkali concentration, fruit tissue type, extraction media, by-product preparation method, and class of polyphenols. As a result more efficient methods for both extraction and characterisation of polyphenols could be evaluated. Fractions of aqueous and methanolic extracts from tomato (Solanum lycopersicum L.) present platelet antiaggregant activity Dec 2011 Eduardo Fuentes Luis A Astudillo <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Margarita Gutiérrez <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Iván Palomo Cardiovascular disease (CVD) is the leading cause of death worldwide. Its prevention emphasizes three aspects: not smoking, physical activity and a healthy diet. Recently, we screened the antithrombotic activity of a selected group of fruits and vegetables. Among them, tomato showed an important effect. The aim of this study was to evaluate and characterize the platelet antiaggregatory activity of tomato (Solanum lycopersicum L.). For this, we obtained aqueous and methanolic tomato extracts and evaluated the effect of pH (2 and 10) and temperature (22, 60 and 100°C) on this activity. Furthermore, in order to isolate the antiaggregant principle, we separated tomato extracts into several fractions (A-D) by size exclusion chromatography. In addition, we evaluated the platelet antiaggregating activity ex vivo in Wistar rats. Aqueous and methanolic extracts of tomato treated at 22, 60 and 100°C and pH 2 and 10 still inhibited platelet aggregation (in vitro). Moreover, it was noted that one of the fractions (fraction C), from both aqueous and methanolic extracts, presented the highest activity (∼70% inhibition of platelet aggregation) and concentration dependently inhibited platelet aggregation significantly compared with control (P < 0.05). These fractions did not contain lycopene but presented two peaks of absorption, at 210 and 261 nm, compatible with the presence of nucleosides. In rats treated with tomato macerates, a mild platelet antiaggregating effect ex vivo was observed. Further studies are required to identify the molecules with platelet antiaggregating activity and antiplatelet mechanisms of action. The CD40-CD40L system in cardiovascular disease Article Aug 2011 ANN MED <here is a image 7d4e8dc4a6b7afdf-e02469d79a2c07d7> Burak Pamukcu Gregory Y H Lip V. A. Snezhitskiy <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Eduard Shantsila The CD40-CD40L system is a pathway which is associated with both prothrombotic and proinflammatory effects. CD40 and its ligand were first discovered on the surface of activated T cells, but its presence on B cells, antigen-presenting cells, mast cells, and finally platelets, is evident. The soluble form of CD40L (sCD40L) is derived mainly from activated platelets and contributes to the pathophysiology of atherosclerosis and atherothrombosis. Indeed, sCD40L has autocrine, paracrine, and endocrine activities, and it enhances platelet activation, aggregation, and platelet-leucocyte conjugation that may lead to atherothrombosis. It has even been suggested that sCD40L may play a pathogenic role in triggering acute coronary syndromes. Conversely, blockade of this pathway with anti-CD40L antibodies may prevent or delay the progression of atherosclerosis. Concentrations of sCD40L also predict risk of future cardiovascular disease in healthy women and clinical outcomes in patients with acute coronary syndromes. However, there are controversial and uncertain points over the application of this biomarker to clinical cardiology. In this review, we provide an overview of potential implications of CD40-CD40L signalling and sCD40L as a biomarker in patients with atherosclerotic vascular diseases. Identification and Assessment of Antioxidant Capacity of Phytochemicals from Kiwi Fruits May 2009 J AGR FOOD CHEM <here is a image 30415acb9038d0d9-83bfb9ab115f8b82> Antonio Fiorentino <here is a image 601381059125401d-c5304274faefa93d> Brigida D'Abrosca <here is a image aa58ab192be3c2e7-60ce2200fbf87f3c> Severina Pacifico Pietro Monaco The kiwi fruit is the edible berry of a cultivar group of the woody vine of several Actinidia species. The most common commercially available, green-fleshed kiwi fruit is the cultivar 'Hayward', which belongs to the Actinidia deliciosa species. An antioxidative screening of kiwi fruit components (peel and pulp) crude extracts was carried out using specific assay media characterized for the presence of highly reactive species such as 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH(•)), H(2)O(2), and O(2)(•-). The Mo(VI) reducing power of the samples was also determined. The phenol and flavonoid contents were quantified. Phytochemical analysis of kiwi peel crude extracts led to the isolation of vitamin E, 2,8-dimethyl-2-(4,8,12-trimethyltridec-11-enyl)chroman-6-ol, as well as α- and δ-tocopherol, 7 sterols, the triterpene ursolic acid, chlorogenic acid, and 11 flavonoids. Chemical fractionation of pulp crude extracts led to the isolation of two caffeic acid glucosyl derivatives and two coumarin glucosydes, besides the three vitamin E, β-sitosterol, stigmasterol, and its Δ(7) isomer, campesterol, chlorogenic acid, and some flavone and flavanol molecules. All of the compounds were tested for their radical scavenging and antioxidant capabilities by measuring their capacity to scavenge DPPH and anion superoxide radical and to reduce a Mo(VI) salt. Biochemical mechanism of platelet activation Oct 1989 Michael H. Kroll <here is a image 912e01159607050c-b602909f388af635> Andrew Schafer Insulin mediated processes in platelets, erythrocytes and monocytes/macrophages: Effects of essential fatty acid metabolism Jan 1995 PROSTAG LEUKOTR ESS <here is a image 8df9702cb64ec4a8-cc0fcea1a4afd9b2> Asim K Duttaroy A Prospective Study of Consumption of Carotenoids in Fruits and Vegetables and Decreased Cardiovascular Mortality in the Elderly Recent evidence suggests that oxidative damage may be involved in atherogenesis, and thus dietary antioxidants, such as beta-carotene, may reduce the risks of cardiovascular disease (CVD). We examined the association between consumption of carotene-containing fruits and vegetables and CVD mortality among 1299 elderly Massachusetts residents who provided dietary information as a part of the Massachusetts Health Care Panel Study. During a mean follow-up of 4.75 years, there were 161 deaths attributable to CVD, 48 of which were due to myocardial infarction. For total CVD death and fatal myocardial infarction, risks were lower among those residents in the highest quartile for consumption of carotene-containing fruits and vegetables as compared with those in the lowest. For death due to CVD, the relative risk (RR) was 0.54 (95% confidence interval (CI), 0.34 to 0.86; P for trend across quartiles, 0.004). For myocardial infarction the RR was 0.25 (95% CI, 0.09 to 0.67; P for trend, 0.002). These observational data are compatible with the hypothesis that increased dietary intake of carotenoids decreases the risks of CVD mortality; however, confounding cannot be ruled out. This hypothesis requires rigorous evaluation in randomized trials of sufficient size to detect reliably whether carotenoids confer small-to-moderate but clinically important protection against CVD. Effects on blood lipids of a blood pressure-lowering diet: The Dietary Approaches to Stop Hypertension (DASH) Trial Effects of diet on blood lipids are best known in white men, and effects of type of carbohydrate on triacylglycerol concentrations are not well defined. Our goal was to determine the effects of diet on plasma lipids, focusing on subgroups by sex, race, and baseline lipid concentrations. This was a randomized controlled outpatient feeding trial conducted in 4 field centers. The subjects were 436 participants of the Dietary Approaches to Stop Hypertension (DASH) Trial [mean age: 44.6 y; 60% African American; baseline total cholesterol: < or = 6.7 mmol/L (< or = 260 mg/dL)]. The intervention consisted of 8 wk of a control diet, a diet increased in fruit and vegetables, or a diet increased in fruit, vegetables, and low-fat dairy products and reduced in saturated fat, total fat, and cholesterol (DASH diet), during which time subjects remained weight stable. The main outcome measures were fasting total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol. Relative to the control diet, the DASH diet resulted in lower total (-0.35 mmol/L, or -13.7 mg/dL), LDL- (-0.28 mmol/L, or -10.7 mg/dL), and HDL- (-0.09 mmol/L, or -3.7 mg/dL) cholesterol concentrations (all P < 0.0001), without significant effects on triacylglycerol. The net reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L, or 10.3 mg/dL (P = 0.052), and by 0.29 mmol/L, or 11.2 mg/dL (P < 0.02), respectively. Changes in lipids did not differ significantly by race or baseline lipid concentrations, except for HDL, which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations. The fruit and vegetable diet produced few significant lipid changes. The DASH diet is likely to reduce coronary heart disease risk. The possible opposing effect on coronary heart disease risk of HDL reduction needs further study. Color in Fruit of the Genus Actinidia : Carotenoid and Chlorophyll Compositions <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Tony Mcghie The carotenoid and chlorophyll contents in the fruit of four species of Actinidia were measured to determine the chemical basis of color in kiwifruit and related Actinidia species. The species studied were the two commercial fruits Actinidia deliciosa cv. Hayward and a yellow-fleshed genotype Actinidia chinensis cv. Hort16A (known commercially as ZESPRI Gold kiwifruit), the yellow fruit of Actinida polygama, and the orange fruit of Actinida macrosperma. As reported previously, ripe fruit of A. deliciosa contain chlorophylls a and b and the carotenoids normally associated with photosynthesis, beta-carotene, lutein, violaxanthin, and 9'-cis-neoxanthin. The carotenoids in A. chinensis were similar to those in A. deliciosa but also contained esterified xanthophylls. Only trace amounts of chlorophyll were present in A. chinensis. The major carotenoid in both A. macrosperma and A. polygama was beta-carotene, with no chlorophyll detected. The yellow color of A. chinensis was mostly due to the reduction of chlorophyll rather than an increase in carotenoid concentration. In contrast to the three yellow/orange species, the green fruit of A. deliciosa retains chlorophyll during maturation and ripening, and esterified xanthophylls are not produced. This suggests that in fruit of A. deliciosa chloroplasts are not converted to chromoplasts as is typical for ripening fruit. Platelet activation in type 2 diabetes mellitus <here is a image 9febedfe3af40e61-5c55f09ecb927fcf> Stefania Basili <here is a image f643bcd713424f7e-fc54f476cf149059> Angela Falco <here is a image 8be8d68016e5e6bf-983666ee3a1737e7> Patrizia Ferroni G Davì The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, pro-thrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population. Cardiovascular Protective Properties of Kiwifruit Extracts in Vitro It is currently accepted that the consumption of fruit-derived antioxidants such as vitamin C, carotenoids, and flavonoids provides a preventive effect against cardiovascular disease. The purpose of the present study was to investigate potential cardiovascular protective properties of aqueous and 70% ethanol extracts from kiwifruit by analyzing the antioxidative, antihypertensive, hypocholesterolemic, and fibrinolytic activities in vitro. Aqueous and 70% ethanol extracts at 50 mg/ml showed DPPH-radical scavenging activities of 72.31% and 70.75%, respectively. Total antioxidant activity in linoleic acid emulsion was 85-88% at 10 mg/ml and 96-98% at 50 mg/ml of kiwifruit extract. Inhibitory activities against angiogensin I-converting enzyme of kiwifruit extracts were 21-26% at 10 mg/ml and 46-49% at 50 mg/ml, and inhibitory activities on HMG-CoA reductase were 13-14% at 10 mg/ml and 19-30% at 50 mg/ml. Fibrinolytic activity of kiwifruit was also observed at a high concentration of 100 mg/ml in both aqueous and 70% EtOH extracts. Based on our results, kiwifruit have potential cardiovascular protective properties in vitro. Aspirin Resistance LANCET <here is a image 1a286792e19069b6-2adfad96715465d3> Graeme J Hankey <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> John Eikelboom Aspirin resistance is the inability of aspirin to reduce platelet production of thromboxane A2 and thereby platelet activation and aggregation. Increasing degrees of aspirin resistance may correlate independently with increasing risk of cardiovascular events. Aspirin resistance can be detected by laboratory tests of platelet thromboxane A2 production or platelet function that depend on platelet thromboxane production. Potential causes of aspirin resistance include inadequate dose, drug interactions, genetic polymorphisms of COX-1 and other genes involved in thromboxane biosynthesis, upregulation of non-platelet sources of thromboxane biosynthesis, and increased platelet turnover. Aspirin resistance can be overcome by treating the cause or causes, and reduced by minimising thromboxane production and activity, and blocking other pathways of platelet activation. Future research is aimed at defining aspirin resistance, developing reliable tests for it, and establishing the risk of associated cardiovascular events. Potential mechanisms of aspirin resistance can then be explored and treatments assessed. Contribution of Platelet-Derived CD40 Ligand to Inflammation, Thrombosis and Neoangiogenesis CURR MED CHEM <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Francesca Santilli G Davì <here is a image 8be8d68016e5e6bf-983666ee3a1737e7> Patrizia Ferroni <here is a image a15733ddd83f200f-48ec3060353bbc5f> Fiorella Guadagni CD40-CD40L interactions have been involved in inflammation and thrombosis. Several diseases are characterized by inflammation, hypercoagulability and increased prevalence of thromboembolic events. In the past decade, a series of preclinical and clinical studies has provided more insight into the pathogenetic mechanisms linking inflammatory mediators to the activation and regulation of the haemostatic system. In particular, the study of CD40-CD40L interactions has greatly contributed to understanding the role of platelets in a variety of pathophysiological conditions, including atherothrombosis, immuno-inflammatory diseases and, possibly, cancer. A wide variety of preclinical and clinical studies have generated clinical interest in the use of CD40L as a prognostic marker of thrombotic risk. However, the use of sCD40L in clinical studies requires reliable methods. For the correct interpretation of results, clinical and research laboratories and physicians must be aware of the limitations of immunoassays for this cytokine, which underlines the need for standardization of preanalytic conditions. This review will focus on biochemical evidence of CD40L involvement in platelet activation, contribution of platelet-derived CD40L to inflammation, thrombosis and neoangiogenesis, and possible methodological pitfalls regarding the appropriate specimen and preparation for laboratory evaluation of blood soluble CD40L as a biomarker in various human diseases characterized by underlying inflammation, such as atherothrombosis, cancer and immuno-inflammatory diseases. In vivo platelet activation is responsible for enhanced vascular endothelial growth factor levels in hypertensive patients Essential hypertension may be a consequence of an abnormal regulation of vascular endothelial growth factor (VEGF). In vivo activation of platelets does result in the release of VEGF. Thus, we investigated whether VEGF production in hypertensive patients is related to in vivo platelet activation, and whether it may be modified by aspirin treatment. Plasma VEGF, soluble (s)P-selectin and thrombin-anti-thrombin complex (TATc) were analyzed in 80 patients with therapeutically controlled essential hypertension and 40 age and sex-matched healthy normotensive controls. The effects of a 6-month treatment with aspirin 100 mg/day on VEGF levels of 20 hypertensive patients were also studied. Plasma VEGF (p<0.0001), sP-selectin (p=0.01) and TATc (p=0.02) levels were higher in hypertensives compared to controls. Multivariate analysis including age, sex, risk factors, cardiovascular disease, anti-hypertensive treatment, sP-selectin and TATc showed that only sP-selectin was an independent predictor of VEGF (beta=0.40, p<0.03). Aspirin treated hypertensives showed a significant reduction of sP-selectin (-26%, p<0.01) and VEGF (-33%, p<0.01) levels. Moreover, the reduction of plasma VEGF levels directly correlated with that of sP-selectin (Rho=0.46, p=0.04). In vivo activation of platelets in hypertensive patients is responsible for enhanced circulating VEGF levels, which are significantly lowered by aspirin treatment. Platelet Activation and Atherothrombosis This review of the role of platelets in atherothrombosis illuminates the surprisingly numerous activities of these tiny, anucleate cells and stresses their participation in the inflammatory component of atherothrombosis. The information is presented in the context of the prevention of atherothrombosis by antiplatelet agents now in clinical use. Kiwifruit: the wild and the cultivated plants
https://www.researchgate.net/publication/324445677_Kiwifruit_and_Human_Platelet_Function
Chapter 80: Referenced Standards, Tennessee Fire Code 2012 | UpCodes UpCodes offers a consolidated resource of construction and building code grouped by jurisdiction Chapter 80 Referenced Standards This chapter lists the standards that are referenced in various sections of this document. The standards are listed herein by the promulgating agency of the standard, the standard identification, the effective date and title, and the section or sections of this document that reference the standard. The application of the referenced standards shall be as specified in Section 102.7 . Title Referenced in code section number Spec 12P—(1995) (Reaffirmed 2000) Specification for Fiberglass Reinforced Plastic Tanks 5704.2.13.1.5 RP 651—(1997) Cathodic Protection of Aboveground Petroleum Storage Tanks 5706.7 , 5706.7.1 Std 653—(2001) Tank Inspection, Repair, Alteration and Reconstruction 5706.7 RP 752—(2003) Management of Hazards Associated with Location of Process Plant Buildings, CMA Managers Guide 5706.7 RP 1604—(1996) Closure of Underground Petroleum Storage Tanks 5704.2.13 RP 1615—(1996) Installation of Underground-petroleum Storage Systems 5704.2.13.1.5 , 5706.7 Std 2000—(1998) Venting Atmosphere and Low-pressure Storage Tanks : Nonrefrigerated and Refrigerated 5704.2.7.3.2 , 5704.2.7.3.6 RP 2001—(2005) Fire Protection in Refineries , 8th Edition 5706.7 RP 2003—(1998) Protection Against Ignitions Arising out of Static, Lightning and Stray Currents 5706.7 Publ 2009—(2002) Safe Welding and Cutting Practices in Refineries , Gas Plants and Petrochemical Plants 5706.7 Std 2015—(2001) Safe Entry and Clearing of Petroleum Storage Tanks 5706.7 , 5706.7.2 RP 2023—(2001) Guide for Safe Storage and Handling of Heated Petroleum-derived Asphalt Products and Crude-oil Residue 5706.7 , 5706.7.3 Publ 2028—(2002) Flame Arrestors in Piping Systems 5704.2.7.3.2 Publ 2201—(2003) Procedures for Welding or Hot Tapping on Equipment in Service 5706.7 RP 2350—(2005) Overfill Protection for Storage Tanks in Petroleum Facilities , 3rd Edition 5704.2.7.5.8 , 5706.4.6 , 5706.7 ASME The American Society of Mechanical Engineers Three Park Avenue New York, NY 10016-5990 Standard reference number Title Referenced in code section number A13.1—2007 Scheme for the Identification of Piping Systems 3509.3 , 5003.2.2.1 , 5303.4.3 , 5503.4.5 , 5703.5.2 A17.1—2007/CSA B44—2007 Safety Code for Elevators and Escalators — with A17.1a/CSA B44a—08 Addenda 508.1.5 , 607.1 , 907.3.3 , 1007.4 , 1007.9 A17.3—2008 Safety Code for Existing Elevators and Escalators 1103.3 A18.1—2008 Safety Standard for Platform Lifts and Stairway Chair Lifts 604.2.6 B16.18—2001 (Reaffirmed 2005) Cast Copper-Alloy Solder Joint Pressure Fittings 909.13.1 B16.22—2001 (Reaffirmed 2005) Wrought Copper and Copper-Alloy Solder-joint Pressure Fittings 909.13.1 B31.1—2007 Power Piping with B31.1a—2008 Addenda 5003.2.2 , Table 5703.6.2 B31.3—2004 Process Piping 5003.2.2.2 , Table 5703.6.2 B31.4—2006 Pipeline Transportation Systems for Liquid Hydrocarbons and Other Liquids Table 5703.6.2 B31.9—2008 Building Services Piping Table 5703.6.2, 5703.6.3 , 5703.6.11 BPVC—2007 ASME Boiler and Pressure Vessel Code (Sections I, II, IV, V & VI, VIII) 5003.2.1 , 5303.2 , 5303.3.2 , 5503.4.3 , 5503.7 , 5704.2.13.1.5 , 5806.3.1 , 5806.4.1 , 5806.4.8 ASTM ASTM International 100 Barr Harbor Drive West Conshohocken, PA 19428-2959 Standard reference number Title Referenced in code section number B 42—02e01 Specification for Seamless Copper Pipe, Standard Sizes 909.13.1 B 43—98(2004) Specification for Seamless Red Brass Pipe, Standard Sizes 909.13.1 B 68—02 Specification for Seamless Copper Tube, Bright Annealed 909.13.1 B 88—03 Specification for Seamless Copper Water Tube 909.13.1 B 251—02e01 Specification for General Requirements for Wrought Seamless Copper and Copper-alloy Tube 909.13.1 B 280—08 Specification for Seamless Copper Tube for Air Conditioning and Refrigeration Field Service 909.13.1 D 56—05 Test Method for Flash Point by Tag Closed Tester 202 D 86—09 Test Method for Distillation of Petroleum Products at Atmospheric Pressure 202 D 92—05a Test Method for Flash and Fire Points by Cleveland Open Cup 202, 2401.2 , 5701.2 D 93—08 Test Method for Flash Point by Pensky-Martens Closed Up Tester 202 D 323—08 Test Method for Vapor Pressure of Petroleum Products (Reid Method) 202 D 2859—06 Standard Test Method for Ignition Characteristics of Finished Textile Floor Covering Materials 804.3.3.1 , 804.3.3.2 D 3278—96(2004)e1 Test Methods for Flash Point of Liquids by Small Scale Closed-cup Apparatus 202 E 84—09 Test Method for Surface Burning Characteristics of Building Materials 202, 803.1 , 803.1.1 , 803.1.2 , 803.5.1 , 803.5.2 , 803.6 , 803.9 , 804.1 , 804.1.1 , 804.2.4 E 108—07a Test Methods for Fire Tests of Roof Coverings 317.3 E 681—04 Test Method for Concentration Limits of Flammability of Chemicals (Vapors and Gases) 202 E 1354—09 Standard Test Method for Heat and Visible Smoke Release Rates for Materials and Products Using an Oxygen Consumption Calorimeter 304.3.2 , 304.3.4 , 318.1 , 808.1 , 808.2 E 1529—06 Test Method for Determining Effects of Large Hydrocarbon Pool Fires on Structural Members and Assemblies 5704.2.9.2.3 E 1537—07 Test Method for Fire Testing of Upholstered Furniture 805.1.1.2 , 805.2.1.2 , 805.3.1.2 , 805.4.1.2 E 1590—07 Test Method for Fire Testing of Mattresses 805.1.2.2 , 805.2.2.2 , 805.3.2.2 , 805.4.2.2 E 1966—07 Test Method for Fire-resistant Joint Systems 202 E 2072—04 Standard Specification for Pholuminescent (Phosphorescent) Safety Markings 1024.4 E 2404—08 Standard Practice for Specimen Preparation and Mounting of Textile, Paper or Vinyl Wall or Ceiling Coverings to Assess Surface Burning Characteristics 803.5.2 , 803.6 E 2573—07a Standard Practice for Specimen Preparation and Mounting of Site-fabricated Stretch Systems to Assess Surface Burning Characteristics 803.9 F 2006—10 Standard/Safety Specification for Window Fall Prevention Devices for Non-Emergency Escape (Egress) and Rescue (Ingress) Windows 1013.8 F 2090—10 Specification for Window Fall Prevention Devices with Emergency Escape (Egress) Release Mechanisms 1013.8 , 1013.8.1 F 2200—05 Standard Specification for Automated Vehicular Gate Construction 503.5 , 503.6 , D103.5 BHMA Builders Hardware Manufacturers' Association 355 Lexington Avenue, 17th Floor New York, NY 10017-6603 Standard reference number Title Referenced in code section number A156.10—2011 American National Standard for Power-operated Pedestrian Doors 1008.1.4.2 A156.19—2007 American National Standard for Power Assist and Low-energy Power-operated Doors 1008.1.4.2 CA State of California Department of Consumer Affairs Bureau of Home Furnishings and Thermal Insulation 3485 Orange Grove Avenue North Highlands, CA 95660-5595 Standard reference number Title Referenced in code section number California Technical Bulletin 129—1992 Flammability Test Procedure for Mattresses for Use in Public Buildings 805.1.1.2 , 805.2.2.2 , 805.3.2.2 , 805.4.2.2 California Technical Bulletin 133—1991 Flammability Test Procedure for Seating Furniture for Use in Public Occupancies 805.1.1.2 , 805.2.1.2 , 805.4.1.2 CGA Compressed Gas Association 4221 Walney Road, 16th Floor Arlington, VA 20151-2923 Standard reference number Title Referenced in code section number C-7—(2004) Guide to the Preparation of Precautionary Labeling and Marking of Compressed Gas Containers 5303.4.2 , 5503.4.2 G-13—(2006) Storage and Handling of Silane and Silane Mixtures (an American National Standard) 6404.1 , 6404.2 , 6405.3 P-1—(2000) Safe Handling of Compressed Gases in Containers 5305.7 ANSI/P-18—(2006) Standard for Bulk Inert Gas Systems at Consumer Sites (an American National Standard) 5501.1 P-20—(2003) Standard for Classification of Toxic Mixtures E103.1.3.1 P-23—(2003) Standard for Categorizing Gas Mixtures Containing Flammable and Nonflammable Components E102.1.2 S-1 .1—(2005) Relief Device Standards—Part 1— Cylinders for Compressed Gases 5303.3.2 , 5503.2 S-1 .2—(2005) Pressure Relief Device Standards—Part 2—Cargo and Portable Tanks for Compressed Gases 5303.3.2 , 5503.2 S-1 .3—(2005) Pressure Relief Device Standards—Part 3—Stationary Storage Containers for Compressed Gases 5303.3.2 , 5503.2 V-1—(2005) Standard for Gas Cylinder Valve Outlet and Inlet Connections 3505.2.1 CGR Coast Guard Regulations c/o Superintendent of Documents U.S. Government Printing Office Washington, DC 20402-9325 Standard reference number Title Referenced in code section number 46 CFR Parts 30, 32, 35 & 39—1999 Shipping 5706.8 CPSC Consumer Product Safety Commission 4330 East West Highway Bethesda, MD 20814 Standard reference number Title Referenced in code section number 16 CFR Part 1500.41—2009 Method for Testing Primary Irritant Substances 202 16 CFR Part 1500.42—2009 Test for Eye Irritants 202 16 CFR Part 1500.44—2009 Method for Testing Extremely Flammable and Flammable Solids 202 16 CFR Part 1500—2009 Hazardous Substances and Articles; Administration and Enforcement Regulations 202, 5601.1.3 , 16 CFR Part 1507—2002 Fireworks Devices 5601.1.3 16 CFR Part 1630—2007 Standard for the Surface Flammability of Carpets and Rugs 804.3.3.1 , 804.3.3.2 DOC U.S. Department of Commerce 1401 Constitution Avenue, NW Washington, DC 20230 Standard reference number Title Referenced in code section number 16 CFR Part 1632—2009 Standard for the Flammability of Mattress and Mattress Pads (FF 4-72, Amended) 805.1.2.1 , 805.2.2.1 , 805.3.2.1 , 805.4.2.1 DOL U.S. Department of Labor c/o Superintendent of Documents U.S. Government Printing Office Washington, DC 20402-9325 Standard reference number Title Referenced in code section number 29 CFR Part 1910.1000—2009 Air Contaminants 202, 2104.2.1 29 CFR Part 1910.1200—2009 Hazard Communication 202, 5603.6 DOTn U.S. Department of Transportation Office of Hazardous Material Safety 1200 New Jersey Avenue, SE East Building, 2nd Floor Washington, DC 20590 Standard reference number Title Referenced in code section number 33 CFR Part 154—1998 Facilities Transferring Oil or Hazardous Material in Bulk 5706.8 33 CFR Part 155—1998 Oil or Hazardous Material Pollution Prevention Regulations for Vessels 5706.8 33 CFR Part 156 —1998 Oil and Hazardous Material Transfer Operations 5706.8 49 CFR Parts 100-185—2005 Hazardous Materials Regulations 202, 3505.4 , 5303.2 , 5503.4.3 , 5503.7 , 5601.1 , 5601.1.3 , 5601.3 , 5706.5.1.15 49 CFR Part 172—2009 Hazardous Materials Tables, Special Provisions, Hazardous Materials Communications, Emergency Response Information and Training Requirements 5604.6.5.2 49 CFR Part 173—2009 Shippers—General Requirements for Shipments and Packagings 5606.3 49 CFR Part 173.137—2009 Shippers—General Requirements for Shipments and Packagings: Class 8—Assignment of Packing Group 202 DOTy U.S. Department of Treasury c/o Superintendent of Documents U.S. Government Printing Office Washington, DC 20402-9325 Standard reference number Title Referenced in code section number 27 CFR Part 55—1998 Commerce in Explosives , as amended through April 1, 1998 202, 5604.6.5.2 EN European Committee for Standardization (EN) Central Secretariat Rue de Stassart 36 B-10 50 Brussels Standard reference number Title Referenced in code section number European Standard EN 1081 1998 Resilient Floor Coverings—Determination of the Electrical Resistance 2309.5.1.1 EPA Environmental Protection Agency Ariel Rios Building 1200 Pennsylvania Avenue, NW Washington, DC 20460 Standard reference number Title Referenced in code section number 40 CFR Part 355—2008 Emergency Planning and Notification H101.4 FCC Federal Communications Commission Wireless Telecommunications Bureau (WTB) 445 12th Street, SW Washington, DC 20554 Standard reference number Title Referenced in code section number 47 CFR Part 90.219—2007 Private Land Mobile Radio Services— Use of Signal Boosters 510.5.4 ICC International Code Council, Inc. 500 New Jersey Avenue, NW, 6th Floor Washington, DC 20001 Standard reference number Title Referenced in code section number ICC A117.1—09 Accessible and Usable Buildings and Facilities 907.5.2.3.4 , 1007.9 , 1010.1 , 1010.7.5 , 1010.10 , 1011.4 , 1022.9 ICC 300—12 Standard on Bleachers , Folding and Telescopic Seating and Grandstands 1028.1.1 , 1028.14.2 IBC—12 International Building Code ® 102.3 , 102.4 , 102.5 , 201.3 ,202, 304.1.3 , 306.1 , 311.1.1 , 311.3 , 313.1 , 317.1 , 408.7.2 , 504.1 , 508.1 , 508.1.2 , 603.2 , 603.5.2 , 603.6.1 , 603.8 , 604.1 , 604.2.9 , 604.2.14.1 , 604.2.14.1.3 , 604.2.15 , 604.2.15.1.1 , 604.2.16 , 605.11 , 607.3 , 608.4 , 608.8 , 701.1 , 704.1 , 801.1 , 803.1 , Table803.3, 803.7.1 , 803.7.2 , 807.1.2 , 807.4.2.2 , 808.1 , 808.2 , 901.4.1 , 901.4.2 , 901.4.3 , 903.2 , 903.2.3.2, 903.2.9.1 , 903.3.1.1.1 , 903.3.2 , 903.3.5.2 , 907.1.1 , 907.2.1 , 907.2.6.2 , 907.2.6.3.3 , 907.2.7 , 907.2.13 , 907.2.18 , 907.2.21 , 907.5.2.1 , 907.5.2.2.4 , 907.6.5 , 908.7 , 909.1 , 909.2 , 909.3 , 909.4.3 , 909.5 , 909.5.2 , 909.5.2.1 , 909.10.5 , 909.11 , 911.2 , 914.1 , 914.2.1 , 914.3.1 , 914.4.1 , 914.5.3 , Table914.8.2, 914.8.2.2 , 914.10 , 1003.2 , 1003.5 , 1004.4 , 1007.2 , 1007.4 , 1007.5 , 1007.6.2 , 1007.7.4 , 1007.8 , 1007.9 , 1008.1.4.1 , 1008.1.4.3 , 1008.1.7 , 1008.1.9.1 , 1008.1.9.11 , 1008.1.10.1 , 1009.3 , 1009.3.1 , 1009.3.1.3 , 1009.3.1.4 , 1009.3.1.5 , 1009.3.1.6 , 1009.3.1.7 , 1009.3.1.8 , 1009.7.2 , 1009.12 , 1009.15 , 1009.16.1 , 1010.1 , 1010.7.4 , 1011.5 , 1012.1 , 1013.2 , 1013.2.1 , 1015.1 , Table1016.2, 1017.3 , 1018.1 , Table1018.1, 1019.4 , 1021.2 , 1021.2.5 , 1022.2 , 1022.3.1 , 1022.4 , 1022.5 , 1022.6 , 1022.7 , 1022.10 , 1022.10.1 , 1022.10.2 , 1023.3 , 1023.5 , 1023.6 , 1025.2 , 1025.3 , 1026.5 , 1028.1.1.1 , 1101.2 , 1101.3 , 1104.5 , 1104.17 , 1104.17.1 , Table 1104.17.2, 2004.6 , 2006.17 , 2007.1 , 2007.4 , 2103.3 , 2107.1 , 2301.1 , 2301.4 , 2303.1 , 2307.4 , 2308.3 , 2308.3.1 , Table2309.3.1, 2309.3.2.3, 2309.3.2.6.1, 2309.3.3, 2310.1 , 2311.1 , 2311.3.1 , 2311.4.1 , 2311.8.1.2.3 , 2301.3 , Table2306.2, 2306.3.1, 2306.3.2.1, 2306.3.2.2, 2306.8 , 2307.2 , 2308.2 , 2404.2 , 2404.3.1 , 2404.3.2.6 , 2404.3.3 , 2405.2 , 2701.1 , 2701.4 , 2703.2.2 , 2703.3.1 , 2703.3.2 , 2703.3.3 , 2703.3.4 , 2703.3.8 , 2703.14 , 2703.14.1 , 2703.14.2 , 2703.15.1 , 2704.3.1 , 2705.2.3.2 , 2705.3.1 , 2705.3.2.1 , 2705.3.3 , 2803.1 , 2905.1 , 2909.2 , 2909.4 , 2909.6 , 3103.8.2 , 3103.8.4 , 3104.1 , 3314.1 , 3403.1 , 5003.2.2.2 , 5003.2.8 , 5003.8.1 , Table5003.8.2, 5003.8.3.1 , 5003.8.4.1 , 5003.9.9 , 5004.13 , 5005.2 , 5005.3.9 , 5101.1 , 5204.3 , 5204.4 , 5204.5 , 5303.16.1 , 5303.16.2 , 5306.2 , 5503.1.2 , 5503.5.2 , 5504.2.1.2 , 5504.2.2.2 , 5505.4.1 , 5604.2 , Table5604.5.2(3), 5605.5 , 5701.3 , 5704.2.7.7 , 5704.2.8.1 , 5704.2.8.2 , 5704.2.9.3 , 5704.2.9.4 , 5704.3.3.5 , 5704.3.7.1 , 5704.3.8 , 5705.3.4 , 5705.3.5.3 , 5705.3.7.1 , 5705.3.7.2 , 5705.3.7.3 , 5705.3.7.4 , 5705.3.7.5.1 , 5706.2.3 , 5706.4.1 , 5906.2.2 , 5906.2.3 , 5906.4.2 , 5806.4.3 , 6003.1.4.2 , 6005.3.1 , 6109.11.2 , 6204.1.2 , 6304.1.2 , 6306.4 , 6404.1.4 , 6604.1 ,B104.2 , Table B105.1, H102.1 IFGC—12 International Fuel Gas Code ® 201.3 , 603.1 , 603.1.2 , 603.3.2.4 , 603.5.2 , 603.8 , 2301.1 , 2301.6 , 2309.3.2.3, 2309.3.2.6, 2404.15.1, 2404.15.2, 2404.16.1, 2504.5 , 3001.1 , 3003.1 , 3004.1 , 3004.2 , 3303.1 , 3303.3 , Table5003.1.1(1), 5801.1 , 5803.1.4 , 6103.1 , 6103.2.1.7 , 6103.3 IMC—12 International Mechanical Code ® 201.3 ,202, 308.3 , 603.1 , 603.1.2 , 603.2 , 603.3 , 603.5.2 , 603.8 , 606.1 , 606.2 , 606.3 , 606.4 , 606.7 , 606.8 , 606.9 606.16 , 608.6.1 , 609.1 , 903.2.11.4 , 904.11 , 907.3.1 , 908.7 , 909.1 , 909.10.2 , 909.13.1 , 1015.5 , 1018.5.1 , 2104.2.1 , 2105.3 , 2301.1 , 2301.6 , 2309.3.2.3, 2311.3.1 , 2311.4.3 , 2311.7.1 , 2404.7 , 2404.7.2 , 2504.5 , 2703.2.2 , 2703.10.4 , 2703.14 , 2803.2 , 2803.3 , 3001.1 , 3003.1 , 3004.2 , 3104.15.1 , 3104.15.2 , 3303.1 , Table5003.1.1(1), 5003.8.4.2 , 5003.8.5.2 , 5003.8.6.2 , 5004.3.1 , 5203.5 , 5303.7.6 , 5303.16.9 , 5305.5 , 5306.2.2 , 5504.2.1.3 , 5504.2.2.3 , 5505.4.1.1 , 5701.3 , 5703.6.1 , 5704.2.8.9 , 5705.3.7.5.1 , 5706.2 , 5706.4.4 , 6003.1.3 , 6003.2.3.2 , 6004.2.2.7 , 6005.3.1 , 6005.3.2 , 6103.2.1.7 IPC—12 International Plumbing Code ® 201.3 , 903.3.5 , 912.5 , 2311.2.3 , 5004.2.2.6 IPMC—12 International Property Maintenance Code ® 311.1.1 IRC—12 International Residential Code ® 102.5 ,202, 1001.1 IWUIC—12 International Wildland-Urban Interface Code ® 304.1.2 ,B103.3 ISO International Organization for Standardization (ISO) ISO Central Secretariat 1 ch, de la Voie-Creuse, Case postale 56 CH-1211 Geneva 20, Switzerland Standard reference number Title Referenced in code section number ISO 8115—86 Cotton Bales—Dimensions and Density Table 2704.2.2.1, Table 5003.1.1(1) NEMA National Electrical Manufacturer's Association 1300 N. 17th Street, Suite 1752 Rosslyn, VA 22209 Standard reference number Title Referenced in code section number 250—2003 Enclosures for Electrical Equipment (1,000 Volt Maximum) 6005.2 NFPA National Fire Protection Association 1 Batterymarch Park Quincy, MA 02169-7471 Standard reference number Title Referenced in code section number 10—10 Portable Fire Extinguishers Table 901.6.1, 906.2 , 906.3 , Table 906.3(1), Table 906.3(2), 906.3.2 , 906.3.4 , 3006.3 , I101.1 11—10 Low-, Medium- and High-expansion Foam 904.7 , 5704.2.9.2.2 12—11 Carbon Dioxide Extinguishing Systems Table 901.6.1, 904.8 , 904.11 12A—09 Halon 1301 Fire Extinguishing Systems Table 901.6.1, 904.9 13—10 Installation of Sprinkler Systems 903.3.1.1 , 903.3.2 , 903.3.5.1.1 , 903.3.5.2 , 904.11 , 905.3.4 , 907.6.3 , 1009.3 , 3201.1 , 3204.2 , Table 3206.2, 3206.9 , 3207.2 , 3207.2.1 , 3208.2.2 , 3208.2.2.1 , 3208.4 , 3210.1 , 3401.1 , 5104.1 , 5106.5.7 , 5704.3.3.9 , Table 5704.3.6.3(7), 5704.3.7.5.1 , 5704.3.8.4 13D—10 Installation of Sprinkler Systems in One- and Two-family Dwellings and Manufactured Homes 903.3.1.3 , 903.3.5.1.1 13R—10 Installation of Sprinkler Systems in Residential Occupancies up to and Including Four Stories in Height 903.3.1.2 , 903.3.5.1.1 , 903.3.5.1.2 , 903.4 14—10 Installation of Standpipe and Hose Systems 905.2 , 905.3.4 , 905.4.2 , 905.6.2 , 905.8 15—12 Water Spray Fixed Systems for Fire Protection 5704.2.9.2.3 16—11 Installation of Foam-water Sprinkler and Foam-water Spray Systems 904.7 , 904.11 17—09 Dry Chemical Extinguishing Systems Table 901.6.1, 904.6 , 904.11 17A—09 Wet Chemical Extinguishing Systems Table 901.6.1, 904.5 , 904.11 20—10 Installation of Stationary Pumps for Fire Protection 913.1 , 913.2 , 913.5.1 22—08 Water Tanks for Private Fire Protection 507.2.2 24—10 Installation of Private Fire Service Mains and Their Appurtenances 507.2.1 , 2809.5 25—11 Inspection, Testing and Maintenance of Water-based Fire Protection Systems 507.5.3 , Table 901.6.1, 904.7.1 , 912.6 , 913.5 , I101.1 30—12 Flammable and Combustible Liquids Code 5703.6.2 , 5703.6.2.1 , 5704.2.7 , 5704.2.7.1 , 5704.2.7.2 , 5704.2.7.3.2 , 5704.2.7.3.6 , 5704.2.7.4 , 5704.2.7.6 , 5704.2.7.7 , 5704.2.7.8 , 5704.2.7.9 , 5704.2.9.3 , 5704.2.9.4 , 5704.2.9.6.1.1 , 5704.2.9.6.1.2 , 5704.2.9.6.1.3 , 5704.2.9.6.1.4 , 5704.2.9.6.1.5 , 5704.2.9.6.2 , 5704.2.9.7.4 , 5704.2.10.2 , 5704.2.11.4 , 5704.2.11.5.2 , 5704.2.12.1 , 5704.3.1 , 5704.3.6 , Table 5704.3.6.3(1), Table 5704.3.6.3(2), Table 5704.3.6.3(3), 5704.3.7.2.3 , 5704.3.8.4 , 5706.8.3 30A—12 Code for Motor Fuel- dispensing Facilities and Repair Garages 2301.4 , 2301.5 , 2301.6 , 2306.6.3 , 2310.1 30B—11 Manufacture and Storage of Aerosol Products 5101.1 , 5103.1 , 5104.1 , Table 5104.3.1, Table 5104.3.2, Table 5104.3.2.2, 5104.4.1 , 5104.5.2 , 5104.6 , 5106.2.3 , 5106.3.2 , Table 5106.4, 5106.5.1 , 5106.5.6 , 5107.1 31—11 Installation of Oil-burning Equipment 603.1.7 , 603.3.1 , 603.3.3 32—11 Dry Cleaning Plants 2107.1 , 2107.3 33—11 Spray Application Using Flammable or Combustible Materials 2404.3.2 34—11 Dipping and Coating Processes Using Flammable or Combustible Liquids 2405.3 , 2405.4.1.1 35—11 Manufacture of Organic Coatings 2901.3 , 2905.4 40—11 Storage and Handling of Cellulose Nitrate Film 306.2 51—07 Design and Installation of Oxygen-fuel Gas Systems for Welding, Cutting and Allied Processes 3501.5 , 3507.1 , 3509.1 51A—12 Acetylene Cylinder Charging Plants 3508.1 52—10 Vehicular Fuel System Code 5301.1 55—10 Standard for the Storage, Use and Handling of Compressed Gases and Cryogenic Fluids in Portable and Stationery Containers Cylinders and Tanks 2309.2.1 , 5501.1 , 5801.1 , 6301.1 58—11 Liquefied Petroleum Gas Code 603.4.2.1.1 , 6101.1 , 6103.1 , 6103.2.1 , 6103.2.1.2 , 6103.2.1.7 , 6103.2.2 , 6104.1 , 6104.3.2 , 6104.4 , 6106.2 , 6106.3 , 6107.2 , 6108.1 , 6108.2 , 6109.11.2 , 6111.3 59A—09 Production, Storage and Handling of Liquefied Natural Gas ( LNG ) 5301.1 , 5501.1 61—08 Prevention of Fires and Dust Explosions in Agricultural and Food Processing Facilities Table 2204.1 69—08 Explosion Prevention Systems 911.1 , 911.3 , Table 2204.1 70—11 National Electrical Code 603.1.3 , 603.1.7 , 603.5.2 , 604.2.15.1 , 605.3 , 605.4 , 605.9 , 605.11 , 606.16 , 610.5 , 904.3.1 , 907.6.1 , 909.11 , 909.12.1 , 909.16.3 , 1208.2, 2006.3.4 , 2104.2.3 , Table 2204.1, 2305.4 , 2308.8.1.2.4 , 2309.2.3 , 2311.3.1 , 2311.8.1.2.4 , 2403.2.1 , 2403.2.1.1 , 2403.2.1.4 , 2403.2.5 , 2403.12.6.1, 2404.9.4 , 2404.15.7, 2504.5 , 2603.2.1 , 2606.4, 2703.7.1 , 2703.7.2 , 2703.7.3 , 2803.4 , 2904.1 , 3304.7 , 5003.7.3 , 5303.7.6 , 5303.8 , 5303.16.11 , 5303.16.14 , 5503.6 , 5503.6.2 , 5703.1 , Table 5703.1.1, 5703.1.3 , 5704.2.8.12 , 5704.2.8.17 , 5706.2.8 , 5803.1.5 , 5803.1.5.1 , 5807.1.10 , 5906.5.5 , 5906.5.6 , 6004.2.2.8 , 6109.15.1 72—10 National Fire Alarm Code 508.1.5 , Table 901.6.1, 903.4.1 , 904.3.5 , 907.2 , 907.2.6 , 907.2.9.3 , 907.2.11 , 907.2.13.2 , 907.3 , 907.3.3 , 907.3.4 , 907.5.2.1.2 , 907.5.2.2 , 907.6 , 907.6.1 , 907.6.2 , 907.6.5 , 907.7 , 907.7.1 , 907.7.2 , 907.8 , 907.8.2 , 907.8.5 , I101.1 80—10 Fire Doors and Other Opening Protectives 703.1.3 , 703.2 , 1008.1.4.3 85—11 Boiler and Combustion System Hazards Code Table 2204.1 86—11 Ovens and Furnaces 3001.1 92B—09 Smoke Management Systems in Malls , Atria and Large Spaces 909.8 99—12 Health Care Facilities 5306.4 101—12 Life Safety Code 1028.6.2 105—10 Installation of Smoke Door Assemblies and Other Opening Protectives 703.1.2 110—10 Emergency and Standby Power Systems 604.1 , 604.3 , 604.4 , 913.5.2 , 913.5.3 111—10 Stored Electrical Energy Emergency and Standby Power Systems 604.1 , 604.3 , 604.4 120—10 Coal Preparation Plants Table 2204.1 160—11 Flame Effects Before an Audience 308.3.2 170—09 Standard for Fire Safety and Emergency Symbols 1024.2.6.1 204—07 Standard for Smoke and Heat Venting Table 901.6.1, 910.5 211—10 Chimneys , Fireplaces, Vents and Solid Fuel-burning Appliances 603.2 241—09 Safeguarding Construction, Alteration and Demolition Operations 3301.1 253—11 Standard Test for Critical Radiant Flux of Floor Covering Systems Using a Radiant Heat Energy Source 804.3.1 , 804.3.2 , 804.4 260—09 Methods of Tests and Classification System for Cigarette Ignition Resistance of Components of Upholstered Furniture 805.1.1.1 , 805.2.1.1 , 805.3.1.1 , 805.4.1.1 261—09 Method of Test for Determining Resistance of Mock-up Upholstered Furniture Material Assemblies to Ignition by Smoldering Cigarettes 805.2.1.1 , 805.3.1.1 , 805.4.1.1 265—11 Method of Fire Tests for Evaluating Room Fire Growth Contribution of Textile Wall Coverings in Full Height Panels and Walls 803.5.1 , 803.5.1.1 , 803.5.1.2 , 803.5.2 , 803.6 286—11 Standard Method of Fire Tests for Evaluating Contribution of Wall and Ceiling Interior Finish to Room Fire Growth 803.1 , 803.1.2 , 803.1.2.1 , 803.5.1 , 803.5.2 , 803.6 289—09 Standard Method of Fire Test for Individual Fuel Packages 806.2 , 807.4.2.1 , 808.3 303—11 Fire Protection Standard for Marinas and Boatyards 905.3.7 , 3603.5 , 3603.6 , 3604.2 318—09 Standard for the Protection of Semiconductor Fabrication Facilities 2703.16 385—07 Tank Vehicles for Flammable and Combustible Liquids 5706.5.4.5 , 5706.6 , 5706.6.1 407—12 Aircraft Fuel Servicing 2006.2 , 2006.3 409—11 Aircraft Hangars 914.8.2 , Table 914.8.2, 914.8.2.1 , 914.8.5 430—04 Storage of Liquid and Solid Oxidizers 6304.1.4 484—12 Combustible Metals Table 2204.1 490—02 Storage of Ammonium Nitrate 5601.1.5 495—10 Explosive Materials Code 202, 911.1 , 911.4 , 5601.1.1 , 5601.1.5 , 5604.2 , 5604.6.2 , 5604.6.3 , 5604.7.1 , 5605.1 , 5606.1 , 5606.5.2.1 , 5606.5.2.3 , 5607.1 , 5607.9 , 5607.11 , 3307.15 498—10 Safe Havens and Interchange Lots for Vehicles Transporting Explosives 5601.1.2 505—11 Powered Industrial Trucks , Including Type Designations, Areas of Use , Maintenance and Operation 5003.7.3 654—06 Prevention of Fire and Dust Explosions from the Manufacturing, Processing and Handling of Combustible Particulate Solids Table 2204.1 655—12 Prevention of Sulfur Fires and Explosions Table 2204.1 664—12 Prevention of Fires and Explosions in Wood Processing and Woodworking Facilities Table 2204.1, 2805.3 701—10 Methods of Fire Tests for Flame-propagation of Textiles and Films 806.2 , 807.1 , 807.1.2 , 807.2 , 807.4.2.2 , 2603.5 , 3104.2 703—12 Fire Retardant Impregnated Wood and Fire Retardant Coatings for Building Materials 803.4 704—12 Identification of the Hazards of Materials for Emergency Response 606.7 , 202, 3104.2 , 5003.2.2.1 , 5003.2.2.2 , 5003.5 , 5003.10.2 , 5005.1.10 , 5005.2.1.1 , 5005.4.4 , 5503.4.1 , 5704.2.3.2 , F101.1, F101.2 720—09 Standard for the Installation of Carbon Monoxide (CO) Warning Equipment in Dwelling Units 908.7 , 908.7.1 , 1103.9 750—10 Water Mist Fire Protection Systems Table 901.6.1 1122—08 Model Rocketry 5601.1.4 1123—10 Fireworks Display 202, 5604.2 , 5608.1 , 5608.2.2 , 5608.5 , 5608.6 1124—06 Manufacture, Transportation, Storage and Retail Sales of Fireworks and Pyrotechnic Articles 202, 5604.2 , 5605.1 , 5605.3 , 5605.4 , 5605.5 1125—12 Manufacture of Model Rocket and High Power Rocket Motors 5601.1.4 1126—11 Use of Pyrotechnics Before a Proximate Audience 5604.2 , 5605.1 , 5608.1 , 5608.2.2 , 5608.4 , 5608.5 1127—08 High Power Rocketry 5601.1.4 1142—12 Water Supply for Suburban and Rural Fire Fighting B103.3 2001—12 Clean Agent Fire Extinguishing Systems Table 901.6.1, 904.10 UL Underwriters Laboratories, Inc. 333 Pfingsten Road Northbrook, IL 60062 Standard reference number Title Referenced in code section number 10C—09 Positive Pressure Fire Tests of Door Assemblies 1008.1.10.1 30—95 Metal Safety Cans —with Revisions through July 2009 5003.9.10 , 5005.1.10 , 5705.2.4 58—96 Steel Underground Tanks for Flammable and Combustible Liquids —with Revisions through July 1998 5704.2.13.1.5 80—07 Steel Tanks for Oil-Burner Fuels and Other Combustible Liquids 610.2 142—06 Steel Aboveground Tanks for Flammable and Combustible Liquids 610.2 , 2306.2.3 199E—04 Outline of Investigation for Fire Testing of Sprinklers and Water Spray Nozzles for Protection of Deep Fat Fryers Single and Multiple Station Smoke Alarms —with Revisions through April 2010 907.2.11 Smoke Detectors for Fire Alarm Signaling Systems 907.2.6.2 Access Control System Units—with Revisions through 2009 Fire Testing of Fire Extinguishing Systems for Protection of Commercial Cooking Equipment Panic Hardware —with Revisions through January 2007 Door, Drapery, Gate, Louver and Window Operators and Systems —with Revisions through February 2010 Recirculating Systems —with Revisions through December 2009 Standard for Test for Surface Burning Characteristics of Building Materials Standard Test Methods for Fire Tests of Roof Coverings— with Revisions through October 2008 Automatically Operated Roof Vents for Smoke and Heat Control Units and Accessories for Fire Alarm Systems —with Revisions through February 2010 Air Filter Units—with revisions through November 2009 Standard for Safety Emergency Lighting and Power Equipment—with revisions through January 2009 Antitheft Alarms and Devices Flammable Liquid Storage Cabinets—with Revisions through May 2006 Standard for Nonmetallic Safety Cans for Petroleum Products—with Revisions through August 2007 Standard for Safety for Metal Waste Paper Containers —with Revisions through August 2007 Glass Fiber Reinforced Plastic Underground Storage Tanks for Petroleum Products, Alcohols, and Alcohol-gasoline Mixtures—with Revisions through May 2006 Relocatable Power Taps—with revisions through October 2009 Fire Tests for Foamed Plastics Used for Decorative Purpose Standard for Luminous Egress Path Marking Systems —with Revisions through April 2010 General Purpose Signaling Devices and Systems —with Revisions through October 2009 Standard for Gas and Vapor Detectors and Sensors—with revisions through September 2007 Tests for Fire Resistance of Building Joint Systems —with Revisions through June 2008 Protected Above-ground Tanks for Flammable and Combustible Liquids —with Revisions through December 1999 Stationary Engine Generator Assemblies—with Revisions through December 2009 Solvent Distillation Units —with Revisions through December 2009 Below-grade Vaults for Flammable Liquid Storage Tanks Fire Tests of Storage Pallets—with Revisions through March 2010
https://up.codes/viewer/tennessee/ifc-2012/chapter/80/referenced-standards
Network Tomography for Understanding Phenotypic Presentations in Aortic Stenosis | JACC: Cardiovascular Imaging AbstractObjectives: This study sought to build a patient−patient similarity network using multiple features of left ventricular (LV) structure and function in patients with aortic stenosis (AS). Th... Network Tomography for Understanding Phenotypic Presentations in Aortic Stenosis Free Access Original Research Grace Casaclang-Verzosa , Sirish Shrestha , Muhammad Jahanzeb Khalil , Jung Sun Cho , Márton Tokodi , Sudarshan Balla , Mohamad Alkhouli , Vinay Badhwar , Jagat Narula , Jordan D. Miller , and Partho P. Sengupta J Am Coll Cardiol Img. 2019 Feb, 12 (2) 236–248 Topic(s): Imaging, Echocardiography Original Research: Precision Medicine for Aortic Stenosis: The Future of Cardiology Today ∗ Graphical abstract <here is a image 44922994a10ddd54-1a8ac94110a598f2> Abstract Objectives: This study sought to build a patient−patient similarity network using multiple features of left ventricular (LV) structure and function in patients with aortic stenosis (AS). The study further validated the observations in an experimental murine model of AS. Background: The LV response in AS is variable and results in heterogeneous phenotypic presentations. Methods: The patient similarity network was developed using topological data analysis (TDA) from cross-sectional echocardiographic data collected from 246 patients with AS. Multivariate features of AS were represented on the map, and the network topology was compared with that of a murine AS model by imaging 155 animals at 3, 6, 9, or 12 months of age. Results: The topological map formed a loop in which patients with mild and severe AS were aggregated on the right and left sides, respectively (p < 0.001). These 2 regions were linked through moderate AS; with upper arm of the loop showing patients with predominantly reduced ejection fractions (EFs), and the lower arm showing patients with preserved EFs (p < 0.001). The region of severe AS showed >3 times the increased risk of balloon valvuloplasty, and transcatheter or surgical aortic valve replacement (hazard ratio: 3.88; p < 0.001) compared with the remaining patients in the map. Following aortic valve replacement, patients recovered and moved toward the zone of mild and moderate AS. Topological data analysis in mice showed a similar distribution, with 1 side of the loop corresponding to higher peak aortic velocities than the opposite side (p < 0.0001). The validity of the cross-sectional data that revealed a path of AS progression was confirmed by comparing the locations occupied by 2 groups of mice that were serially imaged. LV systolic and diastolic dysfunction were frequently identified even during moderate AS in both humans and mice. Conclusions: Multifeature assessments of patient similarity by machine-learning processes may allow precise phenotypic recognition of the pattern of LV responses during the progression of AS. Introduction Aortic stenosis (AS) is the most common valvular lesion, with >1 in 8 individuals aged 75 years and older having moderate or severe AS(1). The disease starts as focal leaflet thickening with calcification and gradually progresses to obstruction of the left ventricular (LV) outflow tract(2). The LV response to AS is associated with LV hypertrophy, subendocardial ischemia, altered myocardial energetics, and fibrosis, which produce varying degrees of LV diastolic and systolic dysfunction(2,3). However, the LV response to AS is variable and is only partly determined by transaortic resistance(2,4,5). Although there is consensus in the cardiology community that phenotypic differentiation of types and stages of AS in association with the biology of the LV is essential for optimum risk stratification and clinical decision-making, strategies to achieve this important goal remain imprecise(5). Advances in the field of genomics and systems biology have allowed the development of computational techniques that can identify complex relationships in data. Specifically, network biology is a powerful model for interpreting and contextualizing large diverse sets of biological data, for elucidating underlying complex biological processes, and creating an understandable model of a complex disease profile(6–8). We sought to use network analysis as an analytical method in which patients with varying stages of AS were represented in a multidimensional space. Using cross-sectional data, a compressed disease map was generated for exploration of possible paths that diseases such as AS can take as valvular dysfunction worsens in patients. We first used cross-sectional echocardiography data from a human population with varying AS severity to develop the disease map. Subsequently, we applied the same network analysis to an experimental murine model of progressive AS to determine whether this model effectively recaptured the phenotypic complexity of the human disease condition, and whether it could be used to guide further investigation into the clinically relevant ventricular and valvular phenotypes that emerge throughout the complex evolution of AS. Methods Patient—patient similarity network Topological data analysis (TDA) uses a machine-learning framework to cluster patients and network visualization to derive novel insights into disease mechanisms. The network, or simplicial complex, that materializes from the compressed representation defines the shape of high-dimensional data(9–13). The fundamental shape of the data space is referred to as a “Reeb graph” in which nodes represent groups of patients who are similar to each other across multiple clinical features, whereas edges connect nodes that contain similar patients. The end result of this process is a 2-dimensional chart that shows a level of similarity among various patient groups, all relative to one another. Two types of parameters are required to generate topological models: a metric that measures the similarity between data points; and lenses that are the functions that describe the distribution of the data and create overlapping bins of the dataset. Multiple lenses can be applied in the same analysis. Each lens has 2 tuning parameters: resolution and gain. Resolution determines the number of bins, whereas gain controls the overlapping between bins. The gain is adjusted so that most data points appear in a comparable number of bins. Equalizing the network distributes the patients evenly across all nodes in the network(9). TDA has been extensively validated and successfully applied in different areas of health sciences, such as gene expression profiling of breast tumors, identifying subgroups of type 2 diabetes, exploring endotypes of asthma, visualizing the syndromic space following central nervous system injury, and describing dynamics of malaria infections in humans and mice(6–8,10–13). TDA of human cohort TDA was performed using a cloud-based analytic platform (version 7.9, Ayasdi, Inc., Menlo Park, California). Seventy-nine separate clinical and echocardiographic variables were included as features. The initial TDA model was built using the following 4 echocardiographic variables: aortic valve area (AVA), LV ejection fraction (EF), LV mass index, and relative wall thickness (RWT) (Figure 1). We used a normalized correlation metric that measures the similarity between 2 points using Pearson’s correlation on a normalized dataset, combined with 2 multidimensional scaling lenses (resolution: 24, gain: 2.5, equalized). <here is a image f8115b4257f5c2af-c6a4df47283d6a4c> Figure 1. Steps of Topological Data Analysis (A)Normalized bivariate correlation matrix of the 4 echocardiographic parameters of the dataset.(B)Data were processed using multidimensional scaling (MDS), and the first and second coordinates were applied as lenses to generate the disease space. The data points are colored according to the aortic peak velocity, which may be resampled several times by topological data analysis (TDA) to cluster patients into nodes(red and blue circles)and connect overlapping patients with edges.(C)TDA provides the compressed representation using nodes and edges for expressive visualization and interpretation. Ao. = aortic; EF = ejection fraction; LV = left ventricular; RWT = relative wall thickness. TDA of mice cohort The TDA network was created using 4 echocardiographic parameters, namely, aortic peak velocity, EF, LV mass index, and RWT. Similar to the TDA network of the human cohort, the network of the mice was created with 2 lenses: metric principal component analysis coordinate 1 (resolution: 27, gain: 2.80, equalized) and metric principal component analysis coordinate 2 (resolution: 38, gain: 3.0, equalized). Study population Human cohort We included 246 patients (age 72 ± 14 years; 50% men) with AS who underwent echocardiographic evaluation at the Division of Cardiology, Heart and Vascular Institute, (Morgantown, West Virginia) from August 2017 to June 2018. Clinical features and risk factors were collected from patient medical records. AS severity was determined according to the recommendations of the European Association of Cardiovascular Imaging and the American Society of Echocardiography(14). Detailed methods for echocardiography assessment are presented in theOnline Appendix. AS phenotypes were defined by the flow, mean gradient, and LV ejection fraction, as follows: normal flow, high-gradient, preserved EF (NFpEF) (SV ≥35 ml/m 2, EF ≥50%) low flow, low-gradient, low ejection fraction (LFLEF) (stroke volume index <35 ml/m 2; EF <50%); and low flow, low-gradient, preserved ejection fraction (LFpEF) (stroke volume index <35 ml/m 2; EF ≥50%). Patient electronic medical records were reviewed for post-echocardiographic follow-up. Endpoints were defined as surgical or transcatheter aortic valve replacement (AVR), hospitalization and/or death from major adverse cardiac and cerebrovascular events (MACCEs) (defined as myocardial infarction, acute coronary syndrome, acute decompensated heart failure, cardiac arrest, arrhythmia, stroke, or transient ischemic attack), and first MACCE hospitalization. The time to each endpoint was measured from index echocardiographic examinations. The West Virginia University Institutional Review Board approved all data collection and analysis. Mouse cohort Echocardiographic data for a murine model of AS (low-density lipoprotein receptor-deficient and/or apolipoprotein B100-only mice on a mixed c57BL/6J-129S7-129S4/SvJae-CBA/J background) were collected from an existing database at the Cardiovascular Disease and Aging Laboratory, Mayo Clinic (Rochester, Minnesota). Echocardiography measurements were performed at 3, 6, 9, and 12 months of age. A detailed description of the methods and protocols for comprehensive assessment of cardiac and valvular function in these mice was previously published and is presented in theOnline Appendix(15). All methods and procedures were approved by the Mayo Clinic Institutional Animal Care and Use Committee. Statistical analysis Comparisons among multiple groups were performed using the Kruskal-Wallis test. Comparisons between a group of interest and the remaining subjects were performed using Pearson’s chi-square test or Fisher’s exact test (for categorical variables) and the nonparametric Kolmogorov-Smirnov test (for continuous variables). The rates of MACCE hospitalization and survival were analyzed using the Cox proportional hazard model. A p value of <0.05 was considered statistically significant. We used R (R Foundation, Vienna, Austria) and Python (Python Software Foundation, Beaverton, Oregon), including the Ayasdi software development kit, for all statistical analyses and TDA generation. Results Disease map of human AS A topological network model was applied to cross-sectional clinical data from 246 consecutive patients with varying degrees of AS (Figures 2A to 2D). Differences in multivariate AS phenotypes were graded by location and color across the topological map. For our study, we referred to the different locations of the circular graph as the right side, middle, left side, top or upper arm, and bottom or lower arm. We also color-coded nodes red to indicate abnormal and/or severe, green and yellow to indicate intermediate, and blue to indicate normal and/or mild phenotypes.Table 1shows the demographic and echo-Doppler distributions for patients grouped according to AVA. (For KS values, please refer toOnline Table 1). <here is a image 519105a939a57897-e3ffa4c0fee40380> Figure 2. Illustration of TDA Network With Coloration of Echocardiographic Parameters The similarity network draws aggregation of patients with severe and mild AS in 2 opposite ends and moderate AS in the top and bottom arms of the loop. Thered colorrepresents the abnormal values, whereasbluerepresents the normal or minor malady in the disease space.(A)Spectrum of mean gradient in humans identified in the network of disease space. High gradients aggregated on theleft side, whereas the low gradients were on theright sidewith the moderate gradients in themiddle.(B)Distribution of valve area on the network.(C)Patient similarity network revealing preserved and reduced ejection fractions (EFs) in the patients with aortic stenosis (AS). The top arm clustered patients with the reduced EF, whereas the bottom arm described the patients with preserved EF. Thered nodesconsist of patients with EFs of ≤50%, whereas theblue nodesconsist of patient with EFs of ≥65%.(D)Distribution of E/e′ as a feature of diastolic dysfunction revealing the pattern of higher E/e′ around moderate and severe AS. The units of thecolor bars on the top right of each panelare the same as inTable 1. TDA = topological data analysis. <table> Table 1.Comparison of the Topological Regions Predominantly∗Containing Patients With Mild, Moderate, and Severe AS<tr><th rowspan=1 colspan=1></th><th rowspan=1 colspan=1> Region of Mild AS</th><th rowspan=1 colspan=1> Region of Moderate AS</th><th rowspan=1 colspan=1> Region of Severe AS</th><th rowspan=1 colspan=1> p Value</th></tr><tbody><tr><td rowspan=1 colspan=1> Age (yrs)</td><td rowspan=1 colspan=1> 68 ± 15 †</td><td rowspan=1 colspan=1> 72 ± 14</td><td rowspan=1 colspan=1> 78 ± 12 ‡</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Male</td><td rowspan=1 colspan=1> 44 (53.66)</td><td rowspan=1 colspan=1> 83 (50.00)</td><td rowspan=1 colspan=1> 49 (49.49)</td><td rowspan=1 colspan=1> 0.828</td></tr><tr><td rowspan=1 colspan=1> Coronary artery disease</td><td rowspan=1 colspan=1> 32 (39.02)</td><td rowspan=1 colspan=1> 66 (39.76)</td><td rowspan=1 colspan=1> 41 (41.41)</td><td rowspan=1 colspan=1> 0.942</td></tr><tr><td rowspan=1 colspan=1> Chronic renal failure</td><td rowspan=1 colspan=1> 12 (14.63)</td><td rowspan=1 colspan=1> 25 (15.06)</td><td rowspan=1 colspan=1> 16 (16.16)</td><td rowspan=1 colspan=1> 0.955</td></tr><tr><td rowspan=1 colspan=1> Hyperlipidemia</td><td rowspan=1 colspan=1> 34 (41.46)</td><td rowspan=1 colspan=1> 75 (45.18)</td><td rowspan=1 colspan=1> 41 (41.41)</td><td rowspan=1 colspan=1> 0.781</td></tr><tr><td rowspan=1 colspan=1> Diabetes mellitus</td><td rowspan=1 colspan=1> 26 (31.71)</td><td rowspan=1 colspan=1> 51 (30.72)</td><td rowspan=1 colspan=1> 24 (24.24)</td><td rowspan=1 colspan=1> 0.446</td></tr><tr><td rowspan=1 colspan=1> Hypertension</td><td rowspan=1 colspan=1> 48 (58.54)</td><td rowspan=1 colspan=1> 92 (55.42)</td><td rowspan=1 colspan=1> 56 (56.57)</td><td rowspan=1 colspan=1> 0.897</td></tr><tr><td rowspan=1 colspan=1> Cerebrovascular accident</td><td rowspan=1 colspan=1> 10 (12.20)</td><td rowspan=1 colspan=1> 29 (17.47)</td><td rowspan=1 colspan=1> 18 (18.18)</td><td rowspan=1 colspan=1> 0.491</td></tr><tr><td rowspan=1 colspan=1> LV end-diastolic diameter (cm)</td><td rowspan=1 colspan=1> 4.73 ± 0.73</td><td rowspan=1 colspan=1> 4.65 ± 0.83 §</td><td rowspan=1 colspan=1> 4.5 ± 0.61 §</td><td rowspan=1 colspan=1> 0.075</td></tr><tr><td rowspan=1 colspan=1> LV posterior wall, diastole (cm)</td><td rowspan=1 colspan=1> 1.01 ± 0.2</td><td rowspan=1 colspan=1> 1.09 ± 0.26</td><td rowspan=1 colspan=1> 1.13 ± 0.27</td><td rowspan=1 colspan=1> 0.012</td></tr><tr><td rowspan=1 colspan=1> LV mass index (g/m 2)</td><td rowspan=1 colspan=1> 89.08 ± 35.11 †</td><td rowspan=1 colspan=1> 101.36 ± 38.25</td><td rowspan=1 colspan=1> 106.85 ± 33.87 ‡</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Relative wall thickness</td><td rowspan=1 colspan=1> 0.45 ± 0.12 ‡</td><td rowspan=1 colspan=1> 0.5 ± 0.19</td><td rowspan=1 colspan=1> 0.54 ± 0.17 ‡</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><th rowspan=1 colspan=1> Types of remodeling pattern</th><td rowspan=1 colspan=1></td><td rowspan=1 colspan=1></td><td rowspan=1 colspan=1></td><td rowspan=1 colspan=1> 0.017</td></tr><tr><td rowspan=1 colspan=1> Concentric remodeling</td><td rowspan=1 colspan=1> 32 (39.02)</td><td rowspan=1 colspan=1> 61 (36.75)</td><td rowspan=1 colspan=1> 39 (39.39)</td><td rowspan=1 colspan=1></td></tr><tr><td rowspan=1 colspan=1> Eccentric hypertrophy</td><td rowspan=1 colspan=1> 7 (8.54)</td><td rowspan=1 colspan=1> 15 (9.04)</td><td rowspan=1 colspan=1> 7 (7.07)</td><td rowspan=1 colspan=1></td></tr><tr><td rowspan=1 colspan=1> Concentric hypertrophy</td><td rowspan=1 colspan=1> 12 (14.63)</td><td rowspan=1 colspan=1> 46 (27.71)</td><td rowspan=1 colspan=1> 36 (36.36)</td><td rowspan=1 colspan=1></td></tr><tr><td rowspan=1 colspan=1> Ejection fraction <50%</td><td rowspan=1 colspan=1> 10 (12.20)</td><td rowspan=1 colspan=1> 36 (21.69) †</td><td rowspan=1 colspan=1> 16 (16.16)</td><td rowspan=1 colspan=1> 0.162</td></tr><tr><td rowspan=1 colspan=1> Doppler stroke volume index <35 ml/m 2</td><td rowspan=1 colspan=1> 35 (42.68) §</td><td rowspan=1 colspan=1> 93 (56.02)</td><td rowspan=1 colspan=1> 76 (76.77) ‡</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> E/A ratio</td><td rowspan=1 colspan=1> 1.36 ± 0.76</td><td rowspan=1 colspan=1> 1.31 ± 0.81</td><td rowspan=1 colspan=1> 1.22 ± 0.83</td><td rowspan=1 colspan=1> 0.397</td></tr><tr><td rowspan=1 colspan=1> Septal e′ (cm/s)</td><td rowspan=1 colspan=1> 6.73 ± 2.4 §</td><td rowspan=1 colspan=1> 6.15 ± 2.23</td><td rowspan=1 colspan=1> 5.74 ± 1.93</td><td rowspan=1 colspan=1> 0.014</td></tr><tr><td rowspan=1 colspan=1> Average E/e′</td><td rowspan=1 colspan=1> 15.33 ± 8.02 §</td><td rowspan=1 colspan=1> 17.54 ± 9.27</td><td rowspan=1 colspan=1> 18.18 ± 9.05</td><td rowspan=1 colspan=1> 0.053</td></tr><tr><td rowspan=1 colspan=1> Left atrial volume index (ml/m 2)</td><td rowspan=1 colspan=1> 37.6 ± 15.11</td><td rowspan=1 colspan=1> 39.67 ± 17.82</td><td rowspan=1 colspan=1> 41.67 ± 17.57 §</td><td rowspan=1 colspan=1> 0.228</td></tr><tr><td rowspan=1 colspan=1> TR peak gradient (mm Hg)</td><td rowspan=1 colspan=1> 28.66 ± 9.62</td><td rowspan=1 colspan=1> 30.87 ± 13.11</td><td rowspan=1 colspan=1> 31.23 ± 14.23</td><td rowspan=1 colspan=1> 0.449</td></tr><tr><td rowspan=1 colspan=1> Aortic valve area (cm 2)</td><td rowspan=1 colspan=1> 1.69 ± 0.25 ‡</td><td rowspan=1 colspan=1> 1.22 ± 0.34 ‡</td><td rowspan=1 colspan=1> 0.84 ± 0.22 ‡</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Mean gradient (mm Hg)</td><td rowspan=1 colspan=1> 11.81 ± 4.11 ‡</td><td rowspan=1 colspan=1> 18.69 ± 10.67</td><td rowspan=1 colspan=1> 27.67 ± 14.84 ‡</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Peak velocity (m/s)</td><td rowspan=1 colspan=1> 2.34 ± 0.31 ‡</td><td rowspan=1 colspan=1> 2.8 ± 0.66</td><td rowspan=1 colspan=1> 3.33 ± 0.81 ‡</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Peak gradient (mm Hg)</td><td rowspan=1 colspan=1> 22.21 ± 6.26 ‡</td><td rowspan=1 colspan=1> 33.19 ± 16.59</td><td rowspan=1 colspan=1> 47.11 ± 22.58 ‡</td><td rowspan=1 colspan=1> <0.001</td></tr></tbody></table> Values are mean ± SD or n (%). AS = aortic stenosis; LV = left ventricular; TR = tricuspid regurgitation. ∗ Nodes containing patients >50% with specific types of AS from sample for defining the regions. † p < 0.01. ‡ p < 0.001. § p < 0.05 between the severe AS type and the remaining types. The network showed aggregation of blue nodes representing low AV mean gradients on the right side, green and yellow nodes with moderate gradients in the middle, and red nodes with high mean gradients on the left side (Figure 2A). This map coincided with the distribution of the AVA (Figure 2B). Overall, despite the clustering patterns, close examination revealed substantial overlap of nodes at the junction between mild and moderate AS and moderate and severe AS. We interpreted these data to mean that there was a significant multidimensional overlap in echocardiographic features across the 3 degrees of AS severity. On examining the distribution of EFs, nodes that predominantly contained patients with reduced EFs (<50%) were found on the upper arm, whereas nodes with preserved EFs were situated on the lower arm (Figure 2C). The early diastolic transmitral flow velocity to mitral annular relaxation velocity ratio (E/e′) was higher in regions of moderate and severe AS (Figure 2D). The looped behavior of the network was preserved even after the addition of the E/e′ ratio as a marker of diastolic function (Online Figure 1). Figure 3A and 3Bshows the distributions of LV mass and the pattern of hypertrophy on the network. Patients with increased LV mass and concentric hypertrophy were predominantly found in the upper arm, extending to the left side toward severe AS. <here is a image c5b011260e982d58-8cd9de0442525d62> Figure 3. Features of LV Hypertrophy Displayed on TDA (A)Patients with reduced EF and severe AS show a higher LV mass index in the network.(B)TDA demonstrating the geometric patterns in the LV, in which the predominant patients with reduced EFs show eccentric and concentric hypertrophy. 0 = normal, 1 = concentric remodeling, 2 = eccentric hypertrophy, and 3 = concentric hypertrophy. Abbreviations as inFigures 1and2. We also examined whether there were differences between moderate AS in the upper and lower arms of the loop (Table 2; for KS values, please refer toOnline Table 2). Patients with moderate AS in the upper arm had lower EFs (p < 0.001), were frequently men (p = 0.013), and a had higher incidence of coronary artery disease (p = 0.003). Although, patients in both arms had equal AVA (p = 0.055), patients in the upper area had a lower peak velocity (p = 0.030), a lower mean gradient (p = 0.024), a higher LV mass index (p < 0.001), and a higher left atrial volume (p = 0.010). <table> Table 2.Comparison of the Topological Regions Predominantly∗Containing Patients With Reduced and Preserved EF in Moderate AS<tr><th rowspan=1 colspan=1></th><th rowspan=1 colspan=1> Moderate: Reduced EF</th><th rowspan=1 colspan=1> Moderate: Preserved EF</th><th rowspan=1 colspan=1> p Value</th></tr><tbody><tr><td rowspan=1 colspan=1> Age (yrs)</td><td rowspan=1 colspan=1> 76 ± 11</td><td rowspan=1 colspan=1> 68 ± 14</td><td rowspan=1 colspan=1> 0.421</td></tr><tr><td rowspan=1 colspan=1> Male</td><td rowspan=1 colspan=1> 29 (63.04)</td><td rowspan=1 colspan=1> 24 (39.34)</td><td rowspan=1 colspan=1> 0.013</td></tr><tr><td rowspan=1 colspan=1> Coronary artery disease</td><td rowspan=1 colspan=1> 25 (54.35)</td><td rowspan=1 colspan=1> 16 (26.23)</td><td rowspan=1 colspan=1> 0.003</td></tr><tr><td rowspan=1 colspan=1> Chronic renal failure</td><td rowspan=1 colspan=1> 8 (17.39)</td><td rowspan=1 colspan=1> 10 (16.39)</td><td rowspan=1 colspan=1> 0.546</td></tr><tr><td rowspan=1 colspan=1> Hyperlipidemia</td><td rowspan=1 colspan=1> 21 (45.65)</td><td rowspan=1 colspan=1> 27 (44.26)</td><td rowspan=1 colspan=1> 0.521</td></tr><tr><td rowspan=1 colspan=1> Diabetes mellitus</td><td rowspan=1 colspan=1> 16 (34.78)</td><td rowspan=1 colspan=1> 18 (29.51)</td><td rowspan=1 colspan=1> 0.355</td></tr><tr><td rowspan=1 colspan=1> Hypertension</td><td rowspan=1 colspan=1> 23 (50.00)</td><td rowspan=1 colspan=1> 31 (50.82)</td><td rowspan=1 colspan=1> 0.544</td></tr><tr><td rowspan=1 colspan=1> Cerebrovascular accident</td><td rowspan=1 colspan=1> 8 (17.39)</td><td rowspan=1 colspan=1> 9 (14.75)</td><td rowspan=1 colspan=1> 0.456</td></tr><tr><td rowspan=1 colspan=1> End-diastolic diameter (cm)</td><td rowspan=1 colspan=1> 5.25 ± 0.8</td><td rowspan=1 colspan=1> 4.27 ± 0.58</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Posterior wall (cm)</td><td rowspan=1 colspan=1> 1.12 ± 0.23</td><td rowspan=1 colspan=1> 0.99 ± 0.15</td><td rowspan=1 colspan=1> 0.005</td></tr><tr><td rowspan=1 colspan=1> LV mass index (g/m 2)</td><td rowspan=1 colspan=1> 122.59 ± 40.67</td><td rowspan=1 colspan=1> 73.67 ± 18.32</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Relative wall thickness</td><td rowspan=1 colspan=1> 0.45 ± 0.14</td><td rowspan=1 colspan=1> 0.47 ± 0.1</td><td rowspan=1 colspan=1> 0.084</td></tr><tr><th rowspan=1 colspan=1> Types of remodeling pattern</th><td rowspan=1 colspan=1></td><td rowspan=1 colspan=1></td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Concentric remodeling</td><td rowspan=1 colspan=1> 7 (15.22)</td><td rowspan=1 colspan=1> 40 (65.57)</td><td rowspan=1 colspan=1></td></tr><tr><td rowspan=1 colspan=1> Eccentric hypertrophy</td><td rowspan=1 colspan=1> 11 (23.91)</td><td rowspan=1 colspan=1> 0 (0.00)</td><td rowspan=1 colspan=1></td></tr><tr><td rowspan=1 colspan=1> Concentric hypertrophy</td><td rowspan=1 colspan=1> 17 (36.96)</td><td rowspan=1 colspan=1> 2 (3.28)</td><td rowspan=1 colspan=1></td></tr><tr><td rowspan=1 colspan=1> Ejection fraction <50%</td><td rowspan=1 colspan=1> 28 (60.87)</td><td rowspan=1 colspan=1> 0 (0.00)</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Doppler stroke volume index (<35 ml/m 2)</td><td rowspan=1 colspan=1> 25 (54.35)</td><td rowspan=1 colspan=1> 28 (45.90)</td><td rowspan=1 colspan=1> 0.252</td></tr><tr><td rowspan=1 colspan=1> E/A ratio</td><td rowspan=1 colspan=1> 1.54 ± 1.0</td><td rowspan=1 colspan=1> 1.08 ± 0.48</td><td rowspan=1 colspan=1> 0.407</td></tr><tr><td rowspan=1 colspan=1> Septal e′ (cm/s)</td><td rowspan=1 colspan=1> 5.25 ± 1.61</td><td rowspan=1 colspan=1> 6.5 ± 2.08</td><td rowspan=1 colspan=1> 0.003</td></tr><tr><td rowspan=1 colspan=1> Average E/e′</td><td rowspan=1 colspan=1> 19.63 ± 9.3</td><td rowspan=1 colspan=1> 16.73 ± 8.96</td><td rowspan=1 colspan=1> 0.088</td></tr><tr><td rowspan=1 colspan=1> Left atrial volume index (ml/m 2)</td><td rowspan=1 colspan=1> 47.46 ± 19.04</td><td rowspan=1 colspan=1> 33.15 ± 13.04</td><td rowspan=1 colspan=1> 0.010</td></tr><tr><td rowspan=1 colspan=1> TR peak gradient (mm Hg)</td><td rowspan=1 colspan=1> 34.98 ± 15.15</td><td rowspan=1 colspan=1> 30.66 ± 11.01</td><td rowspan=1 colspan=1> 0.270</td></tr><tr><td rowspan=1 colspan=1> Aortic valve area (cm 2)</td><td rowspan=1 colspan=1> 1.37 ± 0.33</td><td rowspan=1 colspan=1> 1.22 ± 0.25</td><td rowspan=1 colspan=1> 0.055</td></tr><tr><td rowspan=1 colspan=1> Mean gradient (mm Hg)</td><td rowspan=1 colspan=1> 14.87 ± 6.49</td><td rowspan=1 colspan=1> 20.39 ± 11.02</td><td rowspan=1 colspan=1> 0.024</td></tr><tr><td rowspan=1 colspan=1> Peak velocity (m/s)</td><td rowspan=1 colspan=1> 2.56 ± 0.52</td><td rowspan=1 colspan=1> 2.89 ± 0.65</td><td rowspan=1 colspan=1> 0.030</td></tr><tr><td rowspan=1 colspan=1> Peak gradient (mm Hg)</td><td rowspan=1 colspan=1> 27.26 ± 11.93</td><td rowspan=1 colspan=1> 35.3 ± 16.69</td><td rowspan=1 colspan=1> 0.030</td></tr></tbody></table> Values are mean ± SD or n (%). Abbreviations as inTable 1. ∗ Nodes containing patients >50% with specific types of AS from sample for defining the regions. We further examined the topographic distribution of severe AS phenotypes within the disease map (Figure 4A to 4C). NFpEF severe AS phenotypes were located on 2 spots in the upper and lower left sides (Figure 4A), whereas the LFLEF phenotypes were clustered in the left upper side (Figure 4B) between NFpEF and LFLEF. LFpEF phenotypes aggregated on the left side (Figure 4C).Table 3compares clinical and echocardiographic characteristics of the 3 severe AS phenotypes. (For KS values, refer toOnline Table 3). <here is a image 8cee04808221debd-b05cda7fcbf985c0> Figure 4. Patients With Phenotypes of Severe AS Represented on TDA (A)Nodes containing severe AS patients with the normal flow, preserved EF phenotype (NFpEF).(B)Patients with low flow, low-gradient, low EF (LFLEF) severe AS phenotype aggregating on the nodes in theleft upper sideof the network.(C)Patients with low flow, low-gradient, preserved EF (LFpEF) are seen to span in nodes between NFpEF and LFLEF.(D)Nodes containing severe AS patients who received either transaortic valve replacement, surgical valve replacement, or balloon valvuloplasty. Abbreviations as inFigures 1and2. <table> Table 3.Comparison of the Topological Regions Predominantly∗Containing Patients With LFLEF, LFpEF, and NFpEF Severe AS Phenotypes<tr><th rowspan=1 colspan=1></th><th rowspan=1 colspan=1> LFLEF</th><th rowspan=1 colspan=1> LFpEF</th><th rowspan=1 colspan=1> NFpEF</th><th rowspan=1 colspan=1> p Value</th></tr><tbody><tr><td rowspan=1 colspan=1> Age (yrs)</td><td rowspan=1 colspan=1> 78 ± 11 †</td><td rowspan=1 colspan=1> 77 ± 12 †</td><td rowspan=1 colspan=1> 75 ± 13</td><td rowspan=1 colspan=1> 0.723</td></tr><tr><td rowspan=1 colspan=1> Male</td><td rowspan=1 colspan=1> 27 (58.70)</td><td rowspan=1 colspan=1> 38 (46.91)</td><td rowspan=1 colspan=1> 17 (45.95)</td><td rowspan=1 colspan=1> 0.378</td></tr><tr><td rowspan=1 colspan=1> Coronary artery disease</td><td rowspan=1 colspan=1> 25 (54.35) ‡</td><td rowspan=1 colspan=1> 35 (43.21)</td><td rowspan=1 colspan=1> 11 (29.73)</td><td rowspan=1 colspan=1> 0.080</td></tr><tr><td rowspan=1 colspan=1> Chronic renal failure</td><td rowspan=1 colspan=1> 9 (19.57)</td><td rowspan=1 colspan=1> 15 (18.52)</td><td rowspan=1 colspan=1> 6 (16.22)</td><td rowspan=1 colspan=1> 0.923</td></tr><tr><td rowspan=1 colspan=1> Hyperlipidemia</td><td rowspan=1 colspan=1> 16 (34.78)</td><td rowspan=1 colspan=1> 33 (40.74)</td><td rowspan=1 colspan=1> 19 (51.35)</td><td rowspan=1 colspan=1> 0.308</td></tr><tr><td rowspan=1 colspan=1> Diabetes mellitus</td><td rowspan=1 colspan=1> 13 (28.26)</td><td rowspan=1 colspan=1> 19 (23.46)</td><td rowspan=1 colspan=1> 10 (27.03)</td><td rowspan=1 colspan=1> 0.816</td></tr><tr><td rowspan=1 colspan=1> Hypertension</td><td rowspan=1 colspan=1> 24 (52.17)</td><td rowspan=1 colspan=1> 45 (55.56)</td><td rowspan=1 colspan=1> 23 (62.16)</td><td rowspan=1 colspan=1> 0.654</td></tr><tr><td rowspan=1 colspan=1> Cerebrovascular accident</td><td rowspan=1 colspan=1> 11 (23.91)</td><td rowspan=1 colspan=1> 15 (18.52)</td><td rowspan=1 colspan=1> 4 (10.81)</td><td rowspan=1 colspan=1> 0.307</td></tr><tr><td rowspan=1 colspan=1> LV end-diastolic diameter (cm)</td><td rowspan=1 colspan=1> 4.96 ± 0.64 ‡</td><td rowspan=1 colspan=1> 4.36 ± 0.64 †</td><td rowspan=1 colspan=1> 4.51 ± 0.6</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> LV posterior wall, diastole (cm)</td><td rowspan=1 colspan=1> 1.22 ± 0.29 §</td><td rowspan=1 colspan=1> 1.12 ± 0.26</td><td rowspan=1 colspan=1> 1.08 ± 0.24</td><td rowspan=1 colspan=1> 0.029</td></tr><tr><td rowspan=1 colspan=1> LV mass index (g/m 2)</td><td rowspan=1 colspan=1> 137.61 ± 40.77 §</td><td rowspan=1 colspan=1> 100.92 ± 27.55 †</td><td rowspan=1 colspan=1> 98.19 ± 38.73</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Relative wall thickness</td><td rowspan=1 colspan=1> 0.52 ± 0.14 ‡</td><td rowspan=1 colspan=1> 0.56 ± 0.2 §</td><td rowspan=1 colspan=1> 0.5 ± 0.13</td><td rowspan=1 colspan=1> 0.391</td></tr><tr><th rowspan=1 colspan=1> Types of remodeling pattern</th><td rowspan=1 colspan=1></td><td rowspan=1 colspan=1></td><td rowspan=1 colspan=1></td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Concentric remodeling</td><td rowspan=1 colspan=1> 4 (8.70)</td><td rowspan=1 colspan=1> 37 (45.68)</td><td rowspan=1 colspan=1> 16 (43.24)</td><td rowspan=1 colspan=1></td></tr><tr><td rowspan=1 colspan=1> Eccentric hypertrophy</td><td rowspan=1 colspan=1> 6 (13.04)</td><td rowspan=1 colspan=1> 5 (6.17)</td><td rowspan=1 colspan=1> 2 (5.41)</td><td rowspan=1 colspan=1></td></tr><tr><td rowspan=1 colspan=1> Concentric hypertrophy</td><td rowspan=1 colspan=1> 29 (63.04)</td><td rowspan=1 colspan=1> 25 (30.86)</td><td rowspan=1 colspan=1> 9 (24.32)</td><td rowspan=1 colspan=1></td></tr><tr><td rowspan=1 colspan=1> Ejection fraction <50%</td><td rowspan=1 colspan=1> 26 (56.52) §</td><td rowspan=1 colspan=1> 5 (6.17) †</td><td rowspan=1 colspan=1> 4 (10.81)</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> E/A ratio</td><td rowspan=1 colspan=1> 1.5 ± 0.88</td><td rowspan=1 colspan=1> 1.27 ± 0.98</td><td rowspan=1 colspan=1> 1.17 ± 0.44</td><td rowspan=1 colspan=1> 0.160</td></tr><tr><td rowspan=1 colspan=1> Septal e′ (cm/s)</td><td rowspan=1 colspan=1> 5.31 ± 1.42 †</td><td rowspan=1 colspan=1> 5.73 ± 1.93</td><td rowspan=1 colspan=1> 5.72 ± 1.8</td><td rowspan=1 colspan=1> 0.566</td></tr><tr><td rowspan=1 colspan=1> Average E/e′</td><td rowspan=1 colspan=1> 20.59 ± 10.36 ‡</td><td rowspan=1 colspan=1> 17.76 ± 8.2</td><td rowspan=1 colspan=1> 19.3 ± 9.18</td><td rowspan=1 colspan=1> 0.369</td></tr><tr><td rowspan=1 colspan=1> Left atrial volume index (ml/m 2)</td><td rowspan=1 colspan=1> 50.48 ± 18.97 §</td><td rowspan=1 colspan=1> 39.88 ± 16.01</td><td rowspan=1 colspan=1> 38.49 ± 18.61</td><td rowspan=1 colspan=1> 0.005</td></tr><tr><td rowspan=1 colspan=1> TR peak gradient (mm Hg)</td><td rowspan=1 colspan=1> 32.86 ± 14.4</td><td rowspan=1 colspan=1> 31.31 ± 14.23</td><td rowspan=1 colspan=1> 28.35 ± 11.04</td><td rowspan=1 colspan=1> 0.367</td></tr><tr><td rowspan=1 colspan=1> Aortic valve area (cm 2)</td><td rowspan=1 colspan=1> 0.99 ± 0.36 §</td><td rowspan=1 colspan=1> 0.84 ± 0.21 §</td><td rowspan=1 colspan=1> 0.91 ± 0.23 §</td><td rowspan=1 colspan=1> 0.016</td></tr><tr><td rowspan=1 colspan=1> Mean gradient (mm Hg)</td><td rowspan=1 colspan=1> 22.83 ± 13.1</td><td rowspan=1 colspan=1> 27.18 ± 15.39 §</td><td rowspan=1 colspan=1> 30.0 ± 15.96 §</td><td rowspan=1 colspan=1> 0.082</td></tr><tr><td rowspan=1 colspan=1> Peak velocity (m/s)</td><td rowspan=1 colspan=1> 3.02 ± 0.77</td><td rowspan=1 colspan=1> 3.3 ± 0.84 §</td><td rowspan=1 colspan=1> 3.42 ± 0.85 §</td><td rowspan=1 colspan=1> 0.076</td></tr><tr><td rowspan=1 colspan=1> Peak gradient (mm Hg)</td><td rowspan=1 colspan=1> 38.88 ± 19.87</td><td rowspan=1 colspan=1> 46.62 ± 23.51 §</td><td rowspan=1 colspan=1> 49.74 ± 24.64 §</td><td rowspan=1 colspan=1> 0.065</td></tr></tbody></table> Values are mean ± SD or n (%). LFLEF = low flow, low ejection fraction; LFpEF = low flow, preserved ejection fraction; NFpEF = normal flow, preserved ejection fraction; other abbreviations as inTable 1. ∗ Nodes containing patients >50% with specific types of AS from sample for defining the regions. † p < 0.01. ‡ p < 0.05. § p < 0.001 between the severe AS type and the remaining types. Longitudinal follow-up During a follow-up of 157 days (range: 127 to 209 days), there were 33 MACCE hospitalizations, 4 cardiac deaths, and 35 surgical AVRs, transcatheter AVRs, or balloon valvuloplasties. MACCE hospitalization was equally distributed across all regions. However, there was >3 times the increased risk of transcatheter AVRs, surgical SAVRs, or balloon valvuloplasties (hazard ratio: 3.88; 95% confidence interval: 2.18 to 6.90; p < 0.001) among patients in the severe AS region compared with the remaining patients (Figure 4D). We analyzed follow-up echo-Doppler data of 35 patients who underwent AVR (Figure 5). After AVR, patients recovered their loci from the left side of the network (severe AS) to the middle and right side of the loop (moderate and mild AS). <here is a image 4a0d99411a094ce3-17cd034c798369a9> Figure 5. Patients in Network After AVR (A)Nodes containing patients imaged after aortic valve replacement (AVR) (brown nodes, median follow-up days: 36; range: 15 to 62 days) are depicted over the network and seen to aggregate in the region of mild or moderate AS.(B)Inter-region motion of 2 representative patients (64-year-old man and 80-year-old woman). AVA = aortic valve area; LVMi = left ventricular mass index; MG = mean gradient; other abbreviation as inFigures 1and2. Disease Map of Murine AS The TDA map was generated from echo-Doppler data of 155 mice: 68 (38%) at 3 months old, 5 (2%) at 6 months old, 95 (53.3%) at 9 months old, and 10 (5%) at 12 months old using peak aortic velocity, LV mass index, LVEFs, and RWT in the model. A circular Reeb graph showed striking similarity to the Reeb graph derived from humans (Figure 6), including similar distributions of peak velocity, LV mass index, RWT, and LVEFs (Figures 6A to 6D). <here is a image e49f3300484e30ab-69de7511d65c14c4> Figure 6. TDA From Echocardiography Performed in Mice Model of AS Map of the disease space in mice demonstrating the severity of AS as depicted by(A)aortic peak velocity,(B)EF,(C)LVMi, and(D)RWT. The color densities delineate exacerbation of the condition, whereredsignifies worse andbluesignifies less severe AS. Theright sideof the disease map depicts mice in the first tertile (1.1 to 1.9 m/s), whereas the ones on theleftare in high tertile (2.3 to 4.8 m/s) based on the peak velocity. Abbreviations as inFigures 1,2, and5. For quantitative analysis, we grouped the mice into 3 groups based on the tertile of peak aortic velocity to describe the severity of AS (Table 4, for KS values, refer toOnline Table 4). Mice in the lowest tertile (mild AS) showed larger cusp separation (p < 0.01), higher LVEFs (p < 0.05), RWT (p < 0.001), lower LV mass (p < 0.01), and lower E/e′ (39.9 ± 15.0; p < 0.05). Mice in the highest tertile (severe AS) had smaller cusp separation (p < 0.05), lower RWT (p < 0.001), higher LV end-diastolic dimension (p < 0.01), and higher E/e′ (p < 0.05). Topological locations were like those in humans, where mild AS was clustered on the right, moderate AS in the middle, and severe AS on the left side of the Reeb graph. Similar to human data, distinct differences were observed between the 2 arms of moderate AS. Mice in the upper arm had lower LVEFs (p < 0.001) and larger LV mass (p < 0.001) than mice in the lower arm (Table 5, for KS values, refer toOnline Table 5). <table> Table 4.Comparison of Predominantly∗Low, Intermediate, and High Tertiles of AS Severity in Mice<tr><th rowspan=1 colspan=1></th><th rowspan=1 colspan=1> Predominantly Low</th><th rowspan=1 colspan=1> Predominantly Intermediate</th><th rowspan=1 colspan=1> Predominantly High</th><th rowspan=1 colspan=1> p Value</th></tr><tbody><tr><td rowspan=1 colspan=1> Age (months)</td><td rowspan=1 colspan=1> 6 ± 3 †</td><td rowspan=1 colspan=1> 7 ± 3</td><td rowspan=1 colspan=1> 7 ± 3</td><td rowspan=1 colspan=1> 0.060</td></tr><tr><td rowspan=1 colspan=1> Male</td><td rowspan=1 colspan=1> 30 (34.09) †</td><td rowspan=1 colspan=1> 34 (34.34) †</td><td rowspan=1 colspan=1> 39 (50.65)</td><td rowspan=1 colspan=1> 0.045</td></tr><tr><td rowspan=1 colspan=1> Aortic peak velocity (m/s)</td><td rowspan=1 colspan=1> 1.84 ± 0.44 ‡</td><td rowspan=1 colspan=1> 2.02 ± 0.33 ‡</td><td rowspan=1 colspan=1> 2.58 ± 0.68 ‡</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Cusp separation (mm)</td><td rowspan=1 colspan=1> 0.89 ± 0.18 §</td><td rowspan=1 colspan=1> 0.86 ± 0.16</td><td rowspan=1 colspan=1> 0.81 ± 0.16 †</td><td rowspan=1 colspan=1> 0.005</td></tr><tr><td rowspan=1 colspan=1> Heart rate (beats/min)</td><td rowspan=1 colspan=1> 651.92 ± 83.99</td><td rowspan=1 colspan=1> 656.03 ± 69.91</td><td rowspan=1 colspan=1> 636.59 ± 80.98</td><td rowspan=1 colspan=1> 0.071</td></tr><tr><td rowspan=1 colspan=1> Septum, diastole (mm)</td><td rowspan=1 colspan=1> 0.98 ± 0.14</td><td rowspan=1 colspan=1> 0.98 ± 0.15</td><td rowspan=1 colspan=1> 0.95 ± 0.14</td><td rowspan=1 colspan=1> 0.119</td></tr><tr><td rowspan=1 colspan=1> Septum, systole (mm)</td><td rowspan=1 colspan=1> 1.62 ± 0.25</td><td rowspan=1 colspan=1> 1.65 ± 0.25</td><td rowspan=1 colspan=1> 1.62 ± 0.26</td><td rowspan=1 colspan=1> 0.714</td></tr><tr><td rowspan=1 colspan=1> Isovolumic relaxation time (ms)</td><td rowspan=1 colspan=1> 15.06 ± 6.02 ‡</td><td rowspan=1 colspan=1> 13.78 ± 6.05</td><td rowspan=1 colspan=1> 13.26 ± 6.83 †</td><td rowspan=1 colspan=1> 0.018</td></tr><tr><td rowspan=1 colspan=1> Isovolumic contraction time (ms)</td><td rowspan=1 colspan=1> 7.73 ± 3.76 §</td><td rowspan=1 colspan=1> 7.15 ± 4.3</td><td rowspan=1 colspan=1> 7.18 ± 5.77</td><td rowspan=1 colspan=1> 0.278</td></tr><tr><td rowspan=1 colspan=1> End-diastolic diameter (mm)</td><td rowspan=1 colspan=1> 2.63 ± 0.35 ‡</td><td rowspan=1 colspan=1> 2.75 ± 0.42 §</td><td rowspan=1 colspan=1> 2.97 ± 0.47 §</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> End-systolic diameter (mm)</td><td rowspan=1 colspan=1> 1.37 ± 0.38 ‡</td><td rowspan=1 colspan=1> 1.43 ± 0.39 †</td><td rowspan=1 colspan=1> 1.59 ± 0.41</td><td rowspan=1 colspan=1> 0.003</td></tr><tr><td rowspan=1 colspan=1> Posterior wall, diastole (mm)</td><td rowspan=1 colspan=1> 0.97 ± 0.15</td><td rowspan=1 colspan=1> 0.94 ± 0.13</td><td rowspan=1 colspan=1> 0.93 ± 0.14</td><td rowspan=1 colspan=1> 0.203</td></tr><tr><td rowspan=1 colspan=1> Posterior wall, systole (mm)</td><td rowspan=1 colspan=1> 1.35 ± 0.21</td><td rowspan=1 colspan=1> 1.34 ± 0.22</td><td rowspan=1 colspan=1> 1.33 ± 0.25</td><td rowspan=1 colspan=1> 0.777</td></tr><tr><td rowspan=1 colspan=1> LV mass (mg)</td><td rowspan=1 colspan=1> 67.4 ± 19.73 §</td><td rowspan=1 colspan=1> 70.25 ± 22.38 †</td><td rowspan=1 colspan=1> 75.2 ± 20.78</td><td rowspan=1 colspan=1> 0.034</td></tr><tr><td rowspan=1 colspan=1> Relative wall thickness</td><td rowspan=1 colspan=1> 0.76 ± 0.14 ‡</td><td rowspan=1 colspan=1> 0.72 ± 0.14</td><td rowspan=1 colspan=1> 0.65 ± 0.14 ‡</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Ejection fraction (%)</td><td rowspan=1 colspan=1> 81.77 ± 8.91 †</td><td rowspan=1 colspan=1> 81.13 ± 7.69</td><td rowspan=1 colspan=1> 79.58 ± 7.93</td><td rowspan=1 colspan=1> 0.167</td></tr><tr><td rowspan=1 colspan=1> Fractional shortening (%)</td><td rowspan=1 colspan=1> 49.89 ± 9.21 †</td><td rowspan=1 colspan=1> 49.11 ± 8.5</td><td rowspan=1 colspan=1> 47.53 ± 7.74</td><td rowspan=1 colspan=1> 0.233</td></tr><tr><td rowspan=1 colspan=1> Pulmonary artery acceleration time (ms)</td><td rowspan=1 colspan=1> 12.38 ± 3.29</td><td rowspan=1 colspan=1> 11.73 ± 3.13</td><td rowspan=1 colspan=1> 12.17 ± 6.01</td><td rowspan=1 colspan=1> 0.271</td></tr><tr><td rowspan=1 colspan=1> Pulmonary artery ejection time (ms)</td><td rowspan=1 colspan=1> 44.73 ± 7.05</td><td rowspan=1 colspan=1> 43.62 ± 5.62</td><td rowspan=1 colspan=1> 44.23 ± 6.64</td><td rowspan=1 colspan=1> 0.274</td></tr><tr><td rowspan=1 colspan=1> LV outflow ejection time (ms)</td><td rowspan=1 colspan=1> 39.2 ± 8.15</td><td rowspan=1 colspan=1> 38.98 ± 6.1</td><td rowspan=1 colspan=1> 38.88 ± 6.84</td><td rowspan=1 colspan=1> 0.929</td></tr><tr><td rowspan=1 colspan=1> Average E/e′</td><td rowspan=1 colspan=1> 39.19 ± 15.09 §</td><td rowspan=1 colspan=1> 41.48 ± 16.59</td><td rowspan=1 colspan=1> 46.47 ± 19.53 †</td><td rowspan=1 colspan=1> 0.026</td></tr><tr><td rowspan=1 colspan=1> Septal e′ (mm/s)</td><td rowspan=1 colspan=1> 23.96 ± 6.63 †</td><td rowspan=1 colspan=1> 23.39 ± 6.96</td><td rowspan=1 colspan=1> 22.27 ± 7.5</td><td rowspan=1 colspan=1> 0.202</td></tr><tr><td rowspan=1 colspan=1> E deceleration time (ms)</td><td rowspan=1 colspan=1> 19.14 ± 6.44 §</td><td rowspan=1 colspan=1> 20.49 ± 6.51</td><td rowspan=1 colspan=1> 21.85 ± 7.48</td><td rowspan=1 colspan=1> 0.161</td></tr><tr><td rowspan=1 colspan=1> LV end-diastolic volume (ml)</td><td rowspan=1 colspan=1> 31.27 ± 11.32</td><td rowspan=1 colspan=1> 31.9 ± 12</td><td rowspan=1 colspan=1> 33.84 ± 14.64</td><td rowspan=1 colspan=1> 0.541</td></tr><tr><td rowspan=1 colspan=1> LV end-systolic volume (ml)</td><td rowspan=1 colspan=1> 6.8 ± 4.89</td><td rowspan=1 colspan=1> 7.22 ± 5.17</td><td rowspan=1 colspan=1> 7.54 ± 6.03</td><td rowspan=1 colspan=1> 0.659</td></tr><tr><td rowspan=1 colspan=1> Stroke volume index (ml/g BW)</td><td rowspan=1 colspan=1> 1.03 ± 0.32</td><td rowspan=1 colspan=1> 1.03 ± 0.35</td><td rowspan=1 colspan=1> 1.05 ± 0.36</td><td rowspan=1 colspan=1> 0.937</td></tr></tbody></table> Values are mean ± SD or n (%). Aortic peak velocity is ordered and divided into 3 equal parts denoted as the low (109.1 to 184.5 cm/s), intermediate (185.2 to 234.3 cm/s), and high tertiles (234.5 to 475.5 cm/s). BW = body weight; other abbreviations as inTable 1. ∗ Nodes containing mice >50% with specific types of AS from sample for defining the regions. † p < 0.05. ‡ p < 0.001. § p < 0.01 between the severe AS type and the remaining types. <table> Table 5.Comparison of Upper and Lower Topological Regions in Intermediate AS in Mice<tr><th rowspan=1 colspan=1></th><th rowspan=1 colspan=1> Upper Arm</th><th rowspan=1 colspan=1> Lower Arm</th><th rowspan=1 colspan=1> p Value</th></tr><tbody><tr><td rowspan=1 colspan=1> Age (months)</td><td rowspan=1 colspan=1> 7 ± 3</td><td rowspan=1 colspan=1> 6 ± 3</td><td rowspan=1 colspan=1> 0.281</td></tr><tr><td rowspan=1 colspan=1> Male</td><td rowspan=1 colspan=1> 32 (48.48)</td><td rowspan=1 colspan=1> 13 (32.5)</td><td rowspan=1 colspan=1> 0.054</td></tr><tr><td rowspan=1 colspan=1> Aortic peak velocity (m/s)</td><td rowspan=1 colspan=1> 2.01 ± 0.47</td><td rowspan=1 colspan=1> 2.11 ± 0.45</td><td rowspan=1 colspan=1> 0.327</td></tr><tr><td rowspan=1 colspan=1> Cusp separation (mm)</td><td rowspan=1 colspan=1> 0.88 ± 0.16</td><td rowspan=1 colspan=1> 0.89 ± 0.16</td><td rowspan=1 colspan=1> 0.890</td></tr><tr><td rowspan=1 colspan=1> Heart rate (beats/min)</td><td rowspan=1 colspan=1> 645.2 ± 71.57</td><td rowspan=1 colspan=1> 644.55 ± 95.62</td><td rowspan=1 colspan=1> 0.450</td></tr><tr><td rowspan=1 colspan=1> Septum, diastole (mm)</td><td rowspan=1 colspan=1> 1.03 ± 0.12</td><td rowspan=1 colspan=1> 0.9 ± 0.12</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Septum, systole (mm)</td><td rowspan=1 colspan=1> 1.7 ± 0.26</td><td rowspan=1 colspan=1> 1.54 ± 0.23</td><td rowspan=1 colspan=1> 0.052</td></tr><tr><td rowspan=1 colspan=1> Isovolumic relaxation time (ms)</td><td rowspan=1 colspan=1> 13.21 ± 5.71</td><td rowspan=1 colspan=1> 15.13 ± 5.42</td><td rowspan=1 colspan=1> 0.220</td></tr><tr><td rowspan=1 colspan=1> Isovolumic contraction time (ms)</td><td rowspan=1 colspan=1> 6.72 ± 3.88</td><td rowspan=1 colspan=1> 7.94 ± 3.69</td><td rowspan=1 colspan=1> 0.304</td></tr><tr><td rowspan=1 colspan=1> End-diastolic diameter (mm)</td><td rowspan=1 colspan=1> 3.09 ± 0.37</td><td rowspan=1 colspan=1> 2.58 ± 0.23</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> End-systolic diameter (mm)</td><td rowspan=1 colspan=1> 1.81 ± 0.34</td><td rowspan=1 colspan=1> 1.22 ± 0.24</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Posterior wall, diastole (mm)</td><td rowspan=1 colspan=1> 1.01 ± 0.14</td><td rowspan=1 colspan=1> 0.87 ± 0.11</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Posterior wall, systole (mm)</td><td rowspan=1 colspan=1> 1.31 ± 0.19</td><td rowspan=1 colspan=1> 1.34 ± 0.19</td><td rowspan=1 colspan=1> 0.123</td></tr><tr><td rowspan=1 colspan=1> LV mass (mg)</td><td rowspan=1 colspan=1> 90.04 ± 19.53</td><td rowspan=1 colspan=1> 55.37 ± 9.97</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Relative wall thickness</td><td rowspan=1 colspan=1> 0.67 ± 0.11</td><td rowspan=1 colspan=1> 0.69 ± 0.1</td><td rowspan=1 colspan=1> 0.837</td></tr><tr><td rowspan=1 colspan=1> Ejection fraction (%)</td><td rowspan=1 colspan=1> 73.7 ± 7.83</td><td rowspan=1 colspan=1> 86.15 ± 4.33</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Fractional shortening (%)</td><td rowspan=1 colspan=1> 41.9 ± 6.55</td><td rowspan=1 colspan=1> 54.2 ± 6.11</td><td rowspan=1 colspan=1> <0.001</td></tr><tr><td rowspan=1 colspan=1> Pulmonary artery acceleration time (ms)</td><td rowspan=1 colspan=1> 11.82 ± 3.03</td><td rowspan=1 colspan=1> 11.23 ± 3.46</td><td rowspan=1 colspan=1> 0.744</td></tr><tr><td rowspan=1 colspan=1> Pulmonary artery ejection time (ms)</td><td rowspan=1 colspan=1> 45.46 ± 7.06</td><td rowspan=1 colspan=1> 43.33 ± 5.67</td><td rowspan=1 colspan=1> 0.528</td></tr><tr><td rowspan=1 colspan=1> LV outflow ejection time (ms)</td><td rowspan=1 colspan=1> 40.11 ± 7.05</td><td rowspan=1 colspan=1> 38.05 ± 7.04</td><td rowspan=1 colspan=1> 0.118</td></tr><tr><td rowspan=1 colspan=1> Average E/e′</td><td rowspan=1 colspan=1> 41.35 ± 16.14</td><td rowspan=1 colspan=1> 37.65 ± 11.28</td><td rowspan=1 colspan=1> 0.407</td></tr><tr><td rowspan=1 colspan=1> Septal e′ (mm/s)</td><td rowspan=1 colspan=1> 23.08 ± 7.36</td><td rowspan=1 colspan=1> 24.27 ± 6.38</td><td rowspan=1 colspan=1> 0.155</td></tr><tr><td rowspan=1 colspan=1> E deceleration time (ms)</td><td rowspan=1 colspan=1> 21.19 ± 6.6</td><td rowspan=1 colspan=1> 17.01 ± 4.3</td><td rowspan=1 colspan=1> 0.003</td></tr><tr><td rowspan=1 colspan=1> LV end-diastolic volume (ml)</td><td rowspan=1 colspan=1> 34.19 ± 14.67</td><td rowspan=1 colspan=1> 32.21 ± 12.44</td><td rowspan=1 colspan=1> 0.957</td></tr><tr><td rowspan=1 colspan=1> LV end-systolic volume (ml)</td><td rowspan=1 colspan=1> 7.71 ± 6.52</td><td rowspan=1 colspan=1> 7.32 ± 5.61</td><td rowspan=1 colspan=1> 0.933</td></tr><tr><td rowspan=1 colspan=1> Stroke volume index (ml/g BW)</td><td rowspan=1 colspan=1> 1.11 ± 0.33</td><td rowspan=1 colspan=1> 1.05 ± 0.39</td><td rowspan=1 colspan=1> 0.728</td></tr></tbody></table> Values are mean ± SD or n (%). Aortic peak velocity is ordered and divided into 3 equal parts denoted as the low (109.1 to 184.5 cm/s), intermediate (185.2 to 234.3 cm/s), and high tertiles (234.5 to 475.5 cm/s). Abbreviations as inTables 1and4. Longitudinal progression of AS in mice To understand whether the topological map developed from cross-sectional mouse data was also indicative of the longitudinal progression of AS across their lifetime, we compared the nodes occupied by 2 groups of mice in which data with serial follow-up assessments were available for 3 and 6 months and for 3 and 9 months. By plotting longitudinal data from 7 mice assessed at 3- and 6-month time points, we observed a progressive right-to-left shift in the node locations on the loop space (Figure 7A). At 3 months, all 7 mice were located on the right side (lowest tertile) or in the upper (intermediate tertile) arm of the graph. At the 6-month follow-up, most of the mice had shifted from the right side to the left side, although a few remained in the lowest tertile zone. Similarly, we plotted longitudinal data from 7 mice assessed at 3- and 9-month time points, and we confirmed a similar progression (Figure 7B). At 3 months, the mice were distributed in 10 nodes on the right side of the loop (lowest tertile) and 8 nodes in the middle region (intermediate tertile). There were no mice located in the highest tertile region. However, at 9-month follow-up, a leftward shift in distribution was observed, with mice occupying 7 nodes on the left side (highest tertile of peak aortic velocity) and 4 nodes on the middle lower side of the loop (intermediate velocity zone). Six nodes on the right side of the loop remained occupied, which suggested that after 9 months, features of mild AS still existed. Collectively, these data suggested that the mouse model of AS was able to recapture the phenotypes of human AS using TDA. <here is a image 92a257720e70cbb8-7a4693deaa21a1f8> Figure 7. TDA for Assessing Longitudinal Disease Pathway in Mice A topological network map comparison of the location of mice based upon peak AV velocity at(A)3 and 6 months and(B)3 and 9 months, respectively. Theblue circlessignify 3-month mice, whereasredsignifies AV velocity grade at 6 and 9 months forA and B, respectively. Abbreviations as inFigures 1,2, and6. Discussion AS is prevalent in 1.7% of the population age older than 65 years(1), and prospective natural progression studies are sparse, with the number of patients ranging from 100 to 400(16,17). As with most age-associated diseases, a major challenge in studying the natural progression of AS is that its progression can span decades. For the first time, we described an alternative solution to provide a detailed characterization of the natural progression and subtypes of AS from cross-sectional data using TDA and demonstrated that a mouse model of AS was likely to recapture and parallel several key characteristics of the natural progression of AS in humans. The following sections highlight the implications and potential usefulness of these findings for the fields of both clinical and discovery science. TDA and phenotyping AS AS is a complex and heterogeneous disease with a phenotypic variation in disease progression and a LV response to increased afterload. Aortic valve calcification and stenosis progress at various rates in different patient populations, and the LV response to progressive overload is highly heterogeneous, even within well-defined patient subgroups with AS. Such variability makes this population highly susceptible to the generation of “high dimensional data.” Newer scientific methods like TDA can therefore be useful for extracting meaningful knowledge through direct visualization of the heterogeneous datasets to enhance the potential of improved understanding and treatment of complex disorders like AS(9,13,18). Although clinical stratification of patients at the extreme ends of disease can readily be accomplished with current clinical data (e.g., patients with mild or severe AS with negligible or severe ventricular dysfunction), our model suggested that it might be possible to identify a subset of patients who will experience aggressive deterioration of LV function at a much earlier time point. More specifically, a major important and novel observation in this study was the use of cross-sectional data for identification of 2 connected pathways through which mild forms of AS could progress to clinically severe forms of AS. Notably, one pathway depicted the progression of valvular dysfunction with the preservation of EFs, and the second one suggested an accelerated decline in EFs despite disproportionally lesser degrees of valvular stenosis. Importantly, our study suggested that patients with preserved EFs had lower LV mass than patients with lower EFs, which suggested the existence of fundamental differences in the molecular adaptation to progressive ventricular overload in these 2 groups. We showed that LV systolic and diastolic dysfunction could occur even at early stages of aortic valve disease .More specifically, when tracking changes in EFs across the 3 zones of the TDA loop, our model suggested that a reduction in EF was not simply a linear and proportional consequence of progressive AS. Reduced LVEFs were observed in a significant cluster of patients with moderate AS in our dataset. Our observation was consistent with the findings of the study by Ito et al.(19), who reported that in some patients, the LVEF declined when AVA reached 1.2 cm 2. Although their study reported that a LVEF of <60% in the presence of moderate AS predicted further deterioration of LVEF, our model suggested that TDA modeling might be able to more accurately stratify such patients at an earlier stage for more aggressive medical management. However, a substantial overlap existed in patients with moderate and severe AS for valvulo-ventricular function. Collectively, these observations supported the use of integrative strategies that incorporated changes in LV function and aortic valve function in continuum for assessments of aortic valve syndromes to better understand phenotypic presentations in AS. Mouse model of AS The use of a well-described mouse model of AS (low-density lipoprotein receptor-deficient, apolipoprotein B100-only) fed a high-cholesterol, high-fat diet to induce AS helped illustrate the validity of the TDA method(20–22). One major advantage of studying AS in mice is that they are the only species, other than humans, that have been shown to develop hemodynamically important stenosis(20–22). Perhaps more importantly, the relatively short lifespan of the mouse made it an attractive model for the study of time and/or age-dependent diseases such as AS. Moreover, echocardiographic evaluation of severity of AS in mice was refined using a high resolution imaging system, similar to that used in the present study(15). The reverse translational approach used in the study allowed us to match the echocardiography data between mice and humans to develop 2 closely resembled networks. More specifically, as AS progressed, there was a phenotypic bifurcation of mice with higher LV mass and lower EFs in 1 group and mice with lower LV mass and preserved EFs in the other group. Furthermore, we observed a lower EF in a subset of mice that had yet to reach severe stages of AS. Finally, the longitudinal data showed a variable rate of progression from mild AS, a phenomenon that is also seen in clinical practice. When combined, our observations showed that integrated measures of disease progression were associated not only with changes in valve function but also with Doppler parameters of LV systolic and/or diastolic function. Both progression along the network (seen in the mouse model from milder to higher gradient zones) and recovery along the network (seen in the human model when a patient moved from severe AS to mild AS zones after AVR) helped substantiate that the network model developed from cross-sectional data was also able to capture the longitudinal disease course or recovery(8). Clinical implications of precision phenotyping in AS The valvulo-ventricular complex is an integral part of the disease process from which patients’ symptoms likely arise, but is not due to AS, per se. However, current guidelines rely on velocity and/or gradients, AVA, LVEF, and stroke volume to decide on phenotypic presentation and the timing of intervention(23). Our study provided patient similarity-based recognition of phenotypic presentations and suggested that different stages and grades of disease severity in AS occurred along a phenotypic continuum rather than in arbitrary divisions based on a few isolated measurements and thresholds. Accordingly, some patients with AVA that suggested severe AS showed phenotypic similarity to a lower severity of AS and vice versa. Interestingly, several patients with moderate AS developed LV dysfunction. Our data suggested that several of these patients had phenotypic similarity with severe AS, thereby making the case for early intervention. There is a need to develop precision phenotyping models using machine-learning algorithms so that surveillance and intervention can be tailored to individual patients. In the future, TDA-based analysis of longitudinal data might help clinicians visualize patients on a disease map and predict the natural disease progression based on how patients in a similar cluster progressed over time and how they responded to therapies. Study limitations Our human and mouse data-sets were limited in numbers, and all phenotypes might not have been well represented. Larger cohorts of patients and animal data sampled at multiple time points and assessment of clinical outcomes are needed to validate TDA as a viable methodology for predicting natural disease progression, guiding individual patient treatments, and assessing prognosis. Conclusions We demonstrated the use of TDA as a tool to study the natural progression of disease from cross-sectional and follow-up human data. Our model strongly suggested that both patients with AS and animal models of AS progressed via 1 of 2 predominant pathways as disease progressed from mild to severe stenosis, with 1 pathway preserving EFs and the other pathway characterized by deterioration of EFs. Collectively, our data and TDA model supported the use of integrated valvulo-ventricular stratification of subgroups with AS, which warrants future investigations in both clinical- and discovery-focused studies. Perspectives COMPETENCY IN MEDICAL KNOWLEDGE:Similar to expert clinician knowledge, TDA, without a priori knowledge, can merge multiple transthoracic echocardiographic measurements of AS severity, including LV wall thickness, cavity dimensions, stroke volume, and EFs to extract phenotypic presentations in AS. Furthermore, patients can be individually delineated for mapping disease progression or recovery. TRANSLATIONAL OUTLOOK:Future clinical trials should merit using data-driven approaches like TDA for identifying and risk stratifying AS patient subgroups so that surveillance and interventions can be tailored to individual patients. Appendix Online Data Abbreviations and Acronyms <table><tbody><tr><td> AS</td><td>aortic stenosis</td></tr><tr><td> AVA</td><td>aortic valve area</td></tr><tr><td> AVR</td><td>aortic valve replacement</td></tr><tr><td> EF</td><td>ejection fraction</td></tr><tr><td> LFLEF</td><td>low flow, low-gradient, low ejection fraction</td></tr><tr><td> LFpEF</td><td>low flow, low-gradient, preserved ejection fraction</td></tr><tr><td> LV</td><td>left ventricle</td></tr><tr><td> MACCE</td><td>major adverse cardiac and cerebrovascular event</td></tr><tr><td> NFLEF</td><td>normal flow, low ejection fraction</td></tr><tr><td> NFpEF</td><td>normal flow, preserved ejection fraction</td></tr><tr><td> RWT</td><td>relative wall thickness</td></tr><tr><td> TDA</td><td>topological data analysis</td></tr></tbody></table> Footnotes Dr. Sengupta has been a consultant for Heartsciences, Hitachi Aloka Ltd., and Ultromics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Blase A. Carabello served as Guest Editor for this paper.
https://www.jacc.org/doi/10.1016/j.jcmg.2018.11.025
Minerals | Free Full-Text | Trace-Element Distribution on Sulfide Mineralization in Trento Province, NE Italy Sulfide mineralization in the province of Trento (northeastern Italy) includes various mineral assemblages that are often silver-rich and have been exploited in different phases from the Middle Ages until the 20th century. This study investigates mineralized rocks from three historically important sites (Calisio mount, Erdemolo lake, and the locality of Cinque Valli), providing new analytical data (Inductively Coupled Plasma-Mass Spectrometry on bulk rocks, and Scanning Electron Microscopy on thin sections) that demonstrate that parageneses do not only include galena, chalcopyrite, and sphalerite but also accessory minerals, such as tetrahedrite, tennantite, acanthite, and sulfosalts (matildite/polybasite). This explains the high content of As (up to 278 ppm), Bi (up to 176 ppm), and Sb (up to 691 ppm) that are associated with Pb–Cu–Zn mineralization. Notably, trace-element ratios indicate that, although closely associated from a geographical point of view, the studied sites are not genetically related and have to be referred to in distinct mineralization events, possibly induced by three diverse magmatic and hydrothermal phases that occurred in the Variscan post-orogenic setting. Besides geological and petrogenetic reconstruction, the new data outline potential geochemical risks, as they reveal a high concentration of elements characterized by marked toxicity that can be transferred into the local soil and water. Therefore, future studies should be devoted to better investigating the metal distribution in the surroundings of ancient mining sites and their geochemical behavior during the weathering processes. Trace-Element Distribution on Sulfide Mineralization in Trento Province, NE Italy by Gianluca Bianchini 1,* , Claudio Natali 2 , Paolo Ferretti 3 , Lara Casagrande 4 , Manuel Conedera 5 and Chiara Marchina 1 Dipartimento di Fisica e Scienze della Terra, Università degli Studi di Ferrara, Via Saragat 1, 44122 Ferrara, Italy Dipartimento di Scienze della Terra, Università degli Studi di Firenze, Via G. La Pira 4, 50121 Firenze, Italy Freelance researcher, Via Ponte Alto 30/c, 32020 Rivamonte Agordino (BL), Italy Minerals 2019 , 9 (12), 736; https://doi.org/10.3390/min9120736 Received: 25 October 2019 / Revised: 18 November 2019 / Accepted: 25 November 2019 / Published: 28 November 2019 (This article belongs to the Special Issue Sulfide Geochemistry ) Abstract Keywords: sulfide mineralization Trento trace-elements accessory minerals 1. Introduction Sulfide-bearing rocks in the province of Trento ( Figure 1 ) in northeastern Italy include Ag-rich Pb–Zn–Cu mineralization. Minerals were extracted at several phases since the Middle Ages, and the activity continued until 1964, when the last mine of the Province (Calceranica) closed. Previous studies on local mineralization [ 1 ] generally associated Ag to galena, but detailed geochemical–mineralogical investigations [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ] are still lacking in the literature. The purpose of the current contribution is to provide new analytical data (Inductively Coupled Plasma-Mass Spectrometry on bulk rocks and Scanning Electron Microscopy on polished thin sections) on mineralized rocks from three distinct sites, namely, the Calisio mount, known for galena concentration in Early Triassic carbonate rocks, Erdemolo lake, and Cinque Valli surroundings, both known for the mineralization of mixed (galena–chalcopyrite–sphalerite) sulfides in sialic veins closely related to Permian magmatic rocks. The data offer insight into genetic conditions and also into potential environmental pollution by heavy metals. Figure 1. Simplified ( a ) geographic and ( b ) geological sketches of studied area located in the province of Trento (NE Italy). Symbols denote localities where mineralized rocks were sampled. Red triangle, Calisio mount; red diamond, Erdemolo lake; red pentagon, Cinque Valli site. Geological information was retrieved by map of lithology and structural elements of Trento. 2. Materials and Methods 2.1. Geological Outlines The investigated sites are located in the northeastern sector of the province of Trento ( Figure 1 ), geologically pertaining to the South-Alpine domain. The outcropping crystalline basement consists of metamorphic rocks (phyllades and mica-schists) and igneous granitic (s.l.) intrusions formed during the Variscan orogeny [ 9 , 10 ]. The basement is covered by Permian volcanics consisting of ignimbrites, mainly rhyolitic in composition, of the Athesian Volcanic Group [ 11 , 12 ], and by Triassic sedimentary rocks [ 13 , 14 ], sometimes crosscut by Early Triassic basic dykes [ 15 ]. Sulfide deposits are widespread in the area [ 16 , 17 ], as attested by massive veins (dominated by pyrite) within the Variscan metamorphic basement (as observed in Calceranica) that indicate that the pre-metamorphic volcano-sedimentary sequence (i.e., sedimentary protholites) were already enriched in sulfur, possibly in relation to exhalative deposition induced by ore-bearing hydrothermal fluids into an Early Palaeozoic marine basin. The post-Variscan (Permian) magmatic episodes, characterized by calcalkaline products, and the associated hydrothermal processes remobilized sulfur and metals with the formation of mineralized veins and metasomatic aureolas in the surrounding rock matrices. These occurrences are observed within the lower part of the Athesian Volcanic Group (as observed at the Erdemolo lake site [ 18 ]) or at the contact between intrusive igneous rocks and the metamorphic basement (as observed at the Cinque Valli site [ 19 ]). Early Triassic magmatism, attested by dykes having shoshonite affinity, and associated hydrothermal fluids induced further remobilization and additional ore deposits within the sedimentary sequence [ 1 ], as observed in the Werfen formation outcropping at Calisio mount [ 15 ]. 2.2. Hand-Specimen Description Photographs of the investigated hand specimens are shown in Figure 2 . Mineralized rocks from the Calisio mount are represented by dark oolitic carbonates, locally crosscut by sulfide-bearing veinlets of gray color (see sample MGC2 in Figure 2 a). Some rocks from Erdemolo lake have a porphyric texture in which large (up to 3–4 cm) aggregates of quartz and feldspar are surrounded by a greenish matrix including millimetric sulfide crystals (Sample MGE3 in Figure 2 b), whereas other samples appear almost totally constituted by sulfides (Sample MGE5 in Figure 2 c). Some rocks from Cinque Valli site have equigranular texture with comparable abundance of silicates (mainly quartz and feldspar) and sulfides (Sample MGV5), whereas others are totally dominated by sulfides, mainly represented by brown sphalerite and grey galena (Sample MGV2 in Figure 2 d). The assumption is that (1) rocks from the Calisio mount were mineralized by a fluid that shortly post-dated the deposition of calcareous rocks; (2) rocks from Erdemolo lake are representative of a metasomatic process in which previous magmatic parageneses were affected by propylitic processes due to late-stage magmatic/hydrothermal fluids; and (3) rocks from Cinque Valli are representative of hydrothermal veins crosscutting the basement in a close relationship with magmatic intrusion. Figure 2. Hand-specimen photographs of studied mineralized rocks. ( a ) Sample MGC2 from Calisio mount, where brown oolitic carbonate matrix is crosscut by sulfide (mainly galena) veinlet; ( b ) sample MGE3 from Erdemolo lake characterized by porphyric texture with quartz and feldspar aggregates within a greenish matrix containing millimetric sulfide crystals; ( c ) sample MGE5 from Erdemolo lake constituted by prevalent sulfide (mainly yellow chalcopyrite); ( d ) sample MGV2 from Cinque Valli site mainly constituted by sulfide (with prevalent brown sphalerite and grey galena). 2.3. Analytical Methods Bulk rock geochemical analyses were carried out by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) after dissolution. Bulk rock powders (0.15 g) of 7 samples were digested with HF–HNO 3 on a hot plate. Dissolved samples were dried out and then redissolved in ultrapure water obtained from a Milli-Q purifier system (Direct-Q UV, Millipore, Burlington, MA, USA). Analyses were carried out using a X series Thermo-Scientific spectrometer (Thermo, Bremen, Germany). Specific amounts of Rh and Re were added to the analyzed solutions as an internal standard in order to correct the instrument drift. Accuracy and precision, based on replicated analyses of samples and standards were 10% for all elements, well above the detection limit. Bulk–rock analyses were integrated with an in situ investigation carried out by electron microscope (SEM EVO-40 XVP; Carl Zeiss, Oberkochen, Germany) on polished thin sections. 3. Results 3.1. Bulk Rock Analyses Table 1 20 21 22 Table 1. ICP-MS analyses (expressed in ppm) of mineralized rocks from Calisio mount (MGC), Erdemolo lake (MGE), and Cinque Valli (MGV). Chalcophile elements of the Calisio mount were dominated by Pb (up to 137,048 ppm), clearly indicating that they mainly contain galena. Rocks from Erdemolo lake could be dominated by Pb (up to 101,981 ppm) or by Cu (up to 191,530 ppm), indicating the prevalence of galena or chalcopyrite. Sphalerite was prevalent only in samples from Cinque Valli that showed high concentration (up to 271,351 ppm) of Zn. The concentration ranges of Ag in the investigated rocks varied between 50 and 142 ppm at the Calisio mount, 51 and 311 ppm at Erdemolo lake, and 69 and 118 ppm at Cinque Valli. Considering that Ag is generally associated with galena, we calculated the kg of Ag for each rock for a ton of galena; it appeared that the grade of Ag was up to 2.2 kg/t at the Calisio mount, up to 3.1 kg/t at the Erdemolo lake, and up to 0.4 kg/t at Cinque Valli. Figure 3 Figure 3. Binary diagrams showing elemental ratios can be discriminant of mineralized rocks from the Calisio mount, Erdemolo lake, and Cinque Valli. ( a ) K/Na vs. Fe/Mn, ( b ) Li/Rb vs. Sr/Ba, ( c ) Bi/Tl vs. Cd/Sn, ( d ) Sb/Te vs. As/Se. 3.2. Results of In Situ (SEM) Analyses Scanning electron microscopy (SEM) back-scattered images are reported in Figure 4 and Figure 5 , and EDS, semi-quantitative analyses are reported in Table 2 and Table 3 . Figure 4. Back-scattered scanning electron microscopy (SEM) images of mineralized rocks from Calisio mount. Note that mineralization is not solely composed by galena, and that the paragenesis is remarkably more complex. Abbreviations: Qz = quartz, Gn = galena, Ttr = tetrahedrite, Ccp = chalcopyrite, Cer = cerussite, Py = pyrite, CuCO 3 = copper carbonate. ( a ) shows that the mineralized veinlet, mainly composed by Gn, also contains minor Qz and Ccp, as well as secondary minerals such as Cer; ( b ) shows that Trd is also present in the mineral association; ( c ) and ( d ) emphasize that Trd is altered and resorbed, indicating that this mineral is unstable in supergene condition. Figure 5. Back-scattered scanning electron microscopy (SEM) images of mineralized rocks from the Erdemolo lake. Note that mineralization is not solely composed by galena and chalcopyrite, and that the paragenesis is remarkably more complex. Abbreviations: Qz = quartz, Gn = galena, Ttr = tetrahedrite, Tnt = tennantite, Ccp = chalcopyrite, Py = pyrite, Ac = acanthite, Cst = cassiterite, Plb= polybasite, Mtd = matildite. ( a ) shows the intimate association of Ccp, Gn, Py, Cst, Qz; ( b ) shows the presence of Plb; ( c ) shows the presence of Ac; ( d ) shows the presence of Mtd. Table 2. SEM (EDS) semi-quantitative analyses (wt %) of minerals at Calisio mount; analyses were normalized to 100%. Table 3. SEM (EDS) semi-quantitative analyses (wt %) of minerals at Erdemolo lake; analyses were normalized to 100%. Figure 6 23 Figure 6. Sb/As vs. Ag/Cu interdependence in the tetrahedrite-tennantite series recorded in mineralized rocks from Calisio mount. In rocks from the Erdemolo lake, where galena (containing Ag up to 1.9 wt %) and chalcopyrite are dominant, we recorded other peculiar minerals, such as acanthite, i.e., Ag 2 S (Ag up to 66 wt %) and matildite/polybasite that are Ag–Bi–Sb sulfosalts. Among oxides, cassiterite was observed, and coherently recent literature data [ 24 ] indicate that this mineral can host other trace elements that are comparatively enriched in Erdemolo rocks such as Ti, V, and Sc. In rocks from Cinque Valli, preliminary analyses only recorded principal sulfides sphalerite and galena (containing Ag up to 0.2 wt %); in these rocks, the anomalous content of Cd, Mo, Ga could be hosted in sphalerite as observed by recent researches [ 2 , 8 ], and further investigation is needed to constrain this hypothesis. 4. Discussion The investigated sulfide mineralizations are hydrothermal deposits induced by fluids, plausibly related to magmatic phases. Although geographically concentrated within a small area, the trace-element data indicate that mineralization events were distinct and independent. The Cinque Valli rocks were mineralized in connection with the intrusion of calcalkaline granodiorites into the metamorphic basement, and those of Erdemolo lake were mineralized in connection with the emplacement of calcalkaline volcanic rocks, ranging in composition between andesites and rhyolites. We speculated that mineralization from the Calisio mount, although hosted in sedimentary rocks, is also associated with distal volcanic activity, since coeval shoshonitic dykes were discovered in the surroundings (ca. 10 km from the mineralized zone [ 15 ]). However, although independent, these magmatic phases belong to the same geodynamic post-orogenic framework, as they follow Variscan plate convergence, subduction, and continental collision. In this scenario, mantle sources were variously metasomatized by subduction components that enriched the derived magmas in volatiles (including sulfur) and chalcophile elements, which ultimately released mineralizing fluids in the upper crust [ 25 ]. Silver is often associated with galena, sometimes containing up to 1.9 wt % Ag. These values are high compared with ordinary galena composition [ 26 ], and are recorded in few ore deposits, where tetrahedrite-tennantite (known as minerals of the fahlore group) crystals having notable silver content (known as freibergite) were also observed ([ 27 ] and references therein). The observed high concentration of silver in galena can be explained with the simultaneous enrichment of antimony and/or bismuth because silver can be accommodated in galena as result of coupled substitution with Ag + Sb and/or Ag + Bi for 2 Pb atoms [ 28 , 29 ]; however, this elemental substitution of Pb with Ag (Sb, Bi) is inhibited at low temperatures (below 300 °C [ 29 ]). The record of tetrahedrite-tennantite within the investigated sulfides at the Calisio mount is therefore coherent with the observed wide spectrum of trace elements such as Ag, As, Bi, Sb, and it can be stated that tetrahedrite-tennantite are sulfide analog of amphiboles, suitable for reciprocal solutions [ 30 , 31 , 32 ]. The study of other mineralized areas characterized by significant zoning reveal that Ag-rich minerals of this series generally crystallize in epigenetic conditions from evolved (fractionated) hydrothermal fluids that progressively cooled when migrating from the source zone, which is often related with the emplacement of magmatic bodies [ 33 , 34 , 35 ]. Accordingly, fluid-inclusion studies on these minerals generally indicate genesis by hydrothermal fluids at formation temperatures below 300 °C [ 36 , 37 , 38 ]. However, in our case, textural relationships suggest that tetrahedrite-tennantite could be exsolution products formed during sub-solidus re-equilibration of pre-existing Ag-rich galena during the system cooling (as foreseen by [ 28 ]), and that these minerals become highly reactive in a supergene condition, where they can release their geochemical budget [ 23 ]. 5. Conclusions Ore deposits of the investigated Trento sites are not only characterized by common base metal sulfides, such as sphalerite, galena, and chalcopyrite, but also contain peculiar accessory minerals that host several trace elements. On the whole, geochemistry rules out the occurrence of a unique mineralization phase, and points to distinct events (plausibly related to the various magmatic phases that affected the area), each of which was characterized by a distinctive trace-element fingerprint. Noteworthy, the presence of many accessory minerals and the relative geochemical budget could induce geochemical risks, as toxic elements could be transferred to local soil and water. Author Contributions G.B., C.N., P.F., L.C. sampled the studied rocks and planned the research. C.M. supervised the analyses at the University of Ferrara. M.C. provided useful indication in the interpretation of the data and drawn the figures. Funding This research was funded by FAR2018 provided by the University of Ferrara to G.B. Acknowledgments The authors are grateful to the reviewers who provided suitable suggestions and indications for improving the current version of the manuscript. Conflicts of Interest The authors declare no conflict of interest. References Brusca, C.; Perna, G. Inquadramento e Genesi dei Giacimenti di Galena Argentifera del Monte Calisio (Trento). In Proceedings of the Atti del Convegno “II Monte Calisio e L’argento delle Alpi Dall’antichità al XVIII Secolo, Giacimenti, Storia e Rapporti con la Tradizione Mineraria Mitteleuropea“, Civezzano, Italy, 14–15 October; 1995; pp. 19–30. [ Google Scholar ] Cook, N.J.; Ciobanu, C.L.; Pring, A.; Skinner, W.; Shimizu, M.; Danyushevsky, L.; Saini-Eidukat, B.; Melcher, F. Trace and minor elements in sphalerite: A LA-ICPMS study. Geochim. Cosmochim. Acta 2009 , 73 , 4761–4791. [ Google Scholar ] [ CrossRef ] Cook, N.J.; Etschmann, B.; Ciobanu, C.L.; Geraki, K.; Howard, D.L.; Williams, T.; Rae, N.; Pring, A.; Chen, G.; Johannessen, B.; et al. Distribution and Substitution Mechanism of Ge in a Ge–(Fe)-Bearing Sphalerite. Minerals 2015 , 5 , 117–132. [ Google Scholar ] [ CrossRef ] Cook, N.J.; Ciobanu, C.L.; George, L.; Zhu, Z.-Y.; Wade, B.; Ehrig, K. Trace Element Analysis of Minerals in Magmatic-Hydrothermal Ores by Laser Ablation Inductively-Coupled Plasma Mass Spectrometry: Approaches and Opportunities. Minerals 2016 , 6 , 111. [ Google Scholar ] [ CrossRef ] Junge, M.; Oberthür, T.; Melcher, F. Cryptic variation of chromite chemistry, platinum-group-element and —mineral distribution in the UG-2 chromitite—An example from the Karee Mine, western Bushveld Complex, South Africa. Econ. Geol. 2014 , 109 , 795–810. [ Google Scholar ] [ CrossRef ] Junge, M.; Wirth, R.; Oberthür, T.; Melcher, F.; Schreiber, A. Mineralogical siting of platinum-group elements in pentlandite from the Bushveld Complex, South Africa. Miner. Depos. 2015 , 50 , 41–54. [ Google Scholar ] [ CrossRef ] Goldmann, S.; Junge, M.; Wirth, R.; Schreiber, A. Distribution of trace elements in sphalerite and arsenopyrite on the nanometre-scale—discrete phases versus solid solution. Eur. J. Mineral. 2018 , 31 , 325–333. [ Google Scholar ] [ CrossRef ] Ye, L.; Cook, L.; Ciobanu, C.L.; Yuping, L.; Qian, Z.; Tiegeng, K.; Wei, G.; Yulong, L.; Danyushevskiy, L. Trace and minor elements in sphalerite from base metal deposits in South China: A LA-ICPMS study. Ore Geol. Rev. 2011 , 39 , 188–217. [ Google Scholar ] [ CrossRef ] Sassi, F.P.; Cesare, B.; Mazzoli, C.; Peruzzo, L.; Sassi, R.; Spiess, R. The crystalline basements of the Italian eastern Alps: A review of the metamorphic features. Period. Di Mineral. 2004 , 73 , 23–42. [ Google Scholar ] Spiess, R.; Cesare, B.; Mazzoli, C.; Sassi, R.; Sassi, F.P. The crystalline basement of the Adria microplate in the eastern Alps: A review of the palaeostructural evolution from the Neoproterozoic to the Cenozoic. Rend. Lincei 2010 , 21 , 31–50. [ Google Scholar ] [ CrossRef ] Rottura, A.; Bargossi, G.M.; Caggianelli, A.; Del Moro, A.; Visonà, D.; Tranne, C.A. Origin and significance of the Permian high-K calc-alkaline magmatism in the central-eastern Southern Alps. Italy. Lithos 1998 , 45 , 329–348. [ Google Scholar ] [ CrossRef ] Willcock, M.A.W.; Cas, R.A.F.; Giordano, G.; Morelli, C. The eruption. pyroclastic flow behaviour. and caldera in-filling processes of the extremely large volume (>1290 km 3 ). intra- to extra-caldera. Permian Ora (Ignimbrite) Formation. Southern Alps. Italy. J. Volcanol. Geotherm. Res. 2013 , 265 , 102–126. [ Google Scholar ] [ CrossRef ] Bosellini, A.; Gianolla, P.; Stefani, M. The Triassic Carbonate Platforms of the Dolomites (Northern Italy): Their Evolution and Stratigraphic Framework. Mem. Di Sci. Geol. 2003 , 54 , 111–185. [ Google Scholar ] Avanzini, M.; Bargossi, G.M.; Borsato, A.; Selli, L. Note iIllustrative Della Carta Geologica d’Italia Alla Scala 1:50,000 ; ISPRA-Servizio Geologico d’Italia: Trento, Italy, 2010; p. 060. [ Google Scholar ] Bianchini, G.; Natali, C.; Shibata, T.; Yoshikawa, M. Basic Dykes Crosscutting the Crystalline Basement of Valsugana (Italy): New Evidence of Early Triassic Volcanism in the Southern Alps. Tectonics 2018 , 37 , 2080–2093. [ Google Scholar ] [ CrossRef ] Nimis, P.; Omenetto, P.; Giunti, I.; Artioli, G.; Angelini, I. Lead isotope systematics in hydrothermal sulphide deposits from the centraleastern Southalpine (northern Italy). Eur. J. Mineral. 2012 , 24 , 23–37. [ Google Scholar ] [ CrossRef ] Artioli, G.; Angelini, I.; Tecchiati, U.; Pedrotti, A. Eneolithic copper smelting slags in the Eastern Alps: Local patterns of metallurgical exploitation in the Copper Age. J. Archaeol. Sci. 2015 , 63 , 78–83. [ Google Scholar ] [ CrossRef ] Murara, G. Le Mineralizzazioni a Solfuri Misti Nelle Vulcaniti Atesine, Formazione Andesitica, Dell’alta Val Fersina (Trentino). In Atti del Symposium Internazionale sui Giacimenti Minerari delle Alpi Atti del Symposium Internazionale sui Giacimenti Minerari delle Alpi ; Regione Trentino Alto Adige e CCIA: Trento, Italy, 1966; Volume 2, pp. 471–493. [ Google Scholar ] Barillari, A.; Jobstraibizer, P.G.; Omenetto, P. II Giacimento a Piombo, Zinco e Rame di Cinque Valli in Valsugana (Trentino). In Atti del Symposium Internazionale sui Giacimenti Minerari delle Alpi ; Regione Trentino Alto Adige e CCIA: Trento, Italy, 1966; Volume 3, pp. 769–791. [ Google Scholar ] Shiga, Y.; Urashima, Y. Isomorphous compounds; Galena Clausthalite, and altaite from the Kushikino gold-silver ore deposit, Japan-possible substitutional limits. Min. Geol. 1989 , 39 , 253–260. [ Google Scholar ] Seryotkin, Y.V.; Pal’yanov, G.A.; Savva, N.E. Sulfur–selenium isomorphous substitution and morphotropic transition in the Ag 3 Au(Se,S) 2 series. Russ. Geol. Geophys. 2013 , 54 , 646–651. [ Google Scholar ] [ CrossRef ] Bullock, L.A.; Perez, M.; Armstrong, J.G.; Parnell, J.; Still, J.; Feldmann, J. Selenium and tellurium resources in Kisgruva Proterozoic volcanogenic massive sulphide deposit (Norway). Ore Geol. Rev. 2018 , 99 , 411–424. [ Google Scholar ] [ CrossRef ] Radková, A.B.; Jamieson, H.; Llinská-Voleková, B.; Majzlan, J.; Števko, M.; Chovan, M. Mineralogical controls on antimony and arsenic mobility during tetrahedrite-tennantite weathering at historic mine sites Špania Dolina-Piesky and Ľubietová-Svätodušná, Slovakia. Am. Mineral. 2017 , 102 , 1091–1100. (In Slovak) [ Google Scholar ] Cheng, Y.; Spandler, C.; Kemp, A.; Mao, J.; Rusk, B.; Hu, Y.; Blake, K. Controls on cassiterite (SnO 2 ) crystallization: Evidence from cathodoluminescence, trace-element chemistry, and geochronology at the Gejiu Tin District. Am. Mineral. 2019 , 104 , 118–129. [ Google Scholar ] [ CrossRef ] Pons, M.-L.; Debret, B.; Bouilhol, P.; Delacour, A.; Williams, H. Zinc isotope evidence for sulfate-rich fluid transfer across subduction zones. Nat. Commun. 2016 , 7 , 13794. [ Google Scholar ] [ CrossRef ] [ PubMed ] Giuli, G.; Paris, E.; Wu, Z.; De Panfilis, S.; Pratesi, G.; Cipriani, G. 2005The Structural Role of Ag in Galena (PbS). A XANES Study. Phys. Scr. 2005 , T115 , 387–389. [ Google Scholar ] [ CrossRef ] Pažout, R.; Sejkora, J.; Šrein, V. Ag-Pb-Sb Sulfosalts and Se-rich Mineralization of Anthony of Padua Mine near Poličany—Model Example of the Mineralization of Silver Lodes in the Historic Kutná Hora Ag-Pb Ore District, Czech Republic. Minerals 2019 , 9 , 430. [ Google Scholar ] [ CrossRef ] Amcoff, O. Distribution of silver in massive sulfide ores. Miner. Depos. 1984 , 19 , 63–69. [ Google Scholar ] [ CrossRef ] Chutas, N.I.; Kress, V.C.; Ghiorso, M.S.; Sack, R.O. A solution model for high-temperature PbS-AgSbS2-AgBiS2 galena. Am. Mineral. 2008 , 93 , 1630–1640. [ Google Scholar ] [ CrossRef ] Sack, R.O.; Loucks, R. Thermodynamic properties of tetrahedrite-tennantites: Constraints on the interdependence of the Ag↔Cu. Fe↔Zn. Cu↔Fe. and As↔Sb exchange reactions. Am. Mineral. 1985 , 70 , 1270–1289. [ Google Scholar ] Arlt, T.; Diamond, L.W. Composition of tetrahedrite-tennantite and ‘schwazite’ in the Schwaz silver mines. North Tyrol, Austria. Mineral. Mag. 1998 , 62 , 801–820. [ Google Scholar ] [ CrossRef ] Lynch, J.V.G. Large-scale hydrothermal zoning reflected in the tetrahedrite-freibergite solid solution. Keno hill Ag–Pb–Zn district, Yukon. Can. Mineral. 1989 , 27 , 383–400. [ Google Scholar ] Sack, R.O.; Lynch, J.V.G.; Foit, F. Fahlore as a petrogenetic indicator: Keno Hill Ag–Pb–Zn District. Yukon. Canada. Mineral. Mag. 2003 , 67 , 1023–1038. [ Google Scholar ] [ CrossRef ] Catchpole, H.; Kouzmanov, K.; Fontboté, L. Copper-excess stannoidite and tennantite-tetrahedrite as proxies for hydrothermal fluid evolution in a zoned cordilleran base metal district. Morococha. central Peru. Can. Mineral. 2012 , 50 , 719–743. [ Google Scholar ] [ CrossRef ] Sack, R.O. Note on “large-scale hydrothermal zoning reflected in the tetrahedrite-freibergite solid solution. Keno Hill Ag–Pb–Zn district. Yukon” by J.V. Gregory Lynch. Can. Mineral. 2002 , 40 , 1717–1719. [ Google Scholar ] [ CrossRef ] Hernández, A.N.G.; Akasaka, M. Ag-rich tetrahedrite in the El Zancudo deposit, Colombia: Occurrence. chemical compositions and genetic temperatures. Resour. Geol. 2010 , 218–233. [ Google Scholar ] [ CrossRef ] Keim, M.F.; Walter, B.F.; Neumann, U.; Kreissl, S.; Bayerl, R.; Markl, G. Polyphase enrichment and redistribution processes in silver-rich mineral associations of the hydrothermal fluorite-barite-(Ag–Cu) Clara deposit. SW Germany. Miner. Depos. 2018 , 54 , 155–174. [ Google Scholar ] [ CrossRef ] Figure 1. Simplified ( a ) geographic and ( b ) geological sketches of studied area located in the province of Trento (NE Italy). Symbols denote localities where mineralized rocks were sampled. Red triangle, Calisio mount; red diamond, Erdemolo lake; red pentagon, Cinque Valli site. Geological information was retrieved by map of lithology and structural elements of Trento. Figure 2. Hand-specimen photographs of studied mineralized rocks. ( a ) Sample MGC2 from Calisio mount, where brown oolitic carbonate matrix is crosscut by sulfide (mainly galena) veinlet; ( b ) sample MGE3 from Erdemolo lake characterized by porphyric texture with quartz and feldspar aggregates within a greenish matrix containing millimetric sulfide crystals; ( c ) sample MGE5 from Erdemolo lake constituted by prevalent sulfide (mainly yellow chalcopyrite); ( d ) sample MGV2 from Cinque Valli site mainly constituted by sulfide (with prevalent brown sphalerite and grey galena). Figure 3. Binary diagrams showing elemental ratios can be discriminant of mineralized rocks from the Calisio mount, Erdemolo lake, and Cinque Valli. ( a ) K/Na vs. Fe/Mn, ( b ) Li/Rb vs. Sr/Ba, ( c ) Bi/Tl vs. Cd/Sn, ( d ) Sb/Te vs. As/Se. Figure 4. Back-scattered scanning electron microscopy (SEM) images of mineralized rocks from Calisio mount. Note that mineralization is not solely composed by galena, and that the paragenesis is remarkably more complex. Abbreviations: Qz = quartz, Gn = galena, Ttr = tetrahedrite, Ccp = chalcopyrite, Cer = cerussite, Py = pyrite, CuCO 3 = copper carbonate. ( a ) shows that the mineralized veinlet, mainly composed by Gn, also contains minor Qz and Ccp, as well as secondary minerals such as Cer; ( b ) shows that Trd is also present in the mineral association; ( c ) and ( d ) emphasize that Trd is altered and resorbed, indicating that this mineral is unstable in supergene condition. Figure 5. Back-scattered scanning electron microscopy (SEM) images of mineralized rocks from the Erdemolo lake. Note that mineralization is not solely composed by galena and chalcopyrite, and that the paragenesis is remarkably more complex. Abbreviations: Qz = quartz, Gn = galena, Ttr = tetrahedrite, Tnt = tennantite, Ccp = chalcopyrite, Py = pyrite, Ac = acanthite, Cst = cassiterite, Plb= polybasite, Mtd = matildite. ( a ) shows the intimate association of Ccp, Gn, Py, Cst, Qz; ( b ) shows the presence of Plb; ( c ) shows the presence of Ac; ( d ) shows the presence of Mtd. Figure 6. Sb/As vs. Ag/Cu interdependence in the tetrahedrite-tennantite series recorded in mineralized rocks from Calisio mount. Table 1. ICP-MS analyses (expressed in ppm) of mineralized rocks from Calisio mount (MGC), Erdemolo lake (MGE), and Cinque Valli (MGV). Analyzed Calisio Mount Erdemolo Lake Cinque Valli Element MGC1 MGC2 MGE1 MGE3 MGE5 MGV2 MGV3 Ca 288,513 321,530 7804 29,572 509 140 2005 Mg 85,595 67,562 2271 3242 4076 45.8 684 Al 1891 618 16,143 19,264 23,388 995 4679 Na 114 180 44.1 116 26.2 120 3838 K 308 158 497 1173 1177 283 2194 Li 56.2 19.4 51.5 182 47.8 30.7 48.4 Rb 1.83 0.93 3.03 8.71 3.62 2.61 14.3 Sr 62.8 210 2.37 7.13 1.06 1.62 5.39 Ba 16.0 111 n.d. 4.71 7.04 0.49 8.58 P 44.9 41.1 65.8 81.4 194 19.1 25.0 B 28.7 24.3 13.4 31.2 n.d. 0.86 9.88 Be 0.29 0.25 0.26 0.48 0.11 0.30 0.60 Fe 21,098 18,607 79,475 41,450 303,616 3402 3059 Mn 13,340 6906 1435 2500 2709 12.6 9.08 Ti 38.6 16.1 74.2 92.0 220 2.78 10.1 Cu 1376 791 24,434 15,398 191,530 1132 374 Zn 260 259 90,692 24,671 793 232,752 271,351 Pb 56,276 137,048 101,981 61,735 1249 74,273 38,476 Ag 142 50.7 64.0 311.4 51.7 118 69.3 Sb 602 670 38.1 30.7 38.0 691 194 Bi 0.25 0.35 176 47.2 59.1 1.40 0.31 As 278 86.7 34.8 5.95 42.7 1.78 3.14 Cd 7.2 4.2 409 150 5.06 648 737 Sn 0.58 0.48 61.2 42.1 111 4.47 2.16 Ga 0.47 2.03 2.30 3.09 4.81 59.0 61.0 Se 0.69 0.32 61.0 25.0 52.2 2.86 2.74 Te 0.05 0.06 0.83 0.31 0.17 0.08 0.10 Sc 1.23 0.44 1.21 3.34 5.23 n.d. n.d. V 1.22 1.23 5.22 9.85 17.1 n.d. 2.24 Cr 1.59 0.94 3.17 4.37 8.87 0.35 0.57 Co 5.23 10.4 10.7 6.06 17.0 21.2 24.4 Ni 73.0 75.9 2.89 8.63 2.48 0.44 1.46 Mo 0.02 0.68 0.21 0.42 1.69 1.95 2.65 Tl 0.28 0.59 0.17 0.08 n.d. 0.22 0.06 U 0.60 0.76 0.08 0.12 0.25 n.d. 0.04 n.d. = not detected. Table 2. SEM (EDS) semi-quantitative analyses (wt %) of minerals at Calisio mount; analyses were normalized to 100%. wt % Galena wt % Cerussite S 13.1 12.65 12.55 12.71 12.37 12.35 C 8.48 9.46 10.03 10.02 8.99 Ag 0.46 - - - - 0.20 O 27.53 29.88 31.25 31.22 28.77 Pb 86.44 87.35 87.45 87.29 87.63 87.45 Pb 63.99 60.66 58.73 58.76 62.24 Total 100 100 100 100 100 100 Total 100 100 100 100 100 wt % Tetrahedrite-Tennantite S 25.45 24.62 23.03 25.9 24.88 23.55 23.15 24.82 25.02 25.93 Fe 0.38 1.26 0.61 0.37 0.48 0.51 0.51 - - - Cu 31.87 32.09 27.53 31.58 31.29 26.19 27.11 31.17 30.65 31.42 Zn 6.41 5.86 5.63 6.56 6.11 5.64 6.19 6.34 5.72 6.44 As 7.60 10.55 3.82 15.91 14.53 - 4.55 7.53 11.86 8.74 Ag 2.66 1.09 4.98 - 0.97 8.04 4.65 2.33 2.32 3.73 Sb 15.65 9.9 19.11 3.35 4.74 22.05 18.56 16.04 8.46 13.53 Pb 9.97 14.63 15.29 16.33 17.00 14.02 15.29 11.77 15.97 10.21 Total 100 100 100 100 100 100 100 100 100 100 wt % Chalcopyrite S 38.15 38.04 38.36 37.59 41.65 39.37 40.02 38.19 40.60 Fe 28.81 28.64 28.24 29.46 27.27 26.81 27.46 28.38 27.79 Cu 33.04 33.32 33.40 32.95 31.09 33.83 32.52 33.43 31.62 Total 100 100 100 100 100 100 100 100 100 Table 3. SEM (EDS) semi-quantitative analyses (wt %) of minerals at Erdemolo lake; analyses were normalized to 100%. wt % Galena S 13.13 13.17 13.42 13.62 13.37 13.48 13.27 12.81 13.19 12.94 15.31 Ag 0.27 0.61 0.44 1.17 1.34 1.84 1.90 0.25 - 0.29 0.11 Pb 86.6 86.23 86.14 85.21 85.29 84.68 84.83 86.93 86.81 86.77 84.57 Total 100 100 100 100 100 100 100 100 100 100 100 wt % Chalcopyrite wt % Sphalerite wt % Acanthite S 35.74 35.41 S 36.37 30.16 38.09 S 13.96 17.92 13.77 16.99 Fe 30.64 29.65 Fe 0.93 2.34 1.29 Ag 86.04 82.08 86.23 83.01 Cu 33.62 34.95 Zn 62.7 67.5 60.63 Total 100 100 100 100 Total 100 100 Total 100 100 100 wt % Sulfosalts S 19.71 21.11 20.99 17.05 Cu - - - 3.52 Ag 22.57 29.66 29.3 72.37 Pb 21.95 - - - Sb - - - 7.06 Bi 35.77 49.24 49.71 - Total 100 100 100 100
https://www.mdpi.com/2075-163X/9/12/736/htm#B30-minerals-09-00736
Autoantibodies Against LINE-1 p40 May Be More Common in Patients with Active SLE - The Rheumatologist Autoantibodies Against LINE-1 p40 May Be More Common in Patients with Active SLE Autoantibodies that react with long interspersed nuclear elements (LINE-1) p40 protein may be common in severe and active systemic lupus erythematosus (SLE) patients, according toresearchfrom Victoria Carter, MS, and colleagues. 1 LINE-1, class I transposable elements in DNA, make up 17% of the human genome. Although most LINE-1 copies are mutated and truncated in the human genome, approximately 180 appear to be intact, with a few that continue to retrotranspose and occasionally disrupt genes or regulatory regions by novel insertions, according to the researchers. Because of this response, defense mechanisms have evolved against retro-elements and retroviruses. Some researchers theorize that many human diseases, including cancer and autoimmune diseases, are connected with LINE-1 biology, and several theories link LINE-1 to the development of SLE and its flares. To help test this hypothesis, researchers used highly purified p40 proteins to quantitate immunoglobulin G autoantibodies found in the serum of 172 SLE patients, as well as disease controls (20 patients with systemic sclerosis) and age-matched healthy subjects (78 patients). The first cohort for the study included 10 patients with SLE. In a second SLE cohort, patients were in remission (n=83) or experiencing flare (n=79). The initial group of 10 patients came from the University of Washington Medical Center, Seattle, and the remaining patients were from Skåne University Hospital, Lund, Sweden. In the majority of patients, as well as in many healthy controls, antibodies reactive with p40 proteins were detected. The results were higher in SLE patients, but not those with systemic sclerosis, when compared with healthy controls. Anti-p40 reactivity was higher during a flare among patients in remission ( P=0.03). Anti-p40 reactivity also correlated with several other factors, including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (P=0.0002), type I interferon score (P=006), complement C3 decrease (P=0.0001), anti-DNA antibodies (P<0.0001), anti-C1q antibodies (P=0.004) and a current or past history of nephritis ( P=0.02). The antibodies were correlated inversely with age. In a study of SLE patient sera, the researchers also found a reaction with p40-associated proteins. Within the SLE flare population, patients with high titers had higher SLEDAI scores than patients who were below the cutoff of the 90th percentile or more among healthy controls. Current anti-dsDNA antibodies and complement consumption also were associated with anti-p40 antibody levels. “Collectively, these data indicate that higher anti-p40 levels tend to accompany active disease,” the researchers write. One finding that surprised researchers is a statistically higher inverse correlation of anti-p40 reactivity with SLE patient age ( P<0.0001), which may be partially explained by the higher SLEDAI of younger patients, they write. However, even when the full cohort of SLE patients and healthy controls was split into two groups with an age cutoff at 40 years, researchers found a more marked association of anti-p40 reactivity with SLE in the younger group than in the total cohort. Future Implications“Clearly, anti-p40 antibodies do not by themselves herald clinically relevant autoimmunity, but more likely represent an early phase of self-reactivity that may—or may not—progress towards SLE. … Our findings that nearly all SLE patients have autoantibodies against the LINE-1 p40 protein and that these antibodies are associated with disease activity, specific disease manifestations, low complement, other autoantibodies and type I interferons, taken together, suggest that LINE-1 biology is coupled in some way to SLE pathogenesis,” the researchers write.
https://www.the-rheumatologist.org/article/autoantibodies-against-line-1-p40-may-be-more-common-in-patients-with-active-sle/
Lenovo ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-Port Low-Latency Adapter User Guide 2022-11-08 — The ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter delivers low sub-600µs latency, extremely high message rates, RoCE v2, ... User Guide for Lenovo models including: ThinkSystem Mellanox ConnectX-5 Ex 25 40GbE 2-Port Low-Latency Adapter, ThinkSystem Mellanox ConnectX-5, ThinkSystem Mellanox ConnectX-5 Ex 25, 40GbE 2 Port Low-Latency Adapter, 2-Port Low-Latency Adapter, Low-Latency Adapter, 2-Port Adapter, Adapter ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter Download PDF ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter Product Guide > Lenovo Press ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2 2022-11-08 — The ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter delivers low sub-600µs latency, extremely high message rates, RoCE v2, ... Browser built in viewer PDF Viewer Universal Document Viewer Google Docs View Google Drive View Download Document [pdf] Download Document [Optimized] Document: Text References Not Your Device? Search For Manuals / Datasheets: File Info : application/pdf, 13 Pages, 258.99KB Document lp0901 ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2port Low-Latency Adapter Product Guide The ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter delivers low sub-600µs latency, extremely high message rates, RoCE v2, NVMe over Fabric offloads and embedded PCIe switch. Mellanox provides the highest performance and lowest latency for the most demanding applications: High frequency trading, Machine Learning, Data Analytics, and more. This adapter ships ready to accept 10GbE, 25GbE or 40GbE network connections. The following figure shows the ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter. Figure 1. ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter (heatsink removed) Did you know? NVMe storage solutions are gaining popularity, offering very fast storage access. The evolving NVMe over Fabric (NVMe-oF) protocol leverages the Mellanox RDMA connectivity for remote access. ConnectX-5 offers further enhancements by providing NVMe-oF target offloads, enabling very efficient NVMe storage access with no CPU intervention, and thus improved performance and lower latency. ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 1 Part number information The ordering information is listed in the following table. Table 1. Ordering information Part number Feature Mellanox code equivalent 4XC7A08229 B31C MCX516ABDAT Description ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter The adapter, when shipped as a stand-alone option, includes the following items: One Mellanox ConnectX-5 Ex EN adapter Two QSFP28 to SFP28 transceiver adapters (QSA28) Full-height (3U) bracket attached with low-profile (2U) bracket included in the box Documentation flyer QSA28 adapters: The option part number includes the QSA28 adapters, however when ordering the adapter as part of a server CTO build, the feature code B31C does not include the adapters and they must be ordered separately. Supported transceivers and cables The adapter has two empty QSFP28 cages. The adapter also includes two QSA28 adapters that convert the QSFP28 cages to SFP28 for 25Gb connectivity. The adapter either supports a connection to a 1Gb, 10Gb, 25Gb or 40Gb switch or can share a connection to a 100Gb switch using a 4:1 breakout cable. The following table lists the supported transceivers. Table 2. Transceivers Part number Feature code Description 1Gb transceivers 00FE333 A5DL SFP 1000Base-T (RJ-45) Transceiver 10Gb transceivers 46C3447 5053 SFP+ SR Transceiver 4TC7A78615 BNDR ThinkSystem Accelink 10G SR SFP+ Ethernet transceiver 25Gb transceivers 7G17A03537 AV1B Lenovo 25GBase-SR SFP28 Transceiver (supports 10Gb and 25Gb) 4M27A67041 BFH2 Lenovo 25Gb SR SFP28 Ethernet Transceiver Converters 4G17A10853* B306 Mellanox QSA 100G to 25G Cable Adapter * Two QSA adapters are included with the ConnectX-5 Ex adapter part number, however they are not included with the adapter when ordered with a server as part of a CTO build. For CTO orders, select the QSA adapters separately if needed. This 25 Gb transceiver also supports 10 Gb when used with a Mellanox adapter ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 2 25Gb transceivers: When installed in this 25Gb Ethernet adapter, certain supported 25Gb transceivers (as listed in the above table) are designed to operate at either 25 Gb/s or 10 Gb/s speeds, depending on the negotiation with the connected switch. In most configurations, this negotiation is automatic, however in some configurations you may have to manually set the link speed or FEC mode. The following table lists the supported fiber optic cables and Active Optical Cables. Table 3. Optical cables Part number Feature code Description LC-LC OM3 Fiber Optic Cables (these cables require a transceiver) 00MN499 ASR5 Lenovo 0.5m LC-LC OM3 MMF Cable 00MN502 ASR6 Lenovo 1m LC-LC OM3 MMF Cable 00MN505 ASR7 Lenovo 3m LC-LC OM3 MMF Cable 00MN508 ASR8 Lenovo 5m LC-LC OM3 MMF Cable 00MN511 ASR9 Lenovo 10m LC-LC OM3 MMF Cable 00MN514 ASRA Lenovo 15m LC-LC OM3 MMF Cable 00MN517 ASRB Lenovo 25m LC-LC OM3 MMF Cable 00MN520 ASRC Lenovo 30m LC-LC OM3 MMF Cable SFP+ 10Gb Active Optical Cables 00YL634 ATYX Lenovo 1M SFP+ to SFP+ Active Optical Cable 00YL637 ATYY Lenovo 3M SFP+ to SFP+ Active Optical Cable 00YL640 ATYZ Lenovo 5M SFP+ to SFP+ Active Optical Cable 00YL643 ATZ0 Lenovo 7M SFP+ to SFP+ Active Optical Cable 00YL646 ATZ1 Lenovo 15M SFP+ to SFP+ Active Optical Cable 00YL649 ATZ2 Lenovo 20M SFP+ to SFP+ Active Optical Cable QSFP Active Optical Cables 00YL652 ATZ3 Lenovo 3m 40G QSFP+ to QSFP+ Active Optical Cable 00YL655 ATZ4 Lenovo 5m 40G QSFP+ to QSFP+ Active Optical Cable 00YL658 ATZ5 Lenovo 7m 40G QSFP+ to QSFP+ Active Optical Cable 00YL661 ATZ6 Lenovo 15m 40G QSFP+ to QSFP+ Active Optical Cable 00YL664 ATZ7 Lenovo 20m 40G QSFP+ to QSFP+ Active Optical Cable 7Z57A04256 AX42 Lenovo 1m 40G QSFP+ Active Optical Cable QSFP 40Gb Optical Cables 00VX003 AT2U Lenovo 10m QSFP+ MPO-MPO OM3 MMF Cable 00VX005 AT2V Lenovo 30m QSFP+ MPO-MPO OM3 MMF Cable SFP28 25Gb Active Optical Cables 7Z57A03541 AV1F Lenovo 3m 25G SFP28 Active Optical Cable 7Z57A03542 AV1G Lenovo 5m 25G SFP28 Active Optical Cable 7Z57A03543 AV1H Lenovo 10m 25G SFP28 Active Optical Cable 7Z57A03544 AV1J Lenovo 15m 25G SFP28 Active Optical Cable 7Z57A03545 AV1K Lenovo 20m 25G SFP28 Active Optical Cable QSFP28 100Gb Breakout Active Optical Cables 7Z57A03551 AV1R Lenovo 3m 100G to 4x25G Breakout Active Optical Cable ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 3 Part number 7Z57A03552 7Z57A03553 7Z57A03554 7Z57A03555 Feature code AV1S AV1T AV1U AV1V Description Lenovo 5m 100G to 4x25G Breakout Active Optical Cable Lenovo 10m 100G to 4x25G Breakout Active Optical Cable Lenovo 15m 100G to 4x25G Breakout Active Optical Cable Lenovo 20m 100G to 4x25G Breakout Active Optical Cable The following table lists the supported direct-attach copper (DAC) cables. Table 4. Copper cables Part number Feature code Description QSFP-to-QSFP Cables 49Y7890 A1DP 1m QSFP+-to-QSFP+ cable 49Y7891 A1DQ 3m QSFP+-to-QSFP+ cable 00D5810 A2X8 5m QSFP+ to QSFP+ Cable 00D5813 A2X9 7m QSFP+ to QSFP+ Cable SFP+ 10Gb Passive DAC Cables 00D6288 A3RG 0.5m Passive DAC SFP+ Cable 90Y9427 A1PH 1m Passive DAC SFP+ Cable 00AY764 A51N 1.5m Passive DAC SFP+ Cable 00AY765 A51P 2m Passive DAC SFP+ Cable 90Y9430 A1PJ 3m Passive DAC SFP+ Cable 90Y9433 A1PK 5m Passive DAC SFP+ Cable 00D6151 A3RH 7m Passive DAC SFP+ Cable SFP+ 10Gb Active DAC Cables 00VX111 AT2R Lenovo 1m Active DAC SFP+ Cables 00VX114 AT2S Lenovo 3m Active DAC SFP+ Cables 00VX117 AT2T Lenovo 5m Active DAC SFP+ Cables SFP28 25Gb Passive DAC Cables 7Z57A03557 AV1W Lenovo 1m Passive 25G SFP28 DAC Cable 7Z57A03558 AV1X Lenovo 3m Passive 25G SFP28 DAC Cable 7Z57A03559 AV1Y Lenovo 5m Passive 25G SFP28 DAC Cable QSFP28 100G-to-4x25G Breakout Cables 7Z57A03564 AV22 Lenovo 1m 100G QSFP28 to 4x25G SFP28 Breakout DAC Cable 7Z57A03565 AV23 Lenovo 3m 100G QSFP28 to 4x25G SFP28 Breakout DAC Cable 7Z57A03566 AV24 Lenovo 5m 100G QSFP28 to 4x25G SFP28 Breakout DAC Cable Features ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 4 Features The ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter has the following key features: Ultra-low latency Mellanox ConnectX-5 adapter cards feature exceedingly low latency and hardware-based RDMA technology that is perfect for meeting the needs of the financial services industry. Based on advanced technology providing sub-microsecond latency and a capacity of 200 million messages per second, ConnectX-5 offers the next generation of connectivity today. Mellanox's Messaging Accelerator (VMA) transparently boosts performance for socket-based applications without having to modify the applications. By offloading network processing from the OS, traffic passes directly to the network adapter from the application user space, bypassing the kernel IP stack and minimizing context switches, buffer copies, and interrupts. The result is a reduction in latency by 500% and an increase in application throughput, as compared to applications running on a standard network kernel stack. Cloud, SDN, and NFV environment support Mellanox Accelerated Switching and Packet Processing (ASAP2) Direct technology allows to offload vSwitch/vRouter by handling the data plane in the NIC hardware while maintaining the control plane unmodified. As a result there is significantly higher vSwitch/vRouter performance without the associated CPU load The vSwitch/vRouter offload functions that are supported by ConnectX-5 include Overlay Networks (for example, VXLAN, NVGRE, MPLS, GENEVE, and NSH) headers' encapsulation and de-capsulation, as well as stateless offloads of inner packets, packet headers' re-write enabling NAT functionality, and more. Moreover, the intelligent ConnectX-5 flexible pipeline capabilities, which include flexible parser and flexible match-action tables, can be programmed, which enable hardware offloads for future protocols. ConnectX-5 SR-IOV technology provides dedicated adapter resources and guaranteed isolation and protection for virtual machines (VMs) within the server. With ConnectX-5 Network Function Virtualization (NFV), a VM can be used as a virtual appliance. With full data-path operations offloads as well as hairpin hardware capability and service chaining, data can be handled by the Virtual Appliance with minimum CPU utilization. With these capabilities data center administrators benefit from better server utilization while reducing cost, power, and cable complexity, allowing more Virtual Appliances, Virtual Machines and more tenants on the same hardware. Specifications The adapter has the following technical specifications: PCIe 4.0 x16 host interface Support for MSI/MSI-X mechanisms Two QSFP28 external connectors supporting a transceiver, converter, direct-attach copper (DAC) cable or active optical cable (AOC). Data rates supported: 1, 10, 25 and 40 Gb/s Ethernet TLP (Transaction Layer Packet) Processing Hints (TPH) Embedded PCIe Switch: Up to 8 bifurcations PCIe switch Downstream Port Containment (DPC) enablement for PCIe hot-plug Access Control Service (ACS) for peer-to-peer secure communication Advance Error Reporting (AER) Process Address Space ID (PASID) Address Translation Services (ATS) ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 5 IBM CAPI v2 support (Coherent Accelerator Processor Interface) Support for MSI/MSI-X mechanisms Ethernet: 40GbE / 25GbE / 10GbE / 1GbE IEEE 802.3by, Ethernet Consortium 25, supporting all FEC modes IEEE 802.3ba 40 Gigabit Ethernet IEEE 802.3ae 10 Gigabit Ethernet IEEE 802.3az Energy Efficient Ethernet IEEE 802.3ap based auto-negotiation and KR startup IEEE 802.3ad, 802.1AX Link Aggregation IEEE 802.1Q, 802.1P VLAN tags and priority IEEE 802.1Qau (QCN) Congestion Notification IEEE 802.1Qaz (ETS) IEEE 802.1Qbb (PFC) IEEE 802.1Qbg IEEE 1588v2 Jumbo frame support (9.6KB) IPv4 (RFQ 791) IPv6 (RFC 2460) Enhanced Features: Hardware-based reliable transport Collective operations offloads Vector collective operations offloads PeerDirect RDMA (GPUDirect) communication acceleration 64/66 encoding Extended Reliable Connected transport (XRC) Dynamically Connected Transport (DCT) Enhanced Atomic operations Advanced memory mapping support, allowing user mode registration and remapping of memory (UMR) On demand paging (ODP) MPI Tag Matching Rendezvous protocol offload Out-of-order RDMA supporting Adaptive Routing Burst buffer offload In-Network Memory registration-free RDMA memory access CPU Offloads: RDMA over Converged Ethernet (RoCE) TCP/UDP/IP stateless offload LSO, LRO, checksum offload RSS (also on encapsulated packet), TSS, HDS, VLAN and MPLS tag insertion/stripping, Receive flow steering Data Plane Development Kit (DPDK) for kernel bypass applications Open VSwitch (OVS) offload using ASAP2: Flexible match-action flow tables Tunneling encapsulation/ de-capsulation Intelligent interrupt coalescence Header rewrite supporting hardware offload of NAT router Storage Offloads: NVMe over Fabric offloads for target machine Erasure Coding offload ­ offloading Reed Solomon calculations ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 6 T10 DIF ­ Signature handover operation at wire speed, for ingress and egress traffic Storage protocols: SRP, iSER, NFS RDMA, SMB Direct, NVMe-oF Overlay Networks: RoCE over Overlay Networks Stateless offloads for overlay network tunneling protocols Hardware offload of encapsulation and decapsulation of VXLAN, NVGRE, and GENEVE overlay networks Hardware-Based I/O Virtualization Single Root IOV Address translation and protection VMware NetQueue support SR-IOV: Up to 1K Virtual Functions SR-IOV: Up to 16 Physical Functions per host Virtualization hierarchies (e.g., NPAR and Multi-Host, when enabled): Virtualizing Physical Functions on a physical port SR-IOV on every Physical Function Configurable and user-programmable QoS Guaranteed QoS for VMs HPC Software Libraries: Open MPI, IBM PE, OSU MPI (MVAPICH/2), Intel MPI Platform MPI, UPC, Open SHMEM Management and Control: PLDM for Monitor and Control DSP0248 PLDM for Firmware Update DSP0267 SDN management interface for managing the eSwitch I2C interface for device control and configuration General Purpose I/O pins SPI interface to Flash JTAG IEEE 1149.1 and IEEE 1149.6 Remote Boot: Remote boot over Ethernet Remote boot over iSCSI Unified Extensible Firmware Interface (UEFI) Pre-execution Environment (PXE) Server support ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 7 Server support The following tables list the ThinkSystem servers that are compatible. Table 5. Server support (Part 1 of 2) 1S Intel Edge V2 2S Intel V2 AMD 4S Dense V2 V2 8S SE350 (7Z46 / 7D1X) SE450 (7D8T) ST50 V2 (7D8K / 7D8J) ST250 V2 (7D8G / 7D8F) SR250 V2 (7D7R / 7D7Q) ST650 V2 (7Z75 / 7Z74) SR630 V2 (7Z70 / 7Z71) SR650 V2 (7Z72 / 7Z73) SR670 V2 (7Z22 / 7Z23) SR635 (7Y98 / 7Y99) SR655 (7Y00 / 7Z01) SR645 (7D2Y / 7D2X) SR665 (7D2W / 7D2V) SD630 V2 (7D1K) SD650 V2 (7D1M) SD650-N V2 (7D1N) SN550 V2 (7Z69) SR850 V2 (7D31 / 7D32) SR860 V2 (7Z59 / 7Z60) SR950 (7X11 / 7X12) Part Number Description 4XC7A08229 ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2port Low-Latency Adapter NNNNNNNNNNNNNNNNNNN Y Table 6. Server support (Part 2 of 2) 1S Intel V1 2S Intel V1 Dense V1 4S V1 Part Number Description 4XC7A08229 ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter NNNNNNNNNYYNYNNNYYY Operating system support The adapter supports the following operating systems: Tip: This table is automatically generated based on data from Lenovo ServerProven. ST50 (7Y48 / 7Y50) ST250 (7Y45 / 7Y46) SR150 (7Y54) SR250 (7Y52 / 7Y51) ST550 (7X09 / 7X10) SR530 (7X07 / 7X08) SR550 (7X03 / 7X04) SR570 (7Y02 / 7Y03) SR590 (7X98 / 7X99) SR630 (7X01 / 7X02) SR650 (7X05 / 7X06) SR670 (7Y36 / 7Y37) SD530 (7X21) SD650 (7X58) SN550 (7X16) SN850 (7X15) SR850 (7X18 / 7X19) SR850P (7D2F / 2D2G) SR860 (7X69 / 7X70) ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 8 Table 7. Operating system support for ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port LowLatency Adapter, 4XC7A08229 SD530 (Gen 2) SR630 (Gen 2) SR650 (Gen 2) SR850 (Gen 2) SR850P SR860 (Gen 2) SR950 (Gen 2) SD530 (Gen 1) SR630 (Gen 1) SR650 (Gen 1) SR850 (Gen 1) SR860 (Gen 1) SR950 (Gen 1) Operating systems Microsoft Windows Server 2012 R2 Microsoft Windows Server 2016 Microsoft Windows Server 2019 Microsoft Windows Server 2022 Microsoft Windows Server version 1709 Microsoft Windows Server version 1803 Red Hat Enterprise Linux 6.10 Red Hat Enterprise Linux 6.9 Red Hat Enterprise Linux 7.3 Red Hat Enterprise Linux 7.4 Red Hat Enterprise Linux 7.5 Red Hat Enterprise Linux 7.6 Red Hat Enterprise Linux 7.7 Red Hat Enterprise Linux 7.8 Red Hat Enterprise Linux 7.9 Red Hat Enterprise Linux 8.0 Red Hat Enterprise Linux 8.1 Red Hat Enterprise Linux 8.2 Red Hat Enterprise Linux 8.3 Red Hat Enterprise Linux 8.4 Red Hat Enterprise Linux 8.5 Red Hat Enterprise Linux 8.6 Red Hat Enterprise Linux 9.0 SUSE Linux Enterprise Server 11 SP4 SUSE Linux Enterprise Server 12 SP2 SUSE Linux Enterprise Server 12 SP3 SUSE Linux Enterprise Server 12 SP4 SUSE Linux Enterprise Server 12 SP5 SUSE Linux Enterprise Server 15 SUSE Linux Enterprise Server 15 SP1 SUSE Linux Enterprise Server 15 SP2 SUSE Linux Enterprise Server 15 SP3 SUSE Linux Enterprise Server 15 SP4 Ubuntu 22.04 LTS VMware vSphere Hypervisor (ESXi) 6.0 U3 NNNNNNNYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY NNNNNNNYYY Y YY NNNNNNNYYNN Y Y NNNNNNNYYY Y YY NNNNNNNYYY Y YY NNNNNNNYY Y Y NY NNNNNNNYYY Y YY NNNNNNNYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY NNNNNNNYYY Y YY NNNNNNNYY Y Y NY NNNN YNNYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY NNNNNNNYYY Y YY ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 9 SD530 (Gen 2) SR630 (Gen 2) SR650 (Gen 2) SR850 (Gen 2) SR850P SR860 (Gen 2) SR950 (Gen 2) SD530 (Gen 1) SR630 (Gen 1) SR650 (Gen 1) SR850 (Gen 1) SR860 (Gen 1) SR950 (Gen 1) Operating systems VMware vSphere Hypervisor (ESXi) 6.5 VMware vSphere Hypervisor (ESXi) 6.5 U1 VMware vSphere Hypervisor (ESXi) 6.5 U2 VMware vSphere Hypervisor (ESXi) 6.5 U3 VMware vSphere Hypervisor (ESXi) 6.7 VMware vSphere Hypervisor (ESXi) 6.7 U1 VMware vSphere Hypervisor (ESXi) 6.7 U2 VMware vSphere Hypervisor (ESXi) 6.7 U3 VMware vSphere Hypervisor (ESXi) 7.0 VMware vSphere Hypervisor (ESXi) 7.0 U1 VMware vSphere Hypervisor (ESXi) 7.0 U2 VMware vSphere Hypervisor (ESXi) 7.0 U3 VMware vSphere Hypervisor (ESXi) 8.0 NNNNNNNYY Y Y NY NNNNNNNYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY NNNNNNNYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Y Y Y Y Y Y YYYY Y YY Physical specifications The adapter is a low-profile adapter with the following dimensions: Length: 14.2 cm (5.6 in) Height: 6.9 cm (2.71 in) Operating environment The adapter is supported in the following environment: Temperature (operating): 0 to 55 °C (32 to 131 °F) Temperature (storage): -40 to 70 °C (-40 to 158 °F) Humidity (operating): 10 to 90% non-condensing Humidity (storage): 5 to 90% non-condensing Warranty One-year limited warranty. When installed in a supported server, the adapter assumes the system's base warranty and any warranty upgrade. Agency approvals The adapter conforms to the following standards: Safety: CB / cTUVus / CE EMC: CE / FCC / VCCI / ICES / RCM RoHS: RoHS-R6 Related publications ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 10 Related publications For more information, see the following resources: Mellanox page for ConnectX-5 EN Ethernet adapters: https://www.nvidia.com/en-us/networking/ethernet/connectx-5/ Mellanox User Manuals: https://docs.nvidia.com/networking/display/ConnectX5EN Mellanox Messaging Accelerator (VMA) http://www.mellanox.com/page/software_vma?mtag=vma Networking Options for ThinkSystem Servers https://lenovopress.com/lp0765-networking-options-for-thinksystem-servers Lenovo ServerProven compatibility information: http://www.lenovo.com/us/en/serverproven/ Support page for the adapter: https://datacentersupport.lenovo.com/us/en/search?query= 4XC7A08229 Related product families Product families related to this document are the following: 25 Gb Ethernet Connectivity Ethernet Adapters ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 11 Notices Lenovo may not offer the products, services, or features discussed in this document in all countries. Consult your local Lenovo representative for information on the products and services currently available in your area. Any reference to a Lenovo product, program, or service is not intended to state or imply that only that Lenovo product, program, or service may be used. Any functionally equivalent product, program, or service that does not infringe any Lenovo intellectual property right may be used instead. However, it is the user's responsibility to evaluate and verify the operation of any other product, program, or service. Lenovo may have patents or pending patent applications covering subject matter described in this document. The furnishing of this document does not give you any license to these patents. You can send license inquiries, in writing, to: Lenovo (United States), Inc. 8001 Development Drive Morrisville, NC 27560 U.S.A. Attention: Lenovo Director of Licensing LENOVO PROVIDES THIS PUBLICATION "AS IS" WITHOUT WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF NON-INFRINGEMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Some jurisdictions do not allow disclaimer of express or implied warranties in certain transactions, therefore, this statement may not apply to you. This information could include technical inaccuracies or typographical errors. Changes are periodically made to the information herein; these changes will be incorporated in new editions of the publication. Lenovo may make improvements and/or changes in the product(s) and/or the program(s) described in this publication at any time without notice. The products described in this document are not intended for use in implantation or other life support applications where malfunction may result in injury or death to persons. The information contained in this document does not affect or change Lenovo product specifications or warranties. Nothing in this document shall operate as an express or implied license or indemnity under the intellectual property rights of Lenovo or third parties. All information contained in this document was obtained in specific environments and is presented as an illustration. The result obtained in other operating environments may vary. Lenovo may use or distribute any of the information you supply in any way it believes appropriate without incurring any obligation to you. Any references in this publication to non-Lenovo Web sites are provided for convenience only and do not in any manner serve as an endorsement of those Web sites. The materials at those Web sites are not part of the materials for this Lenovo product, and use of those Web sites is at your own risk. Any performance data contained herein was determined in a controlled environment. Therefore, the result obtained in other operating environments may vary significantly. Some measurements may have been made on development-level systems and there is no guarantee that these measurements will be the same on generally available systems. Furthermore, some measurements may have been estimated through extrapolation. Actual results may vary. Users of this document should verify the applicable data for their specific environment. © Copyright Lenovo 2022. All rights reserved. This document, LP0901, was created or updated on June 16, 2022. Send us your comments in one of the following ways: Use the online Contact us review form found at: https://lenovopress.lenovo.com/LP0901 Send your comments in an e-mail to: [email protected] This document is available online at https://lenovopress.lenovo.com/LP0901. ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 12 Trademarks Lenovo and the Lenovo logo are trademarks or registered trademarks of Lenovo in the United States, other countries, or both. A current list of Lenovo trademarks is available on the Web at https://www.lenovo.com/us/en/legal/copytrade/. The following terms are trademarks of Lenovo in the United States, other countries, or both: Lenovo® RackSwitch ServerProven® ThinkSystem® The following terms are trademarks of other companies: Intel® is a trademark of Intel Corporation or its subsidiaries. Linux® is the trademark of Linus Torvalds in the U.S. and other countries. Microsoft®, Windows Server®, and Windows® are trademarks of Microsoft Corporation in the United States, other countries, or both. Other company, product, or service names may be trademarks or service marks of others. ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter 13 References mailto:[email protected]?subject=Feedback for LP0901 Welcome | ServerProven End-to-End Networking Solutions | NVIDIA Search - Lenovo Support - Lenovo Support US NVIDIA Networking Docs Networking Options for ThinkSystem Servers > Lenovo Press ThinkSystem Mellanox ConnectX-5 Ex 25/40GbE 2-port Low-Latency Adapter Product Guide > Lenovo Press 25 Gb Ethernet Connectivity > Lenovo Press Ethernet Adapters > Lenovo Press Copyright and Trademark Information | Lenovo US | Lenovo US Welcome | ServerProven NVIDIA Mellanox ConnectX-5 Adapters | NVIDIA wkhtmltopdf 0.12.4-dev-4fa8338 Qt 4.8.7
https://manuals.plus/m/70db349b12db230ce79a2d59e9d8e06146e21c6511205e8545313adc395d4cd8
the western origin of Michelsberg farmers [Archive] - Eupedia Forum http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0179742 I didn't read it, just took a peek. Looks like based on mtDNA of a few individuals, IMO not enough to make some firm conclusions It seems to confirm though that the origin of Michelsberg lies in the Atlantic megalithic. PDA View Full Version : the western origin of Michelsberg farmers bicicleur 06-07-17, 08:37 http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0179742 I didn't read it, just took a peek. Looks like based on mtDNA of a few individuals, IMO not enough to make some firm conclusions It seems to confirm though that the origin of Michelsberg lies in the Atlantic megalithic. Fire Haired14 06-07-17, 14:32 Basically what the authors argue is that the Michelsberg farmers in East France/West Germany have more hunter gatherer mtDNA(U5) and affinity to Middle Neolithic mtDNA from the Paris Basin and are therefore not native to Central Europe but from somewhere further west. There's no basis for their claim. I think they argued something so that their paper would be published. The only thing we can say about this Michelsberg mtDNA from eastern France is it is typical of Neolithic Europeans. The N1a result makes me wonder if they were partially descended from eastern groups like LBK. Middle Neolithic/Chalcolithic Iberia and Britain didn't have any N1a. They also had lots more H3 than LBK and Neolithic Hungary. berun 06-07-17, 17:34 There's no basis for their claim. some quotes: Several hypotheses concerning the origin of the Michelsberg culture have been offered, but the one prevailing today (and first introduced in 1959 [19]) considers an origin in the Paris Basin [20±22]. This "occidental hypothesis" was reinforced by the demonstration of an important rupture in pottery traditions between the previous Alsatian cultures and the Michelsberg, combined with the continuity of specific ceramic features with southwestern traditions (in the Paris Basin). Interestingly, ceramic changes observed during the Michelsberg culture development have been accompanied by the apparition of particular funerary practices involving inhumations within circular pits. The mortuary practice of burying people in circular pits appeared simultaneously in the Chasséen culture in the south of France and in the epi-Lengyel MuÈnchshoÈfen culture of Lower Bavaria Indeed, all descriptive analyses showed small genetic distances between the MICH and Middle Neolithic groups from France (Paris Basin, "MNF" group). Subsequently or simultaneously, such a [extra] H-G legacy appeared in the Paris Basin during the Middle Neolithic (5,000±4,000 cal. BC, MNF = 14.6%). .... whereas the MICH group was the only group in Central Europe to present a significant H-G maternal lineage frequency (14.8%). the CV group contained a strong proportion of haplogroups H (H, H1 and H3) and X, which were more common in southern European and Paris Basin farmers you might read a paper before to spew up over it... Fire Haired14 06-07-17, 20:24 you might read a paper before to spew up over it... Ha Ha, maybe I was a little too negative. But it is true that mtDNA can usually tell very little about ethnic-regional origins. I think authors of study's like this make big claims so their papers can get published. Yeah there are little indications in the mtDNA from Michelsberg culture that it originated further south but nothing really convincing. Fire Haired14 06-07-17, 20:28 Michelberg results... H=7 33% H1, H3, H(xH1, H3)=5 K=4 19% U5=3 15%(two contrimed U5b) J1=2 10% T2=2 10% T2c1=1 X=1 5% W=1 5% N1a=1 5% Fire Haired14 06-07-17, 20:31 I found HVR1 matches for one of the K results. All of these matches aren't legitimate matches. The same mutation can pop up in multiple lineages. Some of the matches might be legit. Michelberg culture K-16291t matches Neolithic Scotland; K1a Neolithic Spain; K1a Poland=2 Saudi Arabia=1 India=1 Denmark=2(K1c1) Cato 06-07-17, 21:48 Interesting study, thanks..apparently peoples from France settled eastward during this period, a Western origin (Chassey) had been suggested even for the contemporaneous Lagozza cult. map 8922 MOESAN 06-07-17, 21:56 27 individuals mt-DNA is very few, when so diverse - MOESAN 08-07-17, 12:51 just a detail: the Michelsberg people concerning phenotypes were considered as drifted towards ancient Mesolithic pops compared to LBK people - not to say they were "pure" mesolithic-like... I think the Meso elements sort they had was rather the SOM kind of types, associated by someones to Teviecoid types spite I doubt a little: they were very more "brutal" looking than Teviecoids of Brittany; (geogr. distribution: Eastern Parisian Bassin, Champagne, Lorraine, Eiifel region of Germany, Southern Wallonia I think) - kingjohn 08-07-17, 21:26 Michelberg results... H=7 33% H1, H3, H(xH1, H3)=5 are you sure there is mtdna h3 go to table S.5 there are some h and h1 no h3 ... MOESAN 28-09-17, 14:37 I'm almost sure Y-DNA would have been more HG oriented. This culture was megalithic and at the end of the megalithic cultures as at the end of other Neolithic cultures in Europe, it seems HG males (among them lot of Y-I2a2 but not only) were gaining strength... The presence among them of wellknown neolithic mt-DNA doesn't exclude a Parisian Bassin towards southern Germany move, all the other data converge towards this. the Parisian Bassin at those times were already a melting pot of LBKlike "danubian", Chassean (South Rhône) and HG people.
https://www.eupedia.com/forum/archive/index.php/t-34294.html?s=f8b2df9ad18e41f78ed6911544d65d9c
(PDF) Agricultural land prices development in the Czech Republic and the latest legal development PDF | Agricultural land is the rare resource of strategic importance and its market in the Czech Republic underwent significant development in the last... | Find, read and cite all the research you need on ResearchGate Conference Paper PDF Available Agricultural land prices development in the Czech Republic and the latest legal development November 2017 Conference: Vision 2020: Sustainable Economic development, Innovation Management, and Global Growth At: Madrid Spain Abstract Agricultural land is the rare resource of strategic importance and its market in the Czech Republic underwent significant development in the last decade. A continuous trend of price increase in the last decade resulted in prices that are higher 3.5 times now compared to the year 2006. However the trend was not the same over time and the year 2014 brought even higher price increase than ever before due to legal changes, non-agricultural investors and the end of the economic crisis. Tested hypothesis confirmed that there is statistically significant difference in price development before and after 2014. Legal changes concern the right of first refusal which allowed reaching more easily broader range of potential buyers. Long and medium-term non-agricultural investors were seeking the opportunity of high yield and low risk investments. However the situation may change since the share of non-agricultural investors on total purchase slowly decreases as the costs in the investments increases. Also the re-introduction of the right of first refusal will have a negative impact on the market. Similar negative effect will have CZK appreciation against EUR and USD because of higher costs for foreign investors from Germany, Austria, Netherlands and Belgium. The last significant factor is the increase of the key interest rate which may continue in the future and which increases the costs of credit used for the agricultural land purchase. Agricultural land prices development in the Czech Republic and the latest legal development Ivan Soukal, University of Hradec Kralove Faculty of Informatics an d Management Department of Economics, Hradec Kralove, Czech Republic, [email protected] Agnieszka Tarnowska, Wrocla w University of Economics Depart ment of Management and Food Economy, Wrocław, Poland, agniesz [email protected] Abstract Agricultural land is the rare resource of strategic importance and its market in the Czech Republic underwent s ignificant development in the last decade. A continuous trend of price increase in the last decade resulted in prices that are higher 3.5 times now c ompared to the year 2006. H owever the trend was not the same over time and the year 2014 brought even higher price increase than e ver before due to le gal changes, non-agricultural investors and the e nd of the economic crisis. Tested hypothesis confirmed that there is statistically significa nt difference in price development before and after 2014. Legal changes concern the right of fir st refusal which a llowed reaching more easily broader range of potential buyers. Long and medium-term non-a gricultural i nvestors wer e see king the opportunity of h igh yield and low risk investments. However the situati on may change since the share of non-agricultural investors on total purchase sl owly d ecreases a s the costs in the investments increases. Also the re-introduction of the right of first refusal will have a negative impact on the mar ket. Similar negative effect will have CZK appreciation against EUR a nd USD because of higher costs for f oreign investors from German y, Austria, Netherlands and Belgium. The last signif icant factor is the increase of t he key interest rate which ma y continue in the future and which incre ases the costs of credit used f or the agricultural land purchase. Keywords: agricultural land, price, right of first refusal, Czech Republic. Introduction Agricultural land is the rare resource of strate gic importance for an y country that cares about the food security of its citizens and it participates on G DP as a factor of production. The agricultural land market went through many c hanges during the la st few decades. I t changed from the era of “under-developed” market where less than 0.5 % (Vrbová, N ě mec, 2005) a gricultural land fund traded per year to more than 2.3% traded per y ear (Ministry of Agriculture, 2015) and with a la nd as highl y demanded investment s. With the development of ci vilization this resource w ill decrease (Piwowar, Dziku ć , 2015), and its price will rise. T he last ten years show that the last part of the sentence is more than precise – t he lan d price s are 3.5 times higher than ten years ago. Such increase attrac ts the attention of not just investors but mainly of farmers themselves and government as well. One of the ways how government can influence the agricultural land price development is through legal system although within the limits of EU legal s ystem only. On e of the legal means is the right of fir st refusal which can significantl y delay or sometimes even prevent the agricultural land purc hase. Unlike Poland in the Czech Repu blic is a lot of land in c o-ownership. Co-owners had general right of first ref usal to other co-ownership shares t ill the 31 st December 2013 accordingly t o the Civil code. In 2014 the Civil code Act no. 89/2012 Coll. commonly known as New Civil code (hereinafter re ferred to as NCC) became active and t he right of first r efusal was not a general pri nciple anymore, its exten ded was l imited. Also at the same time non-agric ultural investors became dominant purchase power on the mar ket since agricultural land offered high y ield carrying onl y low ris k. Another im portant feature of 2014 was that this year ended the economic c risis. Vision 2020: Sustainable Economic development, Innovation Management, and Global Growth 2624 We are g oing to analyze the p rice development to find out whether the year 2014 and its two major factors were strong enough to change the price developme nt. We ar e g oing to test a hypothesis on a sample of price before and after the change (the right of fi rst refusal, non-agricultural in vestors became main bu yers on the market, end of crisis). Also we will de scribe t he latest developme nt incl uding re cent NCC n ovelization. NCC implemented change concerns Act no. 460/ 2016, Coll. bringing re-introduction of the right of first refusal. Methods Data for the anal ysis were obtained fr om two sources Cz ech Statistical Office and Farm y.cz. The first source provides the data based on real-estate transfer tax return anal ysed for the w hole tax pa yer population per year. The second source’s methodology is based on monitoring market prices und er a condition that both sides a re well-informed and partici pate voluntarily in trade. We did n ot separate arable land from permane nt grassland and s o land prices per h ectare are average price s per y ear of all agricultural land. Typical s ources of these data are the land auctions. Standard i nflation adjustment was performed on all land price s with a base year 2006. All prices are converted into EUR b y year average exchange rates. Due to a foreign exchange mar ket intervention of Czech National Bank are prices calculated in purchase parit y power exchange rates ( hereinafter referred t o as PPP) as cross-parity from USD/CZK and USD/EUR rate s. Mann–Whitney test (also known as Wilcoxon–Mann–Whitney test) is a suitable method capable of testing ranked data w ith wider usabilit y range than parametri c tests (such as t-te st). This method is widely used in social scie nces for ran ked data, see e. g. Bargagliotti ( 2009) or Aryal and Gabrielli, (2013) who employed Mann –Whitney test price development comparison under differe nt conditions. Mann–Whitne y test is a nonparametric test of the null hypothesis that it i s equally likely that a randomly selected value from one sample will be less than or greater than a randomly selected value from a second sample. The both samples have to be independent of each other and the values have to be ordinal. The hypothesis tests if variable X from sample A with n1 observations and the variable Y fr om the sample B with n2 observations got the same d istribution i.e. the distributi ons of both populations are equal. All observations got the rank. Let R A bet the sum of the ra nks from A sample and R B the sum of ranks f rom the i sample. Test value is the U min from: A A R n n n n U − + ⋅ + ⋅ = 2 ) 1 ( 1 1 2 1 ( 1 ) B B R n n n n U − + ⋅ + ⋅ = 2 ) 1 ( 1 1 2 1 ( 2 ) U ( α ,n1,n2) is the critical value of Mann–Whitne y test for selected α . If U min > U ( α ,n1,n2) then the hypothesis of distributi on match cannot be re jected. If U min < U ( α ,n1,n2) then the hypothesis of distributi on match can be rejected. Hypothesis 1: the distribution of land areas trade per year is equal for years before an d after the liberalization. Linear regression described e.g. b y Hebák (200 5) or Bowerman and O’Connel (1997) is base d on least square method . It solves the problem of finding a linear function that best fits a set of data points. Let us have a set of n pairs of obser vations {yi,xi} . The linear fun ction represen ts the relation of value of the dependent variable Y to the values of a n independent on e X . This functi on describes in other words the relation betwee n the data set a nd the prediction. With one variable a nd a l inear functi on, the pre diction is given by the following eq uation: bX a Y + = ) ( 3 ) Vision 2020: Sustainable Economic development, Innovation Management, and Global Growth 2625 This equation in volves two par ameters which spec ify the interc ept and the slope b of the linear regressi on function. The least square method defines the estimate of these parameters as the values fo r which th e sum of the squares between the dataset a nd the prediction (observed yi and the pre dicted yi) is the least one possible. The minimizati on problem is given b y the following equation: ( ) ( ) ∑ ∑ ∑ − − = − = n i i i n i i i n i bx a y y y 2 2 2 ) ε ( 4 ) The estimation of the parameters is obtained by derivati on of (4) with re spect to a and b and setting them to zero. Results Legal changes Co-owners had general right of first refusal to other co-ownership s hares till the 31 st December 2013 accordingly to the Civil c ode. The only exception was a tra nsfer to the close person. Close person is a legal construct descri bing a situation whe n two persons are so close to each other that a detr iment or harm to one of them, the other would felt as detriment or harm to one's own (generall y a close relative, a spouse, a registered partner, a siblin g, or any other person who would reasonab ly be harmed by another person's detriment). The genera l right of first refusal was applied to both immovable and movable property. The New Civil code became active f rom t he 1 st January 2014 and general right of first ref usal was not applied a nymore. The re gulation of selling a real estate s hare became li beral almost abolishi ng general right of fir st refusal although agricultural plant c o-ownership had a special treatment. Agricultural plant was a new legal construct representing a set of assets cr eated b y entrepreneur and b eing used to perform farming. The right of fir st re fusal w as kept valid concernin g agric ultural plant b ut onl y for a specific case when co-owners got their sh are under the c onditions whe n they could not influence their rights and o bligations fr om the be ginning. This covered mainly a sit uation such as if the co-ownership was b ased on the acquisition by previous owner’s death (by the las t will, by inheritance ag reement). However, at the same time another exception was involve d. Co-owners could not apply ri ght of first refusal if the share tra nsfers was a c o-owner a nd a nother co-owner, his or her spouse, sibling or a direct relative. The right of first r efusal was applicable also in case that a tran sfer was a voluntary c onveyance to prevent ri ght of first r efusal evasion. Alth ough the right of first refusal was kept valid for agricultura l plant in much wider range than for other propert y types, extend was significant ly narrower. The situation cha nged due to a recent New Ci vil code novelizati on by Act no. 460/2016, Coll., na mely article I. § 11 24, 1125 of N CC. The amendment of the New Civil c ode re-intr oduced the general right of first re fusal. As of 1st January 2018 the g eneral ri ght of first refusal will be applied again on all real estate. Therefore, if the co-owner transfers his or her share, the other co-owners can apply right of first refusal. An exception w ill be again concer ning close person and so tr ansfer to a close person cannot be blocked by the right of first refusal. Co-owners will have the right to redeem the seller’s share of ownership ac cording to the size of their s hares, unless the y a gree otherwise. Unlike before the exception will not be applica ble on the co-owner -to-co-owner transfers and so e ven in this case the righ t of first refusal has to be taken into consider ation. This extends the ri ght of fir st r efusal into a general princi ple. The latest amendment of NCC treats co-ownership in a lmost t he sa me wa y as Act no.140/2014, Coll. from Slovakia (valid from 1.6 .2014). This shows continuing legal similarities in f ormer Czec hoslovakian territory. Vision 2020: Sustainable Economic development, Innovation Management, and Global Growth 2626 Price development The y ear 2006 was selected a base year for inf lation adjusted prices per hectar e. Prices wer e converted b y EUR/CZK fo r b oth a verage year exchange rate and avera ge year excha nge r ate in development on the fig. 1 below. active in Januar y 20 14. T herefore a mar k di vides a price de velopment chart below general right of first refusal (till 2013) and without ( 2014 Fig. 1: Development price per Statistical Office, 2017; O ECD, 2017 The chart shows continuous incr ease in land price per hectar e PPP. The increase is described with regression function for prices in EUR {2006, 200 7, …, 2 016} and with regre ssion function f or prices in EUR in PPP {2006, 2007, …, 2016} . Both functions show ver y high index of determi nation suggest ing that the slopes are good price lead in the surveyed period. regarding the EUR and b y a bit more than The hypothesis regardin g the price develop ment before the y ear 2014 and after was tested with t he test criterion 0 below the tabled critical value managed to reject the h ypothesis that the prices of tw o The year 2014 br ought not just a changed and cr eated highly c ompetitive of a local situation and relati vely l ow was a t ypical on e in the previous decade nonagricultural invest ors and so frequent. Agricult ural buyers had t o compete w ith invest ors who a re capable and willi ng to real market pr ices on a new platfor ms suc h as land market aucti ons investment w hich is safer than ot her means o f invest ment agricul tural investors arose also d ue to an expected compensation for the land that cannot or will n ot be r eturned to church w ear 2006 was selected a base year for inf lation adjusted prices per hectar e. Prices wer e converted b y EUR/CZK fo r b oth a verage year exchange rate and avera ge year excha nge r ate in PPP development on the fig. 1 below. As mention ed earlier, a significant le gal chan ge in land mar ket became active in Januar y 20 14. T herefore a mar k di vides a price de velopment chart below into the part with the (till 2013) and without ( 2014 -2016). 1: Development price per hectare in EUR, own calcula tion based on (Farmy.cz, 2017; Czec h Statistical Office, 2017; O ECD, 2017 ; Ministry of Agriculture, 20 09). The chart shows continuous incr ease in land price per hectar e in b oth expressed in EUR and in EU R in PPP. The increase is described with regression function for prices in EUR y = 559,62x + 1769,6 x and with regre ssion function f or prices in EUR in PPP y = 900, 54x + 2496 ,1, x . Both functions show ver y high index of determi nation suggest ing that the slopes are good price lead in the surveyed period. The prices per hectare rose by a bit more than a bit more than 340% from 2006 till 201 6. hypothesis regardin g the price develop ment before the y ear 2014 and after was tested with t he test criterion 0 below the tabled critical value for Mann–Whitney test 2 for alpha 0,05 (two managed to reject the h ypothesis that the prices of tw o samples were from the sa me distribution. a legal environment change but als o an approach of agricultural in vestors changed and cr eated highly c ompetitive environment. Far mers often profited from e xcellent and relati vely l ow local de mand and achie ved favorable land purchase the previous decade . However as t he land beca me more and more attractive to and so opportunities for local favorable lan d purchase became much le ss frequent. Agricult ural buyers had t o compete w ith invest ors who a re capable and willi ng to on a new platfor ms suc h as land market aucti ons seeking a dequate return on is safer than ot her means o f invest ment . Large share of long and me dium tural investors arose also d ue to an expected increase in demand of various churches. compensation for the land that cannot or will n ot be r eturned to church w as a part of restitution process ear 2006 was selected a base year for inf lation adjusted prices per hectar e. Prices wer e converted b y PPP . Se e the price significant le gal chan ge in land mar ket became into the part with the (Farmy.cz, 2017; Czec h in b oth expressed in EUR and in EU R in y = 559,62x + 1769,6 x ∈ y = 900,54x + 2496,1, x  . Both functions show very high in dex of determination suggesting that the slopes a bit more than 350 % hypothesis regarding the price development bef ore the year 2014 an d after was tested wit h the test for alpha 0 ,05 (two -tailed). We distribution. agricultural inves tors profited from e xcellent knowledge favorable land purc hase . This situation However as th e land became more and more attractive to became much le ss frequent. Agricultural buyers had to c ompete with investors wh o are ca pable and willing to pay the seller seeking a dequate r eturn on Large share of long and medium -term non- in d emand of various churches. Regular as a part of r estitution process Vision 2020: Sustainable Economic development, Innovation Management, and Global Growth 2627 closure in 2013. Churches ar e spending money from compen sation also on la nd acquisiti on. medium-term non-agricul tural investor situation and cannot use t he same means of addressing thousands o f land owners by mail or newslet ter campaign. This is w hat specula tive investors try a nd serious investor only discredit oneself by such campaign successful because the y became almost a half o f effective dema nd. However their share very slowl y decreases during t he last years, see the fig. below. However fo reign bu yers are focused almos t only on greater parts of land and it is very ra re that they bu y parts bel ow 5 hectares . Mo st of foreign investors come from Ger many, Austria, Netherla nds and Belgium. Fig. 2: Development of shares on to tal year agricultur (Farmy.cz, 2015; Farmy.cz, 20 16; Farmy.cz, 2017). In 2014 speculative investors (very short campaign a nd a lot of landowners received a bi d with the market price. E xisting or e merging companies are date land price information . Howe ver, the y are not able or willing to pa y the real mar ket price in case of g reater n umber of competitors or an auction. its activities also contribute t o market land on the market. The r ecent market situation is that (5.549; 9.248 ) EUR per hectare and that is ( land price per hectare rose b y 2 5.5% in CZK and 26,7% change is the highest one f or the last fiftee n years. acquisition tax of 4% fr om the tax base which is Generally are the prices in the last buyer. Discussion We managed to reject the h ypothesis that the price s of two s amples were from the same di stribution. This means th at the price development before and after 2014 are not the same. Since th e trend is easy to identify it is natural that ranked based non time series 2006- 2013 it is les s steep than tren d curve that w ould be for years 2014 closure in 2013. Churches ar e spending money from compen sation also on la nd acquisiti on. tural investor does not have an advanta ge in excellent knowledge he same means of addressing thousands o f land owners by mail or newslet ter campaign. This is w hat specula tive investors try a nd serious investor seeking lon g- term or at least such campaign . Serious in vestors compete by better price bid became almost a half o f effective dema nd. However their share very slowl y decreases during t he last years, see the fig. below. All groups c ontain homeland as well as abroad buyers. reign bu yers are focused almos t only on greater parts of land and it is very ra re that they bu y . Mo st of foreign investors come from Ger many, Austria, Netherla nds and 2: Development of shares on to tal year agricultur al land purchase, own elabo ration based on (Farmy.cz, 2015; Farmy.cz, 20 16; Farmy.cz, 2017). investors (very short -term investment or direct resale) intensified considerably campaign a nd a lot of landowners received a bi d with disadvantageous conditions or signif icantly bel ow xisting or e merging companies are trying to b uy a land from owners . Howe ver, the y are not able or willing to pa y the real mar ket price in case of reater n umber of competitors or an auction. Although this group of investors is not generally successful its activities also contribute t o market price increase because they reduce the overall supply of agricultural ecent market situation is that in 2016 was the most c ommon interval of agricu ltural land purchase ) EUR per hectare and that is ( 8.759; 14.598 ) EUR in PPP per hectare. Y ear to year average land price per hectare rose b y 2 5.5% in CZK and 26,7% in EUR due to CZK appreciati on. This rate of change is the highest one f or the last fiftee n years. The price in the fi g. 1 do not include the r of 4% fr om the tax base which is the higher price of the purchase or appraisal in the last year even higher by 4 % because the tax burden was in We managed to reject the h ypothesis that the price s of two s amples were from the same di stribution. This means th at the price development before and after 2014 are not the same. Since th e trend is easy to identify it is natural that ranked based non -parame tric test was negative. If the trend c urve is used on the 2013 it is les s steep than tren d curve that w ould be for years 2014 - 2016. The difference closure in 2013. Churches ar e spending money from compen sation also on la nd acquisiti on. Long and knowledge o f a lo cal he same means of addressing thousands o f land owners by mail or newslet ter term or at least would bid and the y are became almost a half o f effective dema nd. However their share very slowl y All groups c ontain homeland as well as abroad buyers. reign bu yers are focused almos t only on greater parts of land and it is very ra re that they bu y . Mo st of foreign investors come from Ger many, Austria, Netherla nds and al land purchase, own elabo ration based on intensified considerably their or signif icantly bel ow owners without up-to- . Howe ver, the y are not able or willing to pa y the real mar ket price in case of is not generally successful because they reduce the overall supply of agricultural in 2016 was the most c ommon interval of agricu ltural land purchase ) EUR in PPP per hectare. Y ear to year average in EUR due to CZK appreciati on. This rate of The price in the fi g. 1 do not include the r eal estate of the purchase or appraisal one. year even higher by 4 % because the tax burden was in 2016 moved to We managed to reject the h ypothesis that the price s of two s amples were from the same di stribution. This means th at the price development before and after 2014 are not the same. Since th e trend is easy to tric test was negative. If the trend c urve is used on the 2016. The difference Vision 2020: Sustainable Economic development, Innovation Management, and Global Growth 2628 in slope for prices calculated in EUR is as h igh as more than 300%. 2014 was the year of cha nge but we are not able to distinguish whether the factor of easier and faster agricultural land purchase or high interest of non-a gricultural investors in land purchase or the end o f the economic crisis was the main cause. It is likely that it is a combinati on of these three factors an d that one strengthened the ot her one. In the next years 2015 and 2016 w ere all these factors still present i ncreasing the price up t o 9.154 EUR per hectare and 14.450 EUR per hec tare in PPP. The fig. 1 shows significant price increase trend which became even greater in the last three y ears. Agricultural land market prices increased by al most 65% during the last three years. The trend of price increase doubled the level of market prices over a period of only 6 years (f rom 2010 t o 2016). This made the agricultural land one of the highest yield invest ment with very l ow risk. However the market situati on can change. Continuing demands o f the A grarian Chamber o f the Czec h Republic and the A gricultural Committee to establish the ri ght of the first refusal f or lessees as well ma y succeed in the future. However it is less probable that the rest of the demand, extend the right of the first refusal for farmers from the municipality wher e the land is bein g sold and f or state as w ell, will succeed. This w ould be too str ict market intervention and could be seen as infrin gement of common EU market. However, generally any further extension of the right of the first refusal w ould have an impact on price. The group of non- agricultural investors would have m ore limite d acces s to land purchase which would reduce competition on t he de mand side. At the same time, all owners would lose the opportunit y to offer their land to wide range of bu yers and we are not c onsidering the time factor. Alth ough we do not expect any further changes soon because of the parliament e lections in the Oct ober 2017. It is almost im possible to approve such changes before the ele ctions and after the elections it a lways takes a few months bef ore the ministries start working properl y again due to a government negotiati ons. Although further legal change is hi ghly i mprobable we presume the present one wil l be e nough to slow down the price increase. Re-introduction of the right o f the first refusal wa s known from the spring of 2016. This stimulated both the demand and s upply to make a deal before the new re gulation will come into force. The re-introduction creates a problem of c o-owned asset liquidity increasing mainly time needed for tra de. Also as set consolidation will be more demanding task because t he amendment of the NCC brought the right of the first refusal even in case of transfer betwe en two co-owners. Due to these two mentioned factors in the par agraph we except lower amount of land traded in the next year. The next events with an impa ct on the market will be the monetary polic y of the Czec h national bank. Since both groups agricultural and non-agricultural invest ors contain abr oad companies th e exchange rate interventions or ap preciation of CZK would increase their c osts on land acquisition making the investments lees pr ofitable. The CZK continues its stea dy value increase against EUR and USD due t o both transparent and well-managed end of an asymmetric foreign exchange commitment regime a nd moreover due to e xcellent perf ormance which Czech economy s hows during the la st few years. With the lowest unemplo yment rate in the EU and stable GDP growth we expect CZK to appreciate e ven more during the next year up to the EUR/C ZK 25.5. Another factor w hich could cool down the market we see again in t he monetary with increase of the inter est rate. Czech national bank recently increased key interest rate 2T REPO from 0.05% to 0.25%. In case of overcoming of the inflation target another increase is possible. T his would certainly lead to increase of market i nterest rate on credit. This would not just only decrease the number o f p ossible buyers bu t mainly it c ould increase installments of already provided credit at the end of t heir fixed i nterest period. It is possible that some debtors would not be a ble to pay the i nstallments anymore and their land w ould be offered on t he auction. All effects mentioned in this paragraph got effect on the slowdown of observed long-term price increase. Conclusion The agricultural land mar ket development showed si gnificant and steady trend of price increase in t he last decade. The p rice increase was as significant as 350%. A verage land m arket price went from 2 .610 to Vision 2020: Sustainable Economic development, Innovation Management, and Global Growth 2629 9.154 EUR per hectare. If the calculation ta kes into account P PP the amount are even high er: from 4.243 to 14.450 EUR in PPP per hectare. T he market changed significantl y i n the y ear 2014 and the price increase trend is steeper than before. Our h ypothesis that the de velopment before and after the year 2014 was rejected. The main factors of change in 2014 were legal aspects, demand from the side of non- agricultural investors and the end of economic crisis. The legal aspects allowe d landowners on co-owner ship to sell their share to much wi der range of buyers. The fact that they could reach more buy ers without the obstacle in form the right of the f irst refusal increased the competition a nd resulted in price increase. The remai ning factors had als o price increase effect. Increased number and purchase power of non-agricultural investors (long and medium-term ones) became greater than the numbers of agricultural invest ors. High yield carr ying only low risk was the main feature that brought the attenti on of investors on the agricultural land market. The en d of crisis removed not just pessimistic expectations but mainly increased the agricultural business turnover and yield motivating and allowing farmers t o invest in a new land acquisition. Although the price r ise continued in 2015 and 2016 the share of non-agricultural investors dropped by almost 10% as t he costs of land acquisition became higher decre asing an investment yield. We do not expect strong price r ise to continue on the contrary we expect certain market cool down. The factors are mainly legal and macr oeconomic ones. The legal factor concerns the novelization of the NCC which re-introduces general right of the first refusal. The amen dment of the NCC comes into force at the beginning of 2018. There are only very specific excepti ons from right of the first refusal (transfer to close person) whic h means that agricultural land for purchase will r each narr ower range of potential buyers or it will take m ore time. CZK appreciation against both EUR and USD will i ncrease the costs o f an investment for foreign investors that are part of b oth agricultural and non-agricult ural group. Ke y interest rate increase will increase the c osts of credit limiting the demand for a gricultural land purchase. References Aryal, G. , Gabrielli, M. F. (2013). Testing for collusion in asymmetric first-price auctions. International journal of industrial organ ization . 31(1), 26-35. DOI: 10.1016/j.i jindorg.2012.10.002 Bargagliotti, A. E. (2009). Aggregation and decision making using ra nked data. Mathema tical social sciences , 58(3), 354-366. DOI: 10. 1016/j.mathsocsci.2009.07.006 Bowerman, B. L. & O’Connel, T. ( 1997). Applied statistic s: improving busines s p rocesses. Chicago: Irwin. Czech Republic. (2012) Act no. 89/ 2012 Coll. Civil code. Czech Statistical Of fice. (2017). Macroeconomic i ndicators. Re trieved August 2 1, 2 017, f rom: https://www.czso.cz/csu/czso/hmu_cr Farmy.cz. (2015). ZPRÁVA O TRHU S P Ů DOU. Retrie ved August 10, 2017, from: http://www.farmy.cz/dokument y/ZPRAVA-o-trhu-s-pudou-FAR MYCZ-leden-2015.pdf Farmy.cz. (2016). ZPRÁVA O TRHU S P Ů DOU. Retrie ved August 10, 2017, from: http://www.farmy.cz/dokument y/ZPRAVA-o-trhu-s-pudou-FAR MYCZ-leden-2016.pdf Farmy.cz. (2017). ZPRÁVA O TRHU S P Ů DOU. Retrie ved August 10, 2017, from: http://www.farmy.cz/dokument y/ZPRAVA-o-trhu-s-pudou-FAR MYCZ-leden-2017.pdf Hebák, T. (2005). Vícerozm ě rné sta tistické metody (vol. 2). Prague: Inf ormatorium. Ministry of Agriculture. (2009). Summary report 2009. Retrieved August 28, 2017, from: eagri.cz/public/web/file/94705 /SZ_2009_EN.pdf Vision 2020: Sustainable Economic development, Innovation Management, and Global Growth 2630 Ministry of Agriculture. ( 2015). Zelená zpráva 201 5. Retrieved September 2 3, 2017, from: http://eagri.cz/public/web/mze/mi nisterstvo-zemedelstvi/vyrocni-a- hodnotici-zpravy/zpravy-o-stavu- zemedelstvi/zelena-zprava-2015. html OECD. (2017). PPPs and exchange rates. Retrieved August 25, 2017, http://stats.oecd.org/index.asp x?DataSetCode=SNA_TABLE4 Piwowar, A., Dziku ć , M. (2015). Wył ą czenia gruntów rolnych na cele nierolnicze w P olsce w aspekcie ekonomicznym i ekologicznym [in:] Eko logia na pograniczach (eds. W. Wawrzyniak, T. Zaborowski). Pozna ń : Instytut Bada ń I Ekspe rtyz Naukowych w Gorzowie Wlk., 47-55. Slovakia. (2014). Act no.140/20 14, Coll. on the acquisition of the ownership to the agricultural lan d. Vrbová, E., N ě mec, J. (2005) Land market development in t he Czech Republic. Agricul tural ec onomics. 5(2005) 216–220. Vision 2020: Sustainable Economic development, Innovation Management, and Global Growth 2631 ... This growing trend will entail tremendous losses of agricultural land, disrupting sustainable agriculture and depleting food sources (Szturc et al., 2019). While farmers can still enjoy fertile and rich farmland, nonagricultural investors are in dire straits over exorbitant land investment prices (Soukal, 2017) . The re-establishment of the right of first refusal will also disrupt the market. ... ... The re-establishment of the right of first refusal will also disrupt the market. The appreciation of CZK against EUR and USD will produce the same negative effect, imposing inflated prices on investors from Germany, Austria, The Netherlands and Belgium (Soukal et al., 2017) DEVELOPMENT OF AGRICULTURAL, ARABLE LAND AND ORGANIC FARMING IN THE CR, DEVELOPMENT OF LAND PRICES IN SELECTED EU COUNTRIES KRISTINA KABOURKOVÁ The paper compares the development of agricultural and arable land in the Czech Republic between 2000 and 2020. It has been found that the area of agricultural and arable land had decreased. Obviously, the legal norms that are supposed to ensure its protection are not observed in practice and that there can always be found a reason to grant an exception. The paper also examines the development of the prices of agricultural and arable land in selected EU countries between the years 2000 and 2018. In all cases examined, price growth has been recorded. The area of vacant land is decreasing; therefore, the people interested in its purchase are willing to pay high prices. In the paper, the development of organic farming in the CR from the 1990s until present is addressed. There has been a massive development of this way of farming. This could be considered positive, since organic farming is beneficial for the environment, farm animals, and consumers, who can get quality food. ... Czechia is divided into 14 regions and the soil characteristics can be determined based on the ESEU codes for every individual region. There are also stated the Official Land Price (OLP) for individual cadastral territories (municipalities) [18] . The Official Land Price is stated according to ESEU code, which indicates the main soil characteristics. ... ... Based on this, the Official Land Price can be obtained. The Official land price also reflects the soil quality and can be used for soil qualitative changes evaluation as it is based on ESEU [18] . ... The Impact of Crop Mix on Decreasing Soil Price and Soil Degradation: A Case Study of Selected Regions in Czechia (2002–2019) Gebeltová Karel Malec Kamil Maitah Sirohi While the market price of land in Czechia has increased in recent years, the officially set land price, published by the State Land Office and the Research Institute for Soil and Water Conservation, has decreased in several regions (Olomouc, Zlín, South Moravia, Moravian-Silesian, and Central Bohemia Region). Four out of five of these regions are said to have the most fertile soil. The main reason for the official land price decrease has been the re-evaluation of land parcels which are based on field sample testing. Based on these sample tests some parcels have been re-evaluated as less fertile. This paper aims to identify the main determinants, which led to the decrease of the official land price and soil fertility in these regions of Czechia. It has been determined that crop structure significantly differs from the “valuation type structure” which indicates optimal share of individual crops to achieve the optimal yield without soil degradation. It has also been determined that there were statistically significant differences in all selected regions for all observed crops (excluding rapeseed in Moravian-Silesian Region) and Czechia between the shares of individual crops and shares according to the “valuation type structure”. It may be concluded that farmers follow short-term interests (profit) instead of long-term goals (soil fertility) in the selected regions. Moreover, results for Czechia suggest that this trend is becoming more common in every region of Czechia. Thus, the Herfindahl–Hirschman Index was utilized. The Herfindahl–Hirschman Index shows decreasing crop diversity in all selected region, as in Czechia as well. Based on the data analysis, it is possible to identify several crops, which are prevailing (wheat, barley, rapeseed, and fodder crops). Three of these crops (wheat, barley, and rapeseed) in combination with intensive farming and poor crop rotation have been found to be problematic and a potential threat which may cause degradation in soil fertility. Based upon this the following measures have been recommended: First, to focus on proven agricultural practices, including crop rotation and fodder crops. Second, the fodder crops production should be supported, and the structure of the “single area payment subsidies” should reflect the negative impact of the three main prevailing crops (wheat, maize, and barley) on soil fertility and the decrease of livestock production in Czechia.
https://www.researchgate.net/publication/321678572_Agricultural_land_prices_development_in_the_Czech_Republic_and_the_latest_legal_development
Documents Library | Global Forum on Migration and Development Documents Library What can be found in the documents library? The documents library consists of substantive documents and documents that relate to the GFMD process. Among the substantive documents, you can find background papers, research works and other documents that have been used as references in the preparation of the Roundtables or thematic meetings. It is noteworthy that most of these GFMD-related documents were prepared by government-led teams. This approach has helped promote confidence-building and a sense of partnerships between and among governments and key partners in the GFMD process. The process-related documentsinclude the Roundtable concept themes for each annual meeting, the list of GFMD participants, and Reports of Proceedings of the meetings of the GFMD Steering Group and Friends of the Forum. In addition, information on the engagement of the civil society and the business sector can be found. The documents library does not contain the migration and development policies and practices that are stored in the GFMD Database in thePlatform for Partnerships. For whom is the documents library? The GFMD documents library is generally open to the public. The wealth of information that is showcased in the library could be useful for all migration and development enthusiasts - government policy-makers and practitioners, international organizations, civil society, business, researchers and students, and migrants themselves. How should I use the documents library? <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> gfmd_turkey2014-2015_gfmd-gmg_side_event_concept_note_and_agenda.pdf GFMD-GMG Side Event - From Cairo to Addis: Migration, labour mobility and the renewed global partnership for sustainable development (16 Apr 2015, New York) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Concept Note Thematic Meeting 3 on Women Migrants (8 Sept 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Background Note Thematic Meeting 3 on Women Migrants (8 Sept 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Concept Note Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Agenda Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Opening Statement by Ms. Athanassia Ioannou, Greece Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Presentation on "Countering negative messages," Mr. Thibault Chareton, UNAOC Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Keynote Speech by Mr. Stefan Kapferer, Deputy Secretary General of the OECD Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Public Opinions and Immigration: Individual Attitudes, Interest Groups and the Media, OECD Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Transatlantic Trends: Key Findings 2015, Ms. Astrid Ziebarth, German Marshall Fund Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Changing Public Attitudes: Using Evidence to Drive Campaign & Advocacy Work, Ms. Anna Olsen, ILO Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Integración social como Política Pública, Ms. Kathya Rodríguez, Costa Rica Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Communicating Effectively About Migrants and Migration, Ms. Susana Antunes, Portugal Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Assessing the Impact and Effectiveness of Communication Programs, Tools, Mrs. Bilkiss Rajahbalee-Cader, Mauritius Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Negative Messages about Migration, Mr. Leonard Doyle, International Organization for Migration (IOM) Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Opening Remarks by Ambassador Mehmet Samsar, Director General for Consular Affairs, Ministry of Foreign Affairs GFMD-GMG Side Event - From Cairo to Addis: Migration, labour mobility and the renewed global partnership for sustainable development (16 Apr 2015, New York) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Summary Note GFMD-GMG Side Event - From Cairo to Addis: Migration, labour mobility and the renewed global partnership for sustainable development (16 Apr 2015, New York) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Media-Friendly Glossary on Migration, UN Alliance of Civilizations and Panos Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Remittances growth to slow sharply in 2015, World Bank Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Migration and Development Brief - Special Topic: Financing for Development, World Bank Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Why Undocumented or Irregular, Platform for International Cooperation on Undocumented Migrants (PICUM) Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Protecting Undocumented Children: Promising Policies and Practices from Governments, PICUM Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Is Migration Good for the Economy, Organization for Economic Co-operation and Development (OECD) Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Transatlantic Trends: Mobility, Migration and Integration, German Marshall Fund Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva) <here is a image 46e24a5f5c3dd753-460bfb345cd4867d> Public attitudes towards migrant workers in Asia, International Labour Organization (ILO) Thematic Meeting 2 on the Role of Communications (29 Apr 2015, Geneva)
https://www.gfmd.org/docs?f%5B0%5D=field_doc_tags%3A380&f%5B1%5D=field_catergory%3A392&f%5B2%5D=field_doc_tags%3A370&f%5B3%5D=field_thematic_areas%3A7&f%5B4%5D=field_thematic_areas%3A3
N L obo M v Road Accident Fund (38339/2014) [2018] ZAGPJHC 590 (17 September 2018) | Noteup | LawCite N L obo M v Road Accident Fund (38339/2014) [2018] ZAGPJHC 590 (17 September 2018) Download original files PDF format RTF format SAFLII Note: Certain personal/private details of parties or witnesses have been redacted from this document in compliance with the law and SAFLII Policy REPUBLIC OF SOUTH AFRICA IN THE HIGH COURT OF SOUTH AFRICA GAUTENG LOCAL DIVISION, JOHANNESBURG CASE NO.: 2014/38339 In the matter between: N L obo M Plaintiff And ROAD ACCIDENT FUND Defendant JUDGMENT SIBUYI AJ INTRODUCTION [1] The minor child M N (“M”), was born on 30 August 2006. M was involved in a motor vehicle accident on 22 March 2012 at about 07h45 at Immink Road, Zone 5 Diepkloof, Soweto, Gauteng Province. Whilst a pedestrian on his way to school and crossing a street he was knocked down by a minibus taxi. He was allegedly in grade R at the time. He is reported to have had a seizure after the accident and had a depressed level of consciousness. M was immediately taken to Chris Hani Baragwanath Hospital, wherein he was admitted for day and discharged the following day. According to the hospital records he was admitted at 08h45 with pain and right side head laceration. He was diagnosed to have had a focal seizure involving the mouth and the left hand. He had an abrasion and swelling over the right temporal area. CT Scan Brain was reported normal. He was discharged the same day on an anticonvulsant (Epilim). [2] On 26 August 2013, about 1 year 5 months after the accident M was reported to have had a generalised atonic seizure in the early hours of the morning. He was reported to be in Grade 1 and not coping well, unable to write and reported to loose concentration easily. It was reported that his mother was called to M’s school with a complaint of abnormal behaviour in class and screaming inappropriately. He was admitted for overnight observation. He was booked for EEG and referred to Occupation Therapy Department for learning challenges. On the 24 October 2013 he was admitted for a EEG recording. The EEG was reported normal. He was later admitted for seizure, fever and recurrent headaches. He is reported to have had a 3 day history of severe headache. He was also found to have sinusitis. He was now and then treated and put on medication for the above symptoms. [3] On or about 2 July 2014 Dr. Mika Mokabane diagnosed M to have suffered a mild traumatic brain injury (a grade 3 concussion), brief loss of consciousness, with Glasgow coma scale of 15/15 in hospital and currently suffering from late onset post traumatic epilepsy which needs chronic treatment, post concussion headaches, and memory loss problems which needed assessment and treatment. It is common cause between the parties that M had suffered a mild traumatic brain injury and is under medication for chronic epilepsy as a result of the accident. [4] On 27 February 2018 the matter came before me and was allocated to run for three days only. Counsel for both parties informed me that on 8 September 2015 the matter came before Basson J for the first time, merits, undertaking and general damages were settled. In the terms of the order granted by Basson J dated 8 September 2015, general damages were settled at R650 000-00 (Six hundred and fifty thousand rands) and the defendant undertook to provide the plaintiff with an undertaking in terms of section 17(4) of the Road Accident Fund Act 56 of 1996 , to pay 100% of the cost of any future accommodation of M in a hospital or nursing home, or treatment or rendering of service to him or supplying of goods to him arising out of injuries sustained by M in the motor vehicle accident which occurred on 22 March 2012 after such costs have been incurred and upon proof thereof. Hence, the matter was before me to decide only future loss of earnings. The parties had, at roll call, requested allocation for two to three days to run on factual dispute between Educational Psychologist and Industrial Psychologist only. I was informed that the balance of the expert evidence vis Orthopaedic Surgeon, Neurosurgeon, Neurologist, Clinical Psychologist bore common cause facts which were contained in the joint minutes and were not in dispute between the parties. I must point out at this stage that this approach by the parties was ill advised and materially complicated the matter. In my view the matter was not ripe for a hearing. I deal with this issue herein below. COMMON CAUSE FACTS The Neurosurgeons [5] For the sake of brevity and accuracy, I further summarize the the joint minutes of Neurosurgeons who agreed as follows: 5.1 Pre-accident, M enjoyed a good general physical health. During the accident he suffered a mild traumatic brain injury. As a result of the accident he is suffering from post-traumatic epilepsy which will needs chronic medical treatment. Both Neurosurgeons agreed with the views of Dr. Mika Mokabane, the plaintiff’s Neurologist. The Defendant did not instruct a Neurologist. The Clinical Psychologists [6] The Clinical Psychologists, Dr L Maseko and Dr L Roper, although they depart from slight different angles, agreed that the head injury sustained is considered to be of sufficient severity to bring about mild ongoing neuropsychological sequelae. Both noted similar neuro-cognitive sequelae and psychological symptoms on M, which symptoms they observed and measured during his evaluation and assessment in their individual reports following the accident in question. Both experts agreed that the accident related factors have potential to impact negatively on his academic functioning and scholastic progression as already evidenced in his current school performance. However, Dr L Roper (For Defendant) noted that the possible presence of pre-existing cognitive difficulties cannot be excluded considering the minor’s reported socio-demographic context. If present, any such difficulties would probably have been exacerbated by the head injury and post-traumatic epilepsy. [7] They further agreed that following accident, M also suffered significant symptoms of post-traumatic stress disorder. Both experts noted that as a result of the neuropsychological sequelae, M’s interpersonal functioning, his enjoyment and quality of life has decreased since the accident. It was agreed that he has not yet had the benefit of treatment for his post-traumatic stress symptoms and they recommended psychotherapy and neuropsychological intervention as well as supportive family therapy. Lastly, they agreed that M needs to be fairly compensated for the head injury and symptoms suffered. The Occupational Therapists [8] The Occupational Therapists agreed that M needed occupational therapy twice per week, and a routine therapy with an educational / clinical psychologist to monitor and address possible psycho-social deficits. Further, they agreed that M presents with concentration deficits, hyperactivity, delayed learning, reduced gross motor and fine motor skills, visual perceptual deficits, restlessness, and impulsive behaviour. His cognitive, perceptual, coordination, and behavioural deficits, are likely to result in scholastic deficits and will influence his future work competence. Based on his current presentation he will benefit from placement in a remedial school where occupational therapy, psycho-therapy and remedial assistance is supplied on a daily basis. With remedial schooling he may be directed towards a more technical / manual type of employment, which case he will be reliant on his physical abilities to earn an income. Both experts noted that M presents with no neuromuscular limitations preventing him from pursuing a physical career, however given the possibility of post-traumatic epilepsy, he may not be suited for occupations involving driving or the use of dangerous machinery, working on elevated surface or in environments placing him at risk of burns and scalds. As a result, he will suffer a loss of employment opportunities. The Educational Psychologists [9] The Educational Psychologists, Dr M Mtshali(“Mtshali”) and Dr M Maseko(“Maseko”) complied a joint minute on 22 June 2016. Pre-morbid, Maseko noted that scholastically M was probably going to be able to complete grade 12 without any additional specialized educational assistance, Mtshali noted that in the absence of sufficient pre-morbid history of learning (pre-morbid academic records) it cannot be determined with certainty how well M would have been able to apply his qualities under the circumstances and one cannot rule out possibility of pre-morbid learning difficulties beyond reasonable doubt. [10] Post-morbid, under cognitive functioning, Maseko noted that M’s cognitive functioning fell well below average both verbally and non-verbally and Mtshali noted a within average level of functioning. Nevertheless, they both noted M’s inadequacy in the areas of auditory sequential memory, logic memory, attention and concentration as an interference with his ability to perform optimally academically. They further agreed that M’s inattentiveness could interfere with his future learning especially when progressing to next classes as he is currently presenting with learning disabilities due to poor memory and impaired ability to retrieve the bulk meaningful information. Maseko noted that erratic performance confirms that the accident did impact on M’s memory as he appears unable to sustain attention and concentration and perseverance in task completion. In conclusion, Maseko noted that M will probably find it difficult to complete grade 12 as both his verbal and non-verbal cognitive functioning is impaired whilst Mtshali noted that with remedial intervention M may probably complete grade 12 taking into consideration that he still retains his average functioning. [11] Post-morbid, under educational functioning, Maseko and Mtshali noted that scholastically M’s inconsistent and fluctuating auditory processing difficulties may interfere with integration of information. They agreed that attention and concentration difficulties may continue to undermine M’s ability to perform adequately academically. [12] Post-morbid, under emotional functioning, Maseko noted that emotionally and socially, M seems to have experienced major changes. He currently lacks inhibition and when reprimanded he seems to have no clue of what kind of a change of behaviour is expected from him. The experts agreed that M may benefit from psychotherapy for emotional trauma and he appears to present with irritability and anxiety. [13] On M’s future educational prospects the experts agreed that M is a learner with special needs. Maseko recommended an epilepsy school and Mtshali recommended remedial classes in order to meet academic challenges. Maseko noted that without the accident, M would have probably completed grade 12 with entry to a certificate or diploma qualification post matric. Mtshali noted that with remedial intervention M would still probably complete his grade 12 with entry to a certificate or diploma qualification post matric taking into consideration that his head injury is not rated as severe traumatic head injury. THE DISPUTES [14] The Educational Psychologists’ latest joint minute compiled on 9 February 2018 tells a totally different story especially on the intellectual and educational functioning of M and also his future prospects. It appears that the recent change in their views is caused mainly by the recent school report which suggests that M’s intellectual ability falls in the high average. [15] Maseko is now of the view that M’s intellectual ability falls in the average range and not below average as per her initial report. Maseko noted that M’s memory inconsistency may be due to psychological trauma suffered in the accident which is likely to be aggravated by his concussive post traumatic headache. Based on M’s recent school report Mtshali is also singing a different tune. She now opines that M’s intellectual ability is estimated to fall in the high average and not average as per her initial report. Mtshali noted that based on her initial assessment, M did experience some memory inconsistency due to the psychological trauma suffered in the accident under discussion, but noted that based on his recent school report M appeared to have recovered well and the memory inconsistencies appears not to present anymore. [16] On educational functioning Maseko opines that although M seems to perform adequately academically, and that his teacher’s comments indicates him to be displaying a positive attitude towards his learning, the last psycho-educational assessment conducted on 21 June 2015 revealed impairments in his cognitive functioning with fluctuation of memory, and abstract reasoning both verbally and no-verbally. These weaknesses may continue to interfere with his executive functions in higher classes where independent learning is expected to be applied in learned material by way of processing and retention. The recent school is but one of the factors to be taken into account and cannot be conclusive on the educational functioning issue. On the other hand Mtshali opines that based on M’s latest school reports M has stabilized scholastically/educationally as he performed in the high average in all areas of learning, therefore there are no learning difficulties or challenges which can be anticipated to reappear in the next or higher grades. [17] On the future prospects Maseko noted and confirmed during her testimony that M may have had the intellectual potential to have obtained grade 12 (NQ4) level of education should it had not been the presence of memory fluctuation. This impairment would probably continue to undermine his learning potential as post-accident M had already repeated a grade and suffered secondary epileptic injuries. She noted further that M may therefore find it difficult to achieve grade 12 according to his potential due to additional ailments of epilepsy, confirmed concussive post headaches and the psychological trauma suffered in the accident leading to memory fluctuation. These deficits would probably continue to interfere with M’s executive functions in higher grades where bulk of academic work would need independent processing and retention of learned material. The new information from the addendum reports do not negate the previous findings of presence of cognitive impairments relating to memory and poor abstract reasoning abilities. She further opined that having reached age 12 M, who was never taken to a remedial school as per the recommendations, is no longer a candidate for remedial schooling. Further, that M cannot cope in a private remedial school because of his poor English background. [18] To the contrary, Mtshali disagreed and testified that based on M’s latest school report, M appears to be functioning as his pre-accident potential and appears to have stabilized scholastically. If M was still experiencing memory challenges/impairments, it is most probable that he could have been still struggling and not coping with his school work especially from grade 4 and his recent school reports would have still indicated some learning challenges, therefore it has to be agreed that new learning challenges are not anticipated in the next or higher grades which can continue to interfere with his executive functions. Also taking into consideration that it is almost 6 years post-head injury but he is still functioning adequately, therefore it is confirmed that no learning challenges are anticipated in the next or higher grades which can continue to interfere with his executive functions and M appeared to have stabilised scholastically. Based on the above factors, Mtshali contended that it has to be agreed that the head injury sustained by M in the accident did not have the potential to cause any long term cognitive challenges/impairments. The Industrial Psychologists [19] The Industrial Psychologists, Dr M. Malaka (“Malaka”) and Dr O. O. Sechudi (“Sechudi”) complied a joint minute on 14 February 2018. The two Industrial Psychologists did not have the benefit of reading minutes of other experts on the matter. Hence, their post morbid views are not based on sound factual basis. They are out of context and to an extent irrelevant. I deal with this issue herein below. I now summarize their pre-morbid views. Pre-morbid prospects [20] Malaka reported and testified that, but for the accident, M would have been able to obtain grade 12 and would have been able to further his studies at a tertiary institution. In this context, assuming he could have obtained a further education qualification such as a two years diploma/three years degree, he could have been able to enter the labour market first as a semi-skilled worker at R20 600-R59 000-R151 000 per year. In five years or so, given more experience and even in-house training as well as further studies, he would have earned at Paterson C1/C2. In fifteen years or so, he would have earned at Paterson C3/C4. At the age of 45 years, he could have earned at Paterson C5. His ceiling would have been at Paterson D1 at age of 50 years old. At this time, he could have qualified for general annual increment until his retirement at the age of 65 years (Koch: 2017; pages: 129 132) . [21] Sechudi reported and testified that had the accident not occurred, M with the relevant remedial support, might have performed better with his academic studies and be on the right path completing his grade 12. M was going to have a fair chance to compete in an open labour market and securing employment. Upon completion of the studies he would have started searching for a job. A person with such a level of qualification may be considered as an unskilled worker. The claimant would have spent at least 3 years to searching for a job equivalent to the qualification. On securing a job, he would have earned according to Paterson level A2 with gradual progression to Paterson level B3 (Koch, 2017) towards age 45 were he would be reaching his career ceiling. From the age 46, his earnings would have stabilized and he would have earned only additional inflationary increases until retirement age. Sechudi agreed with Malaka that with B. Degree M’s earnings might reach Paterson D1. Post-morbid employment prospects [22] Malaka testified that Maseko is better placed to opine on how far M will go scholastically. Given the expert medical reports as well as the biographical information, it could be indicated that M employment chances will be based on the following two scenarios: First scenario 22.1 In the event where M is able to receive medical support, remedial education and developmental support and is able to progress towards high school education, chances are that he will not pass grade 12. He might acquire basic skills which will provide him with an opportunity to obtain a low entry technical job. However, he will not be able to reach his pre-accident potential. In this respect, he will only be employable at the unskilled levels of the formal labour market. His remuneration will be limited to the to the following unskilled worker scale at R8 100-R20 600-R59 000 per annum (Koch, 2017: page 132). In this regard, he will experience long periods of unemployment. He will have to depend on his physical capacity to do the job. However, he will find it hard to compete for possible job offers, given his mental physical injuries and limitations. When confronted with the recent school report, annexure “E4”, which school report he never took into account when compiling his report, Malaka conceded that the recent school report looks impressive but he insisted that the recent school report is just but one of the factors to be taken into account when considering M’s performance. He conceded that such results are possible with remedial support. Second scenarios: 22.2 In the event where M is not able to find appropriate medical intervention as well as educational placement in accordance with his learning requirements, chances are that he will not be able to progress developmentally and educationally beyond grade 08 education or alternatively, he will not be able to acquire skills necessary to generate a reasonable income in order to live independently. He will have to remain in a supervised and protected environment for the rest of his life. The results of chronic epilepsy is that M will be on chronic epilepsy medication for the rest of his life. He can suffer epilepsy attack at any time. The impact of that is that he cannot drive or climb heights. He will be confined to employment chances of a general labourer or sympathetic work and not fully spect jobs. The result being that even on the lower levels jobs, he remains restricted. Malaka testified that technical school or jobs may not assist M as he may blackout whilst working. M can do courses or jobs that are sedentary inclined like clerical, admin and filing. 22.3 Sechudi on the other hand reported and testified that M”s productivity in his future employment is affected but not limited by his post-accident health condition. He opined that M may still be able to pass grade 12. This possibility is based on the fact that according to him M is able to return to premorbid levels of functioning as reported by the defendant’s Educational Psychologist, Mtshali. Furthermore, it was reported that with remedial intervention, he would still probably passed grade 12. Thus, it is possible for M to secure a meaningful job in the open labour market. It is important to note that should his epilepsy be uncontrollable in the future, M’s intellectual functioning might be affected negatively. The post-accident contingency with health can be invoked. During cross -examination, Sechudi refused to comment on the views expressed by Malaka above and stated that he stand by what he wrote in the joint minute. [23] I now return to the ripeness of the matter. From the out set, I must again say that this matter was not ripe for hearing, but was rushed to court and badly presented. The evidence outlined above bear testimony to my view. Less relevant facts about M were placed before this court. There is no explanation why a relevant witness, M’s mothers was never called by either party to give relevant pre and post morbid evidence about M. Nor were his teachers called to give factual evidence on educational progress, especially where the Educational Psychologists for the parties disagreed on the issue and the recent school report indicated otherwise. Only one of his school reports was discovered and used by the defendant to advance its case. Progressive school reports were necessary to support the defendant’s argument’s below on the future prospects. Briefly stated, not all specific relevant personal circumstances of M are on record. [24] The Educational Psychologists themselves came to court with half baked opinions. They failed to consider the complete factual backgrounds upon which they based their opinions. For example, Mtshali, based on one isolated school report, opines that it has to be agreed that the head injury sustained in the accident under discussion did not have the potential to cause any long term cognitive challenges/impairments on M. According to Mtshali, M appears to be functioning as his pre-accident potential and appears to have stabilized scholastically. On the other hand, Maseko rejects Mtshali’s view on the bases that although M seems to perform adequately academically, and that his teacher’s comments indicates him to be displaying a positive attitude towards his learning, the last psycho-educational assessment conducted on 21 June 2015 revealed impairments in his cognitive functioning with fluctuation of memory, and abstract reasoning both verbally and no-verbally. The recent school report is but one of the factors to be taken into account and cannot be conclusive on the issue. She concluded by stating that an independent holistic psychological educational assessment was necessary to verify whether or not the cognitive functioning challenges or impairments identified earlier were still in existence. However, nobody bothered to conduct such necessary independent assessment before the matter was set down for hearing. There is also no explanation as to why such approach was not followed. Had they done so, the main dispute on the matter would have been narrowed, if not settled by agreement between the Educational Psychologists. [25] An informed view on the above issue was necessary to assist the Industrial Psychologists and actuaries to give their well balanced opinions on the future loss of earnings. At this point, the reports of the Industrial Psychologists and actuaries, which are based on incomplete and disputed facts are less helpful to the court. As Wepener J put it in Nicholson Charlene v RAF [1] : “ [I]t is the function of the court to base its inferences and conclusions on all the facts placed before it.” This Court, in order to arrive at its own decision or finding, must of necessity have regard not only to the expert evidence but also to all the other facts of the case, including the viva voce evidence, the probabilities and the reliability of the witnesses. Kotze J (as he was then) put it as follows in S v Gouws [2] : “ The prime function of an expert seems to me to be to guide the court to a correct decision on questions found within his specified field. His own decision should not, however, displace that of the tribunal which has to determine the issue to be tried.” [26] It is fundamental that experts should have sound factual bases for the opinions they give. Unfortunately, in this case this fundamental rule has not been complied with. Meyer AJ (as he was then) warned against this in Mathebula v RAF [3] at para [13] where he stated the following: “ An expert is not entitled, any more than any other witness, to give hearsay evidence as to any fact, and all facts on which the expert witness relies must ordinarily be established during the trial, except those facts which the expert draws as a conclusion by reason of his or her expertise from other facts which have been admitted by the other party or established by admissible evidence.” [4] One of the duties of an expert witness is that “ An expert witness should state the facts or assumptions upon which his opinion is based. He should not omit to consider material facts which could detract from his concluded opinion” [5] . The Educational Psychologists in this matter, as stated above, failed to observe this rule. They both omitted to consider material facts which could detract from their concluded opinions. They both failed to consider progressive school reports, and or in the light of the recent school report used in court, to do a further independent psychological educational assessment on M to determine the current status of his challenges or impairments. [27] Instead, each Educational Psychologist, based on incomplete facts, chose to express a view only favourable to the party that called them. In Schreider NO & Others v AA & Another [6] Davis J stated as follows at 211J-212B: “ In short, an expert comes to court to give the court the benefit of his or her expertise. Agreed, an expert is called by a particular party, presumably because the conclusion of the expert, using his or her expertise, is in favour of the line of argument of the particular party. But that does not absolve the expert from providing the court with as objective and unbiased an opinion, based on his or her expertise, as possible. An expert is not a hired gun who dispenses his or her expertise for the purposes of a particular case. An expert does not assume the role of an advocate, nor gives evidence which goes beyond the logic which is dictated by the scientific knowledge which that expert claims to possess.” It is common cause that the expert witnesses of the plaintiff that testified mostly tendered evidence that contradicted that of the defendant’s experts. The approach to be followed in a case like this: where there is conflicting expert evidence was set out in Michael and Another v Linksfield Park Clinic (Pty) Ltd and Another [7] as follows at paras [36] and [37]: “ [36] That being so, what is required in the evaluation of such evidence is to determine whether and to what extent their opinions advanced are founded on logical reasoning. That is the thrust of the decision of the House of Lords in the medical negligence case of Bolitho v City and Hackney Health Authority [1997] UKHL 46 ; [1998] AC 232 (HL(E)). With the relevant dicta in the speech of Lord Browne-Wilkinson we respectfully agree. Summarised, they are to the following effect. [37] The court is not bound to absolve a defendant from liability for alleged negligent medical treatment or diagnosis just because evidence of expert opinion, albeit genuinely held, is that the treatment or diagnosis in issue accorded with sound medical practice. The court must be satisfied that such opinion has logical basis, in other words that the expert has considered comparative risks and benefits and has reached ‘a defensible conclusion’.” [28] In this case, I must assess all the expert evidence adduced and take into account the precedents set by our courts in line with the stare decisis principle or doctrine. Without any defensible conclusion from the experts and hard as it is, I must on the facts determine what will be an equitable loss of earning capacity. It is generally accepted that “ Any enquiry into damages for loss of earning capacity is of its nature speculative, because it involves a prediction as to the future, without the benefit of crystal balls, soothsayers, augurs or oracles. All that the Court can do is to make an estimate, which is often a very rough estimate, of the present value of the loss” [8] . I must do the best I can on the material available, “ by either making a round estimate of an amount which seems to be fair and reasonable to me (an entirely a matter of guesswork, a blind plunge into the unknown) or make an assessment, by way of mathematical calculations, on the basis of assumptions resting on the evidence. The validity of this approach depends of course upon the soundness of the assumptions, and these may vary from the strongly probable to the speculative” [9] . I am unable make an assessment, by way of mathematical calculations, on the basis of assumptions resting on the evidence. There is simply not enough evidence to assist in that regard. Instead, I have to make a round estimate of an amount which seems to be fair and reasonable to the court. Counsel for the parties suggested during argument that I adopt a compromised common ground approach on deciding what constitute fair and reasonable figure. [29] I now turn to the arguments on quantification of the plaintiff’s claim for loss of earnings and earning capacity. During argument Counsel for both parties agreed that the pre-morbid value of income uninjured was estimated at R6 566 398.00, as tabulated in Bundle C, page 56 thereof, and that this value may be taken as common cause between the parties. In the light of the facts of this matter, I agree with the parties as the the agreement on this figure seems to be a more reasonable one in the circumstances. Though I may have preferred between 23-25%, the actuary’ s 20% contingency is not unduly generous. The respective Industrial Psychologists experts were also not far apart on the pre-morbid values. As stated above they agreed on most of the pre-morbid aspects. Serious disputes mainly arose on the post-morbid scenarios. [30] Both the plaintiff and the defendant have filed reports by the their respective actuaries. However, none of the actuaries testified. Based on the plaintiff’s actuary quantification, specifically Basis II, it was contended on behalf of the plaintiff, that it will be just and fair to both parties for the court, to accept, for quantification purposes, that it is equally likely that M, pre-morbidly, would have attained a degree. On the same basis, it was submitted on behalf of the plaintiff that it will also be fair to both parties for the court to accept, for quantification purposes, that it is equally likely that M, post-morbidly would have been rendered unemployable. In line with the actuarial quantification in Bundle C, page 56 and applying the 20% pre-morbid and 0% post-morbid contingencies, the net future loss of earnings must be R5 253 118-00. In the vent of the court adopting a middle ground approach, half of this amount plus a reasonable contingency for epilepsy must be awarded to the plaintiff. [31] Counsel for the defendant submitted that based on the defendant’s expert witnesses, M, except for the R325 542-00 which represent his late entry into employment, will suffer no future loss of earnings as his productivity in the future, though affected, is not limited by his post accident health conditions. However, as a compromised common ground, the defendant will accept a net future loss of earnings in the amount of R1 312 297.00, allegedly based on applying the 30% pre-morbid and 50% post-morbid contingencies. [32] In the circumstances I can do no better than award an arbitrary sum, in fixing which I must try to steer a course between generosity at the expense of the defendant and niggardliness at the expense of M. This being the approach, I must take into account the existing undertakings and that general damages were fixed and awarded to the plaintiff separately. Further, the court must guard against any overlapping, and a resulting duplication. On the facts of this matter it is impossible to guess where exactly M will end up educationally and or work wise. Should his epilepsy be controllable in the future, with luck and hard work he might pass grade 12, proceed to obtain a degree and reach Paterson level D1 earning level. In other words, the fortunes of life may be favourable [10] to him. However, there is no guarantee that this will happen. On the other hand, should the epilepsy be uncontrollable, his intellectual functioning might be advisedly affected, making it impossible for him to achieve higher qualifications and or obtain a degree or better employment. [33] However, to predict that on the facts of this matter, he will not pass grade 12 and or that he is rendered unemployable the Sangoma will be stretching the prediction too far. This view is myopic, without any basis, and fails to take into account the mild nature of the injury, views of other experts on the impairments, recent educational progress (including but not limited to the recent report), that with proper utilization of medication the headache and epilepsy may be controlled thereby limiting M’s challenges and or impairments. [34] On the other hand, to say that M, except for the R325 542-00 which represent his late entry into employment, will suffer no future loss of earnings as his productivity in the future, thought affected, is not limited by his post accident health conditions, as argued on behalf to the defendant, one will be ignoring glaring evidence to the contrary dealt with herein above. [35] In the post-accident scenario, it is my view that allowances must be made for the possibility that M’s future academic life as well as his working life may be adversely affected by headaches, epilepsy, anxiety and depression and/or associated aliments. Further, I am in agreement with the experts who opined that M would find himself in future precluded from the following types of work environment which will expose him to flickering lights and or Television screens. That certain sounds (such as loud ringing, some voices or certain music or monotonous noise, and etc) and sensations may trigger his epilepsy. Further, that he may not be suited for occupations involving driving or the use of dangerous machinery, working on elevated surface or in environments placing him at risk of burns and scalds. It is accordingly my view that a reasonable contingency allowance for the epilepsy, headache, and above limitations is appropriate in the post-accident scenario. The late entry into employment, epilepsy condition, post concussion headaches, and tender age, remain significant factors in the circumstances of this matter. [36] Taking all the above facts and circumstances into account, it is my view that an amount of R2 000 000-00 (“Two Million Rands”) ought to be awarded to the plaintiff in respect of loss of earnings and earning capacity. COSTS [37] There are no extraordinary circumstances that may dictate that this Court consider a different costs order than the normal one, which is, that costs should follow the result. ORDER [38] In the result the following order is made: 38.1 the defendant is ordered to pay to the plaintiff an amount of R2 000 000-00 (Two Million Rands), in respect of loss of earnings and earning capacity. 38.2 the defendant is ordered to pay the costs of suit, including the costs of experts. _____________ H.W . SIBUYI Acting Judge of the South Gauteng High Court, Johannesburg CASE NO . : 38339/2014 HEARD ON : 27 February to 1 March 2018 COUNSEL FOR THE PLAINTIFF : Adv. Mjiba ATTORNEYS FOR PLAINTIFF : Nkosi Nkosana Inc. COUNSEL FOR THE DEFENDANT : Adv. Molojoa ATTORNEYS FOR THE DEFENDANT : Nozuko Nxusani Inc. DATE OF JUDGMENT : 17 September 2018 [1] Unreported Case No 07/11453 handed down in the South Gauteng High Court on 30 March 2012 at p 3 thereof. [2] 1967 (4) SA 527 (EC). [3] (05967/05) [2006] ZAGPHC 261 delivered on 8 November 2006. [4] See also Coopers SA (Pty) Ltd v Deutsche Gesellschaft fur Sch ä dingsbekampfung MBH 1976 (3) SA 352 (A) at 371G; Reckitt & Colman SA (Pty) Ltd v S C Johnson & Son SA (Pty) Ltd 1993 (2) SA 307 (A) at 315E; Holtzhauzen v Roodt 1997 (4) SA 766 (W) at 772I. [5] see National Justice Compania Naviera SA v Prudential Assurance Co Ltd1993 (2) Lloyds Reports 68. [6] 2010 (5) SA 203 (WCC) [7] 2001 (3) SA 1188 (SCA). [8] see Southern Insurance Association Ltd v Bailey No. [1984] 1 ALLSA 360 (A), at 368. [9] see Bailey supra, at 368-9 [10] In dealing with the question of contingencies, WINDEYER, J, said in the Australian case of Bresatz v Przibilla (1962) 36 A L J R 212 (H C A) at 213: “ It is a mistake to suppose that it necessarily involves a ‘scaling down’. What it involves depends, not on arithmetic, but on considering what the future may have held for the particular individual concerned . . . . . . . (The) generalisation that there must be a ‘scaling down’ for contingencies seems mistaken. All ‘ contingencies ’ are not adverse: All ‘ vicissitudes’ are not harmful. A particular plaintiff might have had prospects or chances of advancement and increasingly remunerative employment. Why count the possible buffets and ignore the rewards of fortune? Each case depends upon its own facts. In some it may seem that the chance of good fortune might have balanced or even out-weighed the risk of bad.”
https://www.saflii.org/za/cases/ZAGPJHC/2018/590.html
PRIME PubMed | Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice PubMed journal article: Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice. Download Prime PubMed App to iPhone, iPad, or Android Tags Type your tag names separated by a space and hit enter Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice. Brain Res . 2016 Mar 15; 1635:169-79. BR Abstract We screened anti-Aβ1-42 antibodies from a human Alzheimer's disease (AD) specific single chain variable fragment (scFv) phage display library and assessed their effects in APP/PS1 transgenic mice. Reverse transcription-PCR was used to construct the scFv phage display library, and screening identified 11A5 as an anti-Aβ1-42 antibody. We mixed 11A5 and the monoclonal antibody 6E10 with Aβ1-42 and administered the mixture to Sprague-Dawley rats via intracerebroventricular injection. After 30 days, rats injected with the antibody/Aβ1-42 mixture and those injected with Aβ1-42 alone were tested on the Morris water maze. We also injected 11A5 and 6E10 into APP/PS1 transgenic mice and assessed the concentrations of Aβ in brain and peripheral blood by ELISA at 1-month intervals for 3 months. Finally we evaluated behavior changes in the Morris water maze. Rats injected with Aβ1-42 and mixed antibodies showed better performance in the Morris water maze than did rats injected with Aβ1-42 alone. In APP/PS1 transgenic mice, Aβ concentration was lower in the brains of the antibody-treated group than in the control group, but higher in the peripheral blood. The antibody-treated mice also exhibited improved behavioral performance in the Morris water maze. In conclusion, anti-Aβ1-42 antibodies (11A5) screened from the human scFv antibody phage display library promoted the efflux or clearance of Aβ1-42 and effectively decreased the cerebral Aβ burden in an AD mouse model. Links PMC Free PDF Authors +Show Affiliations Wang J Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address: [email protected]. Li N Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, China. Ma J Department of Gastroenterology, The second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, China. Gu Z Department of Radiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Yu L Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Fu X Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Liu X Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Wang J Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. Electronic address: [email protected]. MeSH Alzheimer Disease Amyloid beta-Peptides Amyloid beta-Protein Precursor Animals Antibodies, Monoclonal Brain Disease Models, Animal Humans Infusions, Intraventricular Male Maze Learning Mice Mice, Inbred C57BL Mice, Transgenic Peptide Fragments Peptide Library Presenilin-1 Rats Rats, Sprague-Dawley Pub Type(s) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Language eng PubMed ID 26820640 Citation Wang, Jianping, et al. "Effects of an Amyloid-beta 1-42 Oligomers Antibody Screened From a Phage Display Library in APP/PS1 Transgenic Mice." Brain Research, vol. 1635, 2016, pp. 169-79. Wang J, Li N, Ma J, et al. Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice. Brain Res . 2016;1635:169-79. Wang, J., Li, N., Ma, J., Gu, Z., Yu, L., Fu, X., Liu, X., & Wang, J. (2016). Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice. Brain Research , 1635 , 169-79. https://doi.org/10.1016/j.brainres.2016.01.028 Wang J, et al. Effects of an Amyloid-beta 1-42 Oligomers Antibody Screened From a Phage Display Library in APP/PS1 Transgenic Mice. Brain Res. 2016 Mar 15;1635:169-79. PubMed PMID: 26820640. * Article titles in AMA citation format should be in sentence-case Copy Download MLA AMA APA VANCOUVER TY - JOUR T1 - Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice. AU - Wang,Jianping, AU - Li,Nan, AU - Ma,Jun, AU - Gu,Zhiqiang, AU - Yu,Lie, AU - Fu,Xiaojie, AU - Liu,Xi, AU - Wang,Jian, Y1 - 2016/01/25/ PY - 2015/09/28/received PY - 2016/01/01/revised PY - 2016/01/17/accepted PY - 2016/1/29/entrez PY - 2016/1/29/pubmed PY - 2016/12/15/medline KW - APP/PS1 transgenic mice KW - Alzheimer׳s disease KW - Anti-Aβ antibodies KW - Phage display library SP - 169 EP - 79 JF - Brain research JO - Brain Res VL - 1635 N2 - We screened anti-Aβ1-42 antibodies from a human Alzheimer's disease (AD) specific single chain variable fragment (scFv) phage display library and assessed their effects in APP/PS1 transgenic mice. Reverse transcription-PCR was used to construct the scFv phage display library, and screening identified 11A5 as an anti-Aβ1-42 antibody. We mixed 11A5 and the monoclonal antibody 6E10 with Aβ1-42 and administered the mixture to Sprague-Dawley rats via intracerebroventricular injection. After 30 days, rats injected with the antibody/Aβ1-42 mixture and those injected with Aβ1-42 alone were tested on the Morris water maze. We also injected 11A5 and 6E10 into APP/PS1 transgenic mice and assessed the concentrations of Aβ in brain and peripheral blood by ELISA at 1-month intervals for 3 months. Finally we evaluated behavior changes in the Morris water maze. Rats injected with Aβ1-42 and mixed antibodies showed better performance in the Morris water maze than did rats injected with Aβ1-42 alone. In APP/PS1 transgenic mice, Aβ concentration was lower in the brains of the antibody-treated group than in the control group, but higher in the peripheral blood. The antibody-treated mice also exhibited improved behavioral performance in the Morris water maze. In conclusion, anti-Aβ1-42 antibodies (11A5) screened from the human scFv antibody phage display library promoted the efflux or clearance of Aβ1-42 and effectively decreased the cerebral Aβ burden in an AD mouse model. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/26820640/Effects_of_an_amyloid_beta_1_42_oligomers_antibody_screened_from_a_phage_display_library_in_APP/PS1_transgenic_mice_ DB - PRIME DP - Unbound Medicine ER - Grapherence [↓10 ↑42] Links PMC Free PDF Authors Wang J Li N Ma J Gu Z Yu L Fu X Liu X Wang J MESH Alzheimer Disease Amyloid beta-Peptides Amyloid beta-Protein Precursor Animals Antibodies, Monoclonal Brain Disease Models, Animal Humans Infusions, Intraventricular Male Maze Learning Mice Mice, Inbred C57BL Mice, Transgenic Peptide Fragments Peptide Library Presenilin-1 Rats Rats, Sprague-Dawley Coronavirus Guidelines Latest evidence on COVID-19 from PubMed, WHO, CDC. Visit free Relief Central . Try the Free App: Prime PubMed is provided free to individuals by: Unbound Medicine . Grapherence [↓10 ↑42] Related Citations A Novel scFv Anti-Aβ Antibody Reduces Pathological Impairments in APP/PS1 Transgenic Mice via Modulation of Inflammatory Cytokines and Aβ-related Enzymes. Lack of P-glycoprotein Results in Impairment of Removal of Beta-Amyloid and Increased Intraparenchymal Cerebral Amyloid Angiopathy after Active Immunization in a Transgenic Mouse Model of Alzheimer's Disease. CART modulates beta-amyloid metabolism-associated enzymes and attenuates memory deficits in APP/PS1 mice. Intraperitoneal Administration of Monoclonal Antibody Against Pathologic Aβ42 Aggregates Alleviated Cognitive Deficits and Synaptic Lesions in APP/PS1 Mice. A novel monoclonal antibody against the N-terminus of Aβ1-42 reduces plaques and improves cognition in a mouse model of Alzheimer's disease. [Effects of huannao yicong recipe extract on the learning and memory and related factors of Abeta generation in the brain of APP transgenic mice]. Neuroprotective effects of verbascoside against Alzheimer's disease via the relief of endoplasmic reticulum stress in Aβ-exposed U251 cells and APP/PS1 mice. Presenilin 1 transgene addition to amyloid precursor protein overexpressing transgenic rats increases amyloid beta 42 levels and results in loss of memory retention. Geniposide attenuates insulin-deficiency-induced acceleration of β-amyloidosis in an APP/PS1 transgenic model of Alzheimer's disease. β-asarone improves learning and memory and reduces Acetyl Cholinesterase and Beta-amyloid 42 levels in APP/PS1 transgenic mice by regulating Beclin-1-dependent autophagy. More Home Contact Us Help Privacy / Disclaimer Terms of Service Sign In
https://www.unboundmedicine.com/medline/citation/26820640/Effects_of_an_amyloid_beta_1_42_oligomers_antibody_screened_from_a_phage_display_library_in_APP/PS1_transgenic_mice_
Facts about "Casablanca" : Classic Movie Hub (CMH) Browse Fun Facts and Trivia about at Classic Movie Hub (CMH). <here is a image bf78f8e36794dad7-ec58925fe0d64af1> Casablanca "As Time Goes By" was written by lifelong bachelorHerman Hupfeldand debuted in 1931's Broadway show "Everybody's Welcome", sung byFrances Williams, It had been a personal favorite of playwright and high school teacherMurray Burnettwho, seven years later, visited Vienna just after the Nazis had entered. Later, after visiting a café in south France where a black pianist had entertained a mixed crowd of Nazis, French and refugees, Burnett was inspired to write the melodrama "Everybody Comes to Rick's", which was optioned for production byMartin GabelandCarly Wharton, and later, Warners. After the film's release, "As Time Goes By" stayed on radio's "Hit Parade" for 21 weeks. However, because of the coincidental musicians' union recording ban, the 1931Rudy Valleeversion became the smash hit. (It contains the rarely-sung introductory verse, not heard in the film.)Max Steiner, in a 1943 interview, admitted that the song "must have had something to attract so much attention". "Here's looking at you, kid" was improvised by Humphrey Bogart in the Parisian scenes and worked so well that it was used later on again in the film. He originally used the same line in Midnight . It is also rumored that during breaks, Ingrid Bergman would play poker with other cast members. Since she was still learning English, Bogart would occasionally watch the game, and he added "Here's looking at you" to her poker repertoire. "Rick's Café Américain" was modeled after Hotel El Minzah in Tangiers. Humphrey Bogarthad to wear platform shoes to play alongsideIngrid Bergman. Humphrey Bogart , Ingrid Bergman and Paul Henreid later reprised their roles for a radio performance of on the CBS radio program "The Screen Guild Players", a war benefit show on April 26, 1943. Humphrey Bogart 's wife Mayo Methot continually accused him of having an affair with Ingrid Bergman , often confronting him in his dressing room before a shot. Bogart would come onto the set in a rage. In fact, despite the undeniable on-screen chemistry between Bogart and Bergman, they hardly spoke, and the only time they bonded was when the two had lunch with Geraldine Fitzgerald . According to Fitzgerald, "the whole subject at lunch was how they could get out of that movie. They thought the dialogue was ridiculous and the situations were unbelievable... I knew Bogart very well, and I think he wanted to join forces with Bergman, to make sure they both said the same things." For whatever reasons, Bogart and Bergman rarely spoke after that. S.Z. Sakall, who plays the maitre d' at Rick's Cafe, actually has more screen time thanPeter LorreorSydney Greenstreet. Madeleine Lebeau , who plays Yvonne, and Marcel Dalio , who plays croupier Emil, were husband and wife at the time of filming. They had not long before escaped the Nazis by fleeing their native France. Dooley Wilson (Sam) was a professional drummer who faked playing the piano. As the music was recorded at the same time as the film, the piano playing was actually a recording of a performance by Elliot Carpenter who was playing behind a curtain but who was positioned such that Dooley could watch, and copy, his hand movements. Dooley Wilsonwas borrowed from Paramount at $500 a week. Dooley Wilsonwas, in fact, the only member of the cast to have ever actually visited the city of Casablanca. Joy Page , who played the young Bulgarian wife, was the stepdaughter of studio head Jack L. Warner . She, Humphrey Bogart and Dooley Wilson were the only American-born people in the credited cast. This film was her debut. Hal B. Wallisdidn't wantHumphrey Bogartwearing a hat too often in the film, as he thought it made Bogart look like a gangster. Hal B. Wallis's first choice for director wasWilliam Wyler. Sydney Greenstreet wanted to wear something more ethnic to show that his character had assimilated into the Moroccan lifestyle. This idea was nixed by producer Hal B. Wallis who insisted that he wear his now-iconic white suit. Ingrid BergmanandPaul Henreidmake their first appearance 24 minutes into the film. Ingrid Bergman considered her left side as her better side, and to the extent possible that was the side photographed throughout the film, so she is almost always on the right side of the screen looking towards the left regardless of who is in the shot with her. However, there are several shots where she is to the left and Humphrey Bogart is on the right, including the flashbacks to the street scene in Paris (0:41:50) and the scene at the window (0:43:40). There are also several scenes where Bergman is centered between Paul Henreid and Bogart, suggesting the triangle nature of their relationship; in these shots Henreid is usually to the left and Bogart is usually on the right, including the scene where she and Henreid enter the café at just before the famous "Battle of the Anthems" (1:07:40); the scene where Captain Renault arrests Victor Laszlo (1:34:00); and at the end of the final airport scene (1:39:00). Ingrid Bergman's contract was owned by producerDavid O. Selznick, and producerHal B. Wallissent the film's writers,Philip G. EpsteinandJulius J. Epstein, to persuade Selznick to loan her to Warner Bros. for the picture. After 20 minutes of describing the plot to Selznick, Julius gave up and said, "Oh, what the hell! It's a lot of shit likeAlgiers!" Selznick nodded and agreed to the loan. Ingrid Bergman 's line "Victor Laszlo is my husband, and was, even when I knew you in Paris" was almost cut from the film because during that time it was deemed inappropriate for a film to depict or suggest a woman romancing with another man if she were already married. However, it was pointed out that later in the film she explains that she had thought Laszlo was dead at the time, and the censors allowed the line to stay in. Howard Hawks had said in interviews that he was supposed to direct Casablanca and Michael Curtiz was supposed to direct Sergeant York . The directors had lunch together, where Hawks said he didn't know how to make this "musical comedy", while Curtiz didn't know anything about "those hill people." They switched projects. Hawks struggled on how to direct the scenes that involved singing, namely the "La Marseillaise" scene. It is ironic to note that most of his other films involved at least one singing scene.
https://www.classicmoviehub.com/facts-and-trivia/film/casablanca-1942/?lv=true%2Fpage%2F1%2F%2Fpage%2F2%2F%2Fpage%2F3%2F%2Fpage%2F6%2F%2Fpage%2F1%2F%2Fpage%2F4%2F
Clinician-facilitated cascade testing for hereditary cancer: Effect of race on completion of genetic testing and utilization of cancer surveillance and risk-reducing surgery (426) - Gynecologic Oncology Abstract|Volume 166, SUPPLEMENT 1,S214-S215,August 2022 Clinician-facilitated cascade testing for hereditary cancer: Effect of race on completion of genetic testing and utilization of cancer surveillance and risk-reducing surgery (426) Purchase Academic & Personal: 24 hour online access Corporate R& D Professionals: 24 hour online access Subscribe Save Add To Online LibraryPowered ByMendeley Add To My Reading List Export Citation Create Citation Alert Share Share on Twitter Facebook Linked In Sina Weibo Email more Reprints Request Top Clinician-facilitated cascade testing for hereditary cancer: Effect of race on completion of genetic testing and utilization of cancer surveillance and risk-reducing surgery (426) Muhammad Danyal Ahsan Muhammad Danyal Ahsan Affiliations Weill Cornell Medicine, New York, NY, United StatesSearch for articles by this author Eloise Chapman-Davis, MD Eloise Chapman-Davis Affiliations Weill Cornell Medicine/NY Presbyterian HospitalSearch for articles by this author Nora Badiner, MD Nora Badiner Affiliations Weill Cornell Medicine/NY Presbyterian HospitalSearch for articles by this author Roni Nitecki, MD, MPH Roni Nitecki Affiliations The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesSearch for articles by this author Jose Rauh-Hain, MD, MPH Jose Rauh-Hain Affiliations The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesSearch for articles by this author Charlene Thomas, BA Charlene Thomas Affiliations Weill Cornell Medicine, New York, NY, United StatesSearch for articles by this author Paul Christos, DrPH, MS Paul Christos Affiliations Weill Cornell Medicine, New York, NY, United StatesSearch for articles by this author Stephanie Blank, MD Stephanie Blank Affiliations Icahn School of Medicine at Mount Sinai, New York, NY, United StatesSearch for articles by this author Kevin Holcomb, MD Kevin Holcomb Affiliations Weill Cornell Medicine, New York, NY, United StatesSearch for articles by this author Evelyn Cantillo, MD, MPH Evelyn Cantillo Affiliations Weill Cornell Medicine, New York, NY, United StatesSearch for articles by this author Ravi Sharaf, MD, MS Ravi Sharaf Affiliations Weill Cornell Medicine, New York, NY, United StatesSearch for articles by this author Steven Lipkin, MD, PhD Steven Lipkin Affiliations Weill Cornell Medicine, New York, NY, United StatesSearch for articles by this author Melissa Frey, MD Melissa Frey Affiliations Weill Cornell Medicine, New York, NY, United StatesSearch for articles by this author Show all authors DOI:https://doi.org/10.1016/S0090-8258(22)01648-1 PlumX Metrics Captures Readers:3see details Previous ArticleA nomogram for predicting endometrial cancer risk in asymptomatic women: Addressing disparities in patient populations with limited access and delayed diagnosis (425) Next ArticleThe global burden of gynecologic oncology disease as reflected in clinical trials: An analysis of over 2,000 clinical trials (427) Article info Related Articles This paper is only available as a PDF. To read, PleaseDownload here. Objectives:Cascade genetic testing for hereditary cancer syndromes offers affected, asymptomatic relatives the opportunity to pursue cancer screening and risk-reducing surgery, reducing cancer incidence, morbidity, and mortality. The purpose of this study was to measure the long-term utilization of genetically targeted cancer prevention and quality of life among at-risk relatives offered cascade genetic testing. Methods:We performed a two-year follow-up for relatives enrolled in a pilot study evaluating clinician-facilitated cascade testing via telephone genetic counseling and mailed saliva kit testing. Relatives were contacted by telephone to review utilization of guideline-based mutation-specific recommendations for cancer prevention and early detection and received email questionaries (Hospital Anxiety and Depression Scale, Satisfaction with Decision Scale, Multidimensional Impact of Cancer Risk Assessment). Quality of life scores on the instruments at six months and 2-years follow-up were compared to the time of initial relative contact for cascade testing by the Wilcoxon signed-rank test. Results:Among 96 enrolled relatives, 72 (76%) participated in a two-year follow-up. Fifty-seven (79.2%) participating relatives completed genetic testing. At two years, among relatives with a pathogenic mutation, 21 (95%) completed at least one cancer surveillance intervention, and five (39%) had a risk-reducing surgery as a direct result of the cascade testing. Non-White patients were more likely than White patients to complete cascade genetic testing (100% vs 73.7%, p=0.026). Among relatives with a mutation who were recommended cancer screening, 100% (14) of White relatives completed cancer screening versus 83% (5) of Black relatives. Among relatives with a mutation who were recommended cancer risk-reducing surgery, 57% (4) of White relatives completed surgery versus 0% (0) of Black relatives. Surveys demonstrated low levels of anxiety, depression, distress, and uncertainty with significantly improved combined depression and anxiety scores at 6-month and 2-year follow-up compared to the time of initial relative contact for cascade testing (Table 1). Conclusions:Our findings demonstrate that clinician-facilitated cascade testing can result in the successful completion of genetic testing and utilization of genetically targeted primary disease prevention. Furthermore, a strategy of facilitation eliminated well-described racial disparities in the completion of genetic testing; however, the population was limited by small sample size and minimal diversity. Notably, our data suggest that even after completing genetic testing, race may contribute to the utilization of guideline-based cancer prevention and early detection. Therefore, future strategies to promote equitable care for families with hereditary cancer syndromes must focus not only on access to genetic testing but also on supporting engagement with the medical system following identification of a mutation. To read this article in full you will need to make a payment Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R& D Professionals: 24 hour online access One-time access price info For academic or personal research use, select 'Academic and Personal' For corporate R& D use, select 'Corporate R& D Professionals' Subscribe:Subscribe toGynecologic Oncology Already a print subscriber?Claim online access Already an online subscriber?Sign in Register:Create an account Institutional Access:Sign in to ScienceDirect Article info Identification DOI:https://doi.org/10.1016/S0090-8258(22)01648-1 Copyright © 2022 Elsevier Inc. Published by Elsevier Inc. All rights reserved. ScienceDirectAccess this article on ScienceDirect Related Articles Hide CaptionDownloadSee figure in Article Toggle Thumbstrip Download Hi-res image Download .PPT
https://www.gynecologiconcology-online.net/article/S0090-8258(22)01648-1/pdf
ICC Website Terms of Use - ICC ICC Website Terms of Use Last revised January 3, 2023 1. Acceptance of Terms Pursuant to these Terms of Use, International Code Council, Inc., International Accreditation Service, Inc., ICC Evaluation Service, LLC, Solar Rating and Certification Corporation, General Code, LLC, ICC Community Development Solutions, LLC, ICC NTA, LLC, S. K. Ghosh Associates, LLC, Alliance for National & Community Resilience, Inc., ICC PEI, LLC, and their respective affiliates and subsidiaries (collectively, "We," "Us," "Our," "ICC") provide You limited rights of use and access to Our websites, including https://www.iccsafe.org/ and other websites where these Terms of Use are posted (together, the “Site”), and Our online services, content, products, subscriptions, mobile applications, and software used in connection with any of the foregoing (collectively, “Digital Content”). The Site and Digital Content shall collectively be referred to as the “Services.” By accessing or otherwise using any of the Services, you agree, on behalf of yourself and any other person or entity who uses any Service under your account, including your employer (collectively, “You”), to the following terms and conditions under the Terms of Use, and represent that You and all of your authorized users are of the legal age of majority in your state or jurisdiction of residence and, if applicable, You are authorized by your employer to agree to such terms on your employer’s behalf. The Terms of Use are in addition to and do not nullify, any other agreement between You and Us or any other applicable terms and conditions for the Services. You agree to comply with all rules or restrictions that are posted on the Services. ICC offers a wide range of Digital Content, and additional terms may apply to certain Digital Content. When you use Digital Content (for example, Digital Codes Premium, cdpACCESS, MyICC App, eCode 360), You also will be subject to the guidelines, terms and agreements applicable to that particular Digital Content ("Digital Content Terms"). If a particular term within the Terms of Use is inconsistent with the Digital Content Terms, the relevant term within the Digital Content Terms will control. PLEASE READ THESE TERMS OF USE CAREFULLY BEFORE USING THE SERVICES. THE TERMS OF USE INCLUDE A PROVISION REQUIRING THAT YOU AND WE WILL RESOLVE ANY DISPUTE THROUGH INDIVIDUAL ARBITRATION, UNLESS AN EXCEPTION APPLIES. EACH TIME YOU USE THE SERVICES, YOUR USE INDICATES YOUR FULL ACCEPTANCE OF AND AGREEMENT TO ABIDE BY THE TERMS OF USE IN ITS THEN CURRENT FORM. IF YOU DO NOT ACCEPT THE TERMS AND CONDITIONS STATED IN THE TERMS OF USE, PLEASE DO NOT USE THE SERVICES YOU MAY ALSO AGREE TO THE TERMS OF USE ELECTRONICALLY, WHICH MAY INCLUDE, WITHOUT LIMITATION, CLICKING ON AN “AGREE” OR SIMILAR BUTTON OR CHECKING A BOX THAT IS NEXT TO OR NEAR A LINK TO THE TERMS OF USE. 2. Privacy Policy In addition to reviewing these Terms of Use, You should also read Our Privacy Policyto better comprehend how We collect and use Your personal information. Your use of the Services constitutes Your agreement to Our Privacy Policy. 3. Suspension or Termination of Your Use Your failure to follow the requirements of the Terms of Use may result in suspension or termination of Your access to the Services, without notice, in addition to ICC’s other remedies. ICC further reserves the right to terminate, without notice and in its sole discretion, any user’s access to or use of the Services for any reason. 4. Licenses Subject to your compliance with these Terms of Use and any applicable Digital Content Terms, and your payment of any applicable fees, ICC grants You a limited, non-exclusive, non-transferable, non-sublicensable, revocable license to access and make personal, internal business, and non-commercial use of the Services, including the Digital Content provided by ICC and its licensors, which includes, but is not limited to: Mobile Apps : MyICC App and other mobile apps provided by ICC. cdpACCESS: ICC’s cloud-based system for the code development process. Subscription Products : ICC’s online subscription platform to access and interact with the full range of ICC’s digital titles in the ICC library, offering varying levels of access from single title to the full digital library. Electronic Products : Model, international, state, city and county codes and amendments, standards commentaries, translations, digital books, recordings of code hearings, and references and other digital textual, graphic, video, and database materials. Single User Electronic Products : PDF downloads, code hearing downloads, iQuest single user CD-ROMs, Digital Codes Premium single user, and other Electronic Products that are identified as intended for a single user. For all Single User Electronic Products, the foregoing license ICC grants You is a single seat license to download the Single User Electronic Product to a single computer or device using the identification and password information provided to You by ICC. For Single User Electronic Products, You are permitted to make one back-up copy of the applicable licensed product. Single User Electronic Products are intended and licensed for use by only one authorized user. Multiple User Electronic Products : ICC multiple user Electronic Products include: Digital Codes Premium Multiple User Subscriptions, PDF CDs, iQuest multiple user CD-ROMs and other multiple user Electronic Products that are identified as intended for multiple installation (e.g., 5 seats, 10 seats, etc.). For all Multiple User Electronic Products, the foregoing license that ICC grants You is applicable to the number of computers or devices identified by ICC as eligible to use the identification and password provided to You by ICC. Each Multiple User Electronic Product will identify the number of authorized users that may access and use the Electronic Product on their computers or devices. For any Multiple User Electronic Products that are downloaded to your network and not to individual computers or devices, You may only allow the applicable number of authorized network users associated with the licensed Electronic Product to access and use the Electronic Product via the network. For example, if You purchase a Multiple User Electronic Product for installation on your network with rights for 5 users, You may only allow 5 users to access the Electronic Product via the network at any given time. You will be responsible for ensuring that each authorized user has read and agreed to the Terms of Use and applicable Digital Content Terms. An authorized user may not make an Electronic Product available electronically to anyone other than another authorized user in any fashion. You will provide ICC, upon request, the names and physical and email addresses of each authorized user. The licenses ICC grants to use our Digital Content, as set forth in these Terms of Use and applicable Digital Content Terms, do not include any: resale or commercial use of any Service or Digital Content; derivative use of any Service or Digital Content; downloading, copying, distribution, or display of Digital Content (or portion thereof) or account information to, by, or for the benefit of any third party (for example, a user other than You/the authorized users for a Multiple User Electronic Product); or use of data mining, robots, or similar data gathering and extraction tools with any Service or Digital Content. Please contact us at [email protected] to discuss additional licenses for further uses. All rights not expressly granted to You in these Terms of Use or any applicable Digital Content Terms are reserved and retained by ICC or its licensors. For avoidance of doubt, no Service, nor any part of any Service (including Digital Content or any portion thereof), may be reproduced, displayed, distributed, transferred, sublicensed, sold or otherwise exploited: (i) on a third-party or government website, (ii) for the benefit of a third party, or (iii) for any commercial purpose without express written consent of ICC. You may use the Services only as permitted by law. The licenses granted by ICC terminate if You do not comply with these Terms of Use or any Digital Content Terms. Upon termination of any license granted under the Terms of Use or Digital Content Terms, You must return to ICC or destroy the original and any copies of all Digital Content. 5. Ownership of the Services and Site Information; Intellectual Property Rights The Services, including the Site, Digital Content, and the design and content features thereof (including without limitation, information and other materials, illustrations, product layout, and design, icons, navigational buttons, images, artwork, graphics, photography, text, data, audio sound, software and the like, as well as the selection, assembly and arrangement thereof), are owned by ICC or its affiliates or are licensed from third-party service providers by ICC. The Services, as a whole and in part, are protected by copyright, trademark, service mark, trade name, and other intellectual property and proprietary rights, and all other applicable rights are reserved to ICC or its affiliates or applicable licensors. Except as expressly permitted by the Terms of Use, applicable Digital Content Terms, or any other applicable terms and conditions to which You agree, no portion of the Services may be reprinted, republished, modified, publicly displayed, publicly performed, or distributed in any form without Our express written permission. You may not, and the Terms of Use do not give You permission to, reproduce, reverse engineer, decompile, disassemble, attempt to derive the source code of, modify, adapt, amend, translate, transmit, sell (or participate in any sale), distribute, license, or create derivative works with respect to the Services. Certain components of the Services may be licensed from third parties and all such third-party components of the Services and all intellectual property and proprietary rights related to such third-party components of the Services belong to the respective third parties. You may not remove any copyright, trademark, or other intellectual property or proprietary notice or legend contained on the Services or the third-party components of the Services. You agree not to use the Services, in whole or in part, in any way for any public or commercial purpose or in any other manner that is likely to cause confusion among consumers, that disparages or discredits Us or Our licensors, that dilutes the strength of Our intellectual property or Our licensor’s intellectual property, or that otherwise infringes on Our or Our licensor’s intellectual property rights. You further agree to in no other way misuse the Services, in whole or in part. 6. Services Information is Provided As Is; Use of Services The Services are provided “as is” with all faults. You use the Services, as authorized herein, at Your own risk. The Services may contain errors, omissions, or typographical errors or may be out of date. The Services may change, delete, or be updated at any time and without prior notice. You understand that We cannot and do not guarantee or warrant that files, if any, available for downloading from the Services will be free of infection or viruses, worms, Trojan horses, time bombs, cancelbots, or any other computer programming routines that may damage, detrimentally interfere with, surreptitiously intercept or expropriate any system, data or personal information (collectively, “Hazards”).. You understand that We cannot and do not guarantee or warrant that files, if any, available for downloading from the Services will be free of infection or viruses, worms, Trojan horses, time bombs, cancelbots, or any other computer programming routines that may damage, detrimentally interfere with, surreptitiously intercept or expropriate any system, data or personal information (collectively, “Hazards”). 7. Eligibility to Use the Services The Services are not intended for users under the age of 18. To register for and/or use any Services, You must be at least 18 years old or the age of majority in the jurisdiction where you reside. If You do not meet this requirement, You may only use Services in conjunction with Your parents or guardians. 8. Accurate Information; Registration and Passwords In consideration of Your use of the Services, You agree to: (a) provide true, accurate, and current and complete information as prompted on the Services; and (b) maintain and update such information to keep it true, accurate, current, and complete. If You provide any information that is untrue, inaccurate, not current, or incomplete, or We have reasonable grounds to suspect that such information is untrue, inaccurate, not current, or incomplete, We may suspend or terminate Your use of the Services and/or decline to permit Your continued use of the Services and future access to the Services. You may need a username and password to use certain features of the Services. By selecting a user name, You agree that You will not (i) select or use a name or e-mail address of another person with the intent to impersonate that person; (ii) use a name or e-mail address subject to the rights of any person without authorization; (iii) use a name in violation of the intellectual property rights of any person; or (iv) use a name that We, in Our sole discretion, deem inappropriate or offensive. You are responsible for maintaining the confidentiality of Your password and account and are responsible for all activities (whether by You or by others) that occur under Your password or account. You will notify Us immediately of any unauthorized use of Your password or account or any other breach of security. We assume no liability for any loss or damage arising from any unauthorized use of Your password or account by a third party. 9. Acceptable and Lawful Use of Discussion Forums and Other Interactive Features You may have the opportunity to post, stream, transmit, or otherwise provide ideas, remarks, questions, data, graphics, opinions, designs, customizations, or other content on the Services, including information on bulletin boards, chat rooms, cdpACCESS, or other forums (collectively “User Generated Content”). In interacting with the Services and providing User Generated Content, You mustnot: Engage in any conduct that, in Our sole judgment, restricts or inhibits any other user from using or enjoying the Services; Use the Services to impersonate any person or entity, or falsely state or otherwise misrepresent Your affiliation with a person or entity; Interfere with or disrupt any servers or networks used to provide the Services or its features, or disobey any requirements, procedures, policies, or regulations of the networks We use to provide the Services; Gain unauthorized access to the Services, or any account, computer system, or network connected to the Services, by means such as hacking, password mining, or any other illicit conduct; Engage in advertising or commercial solicitation of any product or service, or to solicit donations of any kind on the Services, without Our written consent; Gather for marketing purposes any email addresses or other personal information that has been posted by other users; Post information or content that we deem in Our sole discretion to be violent, harmful, abusive, hateful, offensive (to persons of or having a particular race, ethnicity, national origin, religion, sex, gender, sexual orientation, disability or medical condition), pornographic, sexually explicit, defamatory, infringing, invasive of personal privacy or publicity rights, harassing, humiliating to other people (publicly or otherwise), libelous, threatening, profane, or otherwise objectionable; Post information or content that is illegal or for which You do not have the right to share (including, without limitation, the disclosure of insider information under securities law or of another party's trade secrets or proprietary information); Post any information or content that is false, misleading, deceptive, fraudulent, contains a Hazard, or may otherwise create a risk of any other loss or damage to any person or property Infringe any third party’s intellectual property, copyright, patent, trademark, trade secret or other proprietary rights or rights of publicity or privacy; Circumvent, including without limitation, by avoiding, bypassing, removing, deactivating, impairing, or descrambling any technological measure to protect the Services; Violate or encourage any conduct that violates any applicable law or regulation; Request, collect or store username, password, or any other account authentication information from other users; or Encourage or enable any other individual to do any of the activities prohibited under these Terms of Use. We shall have the right, but no obligation, to monitor the User Generated Content made available on the Services to determine compliance with the Terms of Use and any other operating rules We establish. We shall have the right in Our sole discretion to edit, refuse to post, or remove any User Generated Content made available on any of the Services. Notwithstanding this right, You shall remain solely responsible for the content of Your User Generated Content (including obtaining any relevant permissions or licenses to authorize the uses of the User Generated Content that You agree to under the Terms of Use). We neither endorse nor are responsible for the accuracy or reliability of any opinion, advice, or statement on any of the of the Services, whether it is provided by Us, Our employees, or a third party. Under no circumstances will We be liable for any loss or damage of any kind caused by reliance on information obtained through any User Generated Content on any of the Services. We are not responsible for any offensive, defamatory, obscene or any other posting made on any of the Services. We reserve the right at all times to disclose any information We believe necessary to satisfy any law, regulation or governmental request, or to refuse to post or to remove any information or materials, in whole or in part, that in Our sole discretion are inappropriate, objectionable or in violation of the Terms of Use or other applicable terms and conditions. We also reserve the right to deny access to the Services or any features of the Services to anyone who violates the Terms of Use or who, in Our sole judgment, interferes with the ability of others to enjoy the Services or infringes the rights of others. Neither We nor any third-party content provider shall assume or have any liability for any action or inaction by Us or any third-party content provider with respect to any conduct, communication or posting on the Services. Any user who feels that a posted message is objectionable or otherwise fails to comply with our requirements for User Generated Content is encouraged to contact Us by email to [email protected]. We are a provider of an interactive computing service as set forth the Communications Decency Act, 47 U.S.C. §230 and expressly reserve Our rights to not be treated as the publisher or speaker of any information provided by another information content provider on the Services or through any interactive features of such Services. 10. User Generated Content You (or your authorized licensor) retain ownership to User Generated Content submitted on the Services. However, by submitting Your User Generated Content to Us, You hereby grant Us the following worldwide, royalty-free, non-exclusive, perpetual, irrevocable, sub-licensable and transferable rights and licenses: to host, cache, store, archive, index, crawl, create algorithms based thereon, modify or transcode the User Generated Content to appropriate media formats, standards or mediums as part of the Services We provide; to use, distribute, reproduce, modify, remix, excerpt, adapt, prepare derivative works of, publicly perform and publicly display the User Generated Content on the Services, including without limitation, in connection with any distribution or syndication arrangement thereof with third parties or third-party sites, in any media format or medium and through any media channels; and to use User Generated Content for advertising, promotional or commercial purposes, including without limitation, the right to publicly display, perform, reproduce and distribute Your User Generated Content in any media format or medium and through any media channels. By submitting User Generated Content for inclusion in the Services, You also grant the following use of and rights to Your User Generated Content to users of ICC Services (“Users”): (i) the non-exclusive license to access Your User Generated Content through the Services; (ii) the ability for Users to rate review and comment on Your User Generated Content; and (iii) the non-exclusive license to use, reproduce, distri
https://www.iccsafe.org/about/website-user-agreement/?__hsfp=3465878509&__hssc=44910843.2.1682855973537&__hstc=44910843.b529899724c4d84fc3c3a714435934a2.1682855973537.1682855973537.1682855973537.1
Biocompatible, bioerodible, hydrophobic, implantable polyimino carbonate article Patent Grant Kohn , et al. February 21, 1 [Massachusetts Institute of Technology] Biocompatible, bioerodible, hydrophobic, implantable polyimino carbonate article Kohn , et al. February 21, 1 Patent Grant 4806621 U.S. patent number 4,806,621 [Application Number 06/820,351] was granted by the patent office on 1989-02-21 for biocompatible, bioerodible, hydrophobic, implantable polyimino carbonate article . This patent grant is currently assigned to Massachusetts Institute of Technology. Invention is credited to Joachim Kohn, Robert S. Langer. <table><tbody><tr><td> United States Patent</td><td> 4,806,621</td></tr><tr><td> Kohn ,   et al.</td><td> February 21, 1989</td></tr></tbody></table> Biocompatible, bioerodible, hydrophobic, implantable polyimino carbonate article Abstract A novel series of articles useful as medical devices, implants and protheses are provided which utilize poly(iminocarbonate) polymeric matrices. These articles are biocompatible, have excellent mechanical properties and degrade into non-toxic residues after introduction in vivo. The articles may be formed in any desired dimensions and configuration and may take specific shape as biodegradable sutures or as orthopedic appliances such as bone plates and the like. <table><tbody><tr><th> Inventors:</th><td> Kohn; Joachim(Brookline, MA) , Langer; Robert S.(Somerville, MA)</td></tr><tr><th> Assignee:</th><td> Massachusetts Institute of Technology(Cambridge, MA) </td></tr><tr><th> Family ID:</th><td> 25230550</td></tr><tr><th> Appl. No.:</th><td> 06/820,351</td></tr><tr><th> Filed:</th><td> January 21, 1986</td></tr></tbody></table> Current U.S. Class: 528/211; 523/113; 523/115; 523/122; 528/128 Current CPC Class: A61L 17/10 (20130101); A61L 27/18 (20130101); A61L 31/06 (20130101); C08G 64/12 (20130101); A61L 27/18 (20130101); C08L 69/00 (20130101); A61L 31/06 (20130101); C08L 69/00 (20130101) Current International Class: A61L 17/00 (20060101); A61L 17/10 (20060101); A61L 27/18 (20060101); A61L 27/00 (20060101); A61L 31/04 (20060101); A61L 31/06 (20060101); C08G 64/12 (20060101); C08G 64/00 (20060101); C08G 063/62 () Field of Search: ;528/211,128 ;424/78 ;523/113,115,122 References Cited [Referenced By] U.S. Patent Documents <table><tbody><tr><th></th><th></th><th></th></tr><tr><td> 3491060</td><td> January 1970</td><td> Schminke et al.</td></tr><tr><td> 3887699</td><td> June 1975</td><td> Yolles</td></tr><tr><td> 4122158</td><td> October 1978</td><td> Schmitt</td></tr><tr><td> 4131648</td><td> December 1978</td><td> Choi et al.</td></tr><tr><td> 4419340</td><td> December 1983</td><td> Yolles</td></tr><tr><td> 4554155</td><td> November 1985</td><td> Allan et al.</td></tr><tr><td></td></tr></tbody></table> Primary Examiner: Anderson; Harold D. Attorney, Agent or Firm: Cook; Paul J. Government Interests The Government has rights in this invention pursuant to Grant Number NIH-2-R01-GM26698-07 awarded by the National Institutes of Health. Claims We claim: 1. An article useful for implantation in an animal comprising a mixture of (a) a solid biocompatible, bioerodible, hydrophobic polyiminocarbonate composition having the recurring structrual unit: ##STR8## wherein R is a divalent aromatic group comprising a non-fused ring and n is at least 2, said article degrading into non-toxic residues after introduction in vivo and (b) a pharmacologically active composition. 2. The article recited in claim 1 wherein R is phenylene. 3. The article recited in claim 1 wherein R is: ##STR9## 4. The article as recited in claim 1 wherein R is: ##STR10## 5. The article as recited in claim 1 wherein R is: ##STR11## and R' is C,-C.sub.6 lower alkylene. 6. The article of claim 1 wherein R is: ##STR12## X is a heteroatom and n is an integer greater than 1. 7. The article of claim 1 wherein R is: ##STR13## 8. The process for administering a pharmacologically active composition to an animal which comprises implanting in said animal the article of any one of claims 2, 3, 4, 5, 6, 7 or 1. Description FIELD OF THE INVENTION The present invention is concerned with biocompatible articles suitable for surgical introduction in vivo and is particularly directed to bioerodible articles which degrade into biocompatible and non-toxic products. BACKGROUND OF THE INVENTION Synthetic polymeric compositions which are bioerodible and biocompatible have become increasingly important and valuable in recent years. One application for such compositions is as surgically implantable biomaterials or prosthetic articles for human and animal subjects in vivo. Consequently, such biomaterials are articles which serve as implants or prostheses, artificial devices introduced into living tissues to replace a missing part of the body; these are exemplified by articles such as vascular grafts, biodegradable sutures and orthopedic appliances such as bone plates and the like. In order for an implantable or prosthetic article to be truly useful, it should be composed of a synthetic polymeric composition having specific characteristics and properties: First, the synthetic composition should provide sufficient elasticity and tensile strength over a preselected minimal time period which will vary with the specific application. Second, the synthetic composition should be non-immunogenic, biocompatible, biodegradable in vivo and yield degradation products which are themselves non-inflammatory, non-toxic and non-antigenic. Despite continuing research effort, very few synthetic polymeric biomaterials have been developed which provide all these desired attributes. Presently known biodegradable polymers such as polylactic acid, polyglycolic acid, polycaprolactones and the various polyamides also all lack the desired mechanical strengths over time [Heller et al, "Theory and Practice of Control Drug Delivery from Bioerodible Polymers", in Controlled Release of Bioactive Material, R. W. Baker Editors, Academic Press, New York, 1908, pp. 1-17; Pitt et al, Biomaterials 2: 215-220 (1981); Chu, C. C., J. Appl. Polym. Sci. 26: 1727-1734 (1981)]. Prior to this invention, polyimidocarbonates have been prepared as disclosed in U.S. Pat. No. 3,491,060. However, these polymers have not been commercially used. Specifically, they have not been considered as materials useful for implantable devices. SUMMARY OF THE INVENTION A bioerodible article useful for prosthesis and implantation is provided which comprises a biocompatible, polyiminocarbonate matrix, prepared in preselected dimensions and configuration, which erodes into non-toxic residues after introduction in vivo. The bioerodible article optionally can contain a pharmacologically active composition which can be released in vivo as the polyiminocarbonate article erodes in vivo. The method of using the article as an implant and prosthesis comprises the step of introducing a specifically configured article into a subject in vivo at a predetermined site. DETAILED DESCRIPTION OF THE DRAWINGS The present invention may be more completely and easily understood when taken in conjunction with the accompanying drawings, in which: FIG. 1 shows the rate of release of Eosin Y from compression molded disks of poly(hydroquinone-iminocarbonate) at 37.degree. C. in 0.1M phosphate buffer (pH 7.4). Eosin Y loadings were 1%, 10% and 30% (w/w) as indicated. FIG. 2 shows the decrease of molecular weight (number average) during hydrolysis (in 0.1M phosphate buffer, pH 7.4, 37.degree. C.) of thin films of poly(Bisphenol A-iminocarbonate). FIG. 3 shows the release of Eosin Y from compression molded disks of poly(Bisphenol A-iminocarbonate) at 37.degree. C. in 0.1M phosphate buffer, pH 7.4. Eosin Y loadings were 1%, 10% and 30% (w/w) as indicated. FIG. 4 shows the release of p-nitroaniline from solvent cast films of poly(Bisphenol A-iminocarbonate) at 37.degree. C. in 0.1M phosphate buffer, pH 7.4. p-Nitroaniline loading was 10% (w/w). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention comprises articles useful as implants or prostheses and methods for their preparation and use. These articles comprise a biocompatible, bioerodible, hydrophobic class of synthetic polyiminocarbonate compositions having the general formula: ##STR1## wherein R contains a non-fused aromatic organic ring and n is greater than 1. This class of polymeric compositions can be formed in preselected dimensions and specific configurations. Regardless of the specific application, these compositions degrade within predictable periods of time after introduction in vivo into non-toxic, non-inflammatory and non-immunogenic residues. The preferred embodiments of the R group within the general formulation given above is exemplified by, but is not limited or restricted to, the entities given in Table I below. TABLE I ______________________________________ R Group ______________________________________ (a) ##STR2## (b) ##STR3## wherein R' is lower alkyl C.sub.1 to C.sub.6, (c) ##STR4## ##STR5## (d) ##STR6## ______________________________________ Also compounds of the general formula below can be utilized: ##STR7## wherein X is O, NH of HR'" where R'" is a low alkyl radical, R" is a residue of a hydrocarbon including polymer such as polyolefins, an oligoglycol or polyglycol such as polyalkylene glycol ether, a polyester, polyurea, polyamine, polyurethane or polyamide. The entire class of polyiminocarbonates can be synthesized using alternative methods of polymerization now known in the art: bulk polymerization [Conix, A., Macro Synth. 2: 9598 (1966)]; solution polymerization [Yoda et al, Bull. Chem. Soc. Japan 32: 1120-1129 (1959)]; and interfacial polymerization [Matsuda et al, Japanese Pat. No. 10,944 (1962)]. The entire class of polyiminocarbonate polymers are bioerodible and depending on the nature of the monomeric repeat unit many of them may be biocompatible. In view of their intended function as an implant or prosthesis to be introduced into a subject in vivo, it is absolutely required that these compositions be non-inflammatory, non-toxic and non-immunogenic; that is biocompatible with the subject's tissues and body fluids in all respects. The articles comprising the present invention degrade (erode) into residues or moieties which are themselves biocompatible and non-toxic. As evidenced by the Examples which follow, each of the articles, regardless of specific polyiminocarbonate formulation used, may be implanted into the cornea of rabbits without causing inflammation even in a minor degree; this is in contrast to presently known compositions (such as polylactic acid matrices) which demonstrate at least minor inflammation of such corneal tissues. Moreover, articles comprising polyiminocarbonate compositions are demonstrably biocompatible as will be described in a study involving subcutaneous implantation of such articles in rats. Despite their presence in the living tissues over a period of weeks, no inflammatory cell infiltration (polymorphonuclear leukocytes, macrophages and lymphocytes) is seen in the tissues adjacent to the implant. Equally important, as the article predictably degrades, the degradation products are demonstrably non-mutagenic, non-cytotoxic and non-teratogenic. It will be appreciated that these properties and characteristics, as well as the mechanical and chemical attributes, identify and distinguish such articles as being singularly suitable as implants or prostheses. The Examples which follow merely serve to illustrate one or more of the abovedescribed characteristics, which are representative of the entire class as a whole. In one aspect of this invention, the polyiminocarbonate is mixed with a pharmacologically active composition for delivery from the implanted article. Examples of suitable biologically active substances are interferon, anti-angiogensis factors, antibodies, antigens, polysaccharieds, growth factors, hormones including insulin, glucogen, parathyroid and pituitary hormones, calcitonin, vasopressin renin, prolactin, growth hormones, thyroid stimulating hormone, corticotropin, follicle stimulating hormone, luteinizing hormone and chorionic gonadotropins; enzymes including trypsin inhibitor, lysozyme, catalase, tumor angiogenesis factor, cartilage factor, transferases, hydrolases, lysases, isomerases, proteases, ligases and oxidoreductases such as esterases, phosphatases, glysidases, and peptidases; enzyme inhibitors such as leupeptin, antipain, chrymostatin and pepstatin; and drugs such as steroids, anticancer drugs or antibiotics. The relative proportions of the composition to be released to form the two-phased system can be modified over a wide range depending upon the molecule to be administered or the desired effect. Generally, the molecule can be present in an amount which will be released over controlled periods of time, according to predetermined desired rates, which rates are dependent upon the initial concentration of the active molecule in the polymeric matrix and the rate of erosion of the polyiminocarbonate. This necessarily implies a quantity of molecules greater than the standard single dosage. Proportions suitable for the purposes of this invention can range from about 0.01 to 50 parts by weight of the active composition to between about 99.99 and about 50 parts by weight of the polymeric matrix, preferably between about 10 and about 30 parts by weight in the case of the biologically active molecule to be implanted to give 100 parts by weight of the final system. The polymeric matrix in the composition to be released can be admixed intimately in any convenient manner, preferably by mixing the components as powders and subsequently forming the mixture into a desired shape such as by thermal forming at a temperature less than that at which the composition will become degraded and at which the polymer has desired morphological properties. Generally, the final composition is formed as a slab which can be circular, rectangular or the like and having a thickness between about 0.1 mm and about 100 mm and a total surface area between about 0.01 cm.sup.2 and about 1,000 cm.sup.2, preferably between about 1 cm.sup.2 and about 100 cm.sup.2. The delivery systems of this invention can be manufactured as devices that can take a wide range of shapes, sizes and forms by delivering the active molecule to different environments of use. For example, the systems can be made as devices including buccal and oral devices, vaginal and intrauterine devices of cylindrical, bullet, elliptical, circular, bulbous, loop, bow or any other shape that lends itself to placement in a particular environment such as an in vivo implant. The devices also include ocular devices of any geometric shape for comfortable placement in the cul de sac such as ellipsoid, bean, banana, circular, rectangular, doughnut, crescent and heart-ring shaped devices. In cross section, the ocular devices can be doubly convex, concave, concavo-convex and the like. The dimensions of the ocular devices can vary according to the size of the eye, with satisfactory eye devices generally having a length of 4-20 mm or a width of 1-15 mm and a thickness of 0.1-4 mm. Other devices made according to this invention include implants, anal, pessaries and prosthetic devices, artificial glands for dispensing a substance pharmaceutically equivalent to the corresponding neutral gland, cervical, nasal, ear and skin devices. The polymeric matrix utilized in the present invention can be manufactured by standard techniques provided as is important to this invention that such manufacture includes process steps such as blending, mixing or the equivalent thereof for structurally defining the system comprising the molecule to be released and the polymeric matrix. For example, one suitable method for making the systems comprises the polymer and an appropriate solvent, thereby to form a casting solution, mixing a known amount of the composition to be released in the casting solution, charging the solution into a mold and then drying the mold, usually under vacuum, causing the polymer to precipitate in forming the matrix with the molecule to be released therein. Alternatively, the polymer in the form of a powder can be admixed with the molecule to be released in the form of a powder and then molded under adequate temperature and pressure to the desired shape, through injection, compression or extrusion. After the polymeric matrix containing the composition or molecule to be released is implanted in the desired aqueous environment, such as in vivo, it erodes by hydrolysis thereby releasing the composition or molecule encapsulated by the polymer. The following examples illustrate the present invention and are not intended to limit the same. EXAMPLE I In this and in the following examples, all solvents were analytical grade. Hydroquinone (99% purity), potassium-t-butoxide, Bisphenol A (>99% purity) were obtained from Aldrich, triethylamine (reagent grade) from Mallinckrodt and cyanogen bromide (reagent grade) from Fisher Scientific. Poly(Bisphenol A-carbonate) [MW=32000] was obtained from Polysciences, Inc., 400 Valley Rd., Warrington, PA. Eosin Y (certification no. CE-D71) and charcoal (activated Darco G60) were purchased from MCB, Norwood, Ohio and p-nitrophenol (>99% purity) was from Fluka, Switzerland. IR-spectroscopy was performed on a Perkin Elmer Series 1420 dispersive spectrophotometer. For transmission spectra KBr pellets were made, or thin polymer films were directly cast onto NaCl plates from diluted solutions of the polymer in methylene chloride. For "multiple internal relectance" spectra, the MIR accessory from Perkin Elmer was used, employing a KRS-5 crystal and a reflectance angle of 45.degree.. Thermal Analysis of polymers was done by "differential scanning caloimetry" (DSC), employing a Perkin Elmer DSC 2 Differential Scanning Calorimeter, equipped with a Perkin System 4 Thermal Analysis Microprocessor Controller and the Perkin Elmer Graphics Plotter 2. Average sample size was 10 mg and a heating rate of 20.degree. C./min was employed. Molecular Weight of polymers was determined by vapor pressure osmometry in a Knauer apparatus. For poly(hydroquinone-iminocarbonate), the solvent was dimethylformamide, and the measuring temperature was 90.degree. C. For all other polymers, the measurement was performed in chloroform at 45.degree. C. Mechanical properties of poly(BPA-iminocarbonate) and poly(BPA-carbonate) were determined on an Instron Model 1122 stress-strain tester at an initial strain rate of 0.1 mm mm.sup.-1 min.sup.-1. BPA is Bisphenol A or 2,2-bis(4-hydroxyphenyl)propane. Polymer films of 0.1 mm thickness were cast in glass dishes from methylene chloride solutions (Table 2). The films were cut into dogbone shape in accordance with ASTM-Designation D882-81 (Standard Test Methods for Tensile Properties of Thin Plastic Sheeting). Prior to testing, the polymer films were dried for 5 days in vacuum and preconditioned by storage over phosphorus pentoxide (0% humidity) at room temperature for 48 hours. Compression Molding. Compression molded disks (diameter: 1.5 cm, thickness: 0.1 cm, weight: 250 mg) were prepared on a "Carver" laboratory press in a stainless steel mold. The appropriate quantities of powdered polymer and sieved particles (mesh 270, <53 um) of model drug were intimately mixed by grinding with a mortar and pestle. The misture was then transferred into the mold and pressed at 20,000 psi as outlined in Table 1. Solvent Casting. Polymer solutions were prepared in methylene chloride and cast in petri dishes made of pyrex glass using the conditions summarized in Table 2. Solvent cast release devices were prepared by adding the appropriate amount of model drug to the polymer solutions. Addition of sieved Eosin Y (mesh 270, <53 um) and vortexing resulted in a uniform suspension of Eosin Y. Addition of p-nitroaniline resulted in a homogeneous solution. After casting, circular disks (diameter: 1.0 cm, thickness: 0.05-0.1 cm) were excised from the dried films with a cork borer. Release Studies. Drug release devices were initially placed for 24 hours into 1 liter of distilled water at room temperature. All model drug released during this time was recorded as "initial burst". Thereafter, the devices were transferred into 10 ml of phosphate buffer (1.0M, pH 7.4) and kept at 37.degree. C. Periodically the buffer was analyzed by spectroscopy (Table 3) for the amount of released model drug and/or the amount of polymer degradation products. After each such analysis the device was transferred into fresh phosphate buffer. Synthesis Purification of commercial hydroquinone. Commercial hydroquinone is lightly colored. The material was purified prior to use as follows: under nitrogen, 20 g hydroquinone were dissolved in 200 ml ethylacetate. The colored solution was repeatedly treated with 1 g activated carbon until a clear, colorless solution was obtained upon filtration. Colorless crystals of high purity hydroquinone were precipitated from this solution by the slow addition of 800 ml hexane. The purified material was dried in vacuum and used immediately. Preparation of 1,4-dicyanatobenzene. The general procedure for preparation of cyanate esters was as follows: a 3-necked, 500 ml round bottom flask (equipped with thermometer, overhead stirrer and dropping funnel) was charged with a solution of 21.4 g cyanogen bromide in 100 ml absolute ether. The system was protected from moisture by a CaCl.sub.2 drying tube and cooled to -10.degree. C. by means of an external acetone-dry ice cooling mixture. 9.9 g freshly purified hydroquinone were dissolved under nitrogen in 150 ml acetone followed by the addition of 20.2 g of triethylamine. This solution was placed into the dropping funnel and kept under an atmosphere of nitrogen. With vigorous stirring, the hydroquinone/triethylamine solution was added to the cyanogen bromide solution over a period of 20 min. Temperature was kept below -5.degree. C. (A dense, white precipitate of triethylamine hydrobromide formed). Stirring was continued for an additional 40 min.; then the reaction mixture was allowed to warm to +10.degree. C. The precipitate was removed by filtration. The slightly colored filtrate was treated with 0.25 g activated carbon, refiltered and rapidly evaporated to dryness at a pressure of 100 mm Hg at 30.degree. C. Crude 1,4-dicyanatobenzene (12.1 g, 84% yield) was obtained as white crystals. The crude material was recrystallized three times from boiling carbon tetrachloride (30 g crude/l). Sometimes an insoluble oily residue remained on the bottom of the hot solution of 1,4-dicyanatobenzene in carbon tetrachloride. This residue was removed by decantation. All recrystallizations were done as quickly as possible in order to minimize exposure of the product to high temperatures. The recrystallized material consisted of fine, long, transparent needles, M.P.=117.degree.-119.degree. C. Preparation of poly(hydroquinone-iminocarbonate). The procedure was as follows: 2.753 (.+-.0.001) g of hydroquinone (freshly purified) and 4.003 (.+-.0.001) g of 1,4-dicyanatobenzene were dissolved under nitrogen in 50 ml acetone in a sealed reaction vessel. Via a syringe, 250 ul of catalyst solution were added (catalyst solution: 56 mg/ml of potassium-t-butoxide in t-butanol). Within 1 min, the solution became noticeably viscous and within 3-5 min, a dense, white precipitate formed. After standing for 1 h at 37.degree. C., the precipitate was extensively extracted with acetone (3 times 250 ml), collected on a Buchner funnel and dried to constant weight in vacuo. Poly(hydroquinone-iminocarbonate) was obtained as a soft powder (6.2 g, 92% yield). Preparation of BPA-dicyanate (2,2-di-(4'-cyanatophenyl)propane). BPA-dicyanate was prepared in the same way as 1,4-dicyanate (see above) with the following modifications: 21.4 g cyanogen bromide were dissolved in 100 ml acetone and placed into the three-necked flask. 20.5 g of BPA and 20.2 g of triethylamine were dissolved in 150 ml acetone and placed in the dropping funnel. No efforts were made to exclude oxygen. After completion of the reaction, the dense precipitate of triethylamine hydrobromide was removed by Buchner filtration. To the clear, colorless filtrate, 500 ml of ice-cold water was added slowly and with stirring over the course of 5 min. A dense, crystalline precipitate of crude BPA-dicyanate formed, which was collected on a Buchner funnel, washed with ice-cold water and rapidly dried over phosphorous pentoxide in vacuum. Crude BPA-dicyanate was obtained as a white crystalline solid (21.5 g, 86% yield). The crude material was recrystallized three times from hexane (16 g crude/l) in the same way as 1,4-dicyanatobenzene (see above). The recrystallized material consisted of long needles, M.P.=82.degree.-83.degree. C. Preparation of poly(BPA-iminocarbonate). 5.7534 (.+-.0.001) g BPA and 7.0137 (.+-.0.001) g BPA-dicyanate were dissolved at room temperature in 15 ml acetone. With stirring, 250 ul catalyst solution was added (catalyst solution: 56 mg/ml of potassium-t-butoxide in t-butanol). Within 5 min, the reaction vessel warmed up noticeably and the solution became viscous. After about 15 min, the reaction mixture completely solidified. It was kept at 37.degree. C. for 2 h, after which the polymer was extracted 3 times with 250 ml acetone and dried in vacuo. Crude poly(BPA-iminocarbonate) was obtained as a tough, transparent solid (12.6 g, 98% yield). EXAMPLE II Toxicological Screening of poly(BPA-iminocarbonate) Preparation of the polymer for toxicological testing was done as follows: a 10% (w/w) solution of crude poly(BPA-imincarbonate) in methylene chloride was filtered and slowly added into a 20 fold excess of isopropanol. Poly(BPA-iminocarbonate) precipitated in large lumps. The precipitated material was collected under sterile conditions and dried in high vacuum to constant weight. Rabbit eye tests were performed as described in Langer et al, J. Biomed. Mat. Res. 15: 267-277 (1981) using solvent cast films (approximate size: 0.1 cm*0.1 cm*0.05 cm) of poly(BPA-iminocarbonate), which were implanted into the corneas of male New Zealand White Rabbits. For subcutaneous implantation circular disks (diameter: 0.3 cm, thickness: 0.05 cm, weight: 2.5 mg) were cut from solvent cast films of purified poly(BPA-iminocarbonate). The disks were sterilized by short immersion in 70% aqueous isopropanol and implanted subcutaneously in the back of male CD-1 mice (CRBL-Kingston). At specific intervals animals were sacrificed, the residual polymer retrieved, the implantation site was inspected for any pathological changes and the histology of tissues surrounding the implant was examined. EXAMPLE III As a starting point for the investigations, we chose poly(hydroquinone-iminocarbonate) as a model system. The IR-spectrum of this material showed absorption bands, which can be assigned to the iminocarbonate bond, in addition to absorptions which corresponded to free cyanate ester and hydroxyl terminal groups. A number of properties of poly(hydroquinone-iminocarbonate) are summarized in Table 4. Due to its insolubility in all tested volatile solvents, poly(hydroquinone-iminocarbonate) could not be solvent cast). Likewise its marked thermal degradation in the molten state precluded high temperature fabrication methods such as injection molding. However, compression molding proved satisfactory and opaque, slightly brittle disks could be prepared. By blending the sieved polymer powder with up to 30% (w/w) of Eosin Y (which served as model compound for hydrophilic, low molecular weight drugs), Eosin Y containing disks were prepared. The release characteristics of these disks (FIG. 1) were strongly dependent on the loading: at a loading of 30% (w/w), the device started to crumble within 3 h and Eosin Y was released rapidly and without correlation to polymer erosion. At low loadings (1%), Eosin Y was released over 400 h at a rate which remained nearly constant with time throughout the entire release process. This result suggests that Eosin Y release is not due to a simple diffusional mechanism. Next poly(BPA-iminocarbonate) was investigated. Some physical and chemical properties of poly(BPA-iminocarbonate) are summarized in Table 4. Contrary to poly(hydroquinone-iminocarbonate), poly(BPA-iminocarbonate) is soluble in many organic solvents. Poly(BPA-iminocarbonate) could be solvent cast, yielding clear, transparent films. From concentrated solutions in methylene chloride (30% w/w) fibers could be drawn. The molecular structure of poly(BPA-iminocarbonate) was confirmed by elemental analysis and IR-spectroscopy. The IR-spectrum of a thin film of poly(BPA-iminocarbonate) is similar to the spectrum of commercially available poly(BPA-carbonate) except for iminocarbonate absorption at 3340 cm.sup.-1 (N--H) and 1680 cm.sup.-1 (C.dbd.N). The stress-strain behavior of poly(BPA-iminocarbonate) was investigated and compared to the behavior of a low molecular weight commercial sample of poly(BPA-carbonate) (MW=32000). Since the stress-strain behavior of polymers depends to a large extent on the way the samples are prepared, cut and preconditioned prior to measurement, care was taken to prepare samples of both polymers in an identical fashion and to test them under the same conditions. The results of these experiments are summarized in Table 5. These data indicate that poly(BPA-iminocarbonate) is a tough, strong polymer with exceptionally high tensile strength. As a general rule, both toughness and tensile strength increase with increasing molecular weight. Therefore, it is encouraging that poly(BPA-iminocarbonate) with a molecular weight of only 12,000 would have mechanical properties which compare favorably to those of commercial poly(BPA-carbonate) resins of much higher molecular weight. In this context, it is interesting to note that for poly(lactic acid) MW=13,000) a tensile strength of 3200 psi has been reported. Although not directly comparable to the measured value, it seems that poly(BPA-iminocarbonate) has a higher tensile strength than poly(lactic acid), which is widely used as biodegradable suture. Monomeric iminocarbonates were previously shown to have two different degradation pathways, depending on the pH of the surrounding medium. However, no information was available pertaining to the mode of hydrolysis of poly(iminocarbonates) at neutral pH. Therefore, an initial study of the hydrolysis of poly(BPA-iminocarbonate) was performed, employing "Multiple Internal Reflectance"-IR-spectroscopy (MIR-IR). Freshly cast films of poly(BPA-iminocarbonates) had MIR-spectra indistinguishable from regular transmission IR-spectra. However, after exposure of these films for only 60 min to 0.1M phosphate buffer (pH 7.4) at 70.degree. C., a strong band at 1770 cm.sup.-1 appeared. This absorption band is characteristic for carbonates and provides evidence for the formation of carbonate bonds during the degradation of poly(BPA-iminocarbonate) at neutral pH. In order to obtain quantitative data on the extent of carbonate formation during hydrolysis, an accelerated degradation study was performed at 70.degree. C. Films of poly(BPA-imincarbonate) (dimensions: 2 cm.times.1 cm.times.0.1 cm) were extensively hydolized in either 0.1N hydrochloric acid (pH 1), 0.1M phosphate buffer (pH 7.4) or 0.1N sodium hydroxide (pH 14) as hydrolysis medium. During the course of hydrolysis, the amount of BPA accumulating in the release medium was monitored by UV spectroscopy. The most rapid hydrolysis was observed in sodium hydroxide: films of poly(BPA-iminocarbonate) dissolved completely within 5 days. 96% of the theoretical amount of BPA could be recovered in the hydrolysis medium. The films became noticeably thinner while maintaining their structural integrity up to the very last stage of degradation. This behavior seemed to indicate "surface erosion". However, since erosion in hot 0.1N NaOH is of no practical interest, this phenomenon was not further investigated. The mechanism of hydrolysis was different in hydrochloric acid and in phosphate buffer (pH 7.4). In those media, the initially transparent films became opaque within 24 h and started to crumble within 2 days. By day 3 , only white, flaky precipitates were left. Surprisingly, at this point only about 7-14% of the theoretical amount of BPA could be recovered from the hydrolysis medium. The release of BPA continued slowly for about 25 days, finally leveling off at a total accumulated recovery of 51% (in HCl) and 72% (in phosphate buffer) of the theoretical amount of BPA. At this point, the white, flaky residues were collected, dried, weighed and analyzed by IR spectroscopy (KBr-pellet). Their IR spectra closely resembled the spectrum of poly(BPA-carbonate). By vapor pressure osmomtry the molecular weight of these residues was found to be 475(.+-.100), suggesting that they consisted mostly of dimers or trimers of BPA-carbonate. The results of this study are summarized in Table 6. These observations suggest that at neutral pH, poly(BPA-iminocarbonate) hydrolyzes by a combination of two different pathways: Backbone cleavage and release of BPA occurs concomitantly to the formation of the more stable carbonate bond. This process results in the formation of the observed white, flaky precipitates. Since carbonate formation is catalyzed by acid, the extent of carbonate formation should increase as the acidity of the hydrolysis medium increases. This expectation was confirmed by experimental results: The overall proportion of carbonate formation was higher in HCl (45%) than in phosphate buffer (28%), (Table 6). In order to obtain an estimate for the rate of hydrolysis at 37.degree. C., the hydrolysis experiments were repeated at that temperature: the hydrolysis of poly(BPA-iminocarbonate) showed the same general pattern as at 70.degree. C. (Table 6), but was markedly slower: for instance, in phosphate buffer (physiological conditions), a solvent cast film (dimensions: 2 cm.times.1 cm.times.0.1 cm) of poly(BPA-iminocarbonate) became opaque by day 40 (no BPA released), holes and cracks were visible by day 61 (5 mol% BPA released), the polymer crumbled on day 109 (11 mol% BPA released) and by day 200, only flaky precipitates of BPA-carbonate were lest (35 mol% BPA released). In a parallel experiment, the changes in the molecular weight (number average) of solvent cast films (dimensions: 2 cm.times.1 cm.times.0.1 cm) of poly(BPA-iminocarbonate) were followed during hydrolysis under physiological conditions. After various hydrolysis times, samples of film were removed, dried, weighed and their residual molecular weight determined by vapor pressure osmometry. As shown in FIG. 7, the molecular weight decreased rapidly, indicating that extensive backbone cleavage occurred within 30 days of exposure to buffer. During this period, the films became opaque and brittle and lost 99% of their initial tensile strength. However, no weight loss occurred--in correspondence to our observation that no BPA is released from the films during this initial stage of the hydrolysis. The use of poly(BPA-iminocarbonate) for drug delivery applications was investigated using p-nitroaniline and Eosin Y as model compounds for low molecular weight, hydrophobic and hydrophilic drugs respectively. In order to compare poly(BPA-iminocarbonate) to poly(hydroquinone-iminocarbonate), compression molded disks of poly(BPA-iminocarbonate) were prepared, containing loadings of 1%, 10% or 30% (w/w) of Eosin Y. These devices were prepared in the same manner as those made of poly(hydroquinone-iminocarbonate). The release profiles (FIG. 3) were dependent on the degree of loading: at high loading (30% w/w), all Eosin Y was released within 8 h, whereas at low loadings (1% and 10% w/w), more sustained release was obtained. As compared to poly(hydroquinone-iminocarbonate), release from poly(BPA-iminocarbonate) was significantly prolonged at the 1% and 10% loading level. Solvent cast films of poly(BPA-iminocarbonate) containing 10% (w/w) of Eosin Y were also tested. Since Eosin Y is insoluble in methylene chloride, these films were heterogeneous two-phase systems consisting of sieved Eosin Y particles (mesh 270, <53 um) dispersed within the polymeric phase. Surprisingly, no Eosin Y could be released from these films beyond a short, initial burst during the first 24 h. In order to study the behavior of more hydrophobic model drugs, solvent cast films were prepared containing 10% (w/w) of p-nitroaniline. Since p-nitroaniline is soluble in methylene chloride, the resulting films were homogeneous. These films were transparent, clear and pliable. The release profile of p-nitroaniline (FIG. 4) is characterized by a lag period of about 15 days. Thereafter, a prolonged period of zero-order release was observed (90 days), which is desirable for many controlled release applications. For the assessment of the possible toxicity of poly(BPA-iminocarbonate), the individual toxicities of the monomers (BPA and BPA-dicyanate) must be considered in addition to the individual toxicities of the known degradation products (carbon dioxide, ammonia, poly(BPA-carbonate) and BPA). Poly(BPA-carbonate) has been studied extensively and is regarded as a non-toxic, biocompatible polymer. Large subcutaneous implants (25 g/kg) in rats had no toxic effect. BPA was also extensively investigated; the LD.sub.50 for oral administration is well above 2 g/kg in all tested species. Furthermore, continuous exposure of mice to a total dose of 865 g/kg over a period of 2 years (equivalent to approximately 1.18 g/kg per day) failed to show carcinogenicity (NCI bioassay). For comparison, use of a polymeric drug delivery system with a volume of about 1 cm.sup.3 could expose the patient to about 1 g of BPA over a period of 200 days resulting in an average daily exposure of about 0.00007 g/kg. The cyanate function (OCN) seems to be devoid of the acute toxicity associated with derivatives of cyanide (CN.sup.-). For example, sodium or potassium cyanate (KOCN) are only moderately toxic (LD.sub.50 for potassium cyanate, i.p. (mouse)=320 mg/kg). Sodium cyanate has been used as an experimental drug in humans for treatment of sickle-cell anemia and estrogen cyanate was administered to women as a contraceptive agent. In general, the non-volatile cyanates have no irritating effect on skin or mucous membranes and very low systemic toxicity in humans. In particular, BPA-dicyanate was extensively tested. These studies (Table 7) indicate that the cyanate function in BPA-dicyanate does not increase the acute toxicity of this compound as compared to BPa itself. Likewise, chronic respiratory exposure of guinea pigs, mice and rats to BPA-dicyanate at a concentration of 400 mg/m.sup.3 (4 hours per day for a total of 4 weeks) did not produce any symptoms of toxicity and no changes in blood chemistry and kidney or liver function were noted. Based on these data, neither the monomers nor the known degradation products of poly(BPA-iminocarbonate) were sufficiently toxic to preclude--a priori--the possible use of poly(BPA-iminocarbonate) in medical applications. Therefore, in vivo tests of the tissue compatibility of poly(BPA-iminocarbonate) were performed. In the rabbit cornea test, no signs of inflammation (4 animals) were detected over a period of 4 months post-implantation. In a second test, poly(BPA-iminocarbonate) was implanted subcutaneously into male CD-1 mice (10 animals). These animals were sacrificed at times ranging from 8 to 24 weeks post-implantation. Gross postmortem observation revealed no inflammation or other lesions at the implantation site in any of the animals. Histological examination showed a very thin layer of connective tissue around the implant; however, there was a complete lack of inflammatory cells (e.g., polymorphonuclear leukocytes, macrophages) at the implantation site. While the above tests do not constitute a complete toxicological assessment, they suggest that poly(BPA-iminocarbonate) implants have a high degree of tissue-compatibility. TABLE 1 ______________________________________ Conditions for Compression Molding Polymer Temperature (.degree.C.) Time (min) ______________________________________ poly(hydroquinone- 70 10 iminocarbonate) poly(BPA-iminocarbonate) 100 20 poly(BPA-carbonate) 150 30 ______________________________________ TABLE 2 ______________________________________ Conditions for Solvent Casting Concentration of Casting Casting Solution Temperature Polymer in % (w/w) (.degree.C.) ______________________________________ poly(BPA-carbonate) 10 37 poly(BPA-iminocarbonate) 20 25 ______________________________________ TABLE 3 ______________________________________ Spectroscopic Determination of Model Drugs and BPA Peak Wavelength Extinction Coefficient Compound (nm) (liter mol.sup.-1 cm.sup.-1) ______________________________________ Eosin Y 518 79400 p-nitroaniline 403 12900 BPA 244 18700 ______________________________________ TABLE 4 ______________________________________ Some Physical Properties of Poly(iminocarbonates) Poly(hydroquinone- Poly(BPA- Property iminocarbonate) iminocarbonate) ______________________________________ appearance white powder tough, trans- parent solid glass transition 61.degree. C. 75.degree. C. temperature (Tg) melting range decomposes before decomposes before melting melting molecular weight 2000 12000 (number average) thermal stability degrades above degrades above 130.degree. C. 160.degree. C. solubility soluble in: soluble in: dimethylsulfoxide, chlorinated, hy- dimethylformamide drocarbons, di- insoluble in: methylformamide, water, alcohol, dimethylsulfox- acetone, ether, ide benzene, chlorinated partially soluble hydrocarbons, hexane in: acetone, benzene insoluble in: water, alcohol, ether, hexane ______________________________________ TABLE 5 ______________________________________ Mechanical Properties of Poly(BPA-iminocarbonate) Poly(BPA- Poly(BPA-carbonate) iminocarbonate).sup.a MW = Property (MW = 12000) MW = 32000.sup.a 70-80000.sup.b ______________________________________ modulus of 112000 psi 134000 psi 320000 psi elasticity yield stress 7000 psi 5780 psi -- tensile strength 7530 psi 6910 psi 10500 psi (nominal) elongation at 38% 109% 60-100% break tensile energy 16 * 10.sup.6 J/m.sup.3 34 * 10.sup.6 J/m.sup.3 -- to break ______________________________________ .sup.a solvent cast films, prepared and tested as described in Materials and Methods .sup.b literature values (12, 13) reported for commercial grade resins, having a molecular weight of about 70000-80000 TABLE 6 ______________________________________ Hydrolysis of Poly(BPA-iminocarbonate) Hydrolysis BPA Carbonate Complete Temper- Hydrolysis Recovered Recovered Hydrolysis ature (.degree.C.) Medium (mol %) (mol %) (days) ______________________________________ 37 0.1 N NaOH >90 0 82 0.1 N HCl 20 72 200 phosphate 35 63 >200 (pH 7.4) 70 0.1 N NaOH >96 0 5 0.1 N HCl 51 45 18 phosphate 72 28 32 (pH 7.4) ______________________________________ TABLE 7 ______________________________________ Toxicity of BPA-dicyanate.sup.a Mode of Administration LD.sub.50 (Rat) ______________________________________ oral >2500 mg/kg subcutaneous >2500 mg/kg inhalation.sup.b >440 mg/m.sup.3 ______________________________________ .sup.a according to data of Farbenwerke Bayer, WuppertalElberfeld, W. Germany .sup.b particles in air * * * * *
https://uspto.report/patent/grant/4806621
Bureau of Land Management: Improvements Needed in Internal Controls over Mining Law Administration Program Funds | U.S. GAO What GAO Found The Department of the Interior's (Interior) Bureau of Land Management's (BLM) Mining Law Administration Program (mining law program)... Bureau of Land Management: Improvements Needed in Internal Controls over Mining Law Administration Program Funds Highlights What GAO Found The Department of the Interior's (Interior) Bureau of Land Management's (BLM) Mining Law Administration Program (mining law program) was appropriated and expended almost $40 million annually from fiscal years 2011 through 2013. Funds are to be used for mining law program activities such as administering mining claims and processing notices for mineral exploration. The mining law program's largest expenditures include personnel compensation and contractual services and supplies, which account for over 96 percent of its expenditures. BLM has designed internal controls, including policies and procedures over mining law program funds, but some of them are inconsistent, outdated, and not effectively communicated. GAO's statistical tests of fiscal year 2013 nonpayroll mining law program expenditures showed that BLM did not effectively implement controls to reasonably assure that such mining law program transactions were properly recorded and supported. Estimated Percentages of Control Deficiencies in Nonpayroll Expenditures of the Mining Law Administration Program (Mining Law Program) for Fiscal Year 2013 Note: All percentage estimates from the tests have margins of error at the 95 percent confidence level of plus or minus 9 percentage points or less. In addition, in interviews conducted at selected BLM offices, GAO found that some employees were charging hours of work to the mining law program based on funding allocations or supervisor instructions rather than the actual work performed, as required by BLM policies. While these examples cannot be generalized to all BLM employees, they illustrate control deficiencies that increase the risk that BLM employees are not charging the program correctly. GAO found that internal control implementation deficiencies were the result of design flaws in BLM's policies and procedures as well as the lack of training and monitoring to reinforce them. Because of these deficiencies, BLM does not have reasonable assurance that mining law program expenditures relate to or are reasonably allocated to the program. As a result, the information in BLM's financial records may be at risk of not reflecting the actual cost of the mining law program. Why GAO Did This Study BLM's mining law program is responsible for managing the exploration and development of minerals, such as gold, silver, and copper, on federal land. The program is funded through fees collected from holders of mining claims and sites, subject to limits in annual appropriations acts, and is appropriated funds from the Department of the Treasury to the extent that the actual fees collected fall short of such limits. GAO was asked to review the funding and spending of the mining law program. This report discusses (1) the amounts appropriated and expended for the program and (2) the extent to which BLM designed and implemented internal controls to reasonably assure that designated funds are spent only on mining law program operations. To address these objectives, GAO (1) reviewed relevant BLM policies and procedures and financial data, (2) conducted tests on a statistical random sample of fiscal year 2013 nonpayroll expenditures, and (3) interviewed BLM officials and employees. Recommendations GAO recommends that BLM (1) review and update its mining law program policies and procedures, as necessary; (2) establish procedures for communicating such changes; (3) develop and implement a related training program; and (4) regularly monitor compliance with its policies and procedures. Interior generally agreed with the findings, concurred with GAO's recommendations, and described actions taken or planned to address each recommendation.
https://www.gao.gov/products/gao-15-562?order=field_status_code&sort=desc
Tucatinib Demonstrates Activity in Heavily Pretreated HER2+ Breast Cancer Promising antitumor activity was seen in patients with& nbsp;heavily pretreated HER2-positive breast cancer with or without brain metastases with the use of tucatinib in combination with capecitabine, trastuzumab, or both agents, according to phase Ib findings published in The Lancet Oncology. Tucatinib Demonstrates Activity in Heavily Pretreated HER2+ Breast Cancer Promising antitumor activity was seen in patients with&nbsp;heavily pretreated HER2-positive breast cancer with or without brain metastases with the use of tucatinib in combination with capecitabine, trastuzumab, or both agents, according to phase Ib findings published in <em>The Lancet Oncology</em>. Rashmi K. Murthy, MD, MBE Promising antitumor activity was seen in patients with heavily pretreated HER2-positive breast cancer with or without brain metastases with the use of tucatinib in combination with capecitabine, trastuzumab (Herceptin), or both agents, according to phase Ib findings published in The Lancet Oncology. 1 In results from the nonrandomized, open-label study, 83% (5/6) of patients with measurable disease treated with tucatinib/capecitabine had an objective response, as did 40% (6/15) of patients receiving tucatinib/trastuzumab. Sixty-one percent (14/23) of patients treated with the combination of all 3 drugs had an objective response. The median duration of response was 8.9 months (range, 1.4-8.9) in the tucatinib/trastuzumab arm, 5.2 months (range, 2.1-7.6) in the tucatinib/capecitabine arm, and 11.0 months (range, 2.9-18.6) with the triplet. &ldquo;Up to 50% of women with HER2-positive metastatic breast cancer experience CNS metastases. When they arise, they can compromise survival and impact quality of life for patients,&rdquo; first author Rashmi K. Murthy, MD, MBE, an assistant professor in the Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, said in a January 2018 interview with Targeted Oncology. &ldquo;There remains an unmet medical need for patients with HER2-positive metastatic breast cancer whose disease has metastasized to the brain,&rdquo; she added. &ldquo;The current systemic therapies do not penetrate the blood-brain barrier well, so there is a need for anti-HER2 agents that successfully do cross over.&rdquo; Sixty patients were recruited at 5 sites in the United States from January 2014 to December 2015. All patients had received prior trastuzumab, 55% had received lapatinib (Tykerb), 65% had received pertuzumab (Perjeta), and 97% had received ado-trastuzumab emtansine (T-DM1; Kadcyla). The median number of unique HER2-targeted treatments was 3 (range, 3-4). Eight patients were assigned to 350 mg of twice-daily tucatinib and 52 were assigned to 300 mg twice daily. Maximum-tolerated dose recommended phase II dose for tucatinib in combination were the primary objectives. Investigators observed no dose-limiting toxicities (DLTs) in the dose-escalation and expansion cohorts in either doublet when tucatinib was administered at the 300-mg dose level. There was a single DLT in the 300-mg dose level in the dose-escalation and expansion triplet cohort (n = 27). The DLT was a grade 4 cerebral edema occurring in a patient with an untreated brain metastasis. The patient had not been treated with corticosteroids before the DLT. The recommended phase II dose of tucatinib was set at 300 mg twice daily. The median progression-free survival (PFS) was 7.8 months (95% CI, 4.1-12.5) in the triplet arm, 7.1 months (95% CI, 4.4-9.7) in the tucatinib/capecitabine arm, and 5.5 months (95% CI, 1.5-10.2) in the tucatinib/trastuzumab arm (n = 18). The clinical benefit rate was 74% in the triplet arm. At baseline, 29 (56%) patients treated at the recommended phase II dose had brain metastases, 12 (41%) of whom had measurable metastases. Seventeen (59%) were either treatment-na&iuml;ve or had progressed despite prior treatment. In the triplet arm, the median PFS was 6.7 months (95% CI, 1.4-12.5) for patients with brain metastases (n = 11). Of those, 5 (42%) had brain-specific objective response, 5 had stable disease, and 1 had progressive disease. One patient was not evaluable. Five (8%) patients, all assigned to 300 mg of tucatinib, died of disease progression within 30 days of their last tucatinib dose. There were no treatment-related deaths reported. Twenty (33%) patients experienced serious adverse events (AEs), 3 (5%) of which were related to the study drug: 1 cerebral edema in the triplet arm with tucatinib administered at 300 mg, 1 incidence of nausea in the 350 mg of tucatinib/capecitabine arm, and 1 incidence of vomiting in the 350 mg of tucatinib/trastuzumab arm. At the recommended phase II dose, the most common (&ge;5%) grade &ge;3 treatment-emergent AEs in all patients were fatigue (8%), diarrhea (7%), and palmar-plantar erythrodysesthesia (7%). There were 4 (15%) incidents of grade 3 diarrhea in the triplet arm and 1 (4%) incident of grade 4. There was 1 grade 3 diarrhea in the tucatinib/capecitabine arm and none in the tucatinib/trastuzumab arm. There was no incidence of grade 4 diarrhea in either doublet arm. &ldquo;[Tucatinib] is such a pure small molecule inhibitor that doesn&rsquo;t have some of the side effects that are problematic for patients, including the most problematic one, which is diarrhea,&rdquo; study coauthor Kimberly L. Blackwell, MD, medical oncologist, Duke Cancer Institute, said in a March 2018 interview with OncLive. &ldquo;It is a very exciting drug because it appears to work and get into the blood-brain barrier space. It looks like its toxicity profile is quite nice, with very low incidence of diarrhea and rash. The low side effect profile is going to make this a very exciting drug to combine with standard chemotherapy, as well.&rdquo; In an accompanying editorial, Luca Gianni, MD, department of Medical Oncology, Ospedale San Raffaele—IRCCS, Milan, Italy, wrote that tucatinib is attractive because of its &ldquo;improved tolerability profile.&rdquo; He noted that it would be &ldquo;remarkable&rdquo; if tucatinib was shown to have a lower incidence of diarrhea with drugs other than capecitabine. 2 &ldquo;The second feature that makes tucatinib appealing is the pattern of antitumor activity,&rdquo; he wrote. &ldquo;The new tucatinib regimens had good or even outstanding activity in women with disease progression who had run out of conventional anti-HER2 options with monoclonal antibodies, trastuzumab emtansine, and other TKIs. This result alone deserves further research that is indeed ongoing in a placebo-controlled trial.&rdquo; &ldquo;So, is there the room and need for yet another HER2-directed drug?&rdquo; he asked. &ldquo;The evidence suggests that there is, provided that the new candidate makes the difference in areas of medical need left behind by the rich armamentarium of HER2-directed drugs that are already available. Tucatinib is a potentially first-in-class HER2-selective TKI that could make that difference.&rdquo; Investigators are evaluating the triplet combination versus placebo in patients with locally advanced or metastatic HER2-positive breast cancer previously treated with a taxane, trastuzumab, pertuzumab, and T-DM1 in the phase II HER2CLIMB trial (NCT02614794). The trial is currently recruiting patients, with an expected primary completion date of September 2020. Reference: 1. Murthy R, Borges VF, Conlin A, et al. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study [published online May 24, 2018]. Lancet Oncol. doi: 10.1016/ S1470-2045(18)30256-0.2. Gianni L. Is there room for another HER2-targeting drug? [published online May 24, 2018]. Lancet Oncol. doi: 10.1016/ S1470-2045(18)30405-4. Andreas Varkaris, MD, PhD In the first-in-human phase 1 ReDiscover trial (NCT05216432), treatment with the PI3Kα inhibitor RLY-2608 resulted in sustained target inhibition with minimal impact on glucose homeostasis and a favorable safety profile in patients with PIK3CA-mutant solid tumors. 1 Interim data from the study also showed that RLY-2608 led to antitumor activity in patients with hormone receptor-positive/HER2-negative breast cancer across PIK3CA genotypes. Among the 16 patients with breast cancer and measurable disease, 9 (56%) experienced radiographic tumor reduction, and 13 (81%) reached either stable disease or partial response. Regarding safety, RLY-2608 showed a differentiated and favorable toxicity profile, and most toxicities were low grade and manageable. Moreover, there were no dose-limiting toxicities observed, and the maximum-tolerated dose has yet to be reached. “So far, we have been able to determine the pharmacokinetic characteristics, pharmacodynamic characteristics, and toxicity profile of this medication in a number of patients. We have treated 42 patients. However, 1 of the major goals of a phase 1 study is to determine the phase 2 recommended dose,” Andreas Varkaris, MD, PhD, told Targeted OncologyTM, in an interview. “We aim to optimize our strategy to determine the phase 2 recommended dose and move rapidly to expansion in a new group of patients that will benefit from therapy.” RLY-2608 is the first allosteric, mutant-selective PI3Kα inhibitor which selectively inhibits PI3Kαmutations over wild-type PI3Kα, with a high degree of selectivity across the kinome and within the PI3K family. Preclinical breast cancer models have shown that treatment with RLY-2608 was comparable with the efficacy of alpelisib (Piqray) and inavolisib (GDC-0077). Alpelisib was granted FDA approval in 2019 in combination with fulvestrant (Faslodex) for patients with hormone receptor-positive, HER2-negative, PIK3CA-mutant advanced or metastatic breast cancer who have progressed on or after endocrine therapy. Unlike alpelisib and inavolisib, RLY-2608 displayed minimal effects on glucose homeostasis. This led to its evaluation in the ReDiscover study. In an interview with Targeted Oncology TM, Varkaris, Massachusetts General Hospital in Boston, discussed findings from the ReDiscover trial and treating patients with PIK3CAmutations. Targeted Oncology: Can you discuss PIK3CAmutations in patients with solid tumors and what this means regarding your ability to treat patients? Varkaris: PIK3CAmutations are relatively common. They're seen in 14% of all solid tumors. But there are some subtypes of solid tumors that we find PIK3CAmore commonly, for example, breast cancer tumors, especially hormone receptor-positive/ HER2-negative, advanced breast cancer tumors, express PIK3CAmutations in up to 40% of the cases. In the past, we have been able to treat these patients with altered generations of PI3Kinhibitors. We have an FDA approved drug called alpelisib, which is equally potent against the mutant, the wild-type enzyme, and has prolonged the life of patients with metastatic breast cancer with these mutations. We look forward to a new generation of inhibitors that will allow us to inhibit the enzyme more potently, without affecting the normal cells, and increase the number of patients that we will be able to treat. Also, by having more targeted therapies, we'll be able to combine these new drugs with other targeted therapies, something that wasn't feasible in the past because of the toxicity profile. Can you discuss the background and rationale for your first-in-human study? At MGH, we led the development of all previous P13K inhibitors, and we were fortunate to see our patients responding from these therapies, especially [patients with] breast cancer. However, many times the toxicity profile is devastated. Also, we are not able to treat patients based on their high hemoglobin for example, diabetic patients or even some overweight patients. Many groups around the world have been trying to develop novel therapies that will be more specific for cancer cells compared with the normal cells. The major difference between the cancer cells and normal cells is the presence of these P1K3CA mutations. A company, among others, managed to develop a PIK3CA-mutant specific inhibitor and we have tested it in the clinic. The background in studies done by the company showed that this inhibitor selectively inhibits the mutant forms of the PI3K compared with the wild-type, and they showed it in animal models. But today, what we presented was that this is also preserved in humans. We are able to hit the target, inhibit tumor growth with reasonable toxicity and without effect on the enzyme, which is a new era for all neutral specific inhibitors. What were recent results from the ReDiscover trial that you can highlight? More than 50% of our patients had tumor volume reduction, shown by images. We have 1 patient that was heavily treated with chemotherapy, HER2-directed therapy, and hormonal therapies that had a dramatic response, both in the clinical setting, laboratory, and radiograph. But we don't only stand in that 1 response. Most of our patients experience benefits. The toxicity profile that we have seen was the expected one by a drug that hits the tumor cells and does not hit the normal PI3K alpha enzyme. We have not observed any severe hyperglycemia, diarrhea, or skin rash. These 3 complications were associated with the earlier generation PI3K inhibitors and limited their efficacy. The data suggests that what we promised to deliver a drug that will hit the tumor cells with limited effect on the PI3K alpha wild-type has been delivered. Based on your findings, what are your next steps with this research? So far, we have been able to determine the pharmacokinetic characteristics, pharmacodynamic characteristics, and toxicity profile of this medication in a number of patients. We have treated 42 patients. However, 1 of the major goals of a phase 1 study is to determine the phase 2 recommended dose. So far, we have not reached any dose limiting toxicity and the maximum tolerated dose has not been determined. We aim to optimize our strategy to determine the phase 2 recommended dose and move rapidly to expansion in a new group of patients that will benefit from therapy. What other research involving these inhibitors has struck your interest recently? There is strong interest in combination therapies with pediatric inhibitors. Unfortunately, in the past, we have not been able to achieve that. And the primary reason was the toxicity profile of PI3K inhibitors. I have been in several discussions including the KRAS meeting and the prostate meeting, and the senior investigators have been asking whether at some point we will be able to combine targeted therapies with the PI3K inhibition pathway that has been implicated in the past with resistance to other targeted therapies. I think this is a good time to enter that era. We have novel therapies that hit the target sufficiently and cause shrinkage on their own. They have a wonderful toxicity profile that we can combine with other medications. If researchers can figure out how to mitigate these toxicities, what role do you think these inhibitors can play in a treatment landscape? I think we have proven that the toxicity profile of these targeted agents, at least the 1 that we [discussed] is favorable. We have not seen toxicities that make us suspicious that these inhibitors won't be able to be combined with other targeted therapies. I think we will live in a new era of precision oncology in which combination targeted therapies will be given to patients with more than 1 driver mutation or with tumors that are driven by a specific oncogene. But we know that resistance may be mediated by PI3K activation. REFERENCE: Varkaris A, Jhaveri K, Perez CA, et al. Pan-mutant and isoform selective PI3Kα inhibitor, RLY-2608, demonstrates selective targeting in a first-in-human study of PI3Kα -mutant solid tumor patients, ReDiscover trial. Presented at: 2023 AACR Annual Meeting; April 14-19, 2023; Orlando, FL. Abstract CT017.
https://www.targetedonc.com/view/tucatinib-demonstrates-activity-in-heavily-pretreated-her2-breast-cancer
Diversity | Free Full-Text | Genetic Structure and Selection Signature in Flora Scent of Roses by Whole Genome Re-Sequencing Roses are important plants, and they are cultivated worldwide for their beautiful flowers, remarkable scent, and nutritious hips. In this study, we re-sequenced the whole genomes of 57 rose cultivars and one wild species that originated from different regions around the world and had different scents, aiming to evaluate their genetic structure and to detect the potential signature of the selective sweep between different scent groups with single-nucleotide polymorphism (SNP) and indel markers. The roses were sequenced at an average depth of 6& times; to the reference genome of Rosa & lsquo;Old blush& rsquo;. A total of 2,375,949 SNPs were obtained. The SNP numbers varied among the 58 samples, with an average of 1,271,906 per sample. The phylogeny and population structure revealed that the roses could be divided into three main clusters; however, the groups were not consistent in terms of geographic origin or scent classification. These indicated that rose cultivars have a complex genetic background due to the extensive hybridization between cultivated roses or wild rosa species worldwide. A selective sweep analysis was conducted to detect the selection signatures in rose scent traits. A total of 2430 candidate genes were identified in the strong scent groups, and were at the top 5% FST compared to the moderate group. These genes were significantly enriched in the KEGG pathways of tyrosine metabolism, cyanoamino acid metabolism, alpha-linolenic acid metabolism (13 genes), and phenylpropanoid biosynthesis (30 genes). When the low-scent group was used as the control, 2604 candidate genes were identified at the top 5% FST that were significantly enriched in the KEGG pathways of alpha-linolenic acid metabolism (15 genes), and glutathione metabolism (23 genes). We also observed genes enriched in pathways including the linoleic acid metabolism (five genes), diterpenoid biosynthesis (six genes), and monoterpenoid biosynthesis (seven genes), although they were not significant. These implied a positive selection of rose cultivars with a strong fragrance in terms of fatty acid derivatives, terpenoids and benzenoids/phenylpropanoids during rose breeding. Our study establishes a foundation for the further large-scale characterization of rose germplasm, improving the genetic knowledge of the background of roses. Genetic Structure and Selection Signature in Flora Scent of Roses by Whole Genome Re-Sequencing Jingtao Hui 1 , Yanhua Cui 1 , Jun Zhang 1 , Guocang Lin 1,* and Yan Li 2,* Xinjiang Academy of Agricultural Science (XAAS), Urumqi 830091, China Authors to whom correspondence should be addressed. Diversity 2023 , 15 (6), 701; https://doi.org/10.3390/d15060701 (registering DOI) Received: 23 March 2023 / Revised: 18 May 2023 / Accepted: 22 May 2023 / Published: 24 May 2023 (This article belongs to the Section Phylogeny and Evolution ) Abstract : Roses are important plants, and they are cultivated worldwide for their beautiful flowers, remarkable scent, and nutritious hips. In this study, we re-sequenced the whole genomes of 57 rose cultivars and one wild species that originated from different regions around the world and had different scents, aiming to evaluate their genetic structure and to detect the potential signature of the selective sweep between different scent groups with single-nucleotide polymorphism (SNP) and indel markers. The roses were sequenced at an average depth of 6× to the reference genome of Rosa ‘Old blush’. A total of 2,375,949 SNPs were obtained. The SNP numbers varied among the 58 samples, with an average of 1,271,906 per sample. The phylogeny and population structure revealed that the roses could be divided into three main clusters; however, the groups were not consistent in terms of geographic origin or scent classification. These indicated that rose cultivars have a complex genetic background due to the extensive hybridization between cultivated roses or wild rosa species worldwide. A selective sweep analysis was conducted to detect the selection signatures in rose scent traits. A total of 2430 candidate genes were identified in the strong scent groups, and were at the top 5% F ST compared to the moderate group. These genes were significantly enriched in the KEGG pathways of tyrosine metabolism, cyanoamino acid metabolism, alpha-linolenic acid metabolism (13 genes), and phenylpropanoid biosynthesis (30 genes). When the low-scent group was used as the control, 2604 candidate genes were identified at the top 5% F ST that were significantly enriched in the KEGG pathways of alpha-linolenic acid metabolism (15 genes), and glutathione metabolism (23 genes). We also observed genes enriched in pathways including the linoleic acid metabolism (five genes), diterpenoid biosynthesis (six genes), and monoterpenoid biosynthesis (seven genes), although they were not significant. These implied a positive selection of rose cultivars with a strong fragrance in terms of fatty acid derivatives, terpenoids and benzenoids/phenylpropanoids during rose breeding. Our study establishes a foundation for the further large-scale characterization of rose germplasm, improving the genetic knowledge of the background of roses. Keywords: single-nucleotide polymorphism (SNP) ; indel ; genome variation ; selection sweep ; KEGG pathway 1. Introduction Roses are among the most commonly cultivated plants worldwide due to their beautiful flowers, remarkable scent [ 1 , 2 ], and economic importance both as ornamental plants and in their use in the perfume industry, which has motivated rose domestication and breeding. During their long cultivation and breeding history in Europe and Asia [ 3 , 4 ], roses underwent several interspecific hybridizations, introgressions and polyploidizations [ 5 , 6 ], leading to a huge amount of cultivars, with >24,000 available varieties (listed in Roberts et al. [ 7 ]). The cultivated rose ancestors derived from 7–10 species from the sections Synstylae ( R. moschata , R. wichurana , and R. multiflora ), Rosa ( R. gallica ), Indicae ( R. chinensis and R. gigantea ), and Pimpinellifoliae ( R. foetida ) [ 8 , 9 ]. Asian roses were introduced to Europe and progressively used in breeding. Rosa rugosa and the Chinese rose ( R. chinensis ) were introduced to Europe at the end of the 18th century [ 2 , 6 , 10 ]. Rosa rugosa is an important plant in the production of perfumes and a valuable germplasm for breeding cultivated roses. The extensive hybridization between this species and native rose species, such as R. blanda and dogroses [ 11 , 12 ], resulted in the emergence of the Hybrid Tea roses (such as Rosa gallica , Rosa damascena , R. chinensis ‘Old Blush’, and R. chinensis ‘Hume’s Blush’) from which most modern roses are derived [ 1 , 8 ]. These complicated breeding and hybridization processes have led to the genetic complexity of roses. Molecular markers, such as RAPD, AFLP, and SSR have been used to characterize the genetic diversity, genetic differentiation, biogeographic pattern, and the conservation of specific groups of roses (from a single or a few species or cultivars to multiple genotypes) from a specific geographic region, such as Rosa rugosa [ 13 , 14 ], R. damascena [ 15 , 16 ], and R. canina [ 17 ]. Rusanov et al. [ 18 ] assessed the genetic relationships between 26 R. damascena accessions and 13 garden Damask roses, demonstrating that R. damascena accessions from Bulgaria, Iran, and India, in addition to old European damask rose varieties, possess identical microsatellite profiles and originate from a common ancestor. However, Gaurav et al. [ 19 ] found significant genetic diversity among exotic R. damascene accessions and damask rose cultivars. Feng et al. [ 20 ] evaluated the genetic diversity and relationships between wild R. rugosa and cultivars, showing that wild accessions and cultivars have a remote genetic relationship, while the main Chinese R. rugosa cultivars have few genetic differences and a narrow genetic background. In contrast, Panwar et al. [ 21 ] suggested that the cultivated rose varieties in India display a high level of genetic variability. These indicated genetic diversities vary according to geographic origin or sampling size. The genetic diversity or genetic relationships between cultivars and wild species have been examined using a wide range of samples. Tan et al. [ 22 ] estimated the genetic diversity and genetic differentiation in old Chinese garden roses using SSR markers, suggesting that rose cultivars evolved from the Old Blush Group to the Odorata group, the Ancient Hybrid China group and the modern rose. Aparna et al. [ 23 ] investigated the genetic diversity of 25 fragrant rose cultivars of exotic and Indian origin, with SSR markers showing that cultivars of Indian origin showed a higher diversity compared to the selected cultivars of American and European origin. Scariot et al. [ 24 ] studied the genetic relationships of 65 old garden roses based on a microsatellite analysis, which suggested that all the genotypes could be clustered into seven major clusters that were substantially consistent with their classification into botanical sections and horticultural groups. Liorzou et al. [ 2 ] obtained a broader view of the evolution of the diversity of roses bred in France during the 19th century by assessing a larger sampling size of up to 1228 accessions. Genetic differentiation was detected between ancient European and Asian accessions, and a temporal shift from a European to an Asian genetic background in cultivated European hybrids during the 19th century was induced by frequent crosses with Asian roses throughout the 19th century and/or the selection for Asiatic traits. In recent years, along with the development of next-generation sequencing, single-nucleotide polymorphism (SNP) has become an important tool for the genotyping of cultivars and genome-wide association studies. Xia et al. [ 25 ] developed high-density SNP markers for rose with 158 Rosa chinensis individuals using SLAF-seq. The whole-genome resequencing (WGRS) technique can generate a larger amount of SNP data in a very cost-effective manner [ 26 ], which can help to better understand the genetic diversity, structure, and genetic basis of plant traits and variations [ 27 , 28 ]. In this study, we present analyses of the whole genome re-sequencing of 57 rose cultivars and one wild rosa species, aiming to evaluate the genetic structure and the relationships between them, and detected the potential signature of selective sweep between different scent groups with a single-nucleotide polymorphism (SNP) and indel markers. The developed SNPs will be useful for genome-wide association studies and in mapping the genes associated with valuable rose traits. 2. Materials and Methods 2.1. Plant Materials A total of 57 rose cultivars and one wild species, R. laxa , were collected. The roses were planted at the Institute of the Xinjiang Academy of Agricultural Sciences. They were divided into the following five groups based on their geographic origin: two from Western Asia, eight from North America, 25 from Europe, one from Australia, 18 from China, and four of unknown origin ( Table S1 ). The leaf tissues were collected in April 2022 and dried in silica gel. 2.2. DNA Extraction and Quantification Genomic DNA from young leaves was extracted using the CTAB method. The concentration and quality of the total genomic DNA were determined using a NanoDrop2000 spectrophotometer (Thermofisher Scientific, Waltham, MA, USA) and then normalized to 10 ng/µL for sequencing. 2.3. Library Construction and Whole Genome Re-Sequencing DNA was fragmented with a Bioruptor (ThermoFisher Scientific, Waltham, MA, USA) that was used to generate an approximately 350 bp library insert size. The quantity and quality controls of the libraries were carried out with Qubit dsDNA HS Assay kit (ThermoFisher Scientific) and the Agilent 2100 Bioanalyzer System (Agilent Technologies, Santa Clara, CA, USA), respectively. Qualified libraries were sequenced on an Illumina HiSeq platform by a commercial service (Biomarker Technologies, Beijing, China). 2.4. Read Mapping, SNP Calling and Annotation The raw sequencing data were filtered for adapter contamination and low-quality reads (pair-end reads with N > 10%, and low-quality bases (Phred-like score < 20) higher than 50%); duplicates were obtained using Trimmomatic and SOAP2. This filtered the high-quality ‘final rawdata’. The high-quality paired-end sequencing reads (150 bp) from each cultivar were mapped to the Rosa chinensis variety ‘Old Blush’ [ 6 ] reference genome using BWA v0.7.12 (University of Hong Kong, Hong Kong, China). The GATK genome analysis toolkit version 4.1.4.1 (Broad Institute, Cambridge, MA, USA) [ 29 ] was used to determine SNPs and indels across all roses using HaplotypeCaller, with the following parameters: QD < 2.0 || MQ < 40.0 || FS > 60.0 || QUAL < 30.0 || MQrankSum < −12.5 || ReadPosRankSum < −8.0 -clusterSize 2 -clusterWindowSize. The SNPs identified by GATK were further filtered based on the criteria of minor allele frequency (MAF: 0.05) and data integrity on site (INT: 0.8) to obtain high-quality SNPs for subsequent analysis. SNP annotation was performed on the basis of the reference genome using snpEff software [ 30 ], and the SNPs were categorized into intergenic regions, upstream or downstream regions, and exons or introns. SNPs in coding exons were further classified as synonymous SNPs or nonsynonymous SNPs. The indels in exons were grouped according to whether they led to a frameshift or not. 2.5. Genetic Diversity Estimation The observed nucleotide diversity or average pairwise divergence (π) and fixation index (Fst) were calculated using vcftools based on the high-confident filtered SNPs. Various measures of genetic diversity, including observed heterozygosity (Ho), polymorphism information content (PIC), and the Shannon index were calculated for the rose groups using the GenoDive program [ 31 ] and the ‘GeneticSubsetter’ package [ 32 ]. 2.6. Population Structure High-confidence SNPs were used to infer the population structure within rose accessions using ADMIXTURE [ 33 ], with K values (the putative number of populations) ranging from 1 to 10. We assessed the number of sub-populations using five-fold cross-validation. A neighbor-joining phylogenetic tree of the rose cultivars was constructed using MEGAX 7.0.14 based on the Nei’s distance, and bootstrapping was repeated 1000 times. 2.7. Screening for Selection Signatures Related to Flora Scent To uncover the genetic variants involved in the selection of rose scent traits in strong-scent cultivars, we calculated the genome-wide distribution of F ST values, including the strong- vs. moderate- and low-scent groups. The F ST for sliding windows was calculated using VCFtools [ 34 ], with a window size of 100 kb and a step size of 10 kb. The windows with the top 5% of values for the F ST simultaneously served as the candidate outliers under strong selective sweeps. All outlier windows were assigned to their corresponding SNPs and genes. The selected genes enriched in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined using BLAST against NR, SwissProt, GO, COG, and KEGG. Multiple comparisons were corrected using the false discovery rate (FDR corrected p < 0.05). 3. Results and Discussion 3.1. Sequencing Statistics and Variation in the Rose Genome A total of 370.81 Gbp of high-quality clean data (Q30 > 94.27%) was obtained from the genome resequencing of the 58 rose accessions, with an average depth of 6.2× ( Table S2 ). A total of 2,375,949 highly consistent SNPs were identified after the use of the SNP filter. The SNP numbers varied among the 57 cultivars, from 890,350 in ‘Yueyuehong’ to 1,557,369 in ‘Grasse Rose’ ( Table S3 ); on average, the SNP in each accession was 1,271,906. Most of the nucleotide changes can be classified as transitions (799,196), with a transition/transversion ratio (Ts/Tv ratio) of 1.685 (ranging from 1.59 in R. rugosa ‘Fenghua’ to 1.74 in Rosa ‘Pink O’Hara’) ( Table S3 , Figure S1 ). This value is slightly higher than that reported in sweet cherry (1.4675) [ 28 ]. The heterozygosity varied in the 58 rose accessions, from 18.30% in R. laxa to 96.5% in R. ‘Yueyuehong’, with a mean value of 57.45% ( Table S3 ). The heterozygosity ratios for the cultivar ‘Fenghua’, R. rugosa ‘Pingyin 1’, R. ‘Lavender bouquet’, R. ‘Chariot’, Rosa sertata × rugosa , and R. rugosa ‘Zizhi’ were 19.57%, 21.52%, 26.58%, 28.84%, 28.03% and 31.84%, respectively, indicating a large difference from the reference genome of ‘Old blush’, whereas the heterozygosity of ‘Yueyuehong’ was 96.5%, implying that the genome of this cultivar was highly consistent with the reference genome. On average, 23.05% (13.98–36.45%) of the total number of SNPs were located in intergenic regions, 13.85% (9.62–20.9%) in intron, 19.5% in upstream, 16.15% in downstream, and 14.1% (9.56–22.26%) in coding regions ( Table 1 , Table S4 ). In line with previous studies, the majority of SNPs were located in non-coding regions. Only a small proportion of the SNPs were observed in the coding region, which is in line with other species [ 35 ]. The SNPs found in CDS were slightly higher in roses than in sweet cherry [ 28 ] and peach [ 36 ]. The SNPs in genic regions include 103,931 synonymous (from 69,364 in ‘Yueyuehong’ to 145,427 in ‘Grasse Rose’), and 83,589 non-synonymous substitutions (from 55,876 in ‘Yueyuehong’ to 115,496 in ‘Grasse Rose’) ( Table S4 ). The non-synonymous-to-synonymous substitution ratio (dN/dS) for the SNPs in the coding regions ranged from 0.766 in ‘Fenghua’ to 0.826 in ‘Chariot’, with an average of 0.806. This is lower than the values reported in other crops or species, such as peach (1.0636) [ 36 ], grapevine (1.1732) [ 37 ], pigeon pea (1.1835) [ 38 ], tomato (1.2334) [ 35 ], Chinese plum (1.3037) [ 39 ], and sweet cherry (1.78) [ 28 ]. Regarding indels, a total of 2,925,938 small insertions or deletions (indels) were identified, of which 1,320,614 were insertions and 1,605,324 were deletions. The indel number also varied in different cultivars, ranging from 312,153 in ‘Yueyuehong’ to 556,043 in ‘Grasse Rose’, with a mean of 444,622 ( Table S5 ). This is lower than the small indels detected from nine Rosa species (between 876,648 and 2,430,123, with an average of 346,498) [ 6 ], which indicated that the cultivated roses have a lower genetic diversity than the wild species, and showed a close genetic background between rugosa and modern roses, as demonstrated by the high synteny between R. rugosa and R. chinensis [ 10 ]. The size of insertions ranged from 1–~200 nucleotides, and deletions were in the range of 1–~300 nucleotides in length ( Figure S2 ). However, most of the insertions and deletions were of a single nucleotide. Di-, tri-, and quadri-nucleotide insertions and deletions accounted for a relatively low percentage of the total indels ( Figure S2 ). In accordance with SNP, the vast majority of the indels were also located upstream or downstream of genes and in the intergenic regions. Only a small proportion (4.59%, 134,209) were located within CDS, of which 59,973 were insertions and 74,236 were deletions ( Table 1 , Table S6 ). The indels detected in CDS also varied in each cultivar. The lowest number of insertions in CDS was found in ‘Yueyuehong’ (4827), and the highest was found in ‘Grasse Rose’ (10,209), with a mean of 7398, while the deletions ranged from 6529 to 12,484, with a mean of 9549 ( Table S6 ). We further analyzed the distribution of large-effect SNPs, genes with non-synonymous SNP and indel, which may potentially disable gene functions. From 22,892 to 30,026 genes with non-synonymous SNP and 9210 to 15,993 genes with indel were found ( Table S7 ). The lowest were found in the ‘Yueyuehong’ and the highest in were found in the ‘Grasse Rose’. 3.2. Genetic Relationships Based on SNP Data Based on 2,375,949 high-quality SNPs, the pairwise genetic distance was determined, and a phylogenetic tree of rose accessions was conducted. The phylogenetic tree was divided into three general clades ( Figure 1 ). Clades I and II contained five and nine rose accessions each. Clade III consisted of the remaining 44 cultivars, in which three subclades (S1–S3) were identified. Subclade 1 (S1) comprised two cultivars (‘Blue ribbon’ and ‘Binquanzhilian’); Subclade 2 (S2) mainly consisted of rugosa roses, including ‘Zizhi’, ‘Pingying 1’, ‘Fenghua’, ‘Hetianshamomeigui’, and ‘Grasse rose’. Furthermore, the ‘Damask’, ‘Tineke’, and two new cultivars, R. laxa × hybrida cv. Tianshan Xiaguang and cv. Tianshan Xiangyun, were included in this subclade. Subclade 3 (S3) was the largest clade, consisting of the remaining 29 cultivars. The cultivars from five geographic sites or those with different scents were mixed, suggesting that the genetic relationships between rose cultivars are complex due to the high number of species of various ploidy levels, the worldwide exchanges of roses for breeding activities, and the high level of interspecific hybridization [ 2 ]. 3.3. Population Structure of Roses A population structure analysis conducted using the Admixture program and SNP data revealed that the 58 accessions could be divided into three groups according to the cross-validation error rate ( Figure 2 ). Of the three groups, Group 1 included the most germplasm, with 39 cultivars. Group 2 comprised 10 cultivars, such as ‘Sweet Chariot’, ‘Meilivoine’, ‘Licorice Tea’, ‘Lavender Bouquet’, ‘Chariot’, ‘Yuki Akari’, and Rosa sertata × rugosa . Group 3 contained eight cultivars, mainly rugosa roses, ‘Fenghua’, ‘Zizhi’, ‘Pingyin 1’, ‘Hetianshamomeigui’, ‘Grasse Rose’, and R. damascena , suggesting a closer relationship among these cultivars, which is in agreement with the phylogenetic tree. Notably, ‘Hetianshamomeigui’, ‘Grasse Rose’, R. laxa × hybrida cv. Tianshan Xiaguang, R. laxa × hybrida cv. Tianshan Xiangyun, ‘Andelie’, and ‘Angela’ showed a mixed genetic background. The K = 4–10 sub-optimal models were also informative; when K = 4, a fourth cluster composed of ‘Fenghua’, ‘Zizhi’, ‘Pingying 1’, and ‘Tineke’ split from cluster 3. Even when K = 10, these four species still clustered together; this is congruent with the results of the phylogenetic tree ( Figure 1 ), indicating that a closer genetic relationship exists between these cultivars. When K = 7, ‘Heitanshamomeigui’, ‘Grasse Rose’, and Damask clustered together into a different group and another cluster, including Rosa sertata × rugosa , ‘Chariot’, ‘Lavender Bouquet’. The close relationship between ‘Heitanshamomeigui’, ‘Grasse Rose’, and Damask was also suggested by previous works [ 40 ]. When K = 9, R. laxa × hybrida cv. Tianshan Xiaguang and cv. Tianshan Xiangyun formed a separate group; these two cold-tolerant cultivars (standing up to −30 °C) were recently developed from hybridization with the garden rose species ‘Fenheping’ and ‘Hongmaozi’ and the cold-tolerant wild species R. laxa [ 41 ]. These two cultivars can grow 3 m high and contain 1000 flowers in a single individual of 3 years old [ 42 ]. These subgroups were also supported by the NJ phylogenetic tree. Consistent with the phylogenetic relationships, rugosa roses were admixed with other cultivars. Rosa rugosa was introduced to Europe at the end of the 18th century and participated in the breeding of cultivated roses in Europe by the extensive hybridization with native rose species [ 2 , 6 , 10 ]. Previous research has found that the frequent crosses with Asian roses throughout the 19th century and/or the selection for Asiatic traits may have induced a temporal shift from a European to an Asian genetic background in cultivated European hybrids during the 19th century [ 2 ]. 3.4. Genetic Diversity The genetic diversity of the three scent groups was calculated with SNP data. The diversity indexes were generally identical. The PIC of the three groups was around 0.21, and the Shannon index was about 0.4 ( Table 2 ), which is mostly in agreement with the estimations for the 21 cultivated and wild roses according to the SSR markers (average PIC of 0.365) [ 19 ]. 3.5. Genome-Wide Detection of Selective Candidate Loci and Genes Associated with Flower Scent The fragrance of roses is one of their most economically valuable characteristics. The main sources of floral fragrances primarily consist of terpenes, aromatic compounds, and fatty acid derivatives [ 43 ]. We performed a selective sweep analysis and detected potential signals in rose scent selection with high-confidence-level SNPs through a calculation of the Fst values of the two pairwise groups (strong scent/moderate scent, strong scent/low scent). Genomic loci with the top 5% of maximum F ST values in each group were identified as selective sweeps in the genome. Compared to the moderate group, a total of 2430 candidate genes in 141 windows were recognized as potentially affected genes related to the flora scent in the strong scent groups at the top 5% of maximum Fst values ( Figure 3 A, Table S8 ). The candidate genes were significantly enriched in KEGG pathways, i.e., tyrosine metabolism (ko00350, FDR-adjusted p = 0.003), cyanoamino acid metabolism (ko00460, FDR-adjusted p = 0.02), alpha-linolenic acid metabolism (ko00592, FDR-adjusted p = 0.02, 13 genes), sulfur metabolism (ko00920, FDR-adjusted p = 0.02), and phenylpropanoid biosynthesis (ko00940, FDR-adjusted p = 0.03, 30 genes) ( Figure 3 B; Table S9 ). Although terpenoid backbone biosynthesis (ko00900, p = 0.05, FDR-adjusted p = 0.33, 9 genes) was not significantly enriched, nine genes were in the top 5% with regard to Fst values. The 30 genes enriched in phenylpropanoid biosynthesis were mainly located on chromosome CM009586.1 (20 genes), followed by CM009585.1 (six genes) and CM009587.1 (three genes). The 13 genes enriched in the alpha-linolenic acid metabolism were mainly located on CM009587.1 (11 genes) and CM009586.1 (two genes). Of the nine genes enriched in the terpenoid backbone biosynthesis pathway, seven genes were located on CM009584.1 and CM009586.1. In addition, a total of 461 candidate genes were identified in 43 windows in the strong-scent groups using the top 1% of maximum Fst values ( Table S10 ). These genes were significantly enriched in KEGG pathways; for instance, pyrimidine metabolism (ko00240, FDR-adjusted p = 0.04, 7 genes), monoterpenoid biosynthesis (ko00902, FDR-adjusted p = 0.04, 3 genes), linoleic acid metabolism (ko00591 p = 0.02, 2 genes), and carotenoid biosynthesis (ko00906, p = 0.07, 2 genes) ( Figure S3 , Table S11 ). When the low-scent group was used as a control, 2604 candidate genes in 96 windows were identified at the top 5% of maximum F ST values ( Figure 4 A, Table S12 ). The 2604 candidate genes at the top 5% maximum F ST were significantly enriched in KEGG pathways, i.e., alpha-linolenic acid metabolism (ko00592, FDR-adjusted p = 0.005, 15 genes), glutathione metabolism (ko00480, FDR-adjusted p = 0.005, 23 genes). In addition, some pathways were also not significantly enriched in genes included in the top 5% Fst sliding windows, including the linoleic acid metabolism (ko00591, p = 0.009, five genes), diterpenoid biosynthesis (ko00904, p = 0.02, six genes), and monoterpenoid biosynthesis (ko00902, p = 0.07, seven genes) ( Figure 4 B, Table S13 ). These functional clusters are biologically relevant to floral volatile traits (aromatic flavor) in strong-scent roses. A total of 794 candidate genes in 47 windows were identified as being in the top 1% of maximum F ST values ( Table S14 ). The alpha-linolenic acid metabolism pathway were significantly enriched in genes (seven genes) identified in the top 1% of Fst sliding windows ( Figure S4 , Table S15 ). The strong-scent roses included 17 cultivars ( Table S1 ), most of which originated from Europe (‘Roger Lambelin’, ‘Andelie’, ‘Angela’, ‘Iceberg’, ‘Crimson Glory’, and ‘Tineke’) and China (‘Bingquanzhilian’, ‘Dianhong’, ‘Hetianshamomeigui’, ‘Pingyin 1’, and ‘Zizhi’). Roses from Europe and China are distinct in their flora fragrance characteristics: the major scent components of European roses include 2-phenylethanol and monoterpenes [ 44 ], whereas Chinese roses (i.e., R. chinensis var. spontanea ) contain high amounts of phenolic methyl ethers (PME), such as 3,5-dimethoxytoluene (DMT) or 1,3,5-trimethoxybenzene (TMB) [ 44 , 45 ]. The biosynthesis of DMT and TMB in Chinese rose species and in many modern varieties are orcinol O-methyltransferases ( OOMT ) [ 46 ]. Although PME biosynthesis was originally restricted to Chinese roses, DMT is a major scent compound of many rose varieties at present, representing up to 90% of total flower volatiles in Tea and Hybrid Tea roses [ 44 , 45 ]. Accordingly, we observed that the OOMT was absent from the candidate region. Nudix hydrolase ( NUDX ) hydrolyses a wide range of organic pyrophosphates, and it participates in the biosynthesis of geraniol [ 1 ]. The overexpression of a R. rugosa NUDX gene enhances the biosynthesis of scent volatiles in petunia [ 47 ]. We also found that NUDX (gene32956) was located in regions with putative selective sweeps ( Tables S8 and S12 ). Terpenes are major scent compounds in roses, and its biosynthesis involves terpene synthase ( TPS ) proteins [ 48 ]. Germacrene D synthase ( GDS ) encodes the enzyme catalyzing germacrene D synthesis [ 1 ]. TPS (gene40968, gene40975, gene48373) ( Table S12 ) and GDS (gene24868, gene48373) ( Tables S8 and S12 ) were also detected in the 5% Fst region. These results indicate that chromosomal regions or genes related to the floral scent might be under selection in strong scent roses. The VOCs are diverse across rose varieties or species [ 49 ]. Monoterpenes represent up to 70% of the scent content in some cultivars, such as the Papa Meilland rose [ 50 ]. The main volatile component of R. chinensis var. spontanea is TMB [ 44 ]. Citronellol, geraniol, nerol and their acetates, and linalool are the main components of the characteristic fragrance of R. rugosa [ 51 ]. The variation in the volatiles of rose flowers of a different geographic origin or species might explain the inconsistency of the candidate genes and enrichment pathways in the two paired groups. We generally observed that some candidate genes were enriched in the alpha-linolenic acid metabolism, the cyanoamino acid metabolism, the terpenoid backbone biosynthesis, the diterpenoid biosynthesis, the monoterpenoid biosynthesis, and the phenylpropanoid biosynthesis pathways in the strong-scent roses, which is in agreement with previous studies demonstrating that most flower fragrance compounds belong to three major biosynthetic pathways: benzenoids/phenylpropanoids, fatty acid derivatives, and terpenoids [ 49 , 52 ]. 4. Conclusions In this study, we re-sequenced the whole genome of 58 roses originating from different regions around the world and with different scents. Phylogeny and structure analyses revealed that the 58 rose accessions did not cluster according to species or geographic origin, but showed a mixed pattern. This indicated that rose cultivars have a complex genetic background due to the extensive hybridization between cultivated roses or wild rose species worldwide. A selective sweep analysis was conducted to detect selection signatures in the scent trait of roses. In the strong-scent roses, the potential genes under selection were mainly involved in fatty acid biosynthesis, and terpenoids and phenylpropanoids biosynthesis; these implied a positive selection of rose cultivars for their strong fragrance during the rose breeding process. Our study has established a foundation for the further large-scale characterization of the rose germplasm, enabling breeders to incorporate diverse germplasm and allelic variants to fine-tune the flowering in rose cultivars and improve the genetic knowledge of the background of roses. Supplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/d15060701/s1 , Table S1: Geographic origin and flora scent characteristics of roses used in this study. Table S2: Summary of whole genome resequencing data of roses. Table S3: Genome-wide SNP variations identified in the roses. Table S4: Annotation of genome-wide SNP variations identified in rose accessions. Table S5: Statistics of genome-wide indel variations identified in the roses. Table S6: Annotation of genome-wide indel variations identified in rose accessions. Table S7: Genes with non-synonymous variations in each accession. Table S8: Chromosomal distribution of identified candidate genes detected between strong/moderate-scent roses with 5% top Fst. Table S9: KEGG pathway enrichment of candidate genes under selection, detected between strong/moderate-scent roses with 5% top Fst. Table S10: Chromosomal distribution of identified candidate genes detected between strong/moderate-scent roses with 1% top Fst. Table S11: KEGG pathway enrichment of candidate genes under selection, detected between strong/moderate scent roses with 1% top Fst. Table S12: Chromosomal distribution of identified candidate genes detected between strong/low-scent roses with 5% top Fst. Table S13: KEGG pathway enrichment of candidate genes under selection, detected between strong/low-scent roses with 5% top Fst. Table S14: Chromosomal distribution of identified candidate genes detected between strong/low-scent roses with 1% top Fst. Table S15: KEGG pathway enrichment of candidate genes under selection, detected between strong/low-scent roses with 1% top Fst. Figure S1: The statistics of SNP type in each cultivar. Figure S2: The length distribution of indel in coding region and whole genome. Figure S3: KEGG enrichment of candidate genes between strong- and moderate-scent roses. The enriched pathways are listed on the left. Colors denote the p -value. The size of each bubble reflects the genes enriched in each pathway. Author Contributions Conceptualization, M.S. and G.L.; Methodology, X.R., Y.Z. and Y.L. (Ya Liu); Formal analysis, Y.L. (Yan Li), J.Y., Y.C. and J.H.; Investigation, M.S. and J.H.; Data curation, Y.L. (Ya Liu), J.Z., Y.Z. and J.Y.; Writing—original draft preparation, M.S. and Y.L. (Yan Li); Writing—review and editing, J.Z., J.Y., J.H., Y.C., J.Z. and G.L.; Visualization, Y.L. (Yan Li), X.R. and Y.L. (Ya Liu); Funding acquisition, M.S. and G.L. All authors have read and agreed to the published version of the manuscript. Funding This research was funded by the basic scientific research fund for the public welfare research institutes of the Xinjiang Uygur Autonomous Region (ky2021125) and the key research and development plan projects of the Xinjiang Uygur Autonomous Region (No. 2021B02005-1). The authors declare that they have no conflict of interest. References Raymond, O.; Gouzy, J.; Just, J.; Badouin, H.; Verdenaud, M.; Lemainque, A.; Vergne, P.; Moja, S.; Choisne, N.; Pont, C.; et al. The Rosa genome provides new insights into the domestication of modern roses. Nat. Genet. 2018 , 50 , 772–777. [ Google Scholar ] [ CrossRef ] [ PubMed ] Liorzou, M.; Pernet, A.; Li, S.B.; Chastellier, A.; Thouroude, T.; Michel, G.; Malecot, V.; Gaillard, S.; Briee, C.; Foucher, F.; et al. Nineteenth century French rose ( Rosa sp.) germplasm shows a shift over time from a European to an Asian genetic background. J. Exp. Bot. 2016 , 67 , 4711–4725. [ Google Scholar ] [ CrossRef ] [ PubMed ] Touw, M. Roses in the middle ages. Econ. Bot. 1982 , 36 , 71–83. [ Google Scholar ] [ CrossRef ] Wang, G. A study on the history of Chinese roses from ancient works and images. Acta Hortic. 2005 , 751 , 347–356. [ Google Scholar ] [ CrossRef ] Esselink, G.D.; Nybom, H.; Vosman, B. Assignment of allelic configuration in polyploids using the MAC-PR (microsatellite DNA allele counting-peak ratios) method. Theor. Appl. Genet. 2004 , 109 , 402–408. [ Google Scholar ] [ CrossRef ] [ PubMed ] Saint-Oyant, L.H.; Ruttink, T.; Hamama, L.; Kirov, I.; Lakhwani, D.; Zhou, N.N.; Bourke, P.M.; Daccord, N.; Leus, L.; Schulz, D.; et al. A high-quality genome sequence of Rosa chinensis to elucidate ornamental traits. Nat. Plants 2018 , 4 , 473–484. [ Google Scholar ] [ CrossRef ] [ PubMed ] Roberts, A.; Debener, T.; Gudin, S. Encyclopedia of Rose Science ; Elsevier: Amsterdam, The Netherlands; Academic Press: Oxford, UK, 2003. [ Google Scholar ] Martin, M.; Piola, F.; Chessel, D.; Jay, M.; Heizmann, P. The domestication process of the Modern Rose: Genetic structure and allelic composition of the rose complex. Theor. Appl. Genet. 2001 , 102 , 398–404. [ Google Scholar ] [ CrossRef ] Smulders, M.J.M.; Arens, P.; Koning-Boucoiran, C.F.S.; Gitonga, V.W.; Krens, F.A.; Atanassov, A.; Atanassov, I.; Rusanov, K.E.; Bendahmane, M.; Dubois, A.; et al. Rosa. In Wild Crop Relatives: Genomic and Breeding Resources ; Kole, C., Ed.; Springer: Berlin, Germany, 2011; pp. 243–275. [ Google Scholar ] Zang, F.Q.; Ma, Y.; Tu, X.L.; Huang, P.; Wu, Q.C.; Li, Z.M.; Liu, T.; Lin, F.R.; Pei, S.R.; Zang, D.K.; et al. A high-quality chromosome-level genome of wild Rosa rugosa . DNA Res. 2021 , 28 , dsab017. [ Google Scholar ] [ CrossRef ] Mercure, M.; Bruneau, A. Hybridization between the escaped Rosa rugosa (Rosaceae) and native R-blanda in eastern North America. Am. J. Bot. 2008 , 95 , 597–607. [ Google Scholar ] [ CrossRef ] Bruun, H.H. Rosa rugosa Thunb. ex Murray. J. Ecol. 2005 , 93 , 441–470. [ Google Scholar ] [ CrossRef ] Nagamitsu, T. Genetic structure in chloroplast and nuclear microsatellites in Rosa rugosa around sea straits in northern Japan. Plant Spec. Biol. 2017 , 32 , 359–367. [ Google Scholar ] [ CrossRef ] Jiang, L.Y.; Zang, D.K. Analysis of genetic relationships in Rosa rugosa using conserved DNA-derived polymorphism markers. Biotechnol. Biotec. Equip. 2018 , 32 , 88–94. [ Google Scholar ] [ CrossRef ] Baydar, N.G.; Baydar, H.; Debener, T. Analysis of genetic relationships among Rosa damascena plants grown in Turkey by using AFLP and microsatellite markers. J. Biotechnol. 2004 , 111 , 263–267. [ Google Scholar ] [ CrossRef ] [ PubMed ] Rai, H.; Raju, D.V.S.; Kumar, M.B.A.; Janakiram, T.; Namita; Krishnan, S.G.; Rana, J.C. Characterization and analysis of genetic diversity among different species of rose ( Rosa species) using morphological and molecular markers. Indian J. Agr. Sci. 2015 , 85 , 240–245. [ Google Scholar ] Jurgens, A.H.; Seitz, B.; Kowarik, I. Genetic differentiation of Rosa canina (L.) at regional and continental scales. Plant Syst. Evol. 2007 , 269 , 39–53. [ Google Scholar ] [ CrossRef ] Rusanov, K.; Kovacheva, N.; Vosman, B.; Zhang, L.; Rajapakse, S.; Atanassov, A.; Atanassov, I. Microsatellite analysis of Rosa damascena Mill. accessions reveals genetic similarity between genotypes used for rose oil production and old Damask rose varieties. Theor. Appl. Genet. 2005 , 111 , 804–809. [ Google Scholar ] [ CrossRef ] Gaurav, A.K.; Namita; Raju, D.V.S.; Ramkumar, M.K.; Singh, M.K.; Singh, B.; Krishnan, S.G.; Panwar, S.; Sevanthi, A.M. Genetic diversity analysis of wild and cultivated Rosa species of India using microsatellite markers and their comparison with morphology based diversity. J. Plant Biochem. Biot. 2022 , 31 , 61–70. [ Google Scholar ] [ CrossRef ] Feng, L.G.; Sheng, L.X.; Shao, D.W.; Tao, J.; Zhao, L.Y. Fluorescent amplified fragment length polymorphism (AFLP) analysis of genetic diversity and relationship of Chinese Rosa rugosa germplasm resources. Afr. J. Biotechnol. 2011 , 10 , 4524–4531. [ Google Scholar ] Panwar, S.; Singh, K.P.; Sonah, H.; Deshmukh, R.K.; Namita; Prasad, K.V.; Sharma, T.R. Molecular fingerprinting and assessment of genetic diversity in rose ( Rosa x hybrida). Indian J. Biotechnol. 2015 , 14 , 518–524. [ Google Scholar ] Tan, J.R.; Wang, J.; Luo, L.; Yu, C.; Xu, T.L.; Wu, Y.Y.; Cheng, T.R.; Wang, J.; Pan, H.T.; Zhang, Q.X. Genetic relationships and evolution of old Chinese garden roses based on SSRs and chromosome diversity. Sci. Rep. 2017 , 7 , 15437. [ Google Scholar ] [ CrossRef ] Aparna, V.; Bhat, K.V.; Janakiram, T.; Prasad, K.V.; Raju, D.V.S.; Sapna, P.; Namitha; Singh, K.P. Assessment of genetic diversity and population structure of fragrant rose ( Rosa x hybrida) cultivars using microsatellite markers. Indian J. Agric. Sci. 2019 , 89 , 212–218. [ Google Scholar ] Scariot, V.; Akkak, A.; Botta, R. Characterization and genetic relationships of wild species and old garden roses based on microsatellite analysis. J. Am. Soc. Hortic. Sci. 2006 , 131 , 66–73. [ Google Scholar ] [ CrossRef ] Xia, A.N.; Yang, A.A.; Meng, X.S.; Dong, G.Z.; Tang, X.J.; Lei, S.M.; Liu, Y.G. Development and application of rose ( Rosa chinensis Jacq.) SNP markers based on SLAF-seq technology. Genet. Resour. Crop. Evol. 2022 , 69 , 173–182. [ Google Scholar ] [ CrossRef ] Li, Y.L.; Ruperao, P.; Batley, J.; Edwards, D.; Martin, W.; Hobson, K.; Sutton, T. Genomic prediction of preliminary yield trials in chickpea: Effect of functional annotation of SNPs and environment. Plant Genome 2022 , 15 , e20166. [ Google Scholar ] [ CrossRef ] Wang, J.D.; Zhang, Z.L.; Gong, Z.L.; Liang, Y.J.; Ai, X.T.; Sang, Z.W.; Guo, J.P.; Li, X.Y.; Zheng, J.Y. Analysis of the genetic structure and diversity of upland cotton groups in different planting areas based on SNP markers. Gene 2022 , 809 , 146042. [ Google Scholar ] [ CrossRef ] Xanthopoulou, A.; Manioudaki, M.; Bazakos, C.; Kissoudis, C.; Farsakoglou, A.M.; Karagiannis, E.; Michailidis, M.; Polychroniadou, C.; Zambounis, A.; Kazantzis, K.; et al. Whole genome re-sequencing of sweet cherry ( Prunus. avium L.) yields insights into genomic diversity of a fruit species. Hortic. Res. 2020 , 7 , 60. [ Google Scholar ] [ CrossRef ] McKenna, A.; Hanna, M.; Banks, E.; Sivachenko, A.; Cibulskis, K.; Kernytsky, A.; Garimella, K.; Altshuler, D.; Gabriel, S.; Daly, M.; et al. The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010 , 20 , 1297–1303. [ Google Scholar ] [ CrossRef ] Cingolani, P.; Platts, A.; Wang, L.L.; Coon, M.; Nguyen, T.; Wang, L.; Land, S.J.; Lu, X.Y.; Ruden, D.M. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w(1118); iso-2; iso-3. Fly 2012 , 6 , 80–92. [ Google Scholar ] [ CrossRef ] Meirmans, P.G.; Van Tienderen, P.H. GENOTYPE and GENODIVE: Two programs for the analysis of genetic diversity of asexual organisms. Mol. Ecol. Notes 2004 , 4 , 792–794. [ Google Scholar ] [ CrossRef ] Graebner, R.C.; Hayes, P.M.; Hagerty, C.H.; Cuesta-Marcos, A. A comparison of polymorphism information content and mean of transformed kinships as criteria for selecting informative subsets of barley ( Hordeum vulgare L. s. l.) from the USDA Barley Core Collection. Genet. Resour. Crop Evol. 2016 , 63 , 477–482. [ Google Scholar ] [ CrossRef ] Alexander, D.H.; Novembre, J.; Lange, K. Fast model-based estimation of ancestry in unrelated individuals. Genome Res. 2009 , 19 , 1655–1664. [ Google Scholar ] [ CrossRef ] Danecek, P.; Auton, A.; Abecasis, G.; Albers, C.A.; Banks, E.; DePristo, M.A.; Handsaker, R.E.; Lunter, G.; Marth, G.T.; Sherry, S.T.; et al. The variant call format and VCFtools. Bioinformatics 2011 , 27 , 2156–2158. [ Google Scholar ] [ CrossRef ] Aflitos, S.; Schijlen, E.; de Jong, H.; de Ridder, D.; Smit, S.; Finkers, R.; Wang, J.; Zhang, G.Y.; Li, N.; Mao, L.K.; et al. Exploring genetic variation in the tomato ( Solanum section Lycopersicon) clade by whole-genome sequencing. Plant J. 2014 , 80 , 136–148. [ Google Scholar ] [ CrossRef ] Li, Y.; Cao, K.; Zhu, G.R.; Fang, W.C.; Chen, C.W.; Wang, X.W.; Zhao, P.; Guo, J.; Ding, T.Y.; Guan, L.P.; et al. Genomic analyses of an extensive collection of wild and cultivated accessions provide new insights into peach breeding history. Genome Biol. 2019 , 20 , 36. [ Google Scholar ] [ CrossRef ] Liang, Z.C.; Duan, S.C.; Sheng, J.; Zhu, S.S.; Ni, X.M.; Shao, J.H.; Liu, C.H.; Nick, P.; Du, F.; Fan, P.G.; et al. Whole-genome resequencing of 472 Vitis accessions for grapevine diversity and demographic history analyses. Nat. Commun. 2019 , 10 , 1190. [ Google Scholar ] [ CrossRef ] Varshney, R.K.; Saxena, R.K.; Upadhyaya, H.D.; Khan, A.W.; Yu, Y.; Kim, C.; Rathore, A.; Kim, D.; Kim, J.; An, S.; et al. Whole-genome resequencing of 292 pigeonpea accessions identifies genomic regions associated with domestication and agronomic traits. Nat. Genet. 2017 , 49 , 1082–1088. [ Google Scholar ] [ CrossRef ] Zhang, Q.X.; Zhang, H.; Sun, L.D.; Fan, G.Y.; Ye, M.X.; Jiang, L.B.; Liu, X.; Ma, K.F.; Shi, C.C.; Bao, F.; et al. The genetic architecture of floral traits in the woody plant Prunus mume . Nat. Commun. 2018 , 9 , 1702. [ Google Scholar ] [ CrossRef ] Sun, M.L.; Zhang, J.; Li, Y.; Lin, G.C. Preliminary study on the phylogenetic relationship of Rosa. rugosa ‘Hetian shamomeigui’. Acta Bot. Boreal. Occident. Sin. 2021 , 41 , 222–233. [ Google Scholar ] Guo, R.H.; Sui, Y.J.; Yang, F.Y.; Liu, H. A new cold-resistant rose cultivar‘Tianshan Xiangyun’. Acta Hortic. Sin. 2011 , 38 , 1417–1418. [ Google Scholar ] [ CrossRef ] Sui, Y.J.; Guo, R.H.; Yang, F.Y.; He, L. Comparative experiment on biological characteristics of cold-resistant rose ‘Tianshan Xiangyun’. Pract. For. Technol. 2012 , 9 , 57–58. [ Google Scholar ] [ CrossRef ] Hirata, H.; Ohnishi, T.; Tomida, K.; Ishida, H.; Kanda, M.; Sakai, M.; Yoshimura, J.; Suzuki, H.; Ishikawa, T.; Dohra, H.; et al. Seasonal induction of alternative principal pathway for rose flower scent. Sci. Rep. 2016 , 6 , 20234. [ Google Scholar ] [ CrossRef ] [ PubMed ] Joichi, A.; Yomogida, K.; Awano, K.; Ueda, Y. Volatile components of tea-scented modern roses and ancient Chinese roses. Flavour Frag. J. 2005 , 20 , 152–157. [ Google Scholar ] [ CrossRef ] Guterman, I.; Shalit, M.; Menda, N.; Piestun, D.; Dafny-Yelin, M.; Shalev, G.; Bar, E.; Davydov, O.; Ovadis, M.; Emanuel, M.; et al. Rose scent: Genomics approach to discovering novel floral fragrance-related genes. Plant Cell 2002 , 14 , 2325–2338. [ Google Scholar ] [ CrossRef ] [ PubMed ] Scalliet, G.; Journot, N.; Jullien, F.; Baudino, S.; Magnard, J.L.; Channelière, S.; Vergne, P.; Dumas, C.; Bendahmane, M.; Cock, J.M.; et al. Biosynthesis of the major scent components 3,5-dimethoxytoluene and 1,3,5-trimethoxybenzene by novel rose O-methyltransferases. FEBS Lett. 2002 , 523 , 113–118. [ Google Scholar ] [ CrossRef ] Sheng, L.; Zang, S.; Wang, J.; Wei, T.; Xu, Y.; Feng, L. Overexpression of a Rosa rugosa Thunb. NUDX gene enhances biosynthesis of scent volatiles in petunia. PeerJ 2021 , 2 , e11098. [ Google Scholar ] [ CrossRef ] Aharoni, A.; Giri, A.P.; Verstappen, F.W.; Bertea, C.M.; Sevenier, R.; Sun, Z.; Jongsma, M.A.; Schwab, W.; Bouwmeester, H.J. Gain and loss of fruit flavor compounds produced by wild and cultivated strawberry species. Plant Cell 2004 , 16 , 3110–3131. [ Google Scholar ] [ CrossRef ] Zhou, L.J.; Yu, C.; Cheng, B.X.; Han, Y.; Luo, L.; Pan, H.T.; Zhang, Q.X. Studies on the volatile compounds in flower extracts of Rosa odorata and R. chinensis . Ind. Crop Prod. 2020 , 146 , 112143. [ Google Scholar ] [ CrossRef ] Magnard, J.L.; Roccia, A.; Caissard, J.C.; Vergne, P.; Sun, P.L.; Hecquet, R.; Dubois, A.; Hibrand-Saint Oyant, L.; Jullien, F.; Nicole, F.; et al. Biosynthesis of monoterpene scent compounds in roses. Science 2015 , 349 , 81–83. [ Google Scholar ] [ CrossRef ] Spiller, M.; Berger, R.G.; Debener, T. Genetic dissection of scent metabolic profiles in diploid rose populations. Theor. Appl. Genet. 2010 , 120 , 1461–1471. [ Google Scholar ] [ CrossRef ] Croteau, R.; Karp, F. Origin of Natural Odorants. In Perfume: Art, Science and Technology ; Muller, P., Lamparsky, D., Eds.; Elsevier Applied Sciences: New York, NY, USA, 1991; pp. 101–126. [ Google Scholar ] Figure 1. The phylogenetic relationship of rose cultivars using SNP markers. The bootstrap values are indicated with bubbles. The classification of floral scent is highlighted with a background color, where pink, purple, and green represent a strong-scent rose, a moderate-scent rose, and a low-scent rose, respectively. The geographic origin of each rose is indicated with a colored star, with a green star for Europe, a red star for China, a blue star for western Asia, a purple star for North America, a yellow star for Australia, and a grey star for cultivars of unknown origin. Figure 1. The phylogenetic relationship of rose cultivars using SNP markers. The bootstrap values are indicated with bubbles. The classification of floral scent is highlighted with a background color, where pink, purple, and green represent a strong-scent rose, a moderate-scent rose, and a low-scent rose, respectively. The geographic origin of each rose is indicated with a colored star, with a green star for Europe, a red star for China, a blue star for western Asia, a purple star for North America, a yellow star for Australia, and a grey star for cultivars of unknown origin. Figure 2. Genetic clustering and differentiation of rose cultivars using SNPs. ( A ) Cluster assignments for K = 2–9 estimated in the admixture. Each bar represents one rose accession, and the colors represent the partitioning of the sample in each group. ( B ) Cross-validation test values for a different number of clusters (K). Figure 2. Genetic clustering and differentiation of rose cultivars using SNPs. ( A ) Cluster assignments for K = 2–9 estimated in the admixture. Each bar represents one rose accession, and the colors represent the partitioning of the sample in each group. ( B ) Cross-validation test values for a different number of clusters (K). Figure 3. Selective sweep analysis between the strong/moderate-scent rose group (moderate-scent rose group as control) to detect selection signatures in strong-scent roses. ( A ) Genomic regions with strong selective signals in strong-scent rose groups. Distribution of F ST values calculated in 10 kb sliding windows with 100 kb increments. A red line indicates the top 1% of F ST distributions and a blue line indicates the top 5% of F ST . ( B ) KEGG enrichment of candidate genes between strong- and moderate-scent roses. The enriched pathways are listed on the left. Colors denote the p -value. The size of each bubble reflects the genes enriched in each pathway. Figure 3. Selective sweep analysis between the strong/moderate-scent rose group (moderate-scent rose group as control) to detect selection signatures in strong-scent roses. ( A ) Genomic regions with strong selective signals in strong-scent rose groups. Distribution of F ST values calculated in 10 kb sliding windows with 100 kb increments. A red line indicates the top 1% of F ST distributions and a blue line indicates the top 5% of F ST . ( B ) KEGG enrichment of candidate genes between strong- and moderate-scent roses. The enriched pathways are listed on the left. Colors denote the p -value. The size of each bubble reflects the genes enriched in each pathway. Figure 4. Selective sweep analysis between strong/low-scent rose groups (low-scent rose group as control) for the detection of selection signatures in strong scent roses. ( A ) Genomic regions with strong selective signals in strong-scent rose groups. Distribution of F ST values calculated in 10 kb sliding windows with 100 kb increments. The red line indicates the top 1% of F ST distributions and the blue line indicates the top 5% of F ST . ( B ) KEGG enrichment of candidate genes between strong- and low-scent roses. The enriched pathways are listed on the left. The colors denote the p -value. The size of each bubble reflects the genes enriched in each pathway. Table 1. Genome-wide variations identified in rose cultivars. Table 1. Genome-wide variations identified in rose cultivars. No. Cultivar Name SNPs Indels Total Intron Intergenic CDS Total Intron Intergenic CDS Total Syn nSyn Total Fram shf Inser Del 1 Rosa ‘Ivor’s Rose’ 1,307,661 180,871 357,630 182,001 99,076 80,251 432,255 78,418 97,408 16,497 10,600 1700 1871 2 Rosa ‘Aladdin’ 1,258,866 180,125 338,831 181,433 98,846 80,034 426,430 79,445 94,316 16,092 10,281 1663 1846 3 Rosa ‘Andelie’ 1,238,244 176,240 332,253 176,035 95,560 77,895 406,270 75,078 89,911 15,188 9746 1543 1743 4 Rosa ‘Angela’ 1,257,173 175,758 335,130 174,741 95,036 77,153 421,227 76,141 93,052 15,838 10,203 1599 1783 5 Rosa ‘Babe’ 1,254,028 179,014 335,073 179,772 97,829 79,282 423,004 78,533 93,541 15,850 10,159 1589 1863 6 Rosa banksiae var. banksiae 1,220,569 174,592 329,302 174,754 95,366 76,933 414,672 77,310 90,923 15,299 9816 1587 1742 7 Rosa ‘White Meillandina’ 1,455,802 203,664 398,167 196,823 106,727 87,123 492,826 89,670 110,284 17,921 11,570 1842 1987 8 Rosa damascena 1# 1,205,798 195,841 277,211 207,499 115,377 89,717 464,886 94,570 91,042 18,232 10,769 2322 2232 9 Rosa ‘Bingquanzhilian’ 1,441,849 202,641 396,580 206,134 111,911 91,262 498,437 91,813 111,189 18,789 11,987 1945 2161 10 Rosa ‘Iceberg’ 1,150,678 164,959 308,738 161,747 87,691 71,697 384,451 71,389 85,039 14,195 9255 1403 1595 11 Rosa ‘Chariot’ 1,175,700 161,796 321,378 148,441 80,045 66,107 383,316 67,533 88,729 13,355 8793 1240 1433 12 Rosa damascena 1,378,891 227,181 319,849 223,694 122,895 97,995 491,676 101,853 96,408 18,680 11,520 2177 2178 13 Rosa ‘Parade’ 1,344,859 188,306 365,677 188,834 102,472 83,572 451,013 82,178 101,481 16,946 10,762 1743 1981 14 Rosa ‘Dianhong’ 1,166,345 189,101 265,223 197,509 108,265 86,622 422,900 85,354 83,559 16,972 10,572 1902 2001 15 Rosa ‘Fanghua’ 1,385,662 200,772 368,013 208,754 114,794 91,101 474,764 90,202 104,295 18,452 11,544 1952 2225 16 Rosa rugosa ‘Fenghua’ 1,036,722 193,705 185,729 210,005 117,634 90,101 445,558 97,471 75,110 19,263 11,253 2566 2404 17 Rosa ‘Licorice Tea’ 1,136,549 157,251 304,052 155,326 84,152 68,800 382,582 67,155 86,877 14,304 9338 1375 1579 18 Rosa ‘Pretty Princess’ 1,328,390 186,719 360,616 187,256 101,600 82,930 449,565 82,503 100,220 16,832 10,697 1770 1958 19 Rosa ‘Spectra’ 1,261,911 183,116 337,586 182,115 99,394 80,141 431,660 81,625 94,174 16,135 10,180 1708 1909 20 Rosa ‘Hetianshamomeigui’ 1,454,887 243,654 316,090 259,965 142,942 113,845 527,405 110,790 99,509 21,811 13,210 2655 2635 21 Rosa ‘Double Delight’ 1,239,876 180,066 330,655 183,079 100,121 80,494 428,276 81,224 93,457 16,176 10,189 1697 1917 22 Rosa ‘Jinbian’ 1,389,521 195,333 374,772 188,660 102,115 83,692 462,745 84,153 103,774 16,969 11,023 1634 1875 23 Rosa ‘Jinhui’ 1,324,109 190,429 358,251 189,323 102,942 83,662 459,353 85,871 102,782 17,380 11,042 1831 2011 24 Rosa ‘Goldmarie’ 1,326,837 195,795 345,111 197,351 108,275 86,314 452,378 87,105 96,942 17,176 10,902 1825 2028 25 Rosa ‘Mascotte’77’ 1,348,336 194,927 360,430 192,203 104,895 84,567 469,425 88,000 103,508 17,083 10,924 1752 1948 26 Rosa ‘Carola’ 1,398,326 199,214 377,170 199,483 108,226 88,377 493,427 90,848 109,282 18,349 11,546 1975 2153 27 Rosa ‘The Generous Gardener’ 1,344,478 189,502 364,040 195,627 106,455 86,312 450,824 83,304 100,009 17,523 11,182 1830 1995 28 Rosa sertata × rugosa 1,188,949 161,730 324,249 157,584 85,441 69,747 387,032 67,988 89,546 14,294 9370 1331 1601 29 Rosa ‘Blue Ribbon’ 1,186,726 167,403 323,515 168,171 91,118 74,532 401,344 73,976 89,491 15,054 9627 1535 1700 30 Rosa ‘Pink O’Hara’ 1,404,933 194,208 394,423 196,383 106,505 87,051 481,736 87,461 110,301 18,279 11,676 1871 2126 31 Rosa ‘Crimson Glory’ 1# 1,254,209 179,744 336,313 187,844 102,570 82,607 434,239 81,397 95,052 16,944 10,652 1889 1989 32 Rosa ‘South Seas’ 1,382,117 205,619 357,989 216,528 120,033 93,629 480,145 93,954 102,703 18,772 11,718 2049 2217 33 Rosa ‘Pengpeng’ 1,299,944 187,800 339,374 192,,915 105,863 84,373 445,309 83,736 96,607 17,124 10,804 1812 1963 34 Rosa rugosa ‘Pingyin 1’ 1,068,091 196,673 193,577 216,731 121,157 93,214 459,201 99,406 78,383 20,376 11,877 2717 2526 35 Rosa centifolia ‘Grasse Rose’ 1,557,369 248,092 363,014 264,223 145,427 115,496 556,043 113,146 109,083 22,693 13,764 2729 2727 36 Rosa ‘Sijifen’ 1,186,996 164,523 327,305 163,319 88,240 72,660 400,260 72,294 90,652 14,989 9652 1532 1691 37 Rosa ‘Suji’ 1,374,657 195,871 369,643 192,156 104,278 85,114 475,784 87,848 105,439 17,346 11,124 1736 1991 38 Rosa ‘Tineke’ 1,159,157 210,645 217,998 228,676 127,223 98,869 493,822 105,818 86,588 21,299 12,533 2800 2607 39 Rosa ‘Meilivoine’ 1,362,014 188,865 369,434 185,994 100,914 82,312 435,751 78,230 98,335 16,317 10,501 1656 1865 40 Rosa cv. Climbers 1 1,394,736 201,047 379,712 188,753 102,074 83,893 480,969 89,538 106,393 16,925 10,894 1738 1911 41 Rosa ‘Sweet Chariot’ 1,265,480 171,094 349,046 166,832 90,227 73,989 420,677 73,409 97,160 15,370 10,085 1453 1680 42 R. laxa × hybrida cv. Tianshan Xiaguang 1,347,767 217,477 325,469 206,677 113,906 90,101 492,222 99,670 98,901 17,269 10,723 1960 2053 43 R. laxa × hybrida cv. Tianshan Xiangyun 1,403,917 217,849 346,639 224,597 123,844 97,794 505,945 101,081 104,130 19,579 11,928 2355 2316 44 Rosa ‘Smooth sunglow’ 1,254,136 181,357 330,425 186,622 101,992 81,998 437,988 82,501 95,271 16,695 10,498 1799 1966 45 Rosa ‘Xinba’ 1,343,121 195,384 355,231 194,716 106,549 85,364 459,931 86,611 101,426 17,221 10,929 1798 1964 46 Rosa ‘Betty Prior’ 1,191,623 171,810 310,885 172,337 93,700 76,147 409,689 75,962 89,231 15,646 9935 1611 1808 47 Rosa ‘Yuki Akari’ 1,249,571 171,664 337,954 166,173 89,677 73,898 408,318 71,764 94,283 14,985 9841 1430 1580 48 Rosa ‘Lavender Bouquet’ 1,185,191 160,931 324,550 155,339 84,065 68,890 385,486 67,797 89,399 13,992 9174 1300 1578 49 Rosa ‘Movie Star’ 1,244,338 180,865 329,689 179,963 97,636 79,745 435,785 81,799 95,067 16,230 10,287 1697 1890 50 Rosa ‘Yueyuehong’ 890,350 127,942 230,090 127,109 69,364 55,876 312,153 55,733 70,197 11,356 7374 1107 1305 51 Rosa ‘Yuncaihong’ 1,151,872 161,160 314,582 157,107 84,982 69,829 389,439 70,746 87,469 14,401 9269 1445 1635 52 Rosa ‘Yuncaixia’ 1,329,661 191,778 350,676 191,567 104,654 84,102 450,467 84,498 97,805 16,986 10,882 1755 1988 53 Rosa ‘Yunxiang’ 1,338,109 196,573 350,437 199,055 108,426 87,843 474,464 90,366 102,291 18,103 11,379 1956 2073 54 Rosa ‘Parkdirektor Riggers’ 1,442,596 209,991 380,201 200,675 108,729 88,996 504,133 94,083 108,625 18,112 11,620 1863 2030 55 Rosa ‘Crimson Glory’ 2# 1,177,506 170,541 312,935 174,296 95,016 76,801 408,205 76,593 90,015 15,600 9887 1682 1795 56 Rosa ‘Roger Lambelin’ 1,217,137 186,897 296,511 195,810 106,976 86,184 447,586 86,031 94,942 17,902 11,291 1959 2084 57 Rosa rugosa ‘Zizhi’ 1,033,306 193,036 187,447 210,695 117,920 90,469 433,119 95,623 73,890 18,770 10,960 2505 2349 58 Rosa laxa 1,052,914 190,259 195,950 211,707 118,848 90,638 439,522 94,254 77,090 19,018 11,129 2538 2362 Syn: Synonymous; nSyn: NonSynonymous. Inser: Insertion; Del: Deletion; Fram shf: Frame shift. Table 2. The diversity index of roses in each scent group. Table 2. The diversity index of roses in each scent group. Group Strong Scent Moderate Scent Low Scent Nei 0.27 0.261 0.255 Ho 0.219 0.223 0.223 PIC 0.216 0.212 0.208 H 0.411 0.405 0.397 Nei: Nei diversity index; Np: Number of polymorphic markers; Ho: Observed heterozygosity; PIC: Polymorphism information content; H: Shannon Wiener index. AMA Style Sun M, Ren X, Liu Y, Yang J, Hui J, Zhang Y, Cui Y, Zhang J, Lin G, Li Y. Genetic Structure and Selection Signature in Flora Scent of Roses by Whole Genome Re-Sequencing. Diversity. 2023; 15(6):701. https://doi.org/10.3390/d15060701 Chicago/Turabian Style Sun, Meile, Xiangrong Ren, Ya Liu, Jing Yang, Jingtao Hui, Yukun Zhang, Yanhua Cui, Jun Zhang, Guocang Lin, and Yan Li. 2023. "Genetic Structure and Selection Signature in Flora Scent of Roses by Whole Genome Re-Sequencing" Diversity15, no. 6: 701. https://doi.org/10.3390/d15060701
https://www.mdpi.com/1424-2818/15/6/701
Fireman John Patrick Hastings Mercantile Marine. Died Friday 7 May 1915 - A Street Near You First World War casualty details for Fireman John Patrick Hastings Mercantile Marine. Date of death Friday 7 May 1915 (aged 40) Mercantile Marine Died: Friday 7 May 1915 (aged 40) + − Data, image and map credits Connected records Lives of the First World War No matching Life Story found Commonwealth War Graves Commission Record: HASTINGS, JOHN PATRICK Additional information: (Served as HESTON). Son of the late Michael and Mary Hastings. Born at Liverpool. Cemetery: TOWER HILL MEMORIAL Cemetery/memorial reference: Country: United Kingdom Additional links Every One Remembered - record for Fireman John Patrick Hastings Records from this Royal British Legion centenary project may include personal stories and, occassionally, images Know of other online sources, including stories and images, connected to this person? Submit additional links Possible matches The following sources have potential matches based on the name and other information associated with this record. They may or may not be connected to this person but are provided for your further research Similar records to Fireman John Patrick Hastings Mercantile Marine. Died Friday 7 May 1915 Trimmer George James Hamel Mercantile Marine Date of death: 07/05/1915 (aged 30) Cemetery: TOWER HILL MEMORIAL Son of Peter and Frances Hamel; husband of Elizabeth Ann Hamel (nee Welch), of 97, Claudin St., Walton, Lancs. Born at Liverpool. Died on the same day Served in the same regiment/ship/squadron Buried/commemorated in the same cemetery Personal information shows the same location (house, school, village etc) Trimmer Joseph Edward Tear Mercantile Marine Date of death: 07/05/1915 (aged 23) Cemetery: TOWER HILL MEMORIAL Son of John and Mary Ann Tear; husband of Sarah Ellen Tear (nee Powell), of 8, Upper Roscommon St., Liverpool. Born in Liverpool. Died on the same day Served in the same regiment/ship/squadron Buried/commemorated in the same cemetery Personal information shows the same location (house, school, village etc) Mess Room Steward James Andrew Johnstone Mercantile Marine Date of death: 07/05/1915 (aged 23) Cemetery: TOWER HILL MEMORIAL Son of James and Mary Frances Johnstone, of 96, Church Rd., Stanley, Liverpool. Born at Liverpool. Died on the same day Served in the same regiment/ship/squadron Buried/commemorated in the same cemetery Personal information shows the same location (house, school, village etc) × About this map Continue Latest update This site was created in November 2018. In its first three days it saw over 240,000 visits, and to date has had over one million visitors. Read more about how it was created and its subsequent success . Previously I posted an appeal for additional funds to cover hosting costs and I am hugely grateful to those who donated. If you want to contribute to the ongoing running of the site, I am of course happy to take donations towards the cost ! About Whilst this personal project started simply as an experiment to explore the local legacy of the First World War, but at a global scale, it has struck me that it is much more than that. At the heart of it is the legacy of those who died in the conflict, and especially the scale of the imapct that that would have had on their local communities, it would also never have been possible without the significant legacy created by those who remained, from the families who sent in photographs of their loved ones and which formed the Imperial War Museum's founding Bond of Sacrifice Collection, through the people who diligently compiled official records in the early 1920s and which formed the Commonwealth War Graves Commission's records, right up to the modern-day professionals, volounteers and individuals who have shaped these records, shared them, and also significantly increased and enriched them, especially under the guise of First World War Centenary projects like Lives of the First World War Data and Sources This project currently contains records for over one million men and women who died whilst serving in the First World War, with over 600,000 locations worldwide, tens of thousands of images, cemeteries, war memorials and much more. It simply wouldn't exist without the core assets that it draws on, enriched by additional information from and links to countless further sources. Core data sources - personal records and images Lives of the First World War - IWM's unique project enabling everyone to share their information, stories and images to compile Life Stories "on nearly 8 million men and women who served in uniform and worked on the home front". Commonwealth War Graves Commission - a unique online collection of the details of every serviceman or woman. Many of the locations here are extracted from what they call the 'Additional information' field, which typically contains text such as "Son of Samuel and Sarah Morley, of Derby; husband of F. M. Morley, of 113, Peel St., Ashbourne Rd., Derby.". Note that this information was collected sevral years after the end of the war and it does not necessarily represent an address that the person had lived at. Imperial War Museums Collections - one of the richest collections of First World War objects and images, most notably in this context the Bond of Sacrifice Collection and the Women's War Work Collection, togther comprising images of nearly 20,000 individuals who served Core data sources - war memorials War Memorial Register - another unique record set from the Imperial War Museum, comprising records of over 78,000 memorials in the British Isles, together with listings of over one million names that appear on them. Places of Pride, the National Register of War Memorials (Australia) - over 1,000 records from across Australia, almost all having photographs and additional information New South Wales War Memorials Register - The register includes over 3,500 memorials in total, with over 2,000 relating to the First World War. Each record has additional information and most have images. Many include lists of those commemorated New Zealand Memorials Register - over 1,000 records from across New Zealand, typically with photographs and additional information Core data sources - portraits With specific regards to the portrait images, these are primarliy, but not exclusively, from one of three sources - the incredible Bond of Sacrifice Collection, the Women's War Work Collection (both Imperial War Museums), or uploaded by volunteers and individuals to the Lives of the First World War site (which itself is run by IWM). I am grateful to them for making all these available under a non-commercial license. As an example of an additional image source, the Royal Welch Fusiliers Museum has provided over 2,000 portraits under an open license. Additional information and statistics on the depth and breadth of sources Additional credits - software and mapping resources Map tiles by Stamen Design , under CC BY 3.0 . Data by OpenStreetMap , under ODbL . Leaflet , the powerful open-source JavaScript library for mobile-friendly interactive maps. Contributing records, reporting errors The data currently presented has all been extracted from official records or from user contributions to the Lives of the First World War site. I would strongly encourage anyone who wants to add further details to find the Life Story of the person and add details there, which can then in future be added to this site The inherrent nature of historic records and using modern automated tools to extract information means there are bound to be issues. I will shortly be adding a 'report error' link to each record that can be used to flag an issue and will be queued up ready to be investigated and fixed. I'm afraid as this is a personal project created in my own time, I cannot respond to individual requests right now. Contact For information, questions and bug reports please contact James Morley @astreetnearyou | [email protected] Close × Share Link to this page: Close × Submit a link to add to this profile Note that all submissions must include a link to a public web page. This is because A Street Near You aggregates and makes discoverable hundreds of thousands of online resources relating to those who died in the First World War, but as a personal project with no funding it cannot provide facilities for the upload of images or additional contributions. If the information you want to include is not currently online you can use external services like Medium, Flickr, Twitter etc. Alternatively contact somewhere like a local history society or set up a Wordpress blog Link Enter a full link for a public webpage e.g. https://www.flickr.com/photos/whatsthatpicture/albums/72157686638320212 Description Enter a short text description that will be displayed as the link on this profile e.g. Portrait of Private John Smith from a family photo album Notes Please add any further notes to support the submission, especially the evidence you have to connect the link to this person. These details will not be published. Image Please check this box if the page submitted contains an image that can be displayed on the profile and map Location Please check this box if the page submitted contains location details that can be displayed on the map Your email Not required, and will never be published or shared, but if you add this we will endeavour to let you know when your submission is published Close
https://astreetnearyou.org/person/2975754/Fireman-John-Patrick--Hastings
An Ecclesiology of Eschatological Accountability | Request PDF Request PDF | An Ecclesiology of Eschatological Accountability | This chapter argues that Amplify’s past, present and future must not be simplistically understood as discrete and mutually exclusive, but as... | Find, read and cite all the research you need on ResearchGate An Ecclesiology of Eschatological Accountability June 2021 DOI: 10.1007/978-3-030-73314-8_5 In book: Doing Church at the Amplify Open and Affirming Conferences (pp.119-147) Authors: <here is a image dc56185b1a458256-a8f22c970f217671> Joseph N. Goh Monash University (Malaysia) Abstract This chapter argues that Amplify’s past, present and future must not be simplistically understood as discrete and mutually exclusive, but as overlapping, mutually informative and symbiotically enriching realities. Similarly, its strengths, weaknesses and projections need to be understood in terms of contiguous spaces that open up more spaces of hope and imagination for doing church at Amplify and beyond. Goh conscripts eschatological formulations by progressive theologians Elizabeth Stuart and Catherine Keller, and public theologian Felix Wilfred’s ideas on ethical auditing to propose that Amplify’s ecclesiology of eschatological accountability is concerned with matters of its impact and sustainability, the interplay between the emotional, intellectual and practical aspects of the Conferences, and a wider spectrum of human representation and participation. <here is a image 175d1bd4b7439d95-754927124da715c1> Living and Loving in Diversity: Australian Multicultural Queer Adventures Book Full-text available Sep 2018 <here is a image 22d77c92414a7207-3d63b71720c3e600> Maria Pallotta-Chiarolli Sad and funny, sexy and sensitive, angry and insightful: the deeply personal stories in this book reflect a rainbow of experiences and emotions, as diverse as the storytellers themselves. Join chief editor Maria Pallotta-Chiarolli and the Australian LGBTIQ Multicultural Council for a journey of discovery through queer multicultural multifaith Australia, with more than sixty voices from across the spectrum of sexualities and genders, families and relationships. Annette Xiberras, lesbian Wurundjeri Elder with a Maltese father, provides a Welcome to Book and insights into her Indigenous-migrant family. Filmmakers Tony Ayres and Franco Di Chiera share their experiences telling stories from minority cultures on Australian screens, while Benjamin Law talks queer Asian-Australian identity, and making The Family Law for SBS. Broadcaster Faustina Agolley talks about being ‘out’ as a woman of colour, and Anton Enus tells us about coming out as a ‘coloured’ gay man in South Africa. Entertainer Paul Capsis reflects on doing Cabaret in the age of Trump while Asiel Adan talks about non-binary gender across the US border in Mexico. Meanwhile, Christos Tsiolkas imagines Ari, the protagonist of his iconic novel Loaded, now middle-aged, during a weekend of mass violence in distant Paris, while Patrick Abboud travels the world so he can come home. Alyena Mohummadally searches for reconciliation between her queer and Muslim identities and Tony Briffa shares a personal story of growing up with intersex variations and the rigidity of Western medicine. Queer conversations: Old-time lesbians, transmen and the politics of research Chapter Full-text available Jan 2010 Catherine Jean Nash Still ‘breadwinners’ and ‘providers’: Singaporean husbands, money and masculinity in transnational marriages Article Full-text available Oct 2014 <here is a image d880522a5559f4b9-d57515ba246a76db> Yi'En Cheng Brenda S. A. Yeoh <here is a image 5d1432851a65bec7-2c48ff483d332f50> Juan Zhang As international marriages continue to be on the rise around the world, and in East and Southeast Asia in particular, there is an increasing need for more focused studies on the phenomenon. While the extant literature has paid attention to the complex dynamics of marital intimacies through a ‘gender-sensitive’ lens, the experiences of men are still largely under-examined. This article considers the gendered and classed subjectivities of Singaporean husbands who have married Vietnamese wives and focuses on ‘money’ as a key vehicle through which the men are able to construct masculinities in the spaces of transnational marriage and family. We argue that these non-migrant men engage with transnational processes and practices strategically in order to reclaim respectable and honourable masculine status. In doing so, they dislodge themselves from the idiom of ‘failed masculinity’ commonly ascribed to men who seek foreign spouses, but at the same time reproduce dominant models of masculinity predicated on ‘breadwinning’ and ‘providing’. This article draws on the narratives of 20 Singaporean Chinese men from a range of social backgrounds to demonstrate the endurance of money and economic potency in the performance of masculinities. A Narratology of Lesbian, Gay, Bisexual, and Transgender Clients’ Experiences Addressing Religious and Spiritual Issues in Counseling Article Full-text available Jul 2011 Juleen K. Buser <here is a image 97de08fdba8eb8a6-cb0dfe7f5f110236> Kristopher Michael Goodrich <here is a image a5b990ecdaa52122-0fd2d5c1ff2a5089> Melissa Luke Trevor J. Buser Although spiritual and religious themes have been found to be salient for lesbian, gay, bisexual, transgender (LGBT) individuals, a paucity of research has explored how these themes are attended to in the counseling context. This qualitative investigation used a narratology approach to explore the counseling experiences of seven LGBT clients around spiritual and religious issues. The narrative which emerged included (a) negative counseling experiences, (b) client perseverance in locating additional counseling, (c) positive counseling experiences, and (d) a reframing of counselor responsibility. The results of this study contain implications for future research, clinical practice, and counselor training. A question of burnout among Reformed Church ministers in The Netherlands Article Full-text available Oct 2004 <here is a image a6e1daab0eb23241-810d3103097f6f1b> Welko Tomic David M. Tomic Will Evers The present study examined to which degree reformed ministers suffer from burnout symptoms, to which degree these symptoms are comparable with other occupational groups and which organizational and personal traits like extroversion and emotional stability, increase the risk of falling victim to burnout. Ministers (n ¼ 424; 83% men, 17% women) completed the following questionnaires: a work-factor questionnaire, the Maslach Burnout Inventory, and the extroversion and emotional stability Personality Inventory. Ministers of the Dutch Reformed Church had identical scores on the three burnout dimensions as their reformed counterparts, a more doctrinal denomination. Compared with workers in other human service professions, ministers scored lower on the three burnout dimensions. Ministers who seriously suffered from pressure of work had high scores on the three dimensions of burnout. Young ministers proved to be more susceptible to burnout than their older counterparts. Gender did not contribute to the onset of burnout. However, lack of social support at home, satisfaction, and motivation may have influenced the ministers' burnout level. Personality factors, such as extroversion and emotional stability, appeared to be significantly related to burnout. Tasks found to be weighty were: to conduct a service and to prepare sermon, pastoral care, administration or managerial and organizational tasks, catechism and meetings. Suggestions for future investigations were made. The Queer Art of Failure Book Sep 2011 Judith Halberstam Queer Culture and Sexuality as a Virtue of Hospitality Chapter Jul 2019 Nancy L. Wilson An Ecclesiological Praxis of Inclusivity toward Sexual Diversity and HIV: Learning from Singapore and the Philippines Article Training and development Challenges of strategy and managing performance in Jordanian banking Purpose – The purpose of this paper is to explore the relationship between organizational strategy, performance management and training and development in the context of the Jordanian banking sector. Design/methodology/approach – Models of strategic human resource management developed in the west are considered for their relevance in Jordan. A mixed methods approach is adopted employing interviews with senior managers and training and development managers, employee questionnaires and documentary analysis. It examines all banks in Jordan including foreign and Islamic banks. Findings – Findings indicate that training and development is not driven by human resource strategy and that it is reactive rather than proactive. Training and development does improve skills, knowledge, attitudes and behaviors but there is little evidence that it increases commitment and satisfaction nor that it contributes to strategic aims in any significant way. The linkages between strategy and training and development are not explicit and strategies are not interpreted through performance management systems. Consequently there is a lack of integration in organizational HR systems and the measurable contribution of training and development to competitive advantage is minimal Practical implications – The paper offers suggestions as to how greater integration between strategy, performance management and training and development might be achieved in the Jordanian context. Originality/value – This paper is the first detailed empirical study of training and development in Jordan to include considerations of transferability of western models to an Arab culture. Keywords Performance management, Culture, Jordan, Training and development, HRD strategy Liberation theology in Asia The Asian context: Liberation theology differs from other theologies in that it starts with an analysis of the context, as it wants to respond to the cries of the people arising from it. As contextual theology we can distinguish it by regions - Latin American, African, Asian, European - and by social groups such as the poor, women, blacks, Dalits, indigenous peoples. However, none of these social or geographical identities can be understood in isolation. Contexts and identities are multiple and overlapping. The realities of class, caste, patriarchy and ethnicity, and of local, regional and global economy are intertwined. A Dalit girl working in a factory in an export-processing zone in India is exploited as an underpaid worker - like other workers around the globe - and suffers from a lack of protection by trade-union rights, while as a woman she suffers from male domination and violence - as other women do - whereas she shares her plight as an 'untouchable' suffering from caste oppression with other outcastes, male and female, in India. What is specific about Asia, especially in contrast with Latin America, is the religio-cultural context. The overwhelming majority of the poor and oppressed in Asia are non-Christians, many of whom adhere to a wide variety of popular religious traditions which are more or less connected with the traditions of the great religions which have shaped dominant Asian cultures. Yet within Asia there are again tremendous differences. Latin America is, compared to Asia, a relatively homogeneous continent in terms of history, language, economic and political developments. Asia has to be subdivided into various regions with different cultural, religious, political and economic histories. Confucian familism and its social/religious embodiment in Christianity: Reconsidering the family discourse from a feminist perspective Transnational lesbian identities: Lessons from Singapore? Lesbians in Asia have come under scholarly attention within the study of nonnormative sexualities. This is due to the theoretical insistence on including accounts of non-Western sexualities and sexual identities that disrupt hegemonic Western practices and meanings as embodied by the globalised lesbian and gay subject. Understandings of sexuality, as this claim goes, have been dominated by Anglo-American images of the 'out' gay person with a fixed and unitary identity who has access to particular sexual rights and freedoms. This conception casts sexuality as an autonomous and anterior aspect of identity, and at the same time, elides the different meanings and expectations placed on sexuality in other contexts. As and where alternative conceptions of what it means to be lesbian and gay emerge, these are indexed against a Western developmental teleology that renders these sexual variations as 'premodern', 'inauthentic', 'not legitimate' or simply 'not lesbian and gay enough', much to the chagrin of Western and non-Western scholars studying sexualities outside the West. Ethnographic studies of female same-sex relations have appeared across Asia, complicating and contributing to this core debate in sexuality studies. These include monographs on female non-normative sexual identities and practices in Japan, India, Indonesia, Hong Kong, Thailand and Taiwan.2 Further exemplary research focusing on lesbians in Asian contexts can be found in Wieringa, Blackwood and Bhaiya's (2007) collection, as well as Khor and Kamano's (2006) edited volume. These works attest to the burgeoning intellectual interest in Asian women's non-normative sexualities. Spiritually Oriented Christian (Pastoral) Counseling: An Integrative Encounter between Western Spirituality and Eastern Orthodox Spirituality Unclean and Compassionate Hand of God The transfer of training and development practices in Japanese subsidiaries in Vietnam <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Anne Vo This paper examines the interaction between ‘home-country’ and ‘host-country’ effects in determining human resource management (HRM) policies and practices in multinational companies (MNCs) in the context of a developing country. The paper is based on an investigation of the training and development strategies for local managers of a sample of Japanese companies operating in Vietnam, and presents clear evidence of the transfer of home-country practices. The sector emerges as a key variable in explaining variations in HRM patterns with a greater number of comprehensive training and development programs recorded in automotive than in fast-moving consumer goods (FMCG) industries. We also argue that developing host countries pose little in the way of formal constraint mechanisms to the transfer of HRM practices, but the instability of the institutional environment and the weakness of its subsystems suggest a complex and challenging situation for MNC operations, and inhibit their ability to maintain their home-country HRM practices. Getting to Zero Embracing Science, Breaking the Silence, and Overcoming Stigma GOD'S MISSION AND HIV/AIDS: SHAPING THE CHURCHES' RESPONSE Gay Asian Masculinities and Christian Theologies Church Renewal by Church Planting: The Significance of Church Planting for the Future of Christianity in Europe The current secularization of Europe faces churches with two challenges: poor contextualization and a lack of credibility. It is clear that innovation is needed to answer these challenges. Planting new churches, instead of being a rapid way to numerical growth (which it is not, at least not in Europe), can become a road to this innovation. This is an important reason to plant churches, apart from other, ecclesiological, and missiological reasons. Church plants are ecclesial laboratories: free havens for missiological experiments. This thesis is defended with an appeal to innovation theory, with historical examples, and with some promising recent developments in one of the most secular countries in Europe: the Netherlands. Reclaiming the Body for Faith This essay examines what it means to be embodied members of the Body of Christ, exploring the metaphor in 1 Corinthians 12:12–27 in terms of gender, race/ethnicity, variant embodiment, abused bodies, and sexual bodies. Insiders, outsiders, advocates and apostates and the religions they study: Location and the sociology of religion Awareness of how researchers’ locations and sympathies influence their research agendas and outcomes has long been a topic for methodological consideration. This article complicates that question by considering the position of the researcher in relation to the position in society of the religions researched, and asks whether what we understand as constituting criticism or advocacy varies depending on whether the religions in question are powerful, dominating traditions or small, new, and/or beleaguered traditions. The Locations Matrix is an application of the insights of standpoint analysis to the question of critical research in the sociology of religion. Researchers’ own locations—as an insider, an outsider, an apostate and/or an advocate—have consequences for the questions they ask, and to whom they address them, as well as how they interpret the data they collect. This article pushes scholars of religion to reflect on the significance of their own location in relation to the location of the religion they study. 'Straight Problems': The Sacralization of Homophobia, Women's Sexuality, Lesbian Invisibility and the British Church
https://www.researchgate.net/publication/352097880_An_Ecclesiology_of_Eschatological_Accountability
Releasing the body to spouse - Pet forum for dogs cats and humans - Pets.ca Releasing the body to spouse Off topic forum # 1 July 9th, 2007, 07:50 PM Lukka'sma Remembering Lukka Join Date: Sep 2006 Location: London Ontario Posts: 2,231 Releasing the body to spouse At work we have a husband of a patient that has refused to pay the high price of a funeral for his dying wife. His wife is palliative and he has made arrangements with our Director of Care to have the body released to him rather than the funeral home. He will then transport the body himself to the crematorium. A service will be held at his church at a very low cost to him. No casket but from what he has explained a box of sorts. I just can't picture this fellow in his 80's loading his wife into his van at the side door and heading off to take care of business. If nothing else I would have thought that there would be some health regulations that say we cannot drive around town with a corpse in the back of our cars. And I am by no means trying to make light of this, I just think it seems so strange on many levels. But who knows, maybe more and more people will get tired of paying thousands to these funeral homes and start doing this too. This request is a new one for me, and I have said goodbye to countless patients over the years but have never had the family take the body and dispose of it before # 2 July 9th, 2007, 07:58 PM Frenchy - Join Date: Nov 2005 Location: Quebec Posts: 30,227 I don't think this is legal in Quebec....He should at least go with the natural buriing, a company offers it now and it's like 1/3 of the usual price. I saw something about this somewhere on the web... # 3 July 9th, 2007, 08:07 PM mummummum - Join Date: Nov 2005 Location: The Hammer Posts: 8,534 It's illegal for a private citizen to transport a dead body in these cirucumstances in Ontario. What's more, the body has to be transported in an approved carrier bag and must be cremated in an approved container. The coroner must approve the cremation in advance. I have had very good dealings with a company called The Simple Alternative. They are very low cost. I know they operate in Toronto ~ not sure about London. I recomment them highly but suggest you caution your Director Care against releasing the body to this fellow unless he is in funeral services himself as your Director can be charged with causing an indignity to a human body. The poor wife, I wonder how she feels about his exceptional ... "frugality" as she lies on her death bed. Last edited by mummummum; July 9th, 2007 at 08:26 PM . # 4 July 9th, 2007, 08:08 PM Frenchy - Join Date: Nov 2005 Location: Quebec Posts: 30,227 Quote: Originally Posted by mummummum The poor wife, I wonder how she feels about his exceptional ... "frugality" as she lies on her death bed. I know :sad: # 5 July 9th, 2007, 10:22 PM LavenderRott Senior Contributor Join Date: Dec 2003 Location: Michigan Posts: 2,671 So - is he just going to prop her up in the passenger seat and use the carpool lane!?! __________________ Sandi # 6 July 9th, 2007, 10:34 PM Lukka'sma Remembering Lukka Join Date: Sep 2006 Location: London Ontario Posts: 2,231 Quote: Originally Posted by LavenderRott So - is he just going to prop her up in the passenger seat and use the carpool lane!?! Nothing would surprise me at this point. I stopped asking questions last evening and just kept thinking this is so messed up!!!! # 7 July 9th, 2007, 10:39 PM LavenderRott Senior Contributor Join Date: Dec 2003 Location: Michigan Posts: 2,671 Quote: Originally Posted by Lukka'sma Nothing would surprise me at this point. I stopped asking questions last evening and just kept thinking this is so messed up!!!! My husband has assured me that he would do the same and deposit my body in the lake where we go to see fireworks for the 4th of July!! __________________ Sandi # 8 July 9th, 2007, 10:40 PM anayah Junior Member Join Date: Jul 2007 Location: California Posts: 0 Re:releasing body to spouse ....But funny ! # 9 July 9th, 2007, 10:51 PM Lukka'sma Remembering Lukka Join Date: Sep 2006 Location: London Ontario Posts: 2,231 Quote: Originally Posted by LavenderRott My husband has assured me that he would do the same and deposit my body in the lake where we go to see fireworks for the 4th of July!! I'll place a plaque in Hart Plaza to celebrate your life # 10 July 9th, 2007, 10:54 PM Lukka'sma Remembering Lukka Join Date: Sep 2006 Location: London Ontario Posts: 2,231 Quote: Originally Posted by LavenderRott My husband has assured me that he would do the same and deposit my body in the lake where we go to see fireworks for the 4th of July!! If your husband ever uses the words shoes and concrete in the same sentence I would get the hell out of there # 11 July 9th, 2007, 11:38 PM Crestedcrazy Senior Member Join Date: Apr 2007 Location: Vancouver Island Canada Posts: 394 :sad: how terribly sad that is! __________________ ~Sheri~ http://www.freewebs.com/crazy4cresteds/index.htm # 13 July 10th, 2007, 05:06 PM wdawson Papa D Join Date: Sep 2005 Location: dog loving hamilton,ont Posts: 4,319 it is against the law to transport a body.......i worked at a crematorium here in hamilton.......i used to pick up the deceased at funeral homes and morgues..we where all registered with the ministry of consumer affairs. __________________ Wayne Dad To : George 18 year beagle, Rest in peace little buddy....love Beathoven 7 year old mutt Maggie 5 year jack russell Felix 15 year tabby Ozzie 12 year tabby Tigger 10 year long hair cat marley just a pup sasha grand pup___________________________________________________________ Lettin the cat outta the bag is a whole lot easier than puttin it back in. Most of the stuff people worry about ain't gonna happen anyway. # 14 July 10th, 2007, 05:27 PM CyberKitten Senior Contributor Join Date: Sep 2004 Location: New Brunswick - Nova Scotia Posts: 4,852 It IS illegal for him to be doing that - almost anywhere in Canada. I say that in the event there is some law somewhere that permits but I know of none!! I have the unfortunate task of often pronouncing poeople deceased and we always wait for whatever funeral home the family has. We'd never release it to the family - it is just not allowed! (Why do I want to say 'It is simply not done!" I also had a neighbour who was a funeral director and they often went to pick up bodies hither and yon. (He once was very unhappy with his son who with my brother - they are the same age - went to pick up a body and they decided on the way back - with the body in the back of the hearse which he was driving - to go through the drive through at McDonald's!! ) Recently, when I was giving a seminar on hematology issues (dealing with blood, poisonous substances ,etc) to some embalmers - one who is fellow I went to school with told me he has a body at his workplace, a death by suicide (fellow jumped in front of a train!) - that the family, who has few resources, is refusing to pick up and he does not know what to do. I suggested Social Services but they usually get involved when a family cannot pay but it seems this family wants nothing to do with a funeral. So, then it becomes the property of the County Coroner. But it still seems sooo sad!!!! __________________ "There are two means of refuge from the miseries of life: music and cats" Albert Schweitzer # 15 July 10th, 2007, 07:53 PM Shaykeija Senior Contributor Join Date: Aug 2004 Posts: 2,585 Quote: Originally Posted by CyberKitten I also had a neighbour who was a funeral director and they often went to pick up bodies hither and yon. (He once was very unhappy with his son who with my brother - they are the same age - went to pick up a body and they decided on the way back - with the body in the back of the hearse which he was driving - to go through the drive through at McDonald's!! ) !! Good god I just had to use an inhaler on that one lol .... # 16 July 10th, 2007, 08:04 PM kiara Senior Member Join Date: Jan 2007 Location: Quebec Posts: 405 Just as I thought I heard it all? This guy sounds like a real nut! I think that his request is illegal??? I guess he will be burying her in his back yard too, to save a buck??? There is apparently a real danger in dead bodies and they have some kind of decomposing bacteria on them. He could be risking his own health!!! # 17 July 10th, 2007, 09:24 PM CyberKitten Senior Contributor Join Date: Sep 2004 Location: New Brunswick - Nova Scotia Posts: 4,852 That is part of it Kiera. Most people do not have infectious diseases to spread when they die but the problem is some do - and we have learned so much more since say, the Middle ages. (not sure why I went back that far but anyway - it is one of those days!). Think of people with people with chemicals in their bodies or who died of infectious diseases - like CJD (illnesses caused by prions) and that kind of thing. It is actually more of a risk for the people who work at funeral homes than anyone else - I mean the likelihood of someone contracting an illness from a deceased relative is so infinitesimal but really, it has more to do with respect for life! Even in death, people must be respected and not merely buried in the back yard. Unless he gets a perit and starts his own cemetery but that's most unusual! People did do that in the 1800's - but usually, they had to still have permission even then! __________________ "There are two means of refuge from the miseries of life: music and cats" Albert Schweitzer # 18 July 10th, 2007, 09:42 PM Maya Queen Join Date: Nov 2004 Posts: 845 I have no assets, no family, i'm curious what will happen to me when I die. There is isn't anyone to pay for a funeral of any sort. Is it illegal to be poor? __________________ I disapprove of what you say, but I will defend to the death your right to say it. ~Voltaire # 19 July 10th, 2007, 10:35 PM Lukka'sma Remembering Lukka Join Date: Sep 2006 Location: London Ontario Posts: 2,231 She passed away around 2:30am on Monday and the coroner released her body to the husband at 11am. Husband took the wife on a stretcher and loaded her from our side door into his make-shift box in his van!!!! Unbelievable # 20 July 10th, 2007, 11:08 PM Maya Queen Join Date: Nov 2004 Posts: 845 I guess thats what happens when you don't have money for a proper funeral. Sad isn't it? __________________ I disapprove of what you say, but I will defend to the death your right to say it. ~Voltaire # 21 July 11th, 2007, 01:46 AM glitterless Senior Member Join Date: Apr 2006 Location: Ontario, Canada Posts: 299 Oh, Maya...I wonder if there is help out there so that you could have those arrangements made prior to your death? I know that my grandparents all had their funeral arrangements made decades in advance, but it was still up to us to tell the hospital which funeral home that they were dealing with and such. I cannot believe that the wife's body was released just like that. Although, I don't think that it should be a crime for us to want to take care of our loved ones ourselves, as long as everything is done legally and safely. I wonder if this woman will make it to the crematorium or if hubby will dispose of her some other way? I suppose we shouldn't joke, though. It's sad that this poor man doesn't have the money to take care of things in a different way. # 22 July 11th, 2007, 06:27 AM gomez Senior Member Join Date: Mar 2005 Posts: 486 Has anyone seen "Little Miss Sunshine"??? __________________ Norfolk Terrier, born 26/12/04 # 23 July 11th, 2007, 06:39 AM LL1 Senior Contributor Join Date: Sep 2004 Posts: 1,326 Thats really strange,and hard to believe it is legal.Even ambulances are not allowed to transport "obviously dead" people in some areas,incl Ontario. # 24 July 11th, 2007, 07:19 AM chico2 Senior Contributor Join Date: Jan 2004 Location: Oakville Ontario Posts: 26,591 To be absolutely honest,I do not want my family to spend $10.000+ for my funeral,it is a big business after all. Hubby and I will be cremated and my/his ashes will be kept until we are both gone and will be put in the same place. Ths poor 80yr old man,might be doing this out of love for his wife,who knows? I am surprised it was legal though,maybe he is a farmer and they have a familyplot on their property,like in the old days __________________ "The cruelest animal is the Human animal" 3 kitties,Rocky(r.i.p my boy),Chico,Vinnie # 25 July 11th, 2007, 07:47 AM papillonmama Senior Member Join Date: Nov 2005 Location: GTA Posts: 747 I don't know about the transporting, but I don't disagree with him regarding the frugal burial. When my grandfather passed a few years ago he was very clear about how he wanted his remains treated, and even though many people fought against his own wishes when he died, his children made sure that his wishes were carried out. His wake was in his home that he had built with his own two hands where he raised his children and where his grandchildren and greatgrandchildren were raised. His body was then cremated and his ashes scattered in the forest where he hunted his entire life. And it was all traditional, no church involvement at all, as were his wishes. It meant a lot to him. Maybe it means a lot to them too, maybe she didn't want a big funeral. Maybe she didn't want her family to be burdened with it financially. Maybe there are a million reasons why he wants it done this way. Maybe she spoke to him about her funeral, it's so hard to know. Maybe he is being cheap, who knows. I just think that sometimes the reasons go beyond what people will tell, and it's not always the reasons that we think. __________________ Some days your the dog and some days your the hydrant ~ Unknown # 26 July 11th, 2007, 08:08 AM chico2 Senior Contributor Join Date: Jan 2004 Location: Oakville Ontario Posts: 26,591 I totally agree,you said it better than me though Since I am not a religous person,church is just not an option,scattering my ashes and those of hubby in a favorite place,would be my wish,Mother Nature would take care of our souls. __________________ "The cruelest animal is the Human animal" 3 kitties,Rocky(r.i.p my boy),Chico,Vinnie # 27 July 11th, 2007, 08:10 AM Rainy Senior Member Join Date: Nov 2004 Location: Pierrefonds,Quebec Posts: 360 Yup,I am no frills,no pictures(umm ewwwww) No open casket and if I had my way no casket at all.Just me and a match thank you very much.He probably did it out of love and respect for his wife.That is what i'm choosing to believe. # 28 July 11th, 2007, 10:29 AM Spirit Senior Member Join Date: Dec 2006 Location: Vancouver, BC Posts: 495 What was this man planning to do with the body, once he left the hospital? Was there maybe a private burial in his own back yard? Doesn't that sort of thing need to be supervised? Was none of this questioned by the person in charge of releasing the body? I think we're missing something here... "Generally, the primary right to custody of a dead body belongs to the surviving spouse.", taken from the book "Long-Term Care and the Law: A Legal Guide for Health Care Professionals" by George D. Pozgar, but don't ask me to explain what that means... copyright I believe was 1992, and I'm unsure of what states/countries this applies to, but it's curious just the same. # 29 July 11th, 2007, 11:47 AM Lukka'sma Remembering Lukka Join Date: Sep 2006 Location: London Ontario Posts: 2,231 Quote: Originally Posted by Spirit What was this man planning to do with the body, once he left the hospital? Was there maybe a private burial in his own back yard? Doesn't that sort of thing need to be supervised? Was none of this questioned by the person in charge of releasing the body. After leaving with the body the man said he was going straight to the crematorium. After that I would imagine her ashes were going home with him as this would also eliminate the cost of a plot. There were three coroners involved with the release and it seemed each one passed the decision on to the other. In the end the body was released though. # 30 July 11th, 2007, 12:29 PM Rick C Senior Contributor Join Date: Jan 2005 Location: Southwest of Calgary, Alberta, on an acreage Posts: 1,140 Quote: Originally Posted by Lukka'sma After leaving with the body the man said he was going straight to the crematorium. After that I would imagine her ashes were going home with him as this would also eliminate the cost of a plot. There were three coroners involved with the release and it seemed each one passed the decision on to the other. In the end the body was released though. I find it stunning the man was allowed to leave with a body. Seriously. He could be planting her in the back 40 right now, without the cost of cremation. Rick C www.goldentales.ca
http://www.pets.ca/forum/showthread.php?p=450082
(PDF) Biodiesel production from vegetable oil: Process design, evaluation and optimization PDF | To investigate the effect of reactor performance/configuration of biodiesel production on process parameters (mass & energy consumption, required... | Find, read and cite all the research you need on ResearchGate Article PDF Available Biodiesel production from vegetable oil: Process design, evaluation and optimization September 2017 Polish Journal of Chemical Technology19(3) DOI: 10.1515/pjct-2017-0048 License CC BY-NC-ND 3.0 Authors: <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hamid Reza Kianimanesh <here is a image dce298b383b09f58-78fb49e5b562c775> Farzin Abbaspour-Aghdam Kharg Petrochemical Complex <here is a image 12e31a1b46ab0baf-206bb60af945eef8> Mehrab Valizadehderakhshan North Carolina Agricultural and Technical State University Abstract and Figures To investigate the effect of reactor performance/configuration of biodiesel production on process parameters (mass & energy consumption, required facilities etc.), two diverse production processes (from vegetable oil) were implemented/designed using Aspen HYSYS V7.2. Two series reactors were taken into account where overall conversion was set to be 97.7% and 70% in first and second processes respectively. Comparative analysis showed that an increase in conversion yield caused to consumption reduction of oil, methanol, cold energy and hot energy up to 9.1%, 22%, 67.16% and 60.28% respectively; further, a number of facilities (e.g. boiler, heat exchanger, distillation tower) were reduced. To reduce mass & energy consumption, mass/heat integration method was employed. Applying integration method showed that in the first design, methanol, cold and hot energy were decreased by 49.81%, 17.46% and 36.17% respectively; while in the second design, oil, methanol, cold and hot energy were decreased by 9%, 60.57% 19.62% and 36.58% respectively. <here is a image 5142d5a25e27477d-f0316a53eac475fa> Batch process in biodiesel production … <here is a image 34a360657fe15b09-92cee3fb43c51de3> Continuous process in biodiesel production … Figures - available via license: Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported P ol. J . Chem. T ech., V ol. 19, No. 3, 2017 49Polish Journal of Chemical Technology, 19, 3,49—55, 10.1515/pjct-2017-0048 Biodiesel production from vegetable oil: Process design, evaluation and optimization Hamid Reza Kianimanesh 1, Farzin Abbaspour-Aghdam 1*, Mehrab Valizadeh Derakhshan 2 1 Sahand University of Technology, Biotechnology Research Center, Faculty of Chemical Engineering, Tabriz, Iran 2 Amirkabir University of Technology (TehranPolytechnic), Departmentof Chemical Engineering, Tehran, Iran * Corresponding author: e-mail: [email protected] To investigate the effect of reactor performance/con figuration of biodiesel production on process parameters (mass & energy consumption, required facilities etc.), two diverse production processes (from vegetable oil) were imple- mented/designed using Aspen HYSYS V7.2. Two series reactors were taken into account where overall conversion was set to be 97.7% and 70% in first and second processes respectively. Comparative analysis showed that an increase in conversion yield caused to consumption reduction of oil, methanol, cold energy and hot energy up to 9.1%, 22%, 67.16% and 60.28% respectively; further, a number of facilities (e.g. boiler, heat exchanger, distillation tower) were reduced. To reduce mass & energy consumption, mass/heat integration method was employed. Apply- ing integration method showed that in the fi rst design, methanol, cold and hot energy were decreased by 49.81%, 17.46% and 36.17% respectively; while in the second design, oil, methanol, cold and hot energy were decreased by 9%, 60.57% 19.62% and 36.58% respectively. Keywords: Process Design, Heat & Mass Integration, Biodiesel, Pinch Technology, Heat Exchanger Network. INTRODUCTION Fossil fuels as well as their derivatives have been the greatest energy source over the recent two centuries. Their imminent depletion as well as environmental consequence of their overuse has motivated researchers around the world to look for renewable, less pollutant, cost-effective and reliable source of energy. Biological fuel has received an attention among other renewable energy sources e.g. energy from sun and wind energy, taking into account both greenhouse issue and reliability. According to International Energy Agency (IEA), in 2011, the global bioenergy use were 1.3 MBOE/D (mil- lion barrels of oil equivalent per day), which will reach to 2.1 MBOE/D and 4.1 MBOE/D by 2020 and 2035 respectively; Furthermore in the year 2035, bioenergy fuel will account for almost 8% of all transportation fuel consumed in the world 1 ; indicating global rise in imple- menting their bio-energy plans over the coming decades. At least three critical goals can be attained through governmental investment on bioenergy, including: (a) lessening the mounting concerns towards greenhouse gasses, (b) less relying on conventional depleting fossil energy and (c)improving the agriculture sector in rural areas to produce the feed for bio-energy industry. It is to be noted that European countries (and Germany at the top of the list)are the pioneers of bioenergy industry today 2 . Signi fi cant deal of research is being carried out throughout the world to apply different sources for bio- energy production as photocurrent generation, biodiesel and bioethanol and bio-hydrogen production and etc 3–4. Comparison between biodiesel and conventional diesel indicates that it has not only decreases the main gre- enhouse gas (CO 2), by 78% over a life-cycle 5, but also can contribute to reduction of CO through combustion 6 . It can be simply used directly in current diesel engines directly and can be blended (in any proportion) with diesel to improve fuel properties 2. The fi nal cost of biodiesel is 1.5–3 times higher than that of the conventional diesel 7, Nevertheless, it constitutes the main obstacle for its production in industrial scale. Some of drawbacks are mainly high energy consumption, low reactor ef fi ciency, and material/energy loss at various extraction/separation processes 8. With the aim of minimization of energy/material consumption and reduction of facility usage, the effect of reactor performance on processing parameters was investigated in this paper. Therefore, in primary opti- mizations, the materials and streams which were used to lose in the process, were collected and recycled back to the process input/feed; further, to prevent energy loss, pinch method – as one of ef ficient methods in integration approach – were employed. In this method the extra energy available in the process were partially used to reduce the utility energy uptake. As such, using identical material load and facilities (with different re- actor ef fi ciency), two different processes were sketched where trans-esteri fi cation reaction under 60 and 1 atm. carried out with overall yield of 97.7% and 70% at each. BIODIESEL Biodiesel is a combination of fatty acid esters which can be used as fuel in diesel engines. The ester acid compounds of the biodiesel increase the oxygen content in fuel, leading to higher combustion yield and reduction of air pollution 2. It can be produced from animal fats, waste oil and plant oils extracted from Soya, Sun fl ower, Palm and Canola 9. Among various candidates mentioned above, oil from oleaginous crops was found to be reliable, source taking into account the quantity, consistency and continuity of the fl ow which should be fed into a biodiesel production plant 10. Apart from the reliability of the source in question, Fatty Acids (FA) from oleaginous crops, though, cannot be used directly in engines due to its low volatility and high viscosity since it may lead to piston knocking, se- dimentation, cocking and other technical troubles 11–12 . To tackle this, researchers have proposed numerous Unauthenticated 50Pol. J. Chem. Tech., Vol. 19, No. 3, 2017 solutions e.g. trans-esteri fi cation which increases the volatility and decreases viscosity index maintaining the heating value of FA 13–14. Trans-esteri fi cation (Eq. 1) is the reaction of Alcohol with Tri-Glyceride (TG) producing Glycerin 15. Together with TG, Free Fatty Acid (FFA) can be found in animal and plant oils. If the FFA content would be higher than 1%, it should be removed or converted to biodiesel (Eq. 2) 16–17. Application of catalyst is of key importance in Eq. 1 and 2 due to the nature of the trans-esteri fi cationre- actions and low solubility of alcohols in FA, and more importantly, low reaction rate, using catalysis has been proposed 10 e.g. acid, alkali and enzyme catalysts. For trans-esteri fi cation of FA obtained from oleaginous crops, homogeneous alkali catalysts are being conventionally used in batch and continuous processes 18–19, Alkali cata- lysts are preferred for biodiesel production because it is faster than acid catalyzed trans-esteri fi cation reaction 20 . However, enzymatic catalysts have not been proved to be appropriate choice due to insuf fi cient reaction rate 21. (1) (2) The produced biodiesel should also possess a number of standards which has been clearly elaborated in ASTM 6751-02 along with their testing methods 10 . Productionprocess Production of biodiesel can be carried out through both batch and continuous procedures. In batch process (Fig. 1) the reactor stirrer operates for 20 min to more than an hour as residence time starting from a vigorous rate down to zero to provide an initial bi-phasic separation of glycerin (higher density) to obtain the fi nal conversion of 85–94%. To further increase the conversion (up to 95%), a two-step series reactor was followed at which glycerin was removed between two stages as can be seen in Figure 1.To separate produced esters and glycerin, a settler or centrifuge can be employed; furthermore, the remaining alcohol in both streams can also be removed by Flash evaporation. Finally, to remove the remaining impurities e.g. salts, catalyst and alcohol, the obtained biodiesel and glycerin were rinsed with water andacid 14, 22 . One of the common modi fi cations in batch production is the application of a series of Completely Stirred Tank Reactors (CSTR) to improve heat transfer and produc- tion yield. As can be seen in Figure 2, the CSTR series can also be replaced by a Plug Flow Reactor (PFR) to increase conversion fraction as well as total processing time which drops to 6–10 minutes only 23. The choice of alternative, however, depends on potential technical Figure 1. Batch process in biodiesel production Figure 2. Continuous process in biodiesel production Unauthenticated Pol. J. Chem. Tech., Vol. 19, No. 3, 201751 troubles, material handling’s manner as well as cost/ bene fi tbalance. Separationofesterandglycerin The separation of ester and glycerin carries out after the production of biodiesel in the reactor (chain) based on the density difference among ester (light phase) and glycerin (heavy phase) in centrifuge, decanter or hydro- -cyclone. The alcohol content of reactor products (mainly methanol) is the key parameter in mutual miscibility of the two phases 24. Alcoholseparation Alcohol separation contributes the whole process to be more cost-effective and environmentally-friendly since it enters to the reactor in extra proportions and is mainly volatile, fl ammable and harmful. Moreover, the separation should be carried out prior to ester-glycerol separation, since as has been noted earlier, alcohol content prevents the binary phase separation of ester- -glycerol due mainly to practical interaction with water 25. Biodieseltreatment Separation and puri fi cation of the produced biodiesel is of critical importance in overall economy of biodiesel production since the cost associated with this steps mo- unts to 60–80% of the total processing cost; furthermore, it may cause a number of serious subsequent technical dif fi culties when using e.g. fi lter plugging, higher soot agglomeration, oil adhesion, oil coagulation, engine knocking and failure 26 . Glycerintreatment Glycerin is considered to be the most important by- -product of the biodiesel production process with its global consumption quantity mounting to 600 Ktonnes per year being used mainly for cosmetics (almost 28%) and medical purposes 27 . The fi nal price, however, dropped dramatically to 7.5 US$/ton from 110 US$/ton between 2004 and 2011 due to signi fi cant increase in global bio- diesel production 25. Employing thermo-chemical and biological methods, it can be converted to highly value-added products e.g. propylene glycol, propanoic acid, acrylic acid, propanol, i-propanol and allylalcohol 28–29 . Using Fisher-Trops method in presence of catalyst, the glycerine may be converted to fuel and hydrogen over relatively low temperatures i.e. 225–300 o C 29–30 . The separated glycerin includes mainly catalyst, sapon and ester along with negligible quantities of phosphate, sulfur, protein, aldehyde, ketone and dissoluble inorganic compounds. Vacuum distillation as well as physic-chemical techniques can be employed for glycerin separation 31. The obtained glycerin may also be used as feed in various industries including food, cosmetics, lubricant etc 32. PROCESS DESIGN HYSYS is a software for steady-state and dynamic process simulation created by Hyprotech as an inte- ractive and fl exible process modeling software 22, 31 . The simulation was carried out using Aspen HYSYS V7.2 employing Triolein (as TG), Oleic acid (as FFA), and m-Oleate as biodiesel as has already been used in pre- vious communications as model representatives 22, 31, 33. To avoid side-stream reactions as well as trans-esteri fi cation, the FFA content was taken to be 0.05% – mass ratio 34. Feed stream was taken as product of NaOH-catalyzed bi-reactor system operating at 60 o Cand 1atm 35–37 with the overall conversion of 97.7%, using two series reactors has already been investigated in previous researches 38–39. Taking into account the low cost, accessibility and handling considerations, methanol was employed in this investigation as the model-type alcohol, since it may not cause difference in chemical structure of fi nalobtained biodiesel 39–40 . In Eq. 1, the TG:Alcohol ratio is 1:3, though it was taken in extra 1:6 for appropriate reactor performance in practice 41–42 . The design was mainly intended to produce 20 m 3 h –1biodiesel with mass concentration of 99.65%. As exchanger pressure loss is about 50 kpa, the increase of pressure in pumps were taken in a level so that the overall pressure would remain almost at 1 atm. all along the process since higher pressure may cause dramatic effects on reactions and costs. NRTL was taken as the governing Equation of State (EOS) for the process, while for decanters; SRK was used 31, 43–44 . As has been showed in Figure 3, feed-streams reacts in Reac. 1 and the downstream lines fl ows to Sep. 1 (Separator 1) to separate un-reacted oils as well as the extra methanol. The separator operates at 25 o C (1 atm) and the separation carries out in a proportion at which the outlet (Reac. 2 feed) possesses of methanol: oil ratio of higher than (or equal to) 6:1. Reac. 2 products including glycerin, methanol, biodiesel and oil were fl own to Sep. 2 (Separator 2) (25 oC) to separate ester (light) and glycerin (heavy). Light phase (ester) was directed to a recycled distillation column (Dist. 1) with R = 1.5 and 6 trays to obtain extra-pure methanol (100%) from biodiesel. Biodiesel-containing fl ow then entered to Sep. 3 (Separator 3) to improve purity and remove remaining catalysts via HCl-NaOH neutralization reaction. HCl and catalyst are fed with identical molar fl ow and reacts with 95% conversion fraction to give 99.65% ultra-pure biodiesel (Table 1). Table 1. Inlet/Outlet material inbiodiesel production process Unauthenticated 52Pol. J. Chem. Tech., Vol. 19, No. 3, 2017 Ef fl uents from Sep. 1 and Sep. 2 having large quan- tities of methanol and glycerin were directed to second distillation tower (Dist. 2) with 5-tray and R = 1.5 to yield pure methanol and glycerin with 100% and 99.54% purity respectively, considering their signi fi cant difference in boiling points. The obtained methanol recycled back to the beginning of process as a feed; while glycerin was sent out to downstream as by-product. Finally, the cold energy (sum of cooler and condenser energies) and the hot energy (sum of heater and boiler energies) required for the process were calculated to be 6194 kw and 6884 kw respectively. HEAT INTEGRATION Reducing the processing costs is one of the major challenges for chemical engineers today; which mainly deals with utility costs. Energy consumption can be balanced partially using heat exchangers where energy exchanges between the cold and hot streams. Optimiza- tion as well as integration methods based generally on thermodynamic and mathematic approaches. Mathematic methods solve modeling problems e.g. Mixed Integer Non-Linear Programming (MINLP) and Mixed Integer Linear Programming (MILP) equations through classical or stochastic methods 44. Thermodynamic methods e.g. Pinch Technology based on thermo-kinetic principals and exergy loss reduction 45 . Pinch technology was fi rst introduced by Linhoffet al. in 1978 to the optimization of heat exchanger networks and lodged pinch point as the critical point of energy consumption 46 . The method was used here to design exchanger ne- twork to reduce energy consumption and loss. Energy consumption reduction, number of used exchangers, re- quired effective area etc., can be assigned as the scope of pinch approach as the fi rst step in pinch design. Energy consumption was taken as the basis of optimization in this study; thereafter, source and demand streams (which can be de fi ned as emission and receiving of energy re- spectively) were determined. Table 2 demonstrates the thermal characteristics of all streams including source and demand, regardless of the outlet streams like glycerol line. HR-1, HR-2, HD-1 and HD-2 represent cooling water leaving reactors and condensers respectively which fl ew subsequently to utility to drop water temperature to 25. C p is also indicating heat capacity of each line which can be calculated using Eq. 3: C p = (Cp in+ Cp out ) ∙ m ∙ /2 (3) Where m ∙is the fl ux and Cp in /Cp out are the heat capacity of inlet/outlet streams. Minimum approach temperature ( ΔT min ) was also taken as 10 in the following calculations. Figure 3. PFD of biodiesel production from vegetable oil Table 2. Source and demand streams and their heat characteristics Unauthenticated Pol. J. Chem. Tech., Vol. 19, No. 3, 201753 To calculate interval temperature as the next step, the inlet and outlet temperatures of hot fl ow must be diffrac- ted from the half of minimum approach temperature of exchangers; and the inlet and outlet cold temperatures should be summed with the half of minimum of approach temperature of exchangers (Eq. 4 and Eq. 5). Interval enthalpy can also be calculated using Eq. 6. Hot Interval Temperature = Hot Tem. – ∆ T min (4) Cold Interval Temperature = Cold Tem. + ∆ T min (5) ∆ H interrval = ∆ T interval[C PCold – C PHot](6) According to Table 3, the required hot and cold energy for the network were found to be zero and 5988.4 kw respectively; where the number “zero” indicates that the source stream is able of providing all energy required by demand stream, whereas 5988.4 kw shows that a make- -up energy with this magnitude should be transferred from utility to process in furtherance of the energy gi- ven by source stream to the demand. Moreover, as can be seen, there is no pinch temperature among interval temperatures con fi rming of no limitation for energy transfer between streams, according to pinch principals. Care should be taken that the exchanger approach tem- perature should not be less than the minimum selected approach temperature. According to Table 2, since the considered source stre- ams were able of providing required network energy, the energy from the rebuilders heat source were not taken into account; additionally, utilization of energy from source stream possessing “300 oC and 1 MPa” merely to warm other streams to the maximum of 60 o C is not cost-effective and it should be saved for essential cases e.g. boilers. Taking all Pinch principals and processing issues into consideration, the plant demonstrated in Figure 4 was plotted and re-characterized. Applying the new system (Fig. 4) in the process, cold and hot energy reduced to 5991.4 kw and 5273.6 kw respectively at which the hot energy is consumed me- rely for heating the distillation reboilers. From Table 4 and Figure 4, HEX-8 can be used as energy source for the second distillation tower’s reboilers which result in 14.68% reduction of cold energy and 16.67% reduction in hot energy consumption. Table 5 provides a com- parative report on the effect caused by applying the integration method. To investigate the effect of conversion on process, similar 20 m 3 h –1 production unit was designed using Table 3. Cold and Hot utility calculation of exchanger network Figure 4. Heat exchanger network in the biodiesel productionprocess Unauthenticated 54Pol. J. Chem. Tech., Vol. 19, No. 3, 2017 & Teyssen, J. (2010). Biofuels: Policies, Standards and Tech- nologies. 2. Gutiérrez, L.F., Sánchez, Ó.J. & Cardona, C.A. (2009). Process integration possibilities for biodiesel production from palm oil using ethanol obtained from lignocellulosic residues of oil palm industry. Biores. Technol. 100(3), 1227–1237. DOI: 10.1016/j.biortech.2008.09.001. 3. Mohammadpour, R., Janfaza, S. & Abbaspour-Aghdam, F. (2014). Light harvesting and photocurrent generation by nanostructured photoelectrodes sensitized with a photosynthetic pigment: A new application for microalgae. Biores. Technol. 163, 1–5. DOI: 10.1016/j.biortech.2014.04.003. 4. ValizadehDerakhshan, M., Nasernejad, B., Abbaspour- -Aghdam, F. & Hamidi, M. (2015). Oil extraction from algae: A comparative approach. Biotechnol. Appl. Bioc. 62(3), 375–382. DOI: 10.1002/bab.1270. 5. Tyson, K.S. (2009). Biodiesel Handling and Use Guide- lines (3rd ed.). Borough, USA: DIANE Publishing Company. 6. Schumacher, L.G. 1995. Biodiesel Emissions Data From Series 60 DDC Engines. in: Bus Operations and Technology Conference . Reno, Nevada. 7. Demirbas, A. (2009). Progress and recent trends in biodie- sel fuels. Energy Conv. Manage. 50(1), 14–34. DOI: 10.1016/j. enconman.2008.09.001. 8. Agarwal, M., Singh, K. & Chaurasia, S. (2012). Simulation and sensitivity analysis for biodiesel production in a reactive distillation column. Pol. J. Chem. Technol. 14(3), 59–65. DOI: 10.2478/v10026-012-0085-2. 9. Hoekman, S.K., Broch, A., Robbins, C., Ceniceros, E. & Natarajan, M. (2012). Review of biodiesel composition, properties, and speci fi cations. Ren Sust. Energy Rev. 16(1), 143–169. DOI: 10.1016/j.rser.2011.07.143. 10. Rutz, D. & Janssen, R. 2007. Biofuel technology hand- book, Munich, Germany, WIP Renewable Energies. 11. Perkins, L.A., Peterson, C.L. & Auld, D.L. 1991. Durability Testing of Transesteri fi ed Winter Rape Oil (Brassica Napus L.) as Fuel in Small Bore, Multi-cylinder, DI, CI Engines. Society of Automotive Engineers. 12. Pestes, M. & Stanislao, J. (1984). Piston Ring Deposits When Using Vegetable Oil as a Fuel. J. Test Eval. 12(2), 24–32. DOI: 10.1520/JTE10699J. 13. Canakci, M. & Van Gerpen, J. (1999). Biodiesel pro- duction via acid catalysis. T ASAE 42(5), 1203–1210. DOI: 10.13031/2013.13285. 14. Gerpen, J.V. (2005). Biodiesel processing and produc- tion. Fuel Process Technol. 86(10), 1097–1107. DOI: 10.1016/j. fuproc.2004.11.005. 15. Kusy, P.F. (1982). Transesteri fi cation of vegetable oils for fuels. Am. Soc. Agric. Enginee. (4–82), 127–137. 16. Balat, M. & Balat, H. (2010). Progress in biodiesel processing. Appl. Energ. 87(6), 1815–1835. DOI:10.1016/j. apenergy.2010.01.012. Table 5. Obtained results from fi rst and second results Table 4. Heat characteristics of distillation tower reboilers same facilities and materials. In the new design, however, two series reactors (X = 70%) were employed. In these conditions, the output biodiesel concentration (mass fraction) in Sep. 3 is 90.8% which was sent to another distillation tower with 5 trays and recycle fl ow ratio 1.5 directly to further increase biodiesel concentration. The upstream line on top of this tower includes biodiesel with appropriate purity, whereas downstream contains a great deal of triolein because more than 30% of the feed remains un-reacted. Therefore puri fi cation reactors for triolein treatment were used as has been used in the earlier design. The downstream line for increasing in purity and recycle to the feed stream sent to separator at 25 oC; this operation resulted in triolein with 99.51% mass concentration. Hence, in this new process, a distillation tower, a heat exchanger, a pump and another separator were added after Sep. 3. In this design, to reduce energy consumption, exchan- ger networks have been designed applying pinch method with the minimum approach temperature of 10 oC; the results were shown in Table 5. CONCLUSION Application of recycle stream and mass integration has reduced methanol consumption up to 49.81% and 60.57% in fi rst and second design respectively. In the second design, since there is still a signi fi cantquantity of un-reacted oil, it can be recycled back into feed and reduce the oil consumption up to 9%. Cold and Hot energies were also reduced 17.46% and 36.17% respectively in fi rst and 19.6% and 36.6% in second design respectively. The number/capacity of used faci- lities increased in some cases as a result of application of integration method; this item can be also optimized depending on relative price of feed, used facilities or other technical considerations. From the results, it can be deduced that the increase of reactor conversion from 70% to 97.7%, caused a si- gni fi cant reduction in consumed oil (9.1%), methanol (22%), cold energy (67%) and hot energy (60.3%); in addition to reduction of a number of used facilities e.g. distillation tower and exchangers, were reduced. LITERATURE CITED 1. Gadonneix, P., de Castro, F.B., de Medeiros, N.F., Drouin, R., Jain, C., Kim, Y.D., Ferioli, J., Nadeau, M.J., Sambo, A. Unauthenticated Pol. J. Chem. Tech., Vol. 19, No. 3, 201755 17. Cho, H.J., Kim, S.H., Hong, S.W. & Yeo, Y.K. (2012). A single step non-catalytic esteri fi cation of palm fatty acid distillate (PFAD) for biodiesel production. Fuel 93(0), 373–380. DOI: 10.1016/j.fuel.2011.08.063. 18. Kiss, A.A. & Bildea, C.S. (2012). A review of biodiesel production by integrated reactive separation technologies. J. Chem. Technol. Biot. 87(7), 861–879. DOI: 10.1002/jctb.3785. 19. Helwani, Z., Othman, M.R., Aziz, N., Kim, J. & Fernando, W.J.N. (2009). Solid heterogeneous catalysts for transesteri fi - cation of triglycerides with methanol: A review. Appl. Catal A-Gen. 363(1–2), 1–10. DOI: 10.1016/j.apcata.2009.05.021. 20. Dawodu, F.A., Ayodele, O.O., Xin, J. & Zhang, S. (2014). Application of solid acid catalyst derived from low value bio- mass for a cheaper biodiesel production. J. Chem. Technol. Biot. 89(12), 1898–1909. DOI: 10.1002/jctb.4274. 21. Ma, F. & Hanna, M.A. (1999). Biodiesel production: a review. Biores. Technol. 70(1), 1–15. DOI: 10.1016/S0960- 8524(99)00025-5. 22. Gomez-Castro, F.I., Rico-Ramirez, V., Segovia-Hernan- dez, J.G., Hernandez-Castro, S. & El-Halwagi, M.M. (2013). Simulation study on biodiesel production by reactive distillation with methanol at high pressure and temperature: Impact on costs and pollutant emissions. Comput. Chem. Eng. 52(0), 204–215. DOI: 10.1016/j.compchemeng.2013.01.007. 23. Portha, J.F., Allain, F., Coupard, V., Dandeu, A., Girot, E., Schaer, E. & Falk, L. (2012). Simulation and kinetic study of transesteri fi cation of triolein to biodiesel using modular reactors. Chem. Eng. J. 207–208(0), 285–298. DOI: 10.1016/j. cej.2012.06.106. 24. Bondioli, P. (2005). Overview from oil seeds to industrial products: Present and future oleochemistry. J. Synth. Lubric. 21(4), 331–343. DOI: 10.1002/jsl.3000210406. 25. Yazdani, S.S. & Gonzalez, R. (2007). Anaerobic fermen- tation of glycerol: a path to economic viability for the biofuels industry. Curr. Opin Biotech. 18(3), 213–219. DOI: 10.1016/j. copbio.2007.05.002. 26. Johnson, D.T. & Taconi, K.A. (2007). The glycerin glut: Options for the value-added conversion of crude glycerol resul- ting from biodiesel production. Environ Prog. 26(4), 338–348. DOI: 10.1002/ep.10225. 27. Veillette, M., Chamoumi, M., Nikiema, J., Faucheux, N. & Heitz, M. (2012). Production of Biodiesel from Microalgae. In: Z. Nawaz, S. Naveed (Eds.), Adv. Chem. Enginee. (245–265). Karachi, Pakistan: InTech. 28. Soares, R.R., Simonetti, D.A. & Dumesic, J.A. (2006). Glycerol as a Source for Fuels and Chemicals by Low-Tem- perature Catalytic Processing. Angew Chem. Int Edit. 45(24), 3982–3985. DOI: 10.1002/anie.200600212. 29. Vaidya, P.D. & Rodrigues, A.E. (2009). Glycerol Refor- ming for Hydrogen Production: A Review. Chem. Eng. Technol. 32(10), 1463–1469. DOI: 10.1002/ceat.200900120. 30. Levy, M. (2013). Simulation of Biodiesel Production Using Reactive Distillation (RD). Bachelor of Science degree Dissertation, Department of Chemical Engineering, University of Florida. Gainesville, Florida, United States. 31. García, M., Gonzalo, A., Sánchez, J.L., Arauzo, J. & Peña, J.Á. (2010). Prediction of normalized biodiesel properties by simulation of multiple feedstock blends. Biores. Technol. 101(12), 4431–4439. DOI: 10.1016/j.biortech.2010.01.111. 32. Galadima, A. & Muraza, O. (2014). Biodiesel production from algae by using heterogeneous catalysts: A critical review. Energy 78(0), 72–83. DOI: 10.1016/j.energy.2014.06.018. 33. Freedman, B., Pryde, E.H. & Mounts, T.L. (1984). Va- riables affecting the yields of fatty esters from transesteri fi ed vegetable oils. J. Am. Oil Chem. Soc. 61(10), 1638–1643. DOI: 10.1007/bf02541649. 34. West, A.H., Posarac, D. & Ellis, N. (2008). Assessment of four biodiesel production processes using HYSYS.Plant. Biores.Technol. 99(14), 6587–6601. DOI: 10.1016/j.bior- tech.2007.11.046. 35. Pokoo-Aikins, G., Nadim, A., El-Halwagi, M. & Mahalec, V. (2010). Design and analysis of biodiesel production from algae grown through carbon sequestration. Clean Technol. Envir. 12(3), 239–254. DOI: 10.1007/s10098-009-0215-6. 36. Samuel, O., Waheed, M., Bolaji, B. & Dairo, O. (2014). Synthesis of Biodiesel from Nigerian Waste Restaurant Cooking Oil: Effect of KOH Concentration on Yield. Global J. Sci. Enginee. Technol. (15), 1–8 . 37. Wong, Y. & Devi, S. (2014). Biodiesel Production from used Cooking Oil. Orient. J. Chem. 30(2), 521–528. DOI: 10.13005/ojc/300216. 38. Slinn, M. & Kendall, K. (2009). Developing the reac- tion kinetics for a biodiesel reactor. Biores. Technol. 100(7), 2324–2327. DOI: 10.1016/j.biortech.2008.08.044. 39. Ye, J., Tu, S. & Sha, Y. (2010). Investigation to biodie- sel production by the two-step homogeneous base-catalyzed transesteri fi cation. Biores. Technol. 101(19), 7368–7374. DOI: 10.1016/j.biortech.2010.03.148. 40. Chisti, Y. (2007). Biodiesel from microalgae. Biotech. Adv. 25(3), 294–306. DOI :10.1016/j.biotechadv.2007.02.001. 41. Berrios, M. & Skelton, R.L. (2008). Comparison of puri- fi cation methods for biodiesel. Chem. Eng. J. 144(3), 459–465. DOI: 10.1016/j.cej.2008.07.019. 42. Romero, R., Natividad, R. & Martínez, S.L. (2011). Biodiesel production by using heterogeneous catalysts. In: M. Manzanera (Eds.), Alternative Fuel, 3–20. Rijeka, Croatia: InTech. 43. Renner, G. & Ekárt, A. (2003). Genetic algorithms in computer aided design. Comp. Aid. Design. 35(8), 709–726. DOI: 10.1016/S0010-4485(03)00003-4. 44. Sánchez, E., Ojeda, K., El-Halwagi, M. & Kafarov, V. (2011). Biodiesel from microalgae oil production in two sequ- ential esteri fi cation/transesteri fi cation reactors: Pinch analysis of heat integration. Chem. Eng. J. 176–177(0), 211–216. DOI: 10.1016/j.cej.2011.07.001. 45. Zhelev, T.K. & Ridol fi , R. (2006). Energy recovery and environmental concerns addressed through emergy–pinch analysis. Energy 31(13), 2486–2498. DOI: 10.1016/j.ener- gy.2005.10.021. 46. Kemp, I.C. (2011). Pinch Analysis and Process Integration: A User Guide on Process Integration for the Ef fi cientUse of Energy (2nd ed.). Oxford, UK: Butterworth-Heinemann. Unauthenticated ... It operates based on a continuous cycle of solvent and leaving the extracts in the extract chamber and contacting the biomass in the batch process. Because this apparatus exposes the biomass to a fresh stream of the organic solvent all along the operation, it accommodates the strongest extraction driving force among all extraction methods, i.e., the reference method [40,57,[60][61] [62] . ... agriculture Extraction of Cannabinoids from Cannabis sativa L. (Hemp)-Review Article Full-text available <here is a image 12e31a1b46ab0baf-206bb60af945eef8> Mehrab Valizadehderakhshan Abolghasem Shahbazi <here is a image ae393627b7ac811c-3ca73d475d2153af> Masoud Kazem-Rostami <here is a image e36e17d61cd69773-0fecc62c0ec06350> Lijun Wang Cannabis plant has long been execrated by law in different nations due to the psychoactive properties of only a few cannabinoids. Recent scientific advances coupled with growing public awareness of cannabinoids as a medical commodity drove legislation change and brought about a historic transition where the demand rose over ten-fold in less than five years. On the other hand, the technology required for cannabis processing and the extraction of the most valuable chemical compounds from the cannabis flower remains the bottleneck of processing technology. This paper sheds light on the downstream processing steps and principles involved in producing cannabinoids from Cannabis sativa L. (Hemp) biomass. By categorizing the extraction technology into seed and trichome, we examined and critiqued different pretreatment methods and technological options available for large-scale extraction in both categories. Solvent extraction methods being the main focus, the critical decision-making parameters in each stage, and the applicable current technologies in the field, were discussed. We further examined the factors affecting the cannabinoid transformation that changes the medical functionality of the final cannabinoid products. Based on the current trends, the extraction technologies are continuously being revised and enhanced, yet they still fail to keep up with market demands. ... Mathematical programming has been widely applied to optimize biodiesel process synthesis problem, considering the economic trade-offs and interactions among subsystems. By far the most systematically considered synthesis problems in biodiesel production is the heat exchanger networks synthesis, separation sequences, and superstructure optimization for alternative technologies [41, 86, 87]. This methodology was implemented by Martin et al. [42] to perform superstructure optimization of biodiesel manufacturing from microalgae and waste vegetable oil. ... An overview to process design, simulation and sustainability evaluation of biodiesel production Article Full-text available Jun 2021 BIOTECHNOL BIOFUELS <here is a image f550b4ec233ea19d-51532ca300a6f6bf> Mustafa Kamal Pasha Lingmei Dai <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Dehua Liu <here is a image 2b6bcb38b1186d77-baecf46d53a3e1dc> Wei du The overwhelming concerns due to over exploitation of fossil resources necessitate the utilization of alternative energy resources. Biodiesel has been considered as one of the most adaptable alternative to fossil-derived diesel with similar properties and numerous environmental benefits. Although there are various approaches for biodiesel production, development of cost-effective and robust catalyst with efficient production methods and utilization of a variety of feedstock could be the optimum solution to bring down the production cost. Considering the complexity of biodiesel production processes, process design, quantitative evaluation and optimization of the biodiesel from whole systems perspectives is essential for unlocking the complexity and enhancing the system performances. Process systems engineering offers an efficient approach to design and optimize biodiesel manufacturing systems by using a variety of tools. This review reflects state-of-the-art biodiesel research in the field of process systems engineering with a particular focus on biodiesel production including process design and simulation, sustainability evaluation, optimization and supply chain management. This review also highlights the challenges and opportunities for the development of potentially sustainable and eco-friendly enzymatic biodiesel technology. ... Most of the studies on biodiesel process simulation evaluate the use of chemical catalysts or production under supercritical conditions (Abdurakhman et al., 2017;Dhar and Kirtania, 2009;Gutiérrez Ortiz and de Santa-Ana, 2017;Heer and Gaikar, 2016; Kianimanesh et al., 2017; Moncada et al., 2014;Sajid et al., 2016;West et al., 2008;Zhang et al., 2003a). The ethanolysis of castor oil was studied by Santana et al. (2010). ... Biodiesel Production Catalyzed by Liquid and Immobilized Enzymes: Optimization and Economic Analysis CHEM ENG RES DES <here is a image bc4bf64bb399bc57-fd72a93545314220> Thalles Allan Andrade <here is a image 147b6996f978fc92-1f489126f508dc70> Mariano Martín <here is a image 37a3b8efd4a8bbac-ad5c8924f4c9a4e7> Massimiliano Errico <here is a image 9773e1c2e7a1310d-f20befbb5f2df739> Knud Villy Christensen Public Link until December 23rd 2018: https://authors.elsevier.com/c/1X-Cyx-vuGRlB. In this work, the use of enzymes as alternative catalysts for the production of biodiesel was evaluated. Due to the high price of enzymes, process optimization and economical evaluation is essential to evaluate the feasibility of their use. Two alternatives were proposed. The first one evaluated the use of liquid enzyme while the second alternative analyzed the use of immobilized enzyme for the transesterification of castor oil. Both alternatives were investigated as an integral part of the whole production plant and optimized considering the profit of the process as objective function. For an annual biodiesel production capacity of 250,000 tons, the process with liquid enzymes resulted in higher total investment costs due to the complex steps for the biodiesel separation. However, the higher cost of immobilized enzymes requires that this enzyme is reused at least 300 times to obtain a profit similar to the liquid enzyme-based process, which resulted in a production cost of 0.78 US$/kg of biodiesel and a plant profit of 51.6 million US$/year for the defined plant capacity. Refining Cannabidiol Using Wiped-Film Molecular Distillation: Experimentation, Process Modeling, and Prediction May 2022 <here is a image 12e31a1b46ab0baf-206bb60af945eef8> Mehrab Valizadehderakhshan <here is a image ae393627b7ac811c-3ca73d475d2153af> Masoud Kazem-Rostami Abolghasem Shahbazi <here is a image e36e17d61cd69773-0fecc62c0ec06350> Lijun Wang Crown evolution kinematics of a camellia oil droplet impacting on a liquid layer Dec 2021 CHINESE PHYS B Zhongyu Shi Guanqing Wang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Xiangxiang Chen Jiangrong Xu The phenomenon of droplet impact on the immiscible liquid is encountered in a variety of scenarios in nature and industrial production. Despite the exhaustive researches, it is not fully clear how the immiscibility of the droplet with impact liquid affects the crown evolution. The present work experimentally investigates the evolution kinematics of crown formed by a normal impact of camellia oil droplet on immiscible water layer. Based on discussion of dynamic impact behaviors for three critical Weber numbers ( We ), the radius of crown and its average spreading velocity are compared with those of previous theoretical models to discuss their applicability to the immiscible liquid. The evolution kinematics (morphology and velocity) are analyzed by considering the effects of We and layer thickness. Furthermore, the ability of crown expansion in radical and vertical directions is characterized by a velocity ratio. The results show that our experimental crown radius still follows a square-root function of evolution time, which agrees with the theoretical predictions. The dimensionless average spreading velocity decreases with We and follows a power-law, while the dimensionless average rising velocity remains constant. The velocity ratio is shown to be linearly increasing with We , demonstrating that the rising movement in crown evolution gradually enhances with We . These results are helpful for further investigation on the droplet impact on immiscible liquid layer. Energy Optimization and Effective Control of Reactive Distillation Process for the Production of High Purity Biodiesel Jul 2021 <here is a image be2d2ffedb90b050-18e67e2ce533bccf> Syed Sadiq Ali <here is a image 7ff6a40af7aa829d-3e5d4520c38a1cdb> Agus Bin Arsad <here is a image 6e02ab17f0945268-e33cb6d103a06fab> Safdar Hossain Sk <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mohammad Asif Biodiesel is a promising renewable energy option that significantly reduces the emission of greenhouse gases and other toxic byproducts. However, a major challenge in the industrial scale production of biodiesel is the desired product purity. To this end, reactive distillation (RD) processes, which involve simultaneous removal of the byproduct during the transesterification reaction, can drive the equilibrium towards high product yield. In the present study, we first optimized the heat exchange network (HEN) for a high purity RD process leading to a 34% reduction in the overall energy consumption. Further, a robust control scheme is proposed to mitigate any feed disturbance in the process that may compromise the product purity. Three rigorous case studies are performed to investigate the effect of composition control in the cascade with the temperature control of the product composition. The cascade control scheme effectively countered the disturbances and maintained the fatty acid mono-alkyl ester (FAME) purity. Statistical Optimization of Biodiesel Production from Salmon Oil via Enzymatic Transesterification: Investigation of the Effects of Various Operational Parameters <here is a image 7261543ee42616be-b12a36f1413b5c5e> Vegneshwaran vasudevan ramakrishnan <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Deepika Dave <here is a image a290d7fe09e4ea33-87f79f674121c96f> Yi Liu <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Wade Murphy The enzymatic transesterification of Atlantic salmon (Salmo salar) oil was carried out using Novozym 435 (immobilized lipase from Candida antartica) to produce biodiesel. A response surface modelling design was performed to investigate the relationship between biodiesel yield and several critical factors, including enzyme concentration (5, 10, or 15%), temperature (40, 45, or 50 °C), oil/alcohol molar ratio (1:3, 1:4, or 1:5) and time (8, 16, or 24 h). The results indicated that the effects of all the factors were statistically significant at p-values of 0.000 for biodiesel production. The optimum parameters for biodiesel production were determined as 10% enzyme concentration, 45 °C, 16 h, and 1:4 oil/alcohol molar ratio, leading to a biodiesel yield of 87.23%. The step-wise addition of methanol during the enzymatic transesterification further increased the biodiesel yield to 94.5%. This is the first study that focused on Atlantic salmon oil-derived biodiesel production, which creates a paradigm for valorization of Atlantic salmon by-products that would also reduce the consumption and demand of plant oils derived from crops and vegetables. Design and simulation of high purity biodiesel reactive distillation process <here is a image be2d2ffedb90b050-18e67e2ce533bccf> Syed Sadiq Ali <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mohammad Asif <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Avijit Basu Biodiesel is a promising energy substitute of fossil fuels since it is produced from renewable and biodegradable sources. In the present work, reactive distillation (RD) process is designed and simulated using Aspen Plus process simulator to produce biodiesel of high purity through esterification reaction. The simultaneous reaction and separation in same unit enhances the biodiesel yield and composition in RD process. Two flowsheets are proposed in present work. In the first flowsheet, the unreacted methanol is recycled back to reactive distillation column. Biodiesel with 99.5 mol% purity is obtained in product stream while the byproduct stream comprises 95.2 mol% water, which has to be treated further. In the second flowsheet, a part of methanol recycle is split and purged. In this case, the biodiesel composition in product stream is 99.7 mol% whereas water composition is 99.9 mol% in byproduct stream, which can be reused for other process without treatment. Extraction and transesterification of vegetable oils with ethanol <here is a image 2f3cc7a106a5efc5-f9dc182855be6022> Regina Lago R. Spiz F. Jablonka Leopold Hartman Production of biodiesel from microalgae HEM IND <here is a image c37ca9af82911a74-4589dc3191ab7cfa> Bojana Danilovic <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jelena M. Avramović <here is a image 153591172aa78c83-acdb7d09a6a587eb> Jovan Ćirić <here is a image 4699e3fb74437dbc-0e262c1d23ee16e1> Vlada Branislav Veljković In recent years, more attention has been paid to the use of third generation feedstocks for the production of biodiesel. Microalgae have emerged as one of the most promising sources for biodiesel production. They are unicellular or colonial photosynthetic organisms, with permanently increasing role in industrial application in the production. of not only chemicals and nutritional supplements, but also the biodiesel. The biodiesel productivity per hectare of cultivation area can be up to 100 times higher for microalgae than for oil crops. Also, microalgae can grow in a variety of environments that are often unsuitable for agricultural purposes. Microalgae oil content varies in different species and can reach Lip to 77% of dry biomass, while the oil productivity by the phototrophic cultivation of microalgae is up to 122 mg/l/d. Variations of the growth conditions and the implementation of the genetic engineering can induce the changes in the composition and productivity of microalgae oil. Biodiesel from microalgae can be produced in two ways: by transesterification of oil extracted from biomass or by direct transesterification of algal biomass (so called in situ transesterification). This paper reviews the curent status of microalgae used for the production of biodiesel including their isolation, cultivation, harvesting and conversion to biodiesel. Because of high Oil productivity, microalgae will play a significant role in future biodiesel production. The advantages of using microalgae as a source for biofuel production are increased efficiency and reduced cost of production. Also, microalgae do not require a lot of space for growing and do not have a negative impact on the global food and water supplies. Disadvantages of using microalgae are more difficult separation of biomass and the need for further research to develop standardized methods for microalgae cultivation and biodiesel production. Currently, microalgae are not yet sustainable option for the commercial production of biodiesel. First of all, the price of biodiesel from microalgae is still higher than the price of diesel, due to high production costs.
https://www.researchgate.net/publication/320349004_Biodiesel_production_from_vegetable_oil_Process_design_evaluation_and_optimization
Machine Translation of "Administrative Measures For The Guangxi Zhuang Autonomous Region, Reserve" (China) Global-Regulation Translation of " Administrative Measures For The Guangxi Zhuang Autonomous Region, Reserve" Administrative Measures For The Guangxi Zhuang Autonomous Region, Reserve Original Language Title: 广西壮族自治区储备粮管理办法 (The 34th ordinary meeting of the People's Government of the Great Britain and Northern Ireland, held on 14 October 2005 to consider the adoption of Decree No. 13 of 26 October 2005 of the People's Government Order No. 13 of the Greater Self-Government Zone, effective 1 December 2005) Chapter I General Article 1, in order to enhance the management of food reserves in the self-government area (hereinafter referred to as reserves in the self-government zone) and to develop this approach in line with relevant national legislation, taking into account the Central Reserve Food Management Regulations. Article II refers to food reserves in self-government zones, which are used by the Government of the self-government reserves to regulate the total food supply and demand for the entire region, stabilize the food market, and meet the food and food prices of major natural disasters or other emergencies. Article 3 units and individuals involved in and participating in the management of food reserves in the self-government area must comply with this approach. Article IV imposes a management system for the direct management of food reserves in self-government zones and for the management of delegated authority. The Government of the people of the city, the district (zone) and its authorities should support and assist in the management of food reserves in the self-government area. Article 5 should strictly govern the management system for the storage of food in the self-government zone, ensure the real, quality and storage of food reserves in the self-governing area, ensure the storage, affordability, adaptability, use and cost savings of food reserves in the self-government area. Article 6. Reforms in the self-government area, the food administration sector, together with the financial sector of the self-government sector, are responsible for the development of the size of the stock of food in the self-government area, the overall burial and the macro-coordinated views used to guide and coordinate food management in the self-government area. Article 7. The food administration in the self-government area is responsible for the management of food reserves in the self-government area, and monitors the quantity, quality and storage of food reserves in the self-government area. The reserve food management in which it belongs is responsible for the management of food reserves in self-government zones and for the quantity, quality and storage of food reserves in self-government zones. Article 8. The financial sector of the self-government area should be involved in the management of food reserves in the self-government area, which is responsible for the acquisition, distribution, transfer, storage, rotation of components and treatment of subsidies, the arrangement of interest in food loans in the self-government area, management costs and price losses, and guarantees timely and full payment of financial subsidies, as well as for monitoring the financial performance of the self-government reserves. Article 9. China's agricultural development banks have a wide range of responsibilities, in accordance with the relevant provisions of the State, to arrange, in a timely and full manner, loans required for the storage of food in self-government zones and to implement credit regulations for the granting of loans. No unit or individual may undermine the storage facilities of food reserves in the self-government zone without stealing, storing or destroying food reserves in the self-government area. Local Governments in the area of food storage in the self-government area should organize, in a timely manner, the destruction of warehousing facilities, theft, looting or damage to the reserves of self-government zones. Chapter II Plans for the storage of food in the autonomous area Article 11. The total size of the reserves in the self-government area is developed by the development reforms in the self-government area, the food administration sector, together with the financial sector of the self-government, and approved by the Government of the people of the autonomous region. Article 12. Storage of food reserves in the self-government area, the BB and the acquisition, sale plan are co-directed by the food administration in the self-governing area, the financial sector and the China Bank for Agricultural Development, in conjunction with the development reforms in the self-government area. Article 13 provides for a balanced rotation system for food reserves in the self-government area, which is generally 30 per cent of the total stock of food stocks in the self-government area. The specific rotation plan was proposed by the Food Management Authority of the Autonomous Region, which is widely approved by the food administration, the financial sector and the China Agricultural Development Bank. Article 14. The Authority on Housing in the Autonomous Region shall report on the specific implementation of the food acquisition, sale, annual rotation plan in the self-government area, as well as on the development reform, financial, food administration sector reserve, and transmit to the Chinese Bank for Agricultural Development. Chapter III Storage of food reserves in self-government zones Article 15. Consequences of food reserves in self-government zones are owned by direct food reserves in self-government zones, and other businesses may also be entrusted with reservoirs. Article 16 Enterprises with reserves in the Autonomous Region shall have the following conditions: (i) The size of the warehouse's capacity to meet the requirements of the self-government area and the conditions of the warehouse are consistent with national standards and technical norms; (ii) Storage equipment that is adapted to food storage functions, warehousing, access to and from food, food varieties, storage of food cycles; (iii) The conditions for the testing of instruments and places of food quality at the level of self-government reserves consistent with national standards and for the detection of temperatures, water subsoils, pest density during the storage period; (iv) Have professional training and access to management technicians, such as food custody, testing, control and certification issued by the competent authorities; (v) The record of the operation management and credibility and the non-serious operation; (vi) The China Bank for Agricultural Development (ADB) has a wide range of credit lines and self-speaking credit management. Article 17 enterprises that apply for the storage of food in the autonomous self-government area shall be eligible for reservoir with the consent of the food administration in the self-government area. Article 19 Surveillance of food reserves in self-governing areas (hereinafter referred to as reserves) in the self-governing area is essential to implement national standards and technical norms related to stockpile food management and to develop a corresponding management system. Article 20 must guarantee the quality requirements for the acquisition and rotation plan for the deposited self-government reserves. Article 21, the licensor shall make use of exclusive storage, exclusive custody, record-keeping, and ensure that the accounts are in keeping with the accounts, in good quality and in stores. Article 22 governs the management of the reserves in the self-government area without the following: (i) Excellencies, seizures; (ii) Accompanied vouchers; (iii) Excellencies and changes in storage sites; (iv) delays in rotation or mismanagement lead to stereotyped, maiming; (v) A set of tools such as low-cost purchases, high-cost selling of low-cost credits, replacement of new foodstuffs and overheading of bank costs; (vi) Financial subsidies such as fraud, crowding, intercepting, diversion of food loans, loan interest, management costs. Article 23 should establish a safe management system for the defence, defence and protection of food reserves, and be equipped with the necessary security protection facilities. Article 24 shall complete the rotation of food reserves in self-government zones within the time specified in the rotation plan. Specific management approaches for the rotation of food in self-government zones are developed by the food administration sector in the self-government area. Article 25 Reservations may not be secured by the reserves of food in the self-government area or by external liquidation of the debt. Reservations are cancelled by law, disbanded or bankruptized by the self-governing reserves of the self-governing area and the credits occupied by the self-governing food management body responsible for the disposal and assumption of the relevant provisions. Article 26 Management costs for food reserves in the self-government area are offset by approval by the financial sector of the self-government zone and the food administration sector in the self-government area in accordance with the reserve cost, cost, value index, etc., of the reserves of food in the self-government area, and by the interest rate of the current agricultural development bank. In accordance with the actual management of food reserves in the self-government area, the food management authority of the self-government zone proposes different types of goods, different storage conditions, cost subsidy programmes and awards for different levels of management, and following the approval of the food administration in the self-government area, the financial sector. The management costs of food reserves in self-government zones, interest subsidies are allocated by the financial sector of the self-government zone to the food management of the reserves in the self-government area, and the self-government reserves food management will manage costs, the interest subsidies are paid in full and in full to the storage enterprise through the sub-group of the agricultural development banks. The cost of food management in the self-government area should be used for cost-related project expenditures related to the management of food reserves in the self-government area and no units and individuals may be stopped and diverted. Article 27 provides for loans for food reserves in self-government zones that are linked to the food inventory value and are administered by the exclusive household and exclusive. Reservation enterprises should distinguish widely from the opening of basic accounts in China's agricultural development banks and accept their credit regulation. The entry costs of food reserves in the self-government area are approved by the food administration sector in the self-government area and by the China Agriculture Development Bank. The self-government sector reserve food management and the depositor's enterprises must implement the approved treasury costs without undue change. Article 33 The food management structure of the self-government zone should provide regular statistical data, analyse the management of storage of food stocks in the self-government area and communicate statistics, analyses to the food administration, the financial sector and the China Bank for Agricultural Development. Chapter IV Use of food reserves in self-government zones Article 31 Development reforms in the self-government area, the food administration sector should establish and improve early warning mechanisms for the use of food stocks in the self-government area, enhance monitoring of market food supply and demand, and make recommendations to the Government of the people of the self-governing region on the use of food reserves. Article 32 arises as follows: (i) In the executive region of the whole region or part of the region, food is clearly not sought or market prices are volatile; (ii) The use of significant natural disasters or other emergencies; (iii) The Government of the people of the self-governing region considers that there is a need to take advantage of other conditions in which food reserves in the self-government area are needed. Article 33 uses food reserves in the self-government area, which is approved by the Government of the people of the self-government region by the development reform of the self-government area, the food administration sector, together with the financial sector of the self-government. The use of programmes should include the use of food stocks, quantity, quality, prices, arrangements for use, transport security. Article 34 Development reforms in the self-government area and the food administration sector should be implemented by specific organizations of the self-governing food management agencies, in accordance with the food use programme approved by the Government of the self-government. In emergencies, the Government of the people of the self-governing region directly orders for the use of food reserves in the self-government area. Support and collaboration should be provided to the relevant sectors of the self-government and to the Government of the local population in implementing instructions and orders for the use of food reserves in the self-government area. No unit or individual may refuse to implement or change unauthorized instructions and orders for the use of food reserves in self-government zones. Oversight inspection Article 36 Food administration, the financial sector, in accordance with their respective responsibilities, shall monitor the implementation of the food regulations and this approach by the self-governing Authority, the depository enterprises, in accordance with their respective responsibilities, and exercise the following functions: (i) Access to the stocktaking enterprise to inspect the quantity, quality and storage of food reserves in the self-government area; (ii) To inform relevant units and personnel about the implementation of the acquisition, sale, rotation plan and the use of instructions and orders in the self-government area; (iii) To receive information, vouchers, on the management of food reserves in self-government zones; (iv) The offence is dealt with by law. Article 37 Food administration in the self-government area, the supervision of the financial sector shall make a written record of the inspection and shall be signed by the supervisor and the main heads of the inspection units. The main head of the inspection unit refused to sign and the supervisor should record the situation. Article 33 Eighteen-household food management authorities, the depositor's company's supervision of the self-government area's financial, audit, food administration and China's agricultural development banks should be in line with the law. No unit or person shall be denied, obstructed and interfered. Article 339, the Authority on Food Stockpiles in the Autonomous Region should strengthen the operation management and inspection of food reserves in the self-governance area, address the number, quality issues in a timely manner, address critical issues that endanger the safe storage of food stocks in the self-government area, take immediate and effective measures and report on the wide-ranging distinction between the food administration, the financial sector and China agricultural development banks. Article 40 China Bank for Agricultural Development should strengthen credit regulation for food deposit loans in self-governing areas, in accordance with the provisions of financial closure. The self-government sector reserve food management, the host company's extensive distinction between the legal credit regulation of China's agricultural development banks, should be synchronized and provided information and information in a timely manner. Article 40 (i) No timely acquisition, sale and annual rotation of food reserves in self-government zones; (ii) To grant eligibility for reserves in the self-government area that do not meet the conditions of generational storage, or to find that the escillary enterprise will no longer be eligible for generational storage and that it is not in accordance with the provisions for the elimination of its saving qualifications; (iii) The discovery of the existence of a reserve company that is not suitable for the storage of food reserves in the self-government area, and that the period of time has not been changed, as prescribed; (iv) Reports received or found violations in a timely manner. Article 42 (i) To deny the implementation or unauthorized alteration of food acquisition, sale, annual rotation plans and instructions, orders; (ii) Options for the selection of a reserve for a commercial reserve that is not eligible for food reserves in the Autonomous Region; (iii) Identify the quantity, quality of food reserves in self-government zones that are not promptly corrected or identify major issues that endanger the security of storage and do not take effective measures to address and report in accordance with the provisions; (iv) Accreditation, obstruction, interference with food administration, finance, auditing and agricultural development banks to perform oversight duties under the law. Article 43, in breach of this approach, has one of the following acts, which are subject to the responsibility of the food administration in the self-governing area to change its duration; in serious circumstances, the inadmissibility of the enterprise may be removed; the warning of the direct responsible supervisors and other direct responsibilities until the removal of the disposal; and the commission of criminal liability in accordance with the law: (i) The bank's self-government reserves are not in accordance with national standards; (ii) No dedicated storage, exclusive custody, specialized recording of food reserves in the self-government area is incompatible with the accounts; (iii) Identification of issues relating to the quantity, quality and storage of food reserves in self-government zones is not addressed in a timely manner; (iv) Accreditation, obstruction, interference with the food administration, finance, auditing and agricultural development banks, or inspection personnel in the storage of food management authorities, in accordance with the law. (v) Restatements and seizures; (vi) Accompanied vouchers; (vii) Excellencies and changes in storage sites; (viii) The delay in rotation or mismanagement resulting in stereotyped and maiming; (ix) To reject the acquisition, sale, rotation plan and the use of instructions, orders and orders for the acquisition, sale, rotation of food reserves in self-government zones; (x) Authorize the automatic use of food reserves in self-government zones; (xi) A combination of low-cost purchases, high-cost sales of low-cost credits, replacement of new foodstuffs for old foods, and overheading bank costs; (xiii) Guarantee or liquidate debts on the basis of food reserves in self-government zones. In violation of this approach, the staff of the executive branch and the Agricultural Development Bank have not been criminalized by law, in violation of the provisions of this approach, by abuse of their functions, by favouring private fraud or by playing a role. Chapter VII Article 41 Article 46
https://www.global-regulation.com/translation/china/166627/administrative-measures-for-the-guangxi-zhuang-autonomous-region,-reserve.html
MR Imaging, MR Spectroscopy, and Diffusion Tensor Imaging of Sequential Studies in Neonates with Encephalopathy | American Journal of Neuroradiology MR Imaging, MR Spectroscopy, and Diffusion Tensor Imaging of Sequential Studies in Neonates with Encephalopathy A.J. Barkovich , S.P. Miller , A. Bartha , N. Newton , S.E.G. Hamrick , P. Mukherjee , O.A. Glenn , D. Xu , J.C. Partridge , D.M. Ferriero and D.B. Vigneron American Journal of Neuroradiology March 2006, 27 (3) 533-547; Abstract BACKGROUND:Although the imaging, spectroscopic, and diffusion characteristics of brains of infants with neonatal encephalopathy have been described, the time course during which these changes evolve is not clear. The results of sequential MR imaging studies—including anatomic MR imaging, proton MR spectroscopy, and diffusion tensor imaging (DTI)—of 10 patients enrolled prospectively in a study of neonatal encephalopathy are reported to help to clarify the time course of changes in different brain regions during the first 2 weeks of life. METHODS:Ten neonates were prospectively enrolled in a study of the evolution of MR findings in neonatal encephalopathy and were studied 2 (8 patients) or 3 (2 patients) times within the first 2 weeks of life. The MR examination included spin-echo T1 and T2-weighted images, DTI, and long echo time (288 milliseconds) proton MR spectroscopy. Diffusion parameters (diffusivity [D av], fractional anisotropy [FA], and individual eigenvalues) were calculated for 10 1-cm 2regions of interest in each hemisphere that were placed based on anatomic landmarks. D avand FA were then measured manually in the same areas on a workstation. Metabolite ratios (NAA/Ch, Cr/Ch, Cr/NAA, Lac/Ch, and Lac/NAA) were calculated in 7 regions of interest. Imaging appearance, diffusion parameters, and metabolite ratios were then evaluated longitudinally (comparing with other studies on the same patient at different times) and cross-sectionally (comparing all studies performed on the same postnatal day). RESULTS:In most of the patients a characteristic evolution of DTI and MR spectroscopy parameters was seen during the first 2 weeks after birth. Although the anatomic images were normal or nearly normal on the first 2 days after birth in most patients, abnormalities were detected on DTI (both visually and by quantitative interrogation of D avmaps) and proton MR spectroscopy (abnormal metabolite ratios). These parameters tended to worsen until about day 5 and then normalize, though in several patients abnormal metabolite ratios persisted. Of interest, as areas of abnormal diffusivity pseudonormalized within one region of the brain they would develop in other areas. Therefore, the pattern of injury looked very different when imaging was performed at different times during this evolution. CONCLUSION:Patterns of injury detected by standard anatomic imaging sequences, DTI sequences, and proton MR spectroscopy varied considerably during the first 2 weeks after injury. The appearance of new areas of reduced diffusion simultaneous with the pseudonormalization of areas that had reduced diffusion at earlier times can result in an entirely different pattern of injury on diffusivity maps acquired at different time points. Awareness of these evolving patterns is essential if studies are performed and interpreted during this critical period of time. During the past 15 years, MR techniques—including MR imaging, diffusion tensor imaging (DTI), and proton MR spectroscopy—have become the tools of choice in the study of brain injury in term neonates. 1 – 23It has become clear that MR techniques are the most sensitive imaging techniques for detecting brain injury and that there is good association between MR findings and neurodevelopmental outcome. 24 – 29Moreover, MR imaging can identify encephalopathic neonates at greatest risk for abnormal outcome. 29With the advent of new techniques for therapy on perinatal and neonatal injury such as head cooling and pharmacological methods, 30 – 32early assessment of the brain by MR techniques may serve as a decision point in determining whether intervention is indicated and, perhaps, what type of intervention. Therefore, it is critical to understand the evolution of early changes in the injured brain. As part of a prospective study of MR in perinatal and neonatal brain injury, 10 patients have been studied sequentially by standard MR imaging, DTI, and proton MR spectroscopy in the early postnatal period, with the first examination being performed in the first 48 hours in all cases. Of interest, the pattern of injury evolved continuously during the first 2 weeks after birth on all techniques. The evolving patterns are described and discussed in this manuscript. Patients and Methods Currently, 6151 consecutive term and near-term babies admitted to our neonatal intensive care unit have been prospectively screened as part of an ongoing study investigating the utility of neonatal brain MR imaging in assessing brain injury of neonates with neonatal encephalopathy. As the imaging characteristics of neonatal injury are well described in the literature, the protocol has recently been modified to better appreciate the early features of injury and, in particular, the changing anatomic MR imaging, DTI, and proton MR spectroscopy characteristics of the neonatal brain as the injury evolves. For this part of the study, 802 babies were screened, 34 had exclusion criteria, 14 met entry criteria, 4 declined participation (via their parents) after initially enrolling in the study, and 10 (8 boys and 2 girls) were enrolled and studied after their parents gave informed consent. Entry criteria for this study are overt neonatal encephalopathy as assessed by a neonatologist or (1) umbilical artery pH <7.1; (2) umbilical artery base deficit >10; or (3) 5-minute Apgar score ≤5. Babies with suspected or confirmed metabolic disorders, congenital malformations, or congenital infections and babies born before 36 weeks’ gestational age were excluded. Normative data were acquired from a cohort of 16 neonates who were recruited from our obstetrics clinic as a part of this study. All underwent this same MR study during the first week of life. The protocol was approved by the human research committee at our institution. Participation in the study was voluntary; the babies were studied only after informed consent was granted by their parents. Of the 10 patients reported in this study, 8 babies were studied twice and 2 were studied 3 times. The first studies were performed as soon as the neonate was judged sufficiently stable by the attending neonatologist. Subsequent studies were performed at times determined by the clinical condition of the neonate, the availability of MR scanner time, and the availability of personnel to accompany the neonate to the scanner. Scans performed within and including the first 24 hours after birth we considered to be performed on day 1 of life, those performed from 24–48 hours were considered as day 2, those from 48–72 hours as day 3, etc. All patients except one (patient 195) were given final diagnoses of neonatal encephalopathy secondary to global hypoxic-ischemic incident. Patient 195 had a normal neonatal course, was delivered vaginally without complications, and was sent to the well-baby nursery, where he was judged “jittery.” Mild hypoglycemia was noted and treated. Neonatal arterial blood gases showed a pH of 7.08, which qualified the baby for admission to this study and the parents consented to participate. The cause for this baby’s signs was not ascertained. The other patients in the study all had complicated deliveries and early postnatal seizures(Table 1). The late prenatal courses of 2 of the subjects were complicated by maternal hypotension, one because of maternal sepsis and the other because of hypotension after epidural placement. Both infants were subsequently born by emergency cesarean section. One child started to seize in utero 3 days before delivery and was delivered emergently after a flat fetal heart rate was detected. The cause of the prenatal seizures was not determined. (Table 1provides more details of the clinical courses.) Table 1: Clinical, anatomic imaging, and diffusion (manual interrogation) data All studies were performed by using a custom-built MR-compatible neonatal incubator and a high-sensitivity specialized neonatal head coil to reduce patient motion, increase patient safety and comfort, and improve signal intensity-to-noise ratio (SNR) of the MR images. 33During scanning, neonatologists monitored the infants and hand-ventilated intubated neonates. Infants were fed before scanning to avoid sedation whenever possible; sedation was used in 8 of the 22 MR images (36%). By using a 1.5T Signa EchoSpeed scanner (GE Medical Systems, Milwaukee, Wis), we performed an MR examination consisting of axial T2-weighted dual spin-echo (TR, 3000 milliseconds; TE, 60/120 milliseconds; 4-mm section thickness) and axial spin-echo (TR, 500 milliseconds; TE, 11 milliseconds; 4-mm section thickness) with an 18-cm field of view (FOV) and a 192 × 256 acquisition matrix. Each of these scans was evaluated separately by 2 pediatric neuroradiologists with experience in neonatal brain MR imaging, who assessed them for the presence and location of any signal intensity abnormalities in the thalami, corticospinal tracts, basal ganglia, cerebral cortex, cerebral white matter, and brain stem. Consensus was reached on all findings. Agreement was high between the 2 reviewers, with kappa value of 90%. We used a multisection spin-echo single-shot echo-planar sequence to perform DTI (TR, 7000 milliseconds; TE, 99.5 milliseconds; 3-mm section thickness; no gap; 3 repetitions per image; with 18 × 36 cm FOV and 128 × 256 acquisition matrix), acquiring axial images through the whole brain with an in-plane resolution of 1.4 × 1.4 mm 2. 34 – 36We acquired 7 images per axial section, including a T2-weighted reference image ( b= 0 seconds/mm 2) and 6 diffusion-weighted images ( b= 700 seconds/mm 2) in noncollinear gradient directions. The MR data were transferred to off-line workstations for postprocessing. From the DTI data, we computed the average diffusivity (D av, also called apparent diffusion coefficient [ADC]), fractional anisotropy (FA), and the 3 eigenvalues of the diffusion tensor (λ 1, λ 2, and λ 3, in decreasing order of magnitude) bilaterally in the basal ganglia, ventrolateral thalami, posterior limbs of the internal capsules, corticospinal tracts in the centrum semiovale, frontal watershed white matter, parietal watershed white matter, calcarine cortex, optic radiations, dorsal visual stream (parietal white matter 1 cm dorsal to the optic radiations), and hippocampi by using previously described methods. 35These regions of interest were placed in the anatomic locations on the echo-planar T2-weighted images without knowledge of the locations of injury as determined by the T1-weighted and T2-weighted images or the D avmaps (Fig 1). In addition, D avand FA maps were generated and were manually interrogated by the same 2 pediatric neuroradiologists with experience in neonatal brain imaging for areas of abnormal diffusivity. Average diffusivity and FA were assessed manually in most patients by placing a 1-mL circular region of interest over regions that appeared subjectively abnormal while recording the lowest value displayed in the region. The reason for this extra step was that the regions measured by standard anatomic voxel placements (discussed above and illustrated inFig 1) did not always include sites of maximal abnormality. As with the spin-echo images, consensus was reached on all findings and agreement was high, with kappa of 0.9. Fig 1. Locations of regions of interest for DTI and MRSI measurements are marked by rectangles. A,Squares showing region of interest locations from which proton spectra ratios were acquired and calculated by automated processing after each MR study of every patient. B,Squares and rectangles showing the 18 regions of interest from which D avand FA values were calculated by automated processing. The T1-weighted images were used to guide the single-voxel MR spectroscopy volume selection, which was performed by using the point-resolved spectroscopic sequence (PRESS) technique to acquire the MR spectra from approximately 5.5 cm 3of tissue for both regions. The spectrum for each location was acquired by using the GE PROBE (PROton Brain Examination) sequence in under 5 minutes with a TR = 2s, TE = 288ms, and 128 acquisitions. The MR spectroscopy timings and voxel localization were chosen to maximize the detection of lactate and to minimize the spectral contamination from extracranial adipose tissues. The 2 spectra were obtained with the same parameters and voxel size centered on the deep gray matter and then in the watershed region of the frontal white matter. Following acquisition the MR spectroscopy data were transferred off-line and analyzed on a computer workstation by using software developed in house for spectral quantification. Both a neuroradiologist and a basic scientist with extensive experience in MR spectroscopy analyzed all of the spectra. The MR spectroscopy data were Fourier transformed and baseline fitted, and the peak areas were integrated for the choline, creatine, N-acetylaspartate (NAA), and lactate resonances. Peak area ratios of lactate/choline, lactate/NAA, and NAA/choline were calculated for each voxel. In 2 patients, data were corrupted and some ratios could not be calculated. These ratios were marked in the data tables as missing data (MD). For the MR spectroscopic imaging (MRSI), the PRESS technique was used to excite a selected region with further localization by 30 chemical shift imaging (CSI) as described elsewhere. 37Optimized shaped pulses designed by using the Shinnar-Le Roux algorithm allowed improved water suppression and section selection profile in comparison with conventional pulses. 38The PRESS selected volume included a region of approximately 60–200 mL, which encompassed most the neonate brains while excluding the spatial inclusion of subcutaneous lipids. Phase-encoding in the PRESS-CSI sequence was used to obtain 8 × 8 × 8, 12 × 12 × 8, or 16 × 8 × 8 3D spectral arrays with a nominal spatial resolution of 1 mL Following a 2–3-minute prescan procedure including autoshimming, 3D PRESS MRSI (with very selective saturation [VSS] pulses to provide improved coverage and excitation profiles) was acquired in a 17- or 19-minute acquisition. The MR images and raw MRSI data were transferred off-line to a Sun UltraSparc workstation (Sun Microsystems, Mountain View, Calif) for analysis by using software developed at our institution for 3D MRSI processing. Spectral processing included 4D Fourier transformations, automatic frequency and phase adjustments, baseline fitting, and peak integration. This software also provides postprocessing alignment of the spatial center of the spectral arrays. This was used to center the MRSI data to the PRESS selected regions and to position 1-cm 3spectral voxels in specific anatomic locations as defined from the MR images by using a custom-designed region of interest tool. The region of interest tool and MRSI display tool were written in the Interactive Display Language (IDL; Research Systems, Inc., Boulder, Colo). To define voxels that were within the selected regions (and not in the saturation bands surrounding the selected volume) and have adequate signal intensity-to-noise (SNR peak height/noise height), the noise and SNR were calculated for each voxel and metabolite. To avoid spuriously large metabolite ratios, ratios are reported only for voxels with a choline SNR >5. To assess the MR spectra in various anatomic locations in the brain, spectral voxels were retrospectively centered in the following regions bilaterally: (1) basal ganglia (BG), (2) thalamus (TH), (3) optic radiations (OR), (4) corticospinal tracts (CS), (5) frontal white matter (FWM), (6) calcarine gray matter (CGM), and (7) parietal white matter (PWM). The locations are shown for a representative case inFig 1. These 7 voxel locations were chosen for several reasons: they include both more mature (deep gray matter) and less mature (frontal white matter) portions of the brain; they involve areas that are important in motor (corticospinal tracts, basal ganglia), visual (calcarine cortex, thalamus), and cognitive (frontal and parietal white matter) function; and they include the regions commonly injured in neonatal brain injury (deep gray nuclei, frontal intervascular boundary zones). Three regions (posterior limb of internal capsule, dorsal visual stream, and hippocampi) in which diffusivity data were assessed could not be adequately assessed by MRSI because of the very small size preventing adequate SNR (posterior limb of internal capsule) or because the regions were outside of the PRESS selected volume. Several voxels from various scattered regions of interest were not assessed in many of the patients because of similar difficulties in SNR or location of the PRESS selected volume. Statistical Analysis Graphic and descriptive statistics were used to present the MR data. The limited sample size and the large number of predictor variables precluded a meaningful statistical analysis of the imaging characteristics and the affected children with regard to outcome and time of study. Results The initial study was performed on day 1 (within 24 hours of birth) in 4 neonates and on day 2 (between 24 and 48 hours after birth) in 6 neonates. The second scan was performed on day 3 (61–64 hours after birth) in 2 neonates, on day 4 (83–91 hours after birth) in 3 neonates, on day 6 in 2, on day 7 in 2, and on day 14 in one. (The patient studied on day 14 was discharged to home and returned for the follow-up scan as an outpatient. The long interval between the first and second scan was caused by scheduling difficulties for both the family and the hospital). The third scan was performed on day 8 in both neonates(Table 1). D avvalues from the voxels sampled by automated processing (Fig 1) are shown inTable 2. Metabolite ratios from the single voxel proton spectroscopy are shown inTable 3. The metabolite ratios from the voxels sampled by automated processing of the MRSI are not shown because the enormous volume of data (8 ratios per voxel times 14 voxels) was too much to display. Similarly, all of the calculated values from the diffusion data are too numerous to display; because analysis of these anisotropy and individual eigenvalues were not revealing but the D avvalues were, only the D avvalues are displayed in the Table. Table 2. Diffusion data from automated processing Table 3: Metabolite ratios from the single voxel proton spectroscopy Spin-Echo and Diffusion Studies Evaluation of Studies by Days after Birth. The visually apparent MR imaging findings changed considerably as the time after birth lengthened. Examinations performed on day 1 showed very subtle findings on the T1 and T2-weighted images(Table 1). One study was completely normal, whereas a second showed only edema (T1 and T2 prolongation) in the basal ganglia or white matter. The third and fourth showed slight hyperintensity in the basal ganglia and at the depths of a few cortical sulci on T1-weighted images; both of these patients (163 and 178) had possible prenatal injury. (Clinical summaries are given inTable 1.) Calculated diffusivity images of these patients showed reduced diffusivity in the watershed regions of cortex (in one patient) or the ventrolateral deep gray nuclei or corticospinal tracts (3 patients); one with reduced diffusivity in the thalami also had reduced diffusion in a small cortical infarct. D avvalues in the affected regions of these patients were reduced between 10% (D avof ∼0.85 mm 2/s in the thalami compared with normal values of about 0.950 mm 2/s) and 60% (0.40 mm 2/s in the thalami) (Tables 1and2); the one with the most significant reduction (Fig 2) in D avhad possible prenatal injury (patient 163). Fig 2. Patient 163. Increasing abnormality from day 1 to day 3. Aand B,Axial D avmaps at age 22 hours (day 1) show reduced diffusion in the ventrolateral thalami ( arrows) and normal-appearing mesial temporal lobes in the region of the uncus. C,Proton MR spectroscopy from left thalamus at 22 hours shows elevated lactate peak (Lac) and normal appearing NAA peak. The peak upfield from lactate is propane diol (ethylene glycol), which is administered as the base for antiseizure medications. Dand E,Axial D avmaps at age 64 hours (day 3) show more extensive reduced diffusivity. The mesial temporal lobes ( D, white arrows) show reduced Dav, as do the cingula ( E, black arrows) and the entire basal ganglia-thalami-insular region ( E, white arrows). F,Proton MR spectroscopy from left thalamus at 64 hours shows interval increase in lactate and decrease in NAA and choline (Ch) compared with creatine (Cr). Of the 6 patients studied initially on day 2, 3 studies showed T1 shortening (T1 hyperintensity) in the basal ganglia and thalami; one of these had normal T2-weighted images, whereas the other had diffuse T2 hyperintensity in the brain. All of these patients had reduced diffusivity in the lateral thalami and posterior limbs of the internal capsules; D avvalues ranged from about 0.50 mm 2/s to 0.65 mm 2/s. One subject also had reduced diffusivity in the left greater than right frontal subcortical white matter; D avvalues were markedly reduced to about 0.50 mm 2/s in the most affected location. The fourth patient initially studied on day 2 had T2 prolongation and blurring of the watershed cortex and underlying white matter (reduced diffusivity was seen in these areas, as well as in the posterior thalami), while the fifth had T1 and T2 prolongation (hypointensity on T1-weighted images, hyperintensity on the T2-weighted images) and reduced diffusivity in the basal ganglia, thalami, and dorsal brain stem. The sixth patient had normal T1 and T2-weighted images and normal brain diffusivity. Normal hyperintensity was seen in the posterior limb of the internal capsule in all patients studied on days 1 and 2, except 2 who were born at 36 and 37 weeks. On the diffusivity maps, D avvalues from anatomic ROIs ranged from 0.60 to 0.90 mm 2/s, which is reduced about 10%–40%, in the basal ganglia and thalami, whereas it was reduced about 15% in the watershed region of the patient with watershed injury (Tables 1and2). The 2 patients studied on day 3 had very different appearances on conventional imaging. Patient 163 (who had a presumed prenatal injury) had hyperintensity of the globi pallidi, putamina, caudates, ventrolateral thalami, and dorsal brain stem on T1-weighted images and a heterogeneous picture on T2-weighted images, with hypointensity in the dorsal brain stem, ventrolateral thalami, and posterior putamina but hyperintensity in the remainder of the thalami and most of the cerebral cortex. Extensively reduced diffusion was seen in the hippocampi, subcortical white matter, basal ganglia, thalami, and corticospinal tracts (D avvalues were reduced 30%–40% throughout the brain in the standard regions of interest, and 60%–70% by manual interrogation) (Fig 2andTables 1and2). In patient 170, the conventional images continued to show T1 and T2 prolongation, whereas the D avmaps showed increasing spatial extent of the regions of reduced diffusivity and the values themselves decreased another 20% in the deep gray nuclei and dorsal brain stem compared with the study performed 27 hours earlier (Fig 3). The normal hyperintensity in the posterior limb of the internal capsule was absent in both; however, patient 163 was born at 37.5 weeks and the lack of hyperintensity may well have been the result of immaturity. Fig 3. Patient 170. Increasing abnormality from day 2 to day 3. A,Axial D avmap at age 34 hours shows extensive reduced diffusion in the lateral thalami (T) and, to a lesser extent, in the posterior left putamen ( white arrow). B,Proton MR spectroscopy from the left thalamus at 34 hours is most remarkable for a moderate lactate peak ( arrow). C,Axial D avmap at age 61 hours shows that extensive reduced diffusivity has developed within the putamina ( arrows). D,Proton MR spectroscopy from the left thalamus at 61 hours shows a marked increase in lactate compared with NAA and choline. Three patients were studied on day 4. Patient 154 had a normal T1-weighted study and had blurring in the watershed regions on the T2-weighted images; reduced diffusion was present in the anterior and posterior watershed regions and in the posterior thalami. Patient 167 had a normal T1-weighted study and the T2-weighted images showed only slight hyperintensity of the cortex at the site of 2 focal infarcts; our standard regions of interest of the D avmaps showed minimally reduced diffusivity of the ventrolateral thalami and posterior limbs of the internal capsules and significantly reduced diffusion at the sites of the infarcts. Manual interrogation of the D avmaps, however, showed more significantly reduced diffusivity, with values reduced about 30% in the ventrolateral thalamus, putamina, and dorsal brain stem. Patient 178 had marked diffuse T1 shortening in the lateral thalami, globi pallidi, posterior putamina, and posterior insular cortices, absence of hyperintensity of the posterior limb of the internal capsule, and extensive reduced diffusivity in the lateral thalami, posterior putamina, and subcortical white matter (Fig 4). D avvalues in patient 178 were 0.50 mm 2/s in the ventrolateral thalamus and dorsal midbrain, 0.55–0.60 mm 2/s in the posterior putamen, 0.70–0.75 mm 2/s in the corticospinal tracts of the centrum semiovale, and 1.20–1.30 mm 2/s in the central white matter of the centrum. No scans were performed on day 5. Fig 4. Patient 178. Evolution of T1, diffusivity, and metabolites over 3 scans during 8 days. A– Cwere performed at day 1 (16 hours), D– Fwere performed at 4 days (84 hours), and G– Iwere performed at 8 days (178 hours). A,Axial T1-weighted image at age 16 hours is normal. B,Axial D avmap at age 16 hours shows a small amount of reduced diffusivity on the ventrolateral thalami ( arrows). Measurements showed a reduction in D avof about 10%. C,Proton MR spectroscopy from the right thalamus at age 16 hours shows minimal elevation of lactate (Lac), but is otherwise normal. D,Axial T1-weighted image at 84 hours shows that the normal hyperintensity in the posterior limb of the internal capsule is no longer seen. Abnormal hyperintensity is seen in the ventrolateral thalami and posterior putamina. E,Axial D avmap at 84 hours shows that reduced diffusivity is now present in the posterior putamina ( arrows). Measurements of D avshowed significant reduction since day 1, with values now 50%–60% or normal (40%–50% reduced) in the thalami and putamina, and dorsal brain stem. Lesser reductions of about 25% were found in the cerebral hemispheric white matter. F,Proton MR spectroscopy from the right thalamus at 84 hours shows an increase in lactate (Lac) and relative reduction of choline and NAA compared with the first study. G,Axial T1-weighted image at 8 days shows that the T1 shortening is becoming less diffuse and more globular ( arrows), with the globular regions being located in the globi pallidi, ventrolateral thalami, and at the junction of the anterior globi pallidi and putamina. H,Axial D avmap at 84 hours shows that reduced diffusivity is now almost exclusively seen in the posterior putamina ( arrows) with the thalamic abnormality nearly completely gone. Measurements showed that the D avvalues of the putamina were still about 30% below normal, but those in the thalami had normalized. I,Proton MR spectroscopy from the right thalamus at 8 days shows that the lactate peak has gotten significantly smaller. Note that the NAA and choline peaks have continued to decrease in size compared with the creatine peak. Of the scans performed on day 6, patient 155 had only subtle diffuse edema, blurring of the cortex in the posterior watershed cortex on T2-weighted images and reduced diffusivity throughout the cerebral hemispheres. In the deep gray matter, diffusivity values were down 10%–30%, whereas values in the hemispheric white matter were 30%–40% below normal. Patient 153 had T1 and T2 shortening in the dorsal brain stem, posterolateral putamina, and lateral thalami with reduced diffusivity (by about 10%–20%) in the posterior thalami, corpus callosum, and extensively through the white matter of the cerebral hemispheres. Both studies performed on day 7 showed extensive diffuse T1 shortening in the affected areas, in the frontal cortex in patient 162 and in the basal ganglia, insula, perirolandic cortex and the calcarine cortex in patient 193. D avmaps showed reduced diffusivity only in the ventrolateral thalami in the former (with D avvalues about 20% below normal on the region of interest and about 30% below normal on the manual assessments) but showed reduced diffusivity also in the cingulum (50% of normal), corpus callosum (60% of normal), optic radiations (70% of normal), and fronto-occipital fasciculus (70% of normal) in the latter (Fig 5). These abnormal D avvalues in the white matter were not detected by our standard region of interest placements (Tables 1and2). Fig 5. Patient 193. New involvement of white matter pathways on second study. Studies performed at day 2 and day 7. A– C,Axial D avmaps at 34 hours show reduced diffusivity (D avreduced by about 50%, black arrows) in the ventrolateral thalami, posterior limbs of internal capsules, and corticospinal tracts in centrum semiovale. No other areas of reduced diffusivity are identified. D,Proton MR spectroscopy from the left basal ganglia at 34 hours shows mild lactate (Lac) elevation. E– H,Axial D avmaps at 148 hours show that diffusivity in the deep gray nuclei has normalized (values were within 5% of normal); however, new areas of reduced diffusivity are seen in what are believed to be the optic radiations ( E, medium white arrows), corpus callosum ( F, small white arrows; G, smaller white arrows), cingulum ( H, medium white arrows), and superior longitudinal fasciculus ( G, larger arrows). I,Proton MR spectroscopy from left basal ganglia at 148 hours shows that lactate (Lac) has increased in comparison with NAA, choline, and creatine. NAA is the most reduced metabolite. On day 8, patient 155 (with watershed injury) showed T1 shortening and T2 prolongation in the watershed cortex, with the posterior regions affected more severely than the anterior regions; D avvalues had normalized. The scan of patient 178 showed a transformation from diffuse, hazy T1 shortening in the basal ganglia to multifocal, globular T1 shortening at the ventrolateral thalami, posterolateral putamina, and the globus pallidus-putamen junctions, heterogeneity of the basal ganglia on T2-weighted images, and reduced diffusion largely localized to the posterior putamina (Fig 4). Manual interrogation of the diffusivity maps revealed that D avvalues of the thalami, corpus callosum, and central white matter had returned to normal, while those of the posterior putamina remained low by about 25%(Table 1). On day 14, patient 195 had a small new focus of T1 shortening in the right frontal white matter, normal T2-weighted images, and normal D avvalues. Evaluation of Sequential Studies. Looking at the sequential studies patient by patient, several patterns become clear, whereas others are suggested. All patients either developed new areas of T1 shortening or developed more extensive T1 shortening on their second scan as compared with their first scan. In patients with the watershed pattern of injury, this was manifested as T1 shortening in the depths of sulci in the watershed regions, whereas the patients with basal ganglia pattern of injury manifested increasing T1 shortening in the basal ganglia, thalami, and perirolandic cortex. By the third study in patient 178 (on day 8), the character of the T1 shortening changed from a diffuse hyperintensity to a more focal, globular hyperintensity that was largely concentrated in the ventrolateral thalamus, posterior putamen and at the globus pallidus-putamen junction (Fig 4). The third study of patient 155, who had primarily watershed injury, did not significantly change from the second study. The abnormalities seen on T2-weighted images were few and did not significantly evolve during the sequential studies, with the exception of the 2 patients who had cortical infarcts (both of these become more conspicuous on the second scan compared with the first) and patient 178 with extensive deep gray matter and cortical injury in whom the third study (178c) showed areas of hypointensity developing in the ventrolateral thalami and posterior putamina, resulting in a heterogeneous appearance to the brain. The abnormalities of diffusivity evolved the most. The initial studies, performed within 48 hours of birth, typically had very localized diffusion abnormalities, with varying reduction of D avvalues. In the neonates with the basal ganglia pattern, reduced diffusivity was most marked in the ventrolateral thalami or the ventrolateral thalami and the posterior limb of the internal capsule with D avvalues ranging from 5% to 30% less than normal in the regional regions of interest and from 10% to 60% less than normal on the manual assessments of the structures; in severe cases, the dorsal brain stem was also involved. If the second study was performed on days 3–5, the area of reduced diffusion in the thalami had grown and reduced diffusion almost invariably involved the basal ganglia and corticospinal tracts; although the D avvalues in the thalami continued to go down (by another 10%–20%) until day 4–5, the D avvalues in the adjacent areas decreased much more (by 20%–30%) (Tables 1and2). This increase in area of abnormal diffusivity was also seen when damage was primarily in the intervascular boundary zones (Fig 6), in addition to those with the deep gray matter pattern of injury. In addition, in 3 patients with the deep gray matter pattern the subcortical white matter developed reduced diffusion (Figs 5). Patient 193, who had a follow-up scan at age 7 days, showed normalization of diffusivity in the ventrolateral thalamus and corticospinal tracts but was found to have new areas of reduced diffusivity (on the D avmaps) in the cingulum, corpus callosum, optic radiations, and fronto-occipital fasciculus (Fig 5). Patient 162, also followed at age 6 days, showed normalization of reduced diffusion in the frontal cortex and subcortical white matter. In patient 178, who had a third scan at age 8 days, the diffusivity returned to normal in the corticospinal tracts and much of the thalami and putamina; reduced diffusion was limited to the posterior putamina, a tiny area in the posterolateral thalami, the corpus callosum, and the corticospinal tracts (Fig 4). In patient 195, who had a follow-up scan at 14 days, the D avmap and D avvalues had returned to completely normal. Download figure Open in new tab Fig 6. Patient 154. Increased volume of injury in vascular boundary zones from 2 to 4 days. Aand B,Axial D avmaps at 49 hours show reduced diffusivity (D avreduced by about 20%, black arrows) in the frontal and parietooccipital intervascular boundary zones. Note also some reduced diffusivity in the posterolateral thalami ( white arrows). C,Proton MR spectroscopy from the left frontal white matter at 49 hours shows mild lactate (Lac) elevation. Dand E,Axial D avmaps at 91 hours show more extensive reduced diffusivity in the frontal and parieto-occipital intervascular boundary zones and new reduced diffusivity along the optic radiations ( black arrows). D avvalues were not significantly changed from the prior study at 49 hours. F,Although the proton MR spectrum does not look significantly changed, measurements showed a 16% decrease in Lac/NAA and a 36% decrease in Lac/Ch in the frontal white matter compared with the study at 49 hours. MR Spectroscopy Unfortunately, in a number of patients some of the regions of interest for some of the white matter areas of interest were located outside of the PRESS selected volume on the 3D acquisitions, and, as a result, no metabolite ratios could be obtained for those regions. In addition, some white matter voxels had inadequate SNR (choline SNR peak height/noise height <5) and were therefore excluded. Nonetheless, good data were obtained for most of the single voxel spectra, for all of the basal ganglia, thalami, and calcarine regions on the 3D acquisitions, and for a large most of the white matter regions on the 3D acquisitions, which allowed a detailed analysis of the evolution of metabolite ratios. Data from the single voxel spectra are displayed inTable 3. NAA/Ch generally went down after injury in the injured region, from the time of the first scan until the second scan. It then went back up again on the third study in the 2 patients with 3 scans. NAA/Ch also went up from day 2 to 14 in patient 195, who had a mild injury. These changes likely reflect both temporary and permanent changes in the quantity of NAA, which is known to decrease after injury, though we cannot be certain that there is not a transient rise in choline after injury (with mobilization of membrane fragments) contributing to the decreasing ratio. After the acute injury, one would expect choline to decrease again and to continue to decrease as part of its normal developmental incorporation into macromolecules. 39 Cr/NAA went up from first to second scan in every patient except patient 162, who was the patient in whom the ADC returned to normal by day 6. The ratio minimally decreased on the third scan in both patients. No recognizable pattern was discerned in the Cr/Ch ratios. Lac/NAA in the basal ganglia and thalami always increased when the first MR spectroscopy was performed on day 1 and the second on day 2, 3, or 4 (4 patients,Figs 2–4). In patient 193, it increased between day 2 and day 7 (Fig 5). Lac/NAA in the watershed voxels was more variable, increasing from day 1 to day 3, staying stable or increasing from day 1 to day 4, decreasing from day 1 to day 5 and day 2 to day 4 (Fig 6), but increasing from day 2 to day 7 and from day 2 to day 14. Of interest, Lac/NAA in patient 163 decreased slightly in the white matter voxels from day 1 to day 3, whereas Lac/NAA was markedly increasing in the basal ganglia and thalami. In both patients with a third study, Lac/NAA decreased in the thalami, basal ganglia, calcarine cortex, and watershed voxels, though the ratio dropped considerably less in the watershed voxels than in the deep gray nuclei. Discussion Many reports have described the MR imaging findings, metabolite ratios, and diffusion characteristics in encephalopathic neonates. 1 – 23Other than the paper of McKinstry et al, 21these works have not addressed the evolution of these MR parameters in individual patients who were studied sequentially. The sequential changes after prenatal, perinatal, or neonatal injury are of importance in that these studies are typically performed at variable times after birth, depending on the severity of the injury, the stability of the neonate, and the availability of scanner time. Various parameters, such as T1 and T2 characteristics, 11 – 13metabolite ratios, 1 , 4 , 11 , 40and diffusivity 14 , 21seem to vary with the time after injury but the timing of the changes, particularly in individual patients, has not been clarified. We report additional patients and spectroscopic results in an attempt to add to the limited knowledge on this subject in humans. A number of interesting results emerge from this study. Probably the most interesting is the observation that both diffusivity and metabolic ratios are abnormal on the first or second day of life and then, in most patients, continue to worsen until the fourth or fifth day, after which they begin to normalize. For example, in patient 178 (who had a basal ganglia pattern of injury), D avwas about 0.85 mm 2/s and Lac/NAA was about 0.25 in the lateral thalami on day 1. By the second study on day 4, D avwas about 0.50 mm 2/s and Lac/NAA was about 0.9, but at the third study on day 8 D avwas about 0.95 mm 2/s and Lac/NAA was about 0.35. These patterns of evolution are similar to those seen in animal models. 41 – 45Studies in infant pigs and rats have shown reduction in ADC 42 – 45and impaired mitochondrial metabolism, with consequent increase in lactate and decrease in ATP 41 , 46during ischemia. These values transiently partially normalize when normal cerebral blood flow and normoxia are restored, only to decrease again after 24–48 hours secondary to what is known as secondary energy failure. 47 – 49Of interest, the most severely affected brain, that of patient 163, had very low D av(about 0.40 mm 2/s) and very high Lac/NAA (1.7) in the thalami at the end of day 1 (22 hours after birth), which suggests that the normalization may not occur in all patients. This observation is consistent with that of Miyasaka et al, 43who found that rats with the most severe injury never experienced recovery but progressed directly to cell necrosis and death. Indeed, the subsequent study of patient 163 revealed D avof about 0.30 mm 2/s and Lac/NAA of 2.8 in the thalami, which shows a clear worsening. Another possible explanation, however, is that patient 163 suffered prenatal injury, as in utero seizures were detected 3 days before birth and a flat fetal heart rate was detected immediately before emergent caesarean section was performed. Thus, it is possible that the transient normalization of D avand lactate occurred before delivery and that worst values may have occurred on day 2–3 after birth (which might have been day 4–5 after injury) instead of day 5 after birth. Unfortunately, a third study could not be performed on this child because of the severity of the injury. Another patient in whom the pattern of evolution was somewhat atypical was patient 155, who had a cortical intravascular boundary zone injury after a history of oligohydramnios, thick meconium at birth, and neonatal depression. The pattern of evolution of D avwas typical for this patient, because the hemispheric voxels showed slight reduction of D avon the first study (about 1.20 mm 2/s on day 1), more significant reduction on the second study (about 0.85 mm 2/s on day 6) and normalization (ranging from 1.20–1.60 mm 2/s on day 8) on the third study; however, Lac/NAA decreased from the first to the second to the third study, and most other ratios showed a similar unidirectional change from the first to the third study. This observation suggests that evolution of changes in metabolism, reflected in metabolite ratios, may have a different time course than those of microstructure, as reflected in D av. It may also reflect differences in the temporal evolution of intravascular boundary zone injury as compared with deep gray matter injury, in addition to the severity of the hypoxic-ischemic insult. Further studies with larger cohorts will be necessary to determine the factors involved. Absence of the normal hyperintensity in the posterior limb of the internal capsule on T1-weighted images has been described as a sensitive early (during the first week of life) sign of brain injury on MR imaging studies. 6Therefore, because all members of our cohort were studied within 48 hours of birth, we specifically looked for this sign. Of interest, the normal hyperintensity was seen in all patients except 2. These 2 patients (patients 153 and 163) were born at gestational ages of 36 and 37 weeks, ages when myelination is not typically sufficient for this hyperintensity to be seen. 50 , 51Thus, it appears that the absence of hypointensity in the posterior limb of the internal capsule, though helpful later in the first week of life, is not a sensitive sign for brain injury in the first 2 days after injury. One very interesting observation of this study is that the pattern of reduced diffusion seemed to change over time on the sequential studies. This was much more dramatic in the patients with the basal ganglia pattern of injury; the pattern did not significantly change in the 2 patients with predominant watershed pattern. In the patients with basal ganglia pattern, the earliest studies showed reduced diffusion in only the ventrolateral thalami or the ventrolateral thalami and the more caudal aspects of the corticospinal tracts (Figs 2–5). Subsequent studies on days 3–5 showed reduced diffusion in the putamina and in the corticospinal tracts all the way to the perirolandic cortex (Figs 3and4). In addition, D avmaps on days 6 or 7 in several of the subjects showed reduced diffusion in the subcortical white matter and in white matter pathways such as the corpus callosum, the cingulum, and what appeared to be the fronto-occipital fasciculus (Fig 5) and the uncinate fasciculus. Moreover, the reduced diffusivity seemed to disappear in certain structures as it appeared in others, so that, for example, as diffusion in the thalami began to normalize, the white matter tracts and putamina began to show reduced diffusion. Consequently, on day 8, the diffusivity map of patient 178 showed reduced diffusivity of the posterior putamina with nearly normal ventrolateral thalami (Fig 4). Had this been the initial study, one might have suggested that the thalami had been spared; however, the diffusivity map from the initial study on day 1 had shown normal putamina and reduced diffusivity in the ventrolateral thalami (Fig 4). Awareness of this phenomenon is critical in the proper interpretation of these studies. Although McKinstry et al have described changes in diffusivity over time, noting that in their series D avwas maximally reduced (by about 35%) between days 2 and 3, and pseudonormalization of D avwas noted after the seventh day 21they did not note evolution of the apparent pattern of injury. The reason for this evolution in the location of abnormal diffusivity may be a different susceptibility of different parts of the brain to injury, because this selective vulnerability has been suggested in the past as the reason that specific areas are sometimes injured in neonatal hypoxic-ischemic injury. 10 , 52Another interesting possibility is raised by the observation of reduced diffusion in multiple white matter fascicles, however, perhaps this represents a type of excitotoxic injury spreading along the axons, or a variant of Wallerian degeneration that results from injury to the neuronal cell soma. Reduced diffusion in white matter tracts secondary to presumed Wallerian degeneration has been described after acute infarction in neonates and children. It is also important to note that the prolonged evolution of brain injury in this cohort is consistent with rodent models of hypoxic-ischemic injury in the immature brain, where cell death, particularly in the thalamus, progresses considerably during the first week after the insult. 54 , 55Again, further studies with larger numbers of patients and, perhaps study of animal models with sequential MR evaluations will be necessary to answer these questions. It is interesting to note that, though lactate levels in general increased to a maximum at 5–6 days and then diminished, Lac/NAA and Lac/Ch continued to be elevated in 2 patients at 7 (patient 193) and 14 days (patient 195), compared with levels on day 2 (seeTable 3). Persistent lactate elevation >1 month after birth has been reported elsewhere after perinatal hypoxia-ischemia 56) and postulated to be the result of persistent abnormal metabolism in the injured regions of brain. The patients in this study were examined at considerably younger ages. Therefore, it is not clear whether the relatively high values on the second scans might be the result of the initial studies (performed at 34 and 44 hours after birth) having sampled the brain tissues before or early in the course of secondary energy failure and, consequently before lactate values had become elevated. Another factor in patient 193 might be the severity of the injury, which may have resulted in longer persistence of lactate elevation. The case of patient 195 is interesting and deserves further discussion. This patient barely qualified for entry into our study, with a somewhat low arterial pH of 7.08. He was admitted to the well-baby nursery, where he was noted to be “jittery” and to have mild hypoglycemia but was otherwise judged to be completely healthy. The initial MR study was normal and the baby was discharged home as a normal neonate; the follow-up MR was scheduled as an outpatient. Because of various complications in the schedules of the MR scanner and the parents, the follow-up MR study was not performed until day 14 of life. Results at that time showed a new, unexpected abnormality in the right frontal white matter and an interval increase in lactate in the cerebral white matter. Neurodevelopmental examination at age 3 months found the infant to be completely normal. These findings raise the interesting possibility that even “normal” neonates can suffer mild brain injuries in the perinatal and neonatal periods. The long-term consequences of such injuries are unknown. Perhaps more information on such situations will come from the ongoing NIH-supported development of a data base of MR imaging parameters of the brains of normal infants. 57 One very important question that should be asked in any study of neonatal encephalopathy is which findings are associated with poor outcomes and which are associated with good outcomes. Unfortunately, the limited number of patients in this study does not permit any definite conclusions in this regard. Moreover, several of our patients had very severe brain injuries and did not survive to undergo follow-up examinations. Many of our subjects had D avvalues below the threshold of 0.75 mm 2/s suggested by Hunt et al 22as an objective prognostic marker for infants with brain injury. This study is hampered by a number of limitations that are characteristic of all studies of sick neonates in busy hospitals. Although attempts were made to study all of the patients at regular times, this goal was not achieved. Initially, it was the intention of this project to study all the neonates in the first 24 hours after birth; unfortunately, it is nearly impossible to transport neonates born at outlying hospitals to our institution, stabilize them, mobilize them for an MR study, and study them safely in such a short timeframe. Therefore, fewer than half of the subjects were studied within 24 hours, with the remainder being studied between 24 and 48 hours. An attempt was made to perform the follow-up scans at variable times 3–6 days after birth, to understand the evolution of MR parameters over that time period. This was achieved reasonably well, though scheduling difficulties resulted in many patients being scanned at slightly different time intervals than hoped. The most extreme example of this was the child in our cohort with the least severe neonatal course (patient 195), whose follow-up MR (as an outpatient) did not occur until 14 postnatal days. Two patients were imaged 3 times, giving the best pictures of the evolution of the brain injury. It is hoped that as more neonates are enrolled into the study, the large number of patients studied will compensate for the varying times and allow an even clearer picture of evolving injury to emerge. In an ideal environment, single patients could be studied more frequently (every other day, for example), but in most institutions the time involved in multiple transports to and from the scanner and paucity of scanner time make this very difficult, if not impossible. Another limitation of this study is common to nearly all studies of neonatal encephalopathy, that precise time of injury was not known in most of the patients. Indeed, as discussed above, one of the patients appeared to develop seizures in utero, 3 days before delivery, and was presumed to have prenatal injury. Another had oligohydramnios and thick meconium present at delivery, which suggest possible prenatal injury. Furthermore, different patterns of injury were seen in the different patients. Two appeared to have mostly cortical damage, in the intervascular boundary zones (watershed regions), whereas 5 had predominant deep gray matter injury and 2 had extensive injury in both cortex and deep gray matter. The timing of evolution may well be different in different injury patterns. Finally, the evolution may differ in injuries of differing severity and causality, even if the pattern is the same. This underscores the importance of serial studies in an individual neonate to clarify these issues. Despite these limitations, this study provides important information for the MR evaluation of encephalopathic neonates. The extent and pattern of injury vary temporally. Particularly in the case of proton spectroscopy and DTI, some areas will appear more severely injured and some less injured, depending on the timing of the scan with respect to the injury. Most important, early studies often underestimate the ultimate extent of damage, even if diffusion and spectroscopy are included. Because it appears from these data that injury is still evolving, it will be interesting to determine, in future studies, whether interventions can reduce or prevent such progression of injury. Footnotes This research was supported by the National Institutes of Health (grant P50 NS35902). These studies were carried out in part in the Pediatric Clinical Research Center, University of California, San Francisco, with funds provided by the National Center for Research Resources (grant 5 M01 RR-01271), U.S. Public Health Service. References Groenendaal F, Veenhoven EH, van der Grond J, et al. Cerebral lactate and N -acetyl-aspartate/choline ratios in asphyxiated full-term neonates demonstrated in-vivo using proton magnetic resonance spectroscopy. Pediatr Res 1994 ; 35 : 148 –51 Preden CJ, Rutherford MA, Sargentoni J, et al. Proton spectroscopy of the neonatal brain following hypoxic-ischemic injury. Dev Med Child Neurol 1993 ; 35 : 502 –10 Bryant DJ, Sargentoni J, Cox IJ, et al. Proton magnetic resonance spectroscopy of term infants with hypoxic ischaemic injury. In: Proceedings of the Society of magnetic resonance. San Francisco; 1994 ; 336 Hanrahan JD, Sargentoni J, Azzopardi D, et al. Cerebral metabolism within 18 hours of birth asphyxia: a proton magnetic resonance spectroscopy study. Pediatr Res 1996 ; 39 : 584 –90 Rutherford M, Pennock J, Schwieso J, et al. Hypoxic ischaemic encephalopathy: early and late magnetic resonance findings in relation to outcome. Arch Dis Child Fetal Neonatal Ed 1996 ; 75 : F145 –F151 Rutherford M, Pennock J, Schwieso JE, et al. Hypoxic-ischemic encephalopathy: early magnetic resonance imaging findings and their evolution. Neuropediatrics 1995 ; 26 : 183 –91 Robertson R, Ben-Sira L, Barnes P, et al. MR line scan diffusion weighted imaging of term neonates with perinatal brain ischemia. AJNR Am J Neuroradiol 1999 ; 20 : 1658 –70 Barnett A, Mercuri E, Rutherford M, et al. Neurological and perceptual-motor outcome at 5–6 years of age in children with neonatal encephalopathy: relationship with neonatal brain MRI. Neuropediatrics 2002 ; 33 : 242 –48 Cowan F, Rutherford M, Groenendaal F, et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003 ; 361 : 736 –42 Barkovich AJ. MR and CT evaluation of profound neonatal and infantile asphyxia. AJNR Am J Neuroradiol 1992 ; 13 : 959 –72 Barkovich AJ, Baranski K, Vigneron D, et al. Proton MR spectroscopy in the evaluation of asphyxiated term neonates. AJNR Am J Neurorad 1999 ; 20 : 1399 –405 Barkovich AJ, Sargent SK. Profound asphyxia in the preterm infant: imaging findings. AJNR Am J Neuroradiol 1995 ; 16 : 1837 –46 Barkovich AJ, Westmark KD, Ferriero DM, et al. Perinatal asphyxia: MR findings in the first 10 days. AJNR Am J Neuroradiol 1995 ; 16 : 427 –38 Barkovich AJ, Westmark KD, Bedi HS, et al. Proton spectroscopy and diffusion imaging on the first day of life after perinatal asphyxia: preliminary report. AJNR Am J Neuroradiol 2001 ; 22 : 1786 –94 Sie L, van der Knaap M, van Wezel-Meijler G, et al. Early MR features of hypoxic-ischemic brain injury in neonates with periventricular densities on sonograms. AJNR Am J Neuroradiol 2000 ; 21 : 852 –61 Krägeloh-Mann I, Helber A, Mader I, et al. Bilateral lesions of thalamus and basal ganglia: origin and outcome. Dev Med Child Neurol 2002 ; 44 : 477 –84 Pasternak JF, Gorey MT. The syndrome of acute near total intrauterine asphyxia in the term infant. Pediatr Neurol 1998 ; 18 : 391 –98 Roland EH, Poskitt K, Rodriguez E, et al. Perinatal hypoxic-ischemic thalamic injury: clinical features and neuroimaging. Ann Neurol 1998 ; 44 : 161 –66 Wolf RL, Zimmerman RA, Clancy R, et al. Quantitative apparent diffusion coefficient measurements in term neonates for early detection of hypoxic-ischemic brain injury: initial experience. Radiology 2001 ; 218 : 825 –33 Rutherford M, Counsell S, Allsop J, et al. Diffusion weighted magnetic resonance imaging in term perinatal brain injury: a comparison with site of lesion and time from birth. Pediatrics 2004 ; 114 : 1004 –14 McKinstry R, Miller J, Snyder A, et al. A prospective, longitudinal diffusion tensor imaging study of brain injury in newborns. Neurology 2002 ; 59 : 824 –33 Hunt RW, Neil JJ, Coleman LT, et al. Apparent diffusion coefficient in the posterior limb of the internal capsule predicts outcome after perinatal asphyxia. Pediatrics 2004 ; 114 : 999 –1003 Hüppi PS, Murphy B, Maier SE, et al. Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging. Pediatrics 2001 ; 107 : 455 –60 Barkovich AJ, Hajnal BL, Vigneron D, et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol 1998 ; 19 : 143 –50 Mercuri E, Atkinson J, Braddick O, et al. Visual function in full-term infants with hypoxic-ischemic encephalopathy. Neuropediatrics 1997 ; 28 : 155 –61 Mercuri E, Haataja L, Guzzetta A, et al. Visual function in term infants with hypoxic-ischaemic insults: correlation with neurodevelopment at 2 years of age . Arch Dis Child Fetal Neonatal Ed 1999 ; 80 : F99 –104 Mercuri E, Rutherford M, Cowan F, et al. Early prognostic indicators of outcome in infants with neonatal cerebral infarction: a clinical, electroencephalogram, and magnetic resonance imaging study. Pediatrics 1999 ; 103 : 39 –46 Miller SP, Newton N, Ferriero DM, et al. Predictors of 30-month outcome following perinatal depression: role of proton MRS and socio-economic factors. Pediatr Res 2002 ; 52 : 71 –77 Miller SP, Ramaswamy V, Michelson D, et al. Patterns of brain injury in term neonatal encephalopathy. J Pediatr 2005 ; 146 : 453 –60 Ferriero DM. Neonatal brain injury. N Engl J Med 2004 ; 351 : 1985 –95 Taylor DL, Mehmet H, Cady EB, et al. Improved neuroprotection with hypothermia delayed by 6 hours following cerebral hypoxia-ischemia in the 14-day-old rat. Pediatr Res 2002 ; 51 : 13 –19 Vannucci RC, Perlman JM. Interventions for perinatal hypoxic-ischemic encephalopathy. Pediatrics 1997 ; 100 : 1004 –14 Dumoulin CL, Rohling KW, Piel JE, et al. Magnetic resonance imaging compatible neonate incubator. Concept Magne Reson (Magn Reson Eng) 2002 ; 15 : 117 –28 Maas L, Mukherjee P, Carballido-Gamio J, et al. Early laminar organization of the human cerebrum demonstrated with diffusion tensor imaging in extremely premature infants. Neuroimage 2004 ; 22 : 1134 –40 Partridge SC, Mukherjee P, Henry R, et al. Diffusion tensor imaging: serial quantitation of white matter tract maturity in premature newborns. Neuroimage 2004 ; 22 : 1302 –14 DeIpolyi AR, Mukherjee P, Gill K, et al. Comparing microstructural and macrostructural development of the cerebral cortex in premature newborns: diffusion tensor imaging versus cortical gyration. Neuroimage 2005 ; 27 : 579 –86 Vigneron DB, Barkovich AJ, Noworolski SM, et al. Three-dimensional proton MR spectroscopic imaging of premature and term neonates. AJNR Am J Neuroradiol 2001 ; 22 : 1424 –33 Pauly J, Le Roux P, Nishimura D, et al. Parameter relations for the Shinnar-Le Roux selective excitation pulse design algorithm. IEEE Trans Med Imaging 1991 ; 10 : 53 –65 Kreis R, Ernst T, Ross BD. Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Mag Res Med 1993 ; 30 : 424 –37 Hanrahan JD, Cox IJ, Azzopardi D, et al. Relation between proton magnetic resonance spectroscopy within 18 hours of birth asphyxia and neurodevelopment at 1 year of age. Dev Med Child Neurol 1999 ; 41 : 76 –82 Penrice J, Lorek A, Cady EB, et al. Proton magnetic resonance spectroscopy of the brain during acute hypoxia-ischemia and delayed cerebral energy failure in the newborn piglet. Pediatr Res 1997 ; 41 : 795 –802 Thornton JS, Ordidge RJ, Penrice J, et al. Anisotropic water diffusion in white and gray matter of the neonatal piglet brain before and after transient hypoxia-ischaemia. Magn Res Imag 1997 ; 15 : 433 –40 Miyasaka N, Kuroiwa T, Zhao FY, et al. Cerebral ischemic hypoxia: discrepancy between apparent diffusion coefficients and histologic changes in rats. Radiology 2000 ; 215 : 199 –204 Qiao M, Malisza KL, Del Bigio MR, et al. Transient hypoxia-ischemia in rats: changes in diffusion-sensitive MR imaging findings, extracellular space, and Na+-K+ adenosine triphosphatase and cytochrome oxidase activity. Radiology 2002 ; 223 : 65 –75 Nedelcu J, Klein MA, Aguzzi A, et al. Biphasic edema after hypoxic-ischemic brain injury in neonatal rats reflects early neuronal and late glial damage. Pediatr Res 1999 ; 46 : 297 –304 Hope PL, Costello AM, Cady EB, et al. Cerebral energy metabolism studied with phosphorus NMR spectroscopy in normal and birth-asphyxiated infants. Lancet 1984 ; 2 : 366 –70 Azzopardi D, Wyatt JS, Cady EB, et al. Prognosis of newborn infants with hypoxic-ischemic injury assessed by phosphorus magnetic resonance spectroscopy. Pediatr Res 1989 ; 25 : 445 –51 Lorek A, Takei Y, Cady EB, et al. Delayed (“secondary”) cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy. Pediatr Res 1994 ; 36 : 699 –706 Sie LTL, van der Knaap MS, van Wezel-Meijler G, et al. MRI assessment of myelination of motor and sensory pathways in the brain of preterm and term born infants. Neuropediatrics 1997 ; 28 : 97 –105 Counsell S, Maalouf E, Fletcher A, et al. MR imaging assessment of myelination in the very preterm brain. AJNR Am J Neuroradiol 2002 ; 23 : 872 –81 McQuillen PS, Ferriero DM. Selective vulnerability in the developing central nervous system. Pediatr Neurol 2004 ; 30 : 227 –35 Mazumdar A, Mukherjee P, Miller J, et al. Diffusion-weighted imaging of acute corticospinal tract injury preceding Wallerian degeneration in the maturing human brain. AJNR Am J Neuroradiol 2003 ; 24 : 1057 –66 Northington FJ, Ferriero DM, Flock DL, et al. Delayed neurodegeneration in neonatal rat thalamus after hypoxia-ischemia is apoptosis. J Neurosci 2001 ; 21 : 1931 –38 Northington FJ, Ferriero DM, Graham EM, et al. Early neurodegeneration after hypoxia-ischemia in neonatal rat is necrosis while delayed neuronal death is apoptosis. Neurobiol Dis 2001 ; 8 : 207 –19 Hanrahan JD, Azzopardi D, Cowan FM, et al. Persistent increases in cerebral lactate concentration after birth asphyxia. Pediatr Res 1998 ; 44 : 304 –11 McKinstry RC and the NIH Brain Development Cooperative Group. MR imaging study of normal brain development. Presented at: 13th Annual Meeting of the International Society of Magnetic Resonance in Medicine, Miami, Fla., May 7-13, 2005 Received July 21, 2005. Accepted after revision August 3, 2005.
https://www.ajnr.org/node/6905.full.print
$260 in 1955 → 2020 | Inflation Calculator The 3.55% inflation rate means $260 in 1955 is equivalent to $2,510.86 in 2020. This inflation calculator uses the official US consumer price index. $260 in 1955 is worth $2,510.86 in 2020 Amount $ 260 Start year End year Value of $260 from 1955 to 2020 $260 in 1955 is equivalent in purchasing power to about $2,510.86in 2020, an increase of $2,250.86 over 65 years. The dollar had an average inflation rate of 3.55% per yearbetween 1955 and 2020, producing a cumulative price increase of 865.72%. This means that prices in 2020 are 9.66 times as high as average prices since 1955, according to the Bureau of Labor Statistics consumer price index. The inflation rate in 1955 was -0.37%. The inflation rate in 2020 was 1.23%. The 2020 inflation rate is lower compared to the average inflation rate of 5.53% per year between 2020 and 2023. Contents Overview Buying Power of $260 Inflation by City / Country Inflation by Spending Category Formulas & How to Calculate Comparison to S&P 500 Index Data Source Inflation from 1955 to 2020 Cumulative price change 865.72% Average inflation rate 3.55% Converted amount $260 base $2,510.86 Price difference $260 base $2,250.86 CPI in 1955 26.800 CPI in 2020 258.812 Inflation in 1955 -0.37% Inflation in 2020 1.23% $260 in 1955 $2,510.86 in 2020 USD inflation since 1955 Annual Rate, the Bureau of Labor Statistics CPI Buying power of $260 in 1955 This chart shows a calculation of buying power equivalence for $260 in 1955 (price index tracking began in 1635). For example, if you started with $260, you would need to end with $2,510.86 in order to "adjust" for inflation (sometimes refered to as "beating inflation"). When $260 is equivalent to $2,510.86 over time, that means that the "real value" of a single U.S. dollar decreases over time. In other words, a dollar will pay for fewer items at the store. This effect explains how inflation erodes the value of a dollar over time. By calculating the value in 1955 dollars, the chart below shows how $260 is worth less over 65 years. According to the Bureau of Labor Statistics, each of these USD amounts below is equal in terms of what it could buy at the time: Dollar inflation: 1955-2020 Year Dollar Value Inflation Rate 1955 $260.00 -0.37% 1956 $263.88 1.49% 1957 $272.61 3.31% 1958 $280.37 2.85% 1959 $282.31 0.69% 1960 $287.16 1.72% 1961 $290.07 1.01% 1962 $292.99 1.00% 1963 $296.87 1.32% 1964 $300.75 1.31% 1965 $305.60 1.61% 1966 $314.33 2.86% 1967 $324.03 3.09% 1968 $337.61 4.19% 1969 $356.04 5.46% 1970 $376.42 5.72% 1971 $392.91 4.38% 1972 $405.52 3.21% 1973 $430.75 6.22% 1974 $478.28 11.04% 1975 $521.94 9.13% 1976 $552.01 5.76% 1977 $587.91 6.50% 1978 $632.54 7.59% 1979 $704.33 11.35% 1980 $799.40 13.50% 1981 $881.87 10.32% 1982 $936.19 6.16% 1983 $966.27 3.21% 1984 $1,007.99 4.32% 1985 $1,043.88 3.56% 1986 $1,063.28 1.86% 1987 $1,102.09 3.65% 1988 $1,147.69 4.14% 1989 $1,202.99 4.82% 1990 $1,267.99 5.40% 1991 $1,321.34 4.21% 1992 $1,361.12 3.01% 1993 $1,401.87 2.99% 1994 $1,437.76 2.56% 1995 $1,478.51 2.83% 1996 $1,522.16 2.95% 1997 $1,557.09 2.29% 1998 $1,581.34 1.56% 1999 $1,616.27 2.21% 2000 $1,670.60 3.36% 2001 $1,718.13 2.85% 2002 $1,745.30 1.58% 2003 $1,785.07 2.28% 2004 $1,832.61 2.66% 2005 $1,894.70 3.39% 2006 $1,955.82 3.23% 2007 $2,011.53 2.85% 2008 $2,088.76 3.84% 2009 $2,081.33 -0.36% 2010 $2,115.47 1.64% 2011 $2,182.24 3.16% 2012 $2,227.40 2.07% 2013 $2,260.03 1.46% 2014 $2,296.69 1.62% 2015 $2,299.42 0.12% 2016 $2,328.43 1.26% 2017 $2,378.03 2.13% 2018 $2,437.31 2.49% 2019 $2,480.26 1.76% 2020 $2,510.86 1.23% 2021 $2,628.82 4.70% 2022 $2,839.20 8.00% 2023 $2,950.49 3.92%* * Compared to previous annual rate. Not final. See inflation summary for latest 12-month trailing value. This conversion table shows various other 1955 amounts in 2020 dollars, based on the 865.72% change in prices: Conversion: 1955 dollars in 2020 Initial value Equivalent value $1 dollar in 1955 $9.66 dollars in 2020 $5 dollars in 1955 $48.29 dollars in 2020 $10 dollars in 1955 $96.57 dollars in 2020 $50 dollars in 1955 $482.86 dollars in 2020 $100 dollars in 1955 $965.72 dollars in 2020 $500 dollars in 1955 $4,828.58 dollars in 2020 $1,000 dollars in 1955 $9,657.15 dollars in 2020 $5,000 dollars in 1955 $48,285.76 dollars in 2020 $10,000 dollars in 1955 $96,571.52 dollars in 2020 $50,000 dollars in 1955 $482,857.59 dollars in 2020 $100,000 dollars in 1955 $965,715.17 dollars in 2020 $500,000 dollars in 1955 $4,828,575.87 dollars in 2020 $1,000,000 dollars in 1955 $9,657,151.74 dollars in 2020 Inflation by City Inflation can vary widely by city, even within the United States. Here's how some cities fared in 1955 to 2020 (figures shown are purchasing power equivalents of $260): San Francisco, California : 3.90% average rate, $260 → $3,131.99 , cumulative change of 1,104.61% Seattle, Washington : 3.74% average rate, $260 → $2,835.95 , cumulative change of 990.75% Boston, Massachusetts : 3.73% average rate, $260 → $2,803.15 , cumulative change of 978.14% New York : 3.68% average rate, $260 → $2,716.03 , cumulative change of 944.63% Philadelphia, Pennsylvania : 3.49% average rate, $260 → $2,415.72 , cumulative change of 829.12% Atlanta, Georgia : 3.46% average rate, $260 → $2,366.76 , cumulative change of 810.29% Houston, Texas : 3.43% average rate, $260 → $2,325.56 , cumulative change of 794.45% Chicago, Illinois : 3.41% average rate, $260 → $2,302.22 , cumulative change of 785.47% Detroit, Michigan : 3.36% average rate, $260 → $2,232.32 , cumulative change of 758.59% San Francisco, California experienced the highest rate of inflation during the 65 years between 1955 and 2020 (3.90%). Detroit, Michigan experienced the lowest rate of inflation during the 65 years between 1955 and 2020 (3.36%). Note that some locations showing 0% inflation may have not yet reported latest data. Inflation by Country Inflation can also vary widely by country. For comparison, in the UK £260.00 in 1955 would be equivalent to £6,948.74 in 2020, an absolute change of £6,688.74 and a cumulative change of 2,572.59%. In Canada, CA$260.00 in 1955 would be equivalent to CA$2,519.52 in 2020, an absolute change of CA$2,259.52 and a cumulative change of 869.04%. Compare these numbers to the US's overall absolute change of $2,250.86 and total percent change of 865.72%. Inflation by Spending Category CPI is the weighted combination of many categories of spending that are tracked by the government. Breaking down these categories helps explain the main drivers behind price changes. This chart shows the average rate of inflation for select CPI categories between 1955 and 2020. Compare these values to the overall average of 3.55% per year: Category Avg Inflation (%) Total Inflation (%) $260 in 1955 → 2020 Food and beverages 3.91 1,107.05 3,138.34 Housing 4.19 1,345.55 3,758.42 Apparel 1.57 175.34 715.89 Transportation 3.21 681.30 2,031.37 Medical care 5.29 2,744.95 7,396.88 Recreation 1.11 105.05 533.12 Education and communication 1.85 229.75 857.36 Other goods and services 4.99 2,265.56 6,150.45 The graph below compares inflation in categories of goods over time. Click on a category such as "Food" to toggle it on or off: For all these visualizations, it's important to note that not all categories may have been tracked since 1955. This table and charts use the earliest available data for each category. Inflation rates of specific categories Medical Care · Housing · Rent · Food · More Inflation-adjusted measures S&P 500 price · S&P 500 earnings · Shiller P/E How to calculate inflation rate for $260, 1955 to 2020 Our calculations use the following inflation rate formula to calculate the change in value between 1955 and 2020: CPI in 2020 CPI in 1955 × 1955 USD value = 2020 USD value Then plug inhistorical CPI values. The U.S. CPI was 26.8 in the year 1955 and 258.81166666667 in 2020: 258.81166666667 26.8 × $260 = $2,510.86 $260 in 1955 has the same "purchasing power" or "buying power" as $2,510.86 in 2020. To get the total inflation rate for the 65 years between 1955 and 2020, we use the following formula: CPI in 2020 - CPI in 1955 CPI in 1955 × 100 = Cumulative inflation rate (65 years) Plugging in the values to this equation, we get: 258.81166666667 - 26.8 26.8 × 100 = 866% Comparison to S&P 500 Index The average inflation rate of 3.55% has a compounding effect between 1955 and 2020. As noted above, this yearly inflation rate compounds to produce an overall price difference of 865.72% over 65 years. To help put this inflation into perspective, if we had invested $260 in the S&P 500 index in 1955, our investment would be nominallyworth approximately $194,569.87in 2020. This is a return on investment of 74,734.57%, with an absolute return of $194,309.87 on top of the original $260. These numbers are not inflation adjusted, so they are considered nominal. In order to evaluate the realreturn on our investment, we must calculate the return with inflation taken into account. The compounding effect of inflation would account for 89.64% of returns ($174,422.12) during this period. This means the inflation-adjusted realreturn of our $260 investment is $19,887.75. You may also want to account for capital gains tax, which would take your real return down to around $16,905 for most people. Investment in S&P 500 Index, 1955-2020 Original Amount Final Amount Change Nominal $260 $194,569.87 74,734.57% Real Inflation Adjusted $260 $20,147.75 7,649.13% Information displayed above may differ slightly from other S&P 500 calculators. Minor discrepancies can occur because we use the latest CPI data for inflation, annualized inflation numbers for previous years, and we compute S&P price and dividends from January of 1955 to latest available data for 2020 using average monthly close price. Data source & citation Raw data for these calculations comes from the Bureau of Labor Statistics' Consumer Price Index(CPI), established in 1913. Price index data from 1774 to 1912 is sourced from ahistorical studyconducted by political science professor Robert Sahr at Oregon State University and from the American Antiquarian Society. Price index data from 1634 to 1773 is from the American Antiquarian Society, using British pound equivalents.
https://www.in2013dollars.com/us/inflation/1955?amount=260&endYear=2020
Difference between revisions of "40d Talk:Aquifer" - Dwarf Fortress Wiki Difference between revisions of "40d Talk:Aquifer" <table><tbody><tr><td colspan=2> Revision as of 23:27, 29 April 2009 (edit) Erathoniel (talk|contribs) (Fishing in Aquifers) ← Older edit</td><td colspan=2> Revision as of 20:59, 18 May 2009 (edit) (undo) Nikayah (talk|contribs) (→‎Aquifer Removal?:new section) Newer edit →</td></tr><tr><td colspan=2> Line 282:</td><td colspan=2> Line 282:</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td></td><td> Yes, actually. [[User:Erathoniel|Erathoniel]] 23:27, 29 April 2009 (UTC)</td><td></td><td> Yes, actually. [[User:Erathoniel|Erathoniel]] 23:27, 29 April 2009 (UTC)</td></tr><tr><td colspan=2></td><td> +</td><td></td></tr><tr><td colspan=2></td><td> +</td><td> == Aquifer Removal? ==</td></tr><tr><td colspan=2></td><td> +</td><td></td></tr><tr><td colspan=2></td><td> +</td><td> If one were to remove all the aquifer tiles (Probably some water pumping would be necessary) would they then effectively remove that part of the aquifer entirely? --[[User:Nikayah|Nikayah]] 20:59, 18 May 2009 (UTC)</td></tr></tbody></table> Toady mentioned somewhere that, at the moment, only subterrainian water sources can grow towercaps. He then explicitly mentioned underground rivers and lakes, but would an aquifer work as well? If so, given the scarcity of underground water sources, this would provide another bonus to having an aquifer. Thexor I don't believe they count. AFAIK, it applies only to standing water. -- JT Contents 1 My plan for dealing with an aquifer 2 notes from nov1 version 3 Unmarked Aquifer? 4 Stone method 5 Cave-In Method 6 Related threads 7 Conglomerate? 8 Sandy clay 9 Fishing 10 Aquifer Removal? My plan for dealing with an aquifer The DF Map Archive has never worked for me, so I was unable to make use of the link to the example. Also, I was playing on a map entirely covered in a layer of aquifer, so I couldn't mine any stone for mechanism purposes. Fortunately, I had tons and tons of wood (if you're gonna be on an aquifer map, you might as well get a heavily forested one) I discovered that because of the way mechanical buildings are handled, you can use a pump as a pretty reasonable surrogate for gear assemblies - and currently, you don't need stone to make pumps, because wood blocks can be used in place of stone blocks. So, here's how I dealt with the aquifer: Legend: | ^,V,<-,->: Pumps, oriented to pump from dash to "arrow" point for clarity | w: water-filled channel >: down stairway <: up stairway X: up/down stairway =,ǁ: horizontal axles #: normal walls *: banks of waterwheels (with channels dug under them, of course. Build the horizontal axle first so they'll hang off it) A note: the amount of effort it takes to wall off a square with this method is pretty much constant with regard to size, which means that it's better to build a great big aquifer-free area and not need most of it than to build a small one and realize you're gonna have to expand it. Also, great big ridiculous projects are more fun! So, to build one wall of the new floor (I ended up doing both parallel walls at the same time): ########################## #.wwww>..................# #.w<-ww->w...............# #.w<-ww->w...............# #.w<-ww->w...............# #.w<-ww->w...............# .... repeat until you will be clearing out enough space. #.w<-ww->w...............# #.w<-ww->w...............# #.w<-ww->w...............# #.wǁ..>ǁ.................# The O-SHID (Occupational Safety and Health Inspection Dwarf) #.wǁ...ǁ.................# <== requires that these axles be built last in order to #.wǁ...ǁ.................# <== minimize death by drowning, accidental flooding of the fortress, #.wǁ...ǁ.................# and carp-related incidents. #.wǁ...ǁ.................# #.w^===^==============^..# #.w|...|..............|..# #.wǁ..................ǁ..# <== These axles are a bit important. I didn't use them once #.***wwwwwwwwwwwwwwww***.# but had north-facing pumps, and nearly flooded the excavation room. #.***................***.# Also, they're what keeps the waterwheel from collapsing #.***................***.# #.***................***.# ########################## You can easily add more waterwheels to the south if you need moar powah. If they haven't started yet, you can prime the waterwheels by running one of the pumps manually for a few seconds. Going from left to right (again, I did the two parallel walls here simultaneously): ########################## #........................# #..wwwwwwwwwwwwwwwwwwwww.# #..^^^^^^^^^^^^^^^^^^^^^.# #..|||||||||||||||||||||.# #.>ǁwwwwwwwwwwwwwwwwwwww.# #.wǁwwwwwwwwwwwwwwwwwwww.# #.w|||||||||||||||||||||.# #.wvvvvvvvvvvvvvvvvvvvvv.# #.wǁwwwwwwwwwwwwwwwwwww..# <= Even though you can't see it (not even in-game!) #.wǁ.....................# there's channels under the axle here and above. #.wǁ.....................# They're fine just hanging out as long as they're #.wǁ.....................# between two mechanisms #.wǁ.....................# #.w^===^==============^..# #.w|...|..............|..# #.wǁ..................ǁ..# #.***wwwwwwwwwwwwwwww***.# #.***................***.# #.***................***.# #.***................***.# ########################## Note that when you rotate 90 degrees and start working on the new walls, you'll almost certainly have to re-floor some aquifer channels. You'll want to make the inside of the pumped out area look like this: ### ##<# #++# #+X# #+.# #+.# #+.# #+.# #+.# #+.# #+X# #++# ##<# ### Which means queue up the up/down stairways and the walls on the left side first, then the two walls on the right. Water can flow through corners, but dwarves can't build through that tight gap. You put in two stairways, one near each end, so that when you rotate 90 degrees and do it again in the other direction you'll have a stairway pre-built. The main benefit of this two-pump system is that, in my experience, it minimizes the amount of micromanagement you'll be doing. I found that I only had to unsuspend each wall (that is, the entire thing, not individual segments) four or five times before it was done, with the most egregious bits being the end walls (which is understandable, they've got an unpumped area next to them). It does leak a very little bit; you should expect splatterings of 1 and 2 depth water all over the place. If you see anything deeper over a non-channel square, something's sprung a leak and it's time to call in the O-SHID and shut everything down. Note that your re-walling dwarves will be quite happy most of the time, what with all the mist they'll be walking through constantly. Once you've got a square bit of area blocked off, you'll have to shift a bank of pumps back one square, dig out all the remaining aquifer tiles in the center, and pump out the remaining water. Then dig downward and hope you don't have to do this again! Anyway, I hope this is useful. I didn't put it this on the main article because it's like four AM here. notes from nov1 version this is a cleaned-up chat log from #bay12games on Nov 01 11:07 (PST). Pasting it here until the information works its way in to the wiki page. <sinoth> VeryInky: you seem to be the aquifer expert. have you found a way to get around them without magma? <VeryInky> Pumps . But pumps require stone. If you have access to stone, the aquifer shouldn't be that much of a problem. The key draining the aquifer square, then building floodgate. <sinoth> so the aquifer has a finite amount of water in it, unlike brooks and rivers? <VeryInky> Unlimited. It's an infinite water source. It's been sort of fixed in the new version, so getting past the aquifer is much easier. <sinoth> what changed to make it easier? don't see it on the dev_notes <VeryInky> Non dirt squares no longer automatically refill. IN other words, it's now possible to make a wall and block the aquifer. So you can build deeper; wasn't possible before. <sinoth> ah ok, thanks much :) <VeryInky> It's none the less MUCH easier with magma. Dig channels until you reach the aquifer, then divert magma into it. It turns into solid obsidian and you can just continue on. <sinoth> i wasn't aware you could build pumps solely with stone. don't you need the screw thing , made out of metal or wood? <VeryInky> Requires a stone, but you can make the screw and pipes out of wood. The problem is getting that stone. A stone. Unmarked Aquifer? Is it possible to have an aquifer if it was not listed on the pick an area screen? Normally if you are going to enter an area with an aquifer, I have noticed that it shows you with a band of blue at the level that it is located, and the game asks if you are sure you want to settle there. In my case, there was no aquifer listed, and I received no warning, but I cannot go below a layer of yellow sand without hitting Damp Stone (actually it is Damp Loam) The map does have a river, do you get Aquifer with a river automatically? You only get information on the square that your local area is centered on. Thus you can have an aquifer on part of the map without it being listed. --Ikkonoishi21:12, 6 November 2007 (EST) Yeah, I had a section of chalk containing an unmarked aquifer in a mostly igneous area.. luckily I was able to just dig around it.Anydwarf01:57, 8 November 2007 (EST) Stone method Some maps have an aquifer that doesn't span all of the map's biomes, in which case the aquifer is easy to avoid by paying attention to where the different biomes are situated. Is that what this section is referring to, or can there really be "holes" in an aquifer? -- Peristarkawan I have found rock pockets in an aquifer that were dry. They are rare and hard to find, when they are there at all.Geekwad17:05, 6 November 2007 (EST) Rumours on the ofurms are that ore squares don't generate water, so if you can find enough in one place you can dig through them. I don't know if this is accurate. --Lacero05:46, 8 November 2007 (EST) Cave-In Method So I read that a cave-in would make the aquifier mineable... Has this changed recently? I setup a cave-in as follows and the water's still flooding. Did I do it wrong? Legend: # Natural Wall . Natural Floor > Stairs Down < Stairs Up ~ Water _ Channel with water beneath Aquifier level: ####### #~~~~~# #~~~~~# #~~~~~# #~~~~~# #~~~~~# #~~~~~# #~~~~## ##<<<# ##### Aquifier +1: ####### #_____# #_____# #_____# #_____# #_____# #_____# #____<# ##>>>## Aquifier +2: ####### #_____# #_..._# #_..._# #_..._# #_..._# #_...*# #____># ####### I then dug out the * tile and caused the cave-in. The aquifier water is still all at 7 depth, even after Bilging (having dwarves fill a pond elsewhere with the water from here) was I supposed to hit the walls of the Aquifier level with the cave-in? AFAIK, the cave-in method is a bug exploit that you use to change the type of tile. You use the cave in to change the some of the aquifer tiles into non-aquifer tiles and then mine through the center. VengefulDonut Thanks, I'll still try it at some point, but I'll pump out water and make walls to go through it mainly.--CrushU11:51, 12 March 2008 (EDT) It worked for me, kind of (the aquifer was two layers deep and there was only enough material for me to penetrate the top layer by this method). Here's a side view of what I did, with # representing non-aquifer soil, = representing the interstitial "floor" material, % representing aquifer soil, and ~ representing open water where I channeled out the aquifer level: Surface ============= ### ##### ### level 1 underground === ===== === ### ### level 2 underground ==== ==== %%%%~~~~~%%%% level 3 underground - aquifer ============= ############# After I had this all set up, I channeled out the surface floor material holding that suspended block up and let 'er fall: Surface === === ### ### level 1 underground === === ### ### level 2 underground ============= %%%%#####%%%% level 3 underground - aquifer ============= ############# level 4 underground The slab of non-aquifer material in the aquifer level could be dug through normally. Perhaps the key is in not just dropping a layer of interstitial floor material, but in dropping an entire level's thickness. The water that had been sitting in the channeled-out portion of the aquifer squooshed up onto level 2, but that was easily dealt with by digging a side chamber to let it drain away into since it didn't replenish. Conglomerate? I've never seen a Conglomerate layer without an aquifer in it. Thoughts? I have, but it usually requires multiple conglomerate layers. Ie, if you have >2-3 the bottom layers should be dry. Also, if you don't otherwise have an aquifer and have conglomerate.. but that doesn't happen very often. -- My current map has an aquifer throughout, and there are patches of sandy clay that definitely contain water. Fishing Is it possible to fish in an aquifer? I found one right by a volcano, and I wanna know if I have to brave the fire imps. -Erath (unsigned) Yes, actually. Erathoniel Aquifer Removal? If one were to remove all the aquifer tiles (Probably some water pumping would be necessary) would they then effectively remove that part of the aquifer entirely? -- Nikayah
https://dwarffortresswiki.org/index.php?diff=11496&oldid=11495&title=40d_Talk%3AAquifer
Materials Data on LaNi5H7 by Materials Project (Dataset) | OSTI.GOV The U.S. Department of Energy's Office of Scientific and Technical Information Title: Materials Data on LaNi5H7 by Materials Project Full Record Other Related Research Abstract LaNi5H7 crystallizes in the hexagonal P6_3mc space group. The structure is three-dimensional. La2+ is bonded to twelve H1- atoms to form LaH12 cuboctahedra that share corners with six equivalent LaH12 cuboctahedra, corners with six equivalent NiH4 tetrahedra, edges with nine NiH4 tetrahedra, and faces with two equivalent LaH12 cuboctahedra. There are a spread of La–H bond distances ranging from 2.55–2.69 Å. There are three inequivalent Ni1+ sites. In the first Ni1+ site, Ni1+ is bonded to four H1- atoms to form NiH4 tetrahedra that share corners with two equivalent LaH12 cuboctahedra, corners with six NiH4 tetrahedra, and edges with two equivalent LaH12 cuboctahedra. There are a spread of Ni–H bond distances ranging from 1.62–1.66 Å. In the second Ni1+ site, Ni1+ is bonded to four H1- atoms to form NiH4 tetrahedra that share corners with six equivalent NiH4 tetrahedra and edges with three equivalent LaH12 cuboctahedra. There is one shorter (1.61 Å) and three longer (1.66 Å) Ni–H bond length. In the third Ni1+ site, Ni1+ is bonded in a trigonal non-coplanar geometry to three equivalent H1- atoms. All Ni–H bond lengths are 1.63 Å. There are three inequivalent H1- sites. In the first H1- site, H1- is bonded in more » a 5-coordinate geometry to two equivalent La2+ and three Ni1+ atoms. In the second H1- site, H1- is bonded in a tetrahedral geometry to four Ni1+ atoms. In the third H1- site, H1- is bonded in a 2-coordinate geometry to two equivalent La2+ and two equivalent Ni1+ atoms. « less Authors: The Materials Project Publication Date: 2020-07-14 Research Org.: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). LBNL Materials Project Sponsoring Org.: USDOE Office of Science (SC), Basic Energy Sciences (BES) Contributing Org.: MIT; UC Berkeley; Duke; U Louvain OSTI Identifier: 1199652 Report Number(s): mp-23671 DOE Contract Number: AC02-05CH11231; EDCBEE Resource Type: Data Resource Relation: Related Information: https://materialsproject.org/citing Country of Publication: United States Language: English Subject: 36 MATERIALS SCIENCE ; crystal structure ; LaNi5H7 ; H-La-Ni Citation Formats MLA APA Chicago BibTeX The Materials Project. Materials Data on LaNi5H7 by Materials Project . United States: N. p., 2020. Web. doi:10.17188/1199652. Copy to clipboard The Materials Project. Materials Data on LaNi5H7 by Materials Project . United States. https://doi.org/10.17188/1199652 Copy to clipboard The Materials Project. 2020. "Materials Data on LaNi5H7 by Materials Project". United States. https://doi.org/10.17188/1199652. https://www.osti.gov/servlets/purl/1199652. Copy to clipboard @article{osti_1199652, title = {Materials Data on LaNi5H7 by Materials Project}, author = {The Materials Project}, abstractNote = {LaNi5H7 crystallizes in the hexagonal P6_3mc space group. The structure is three-dimensional. La2+ is bonded to twelve H1- atoms to form LaH12 cuboctahedra that share corners with six equivalent LaH12 cuboctahedra, corners with six equivalent NiH4 tetrahedra, edges with nine NiH4 tetrahedra, and faces with two equivalent LaH12 cuboctahedra. There are a spread of La–H bond distances ranging from 2.55–2.69 Å. There are three inequivalent Ni1+ sites. In the first Ni1+ site, Ni1+ is bonded to four H1- atoms to form NiH4 tetrahedra that share corners with two equivalent LaH12 cuboctahedra, corners with six NiH4 tetrahedra, and edges with two equivalent LaH12 cuboctahedra. There are a spread of Ni–H bond distances ranging from 1.62–1.66 Å. In the second Ni1+ site, Ni1+ is bonded to four H1- atoms to form NiH4 tetrahedra that share corners with six equivalent NiH4 tetrahedra and edges with three equivalent LaH12 cuboctahedra. There is one shorter (1.61 Å) and three longer (1.66 Å) Ni–H bond length. In the third Ni1+ site, Ni1+ is bonded in a trigonal non-coplanar geometry to three equivalent H1- atoms. All Ni–H bond lengths are 1.63 Å. There are three inequivalent H1- sites. In the first H1- site, H1- is bonded in a 5-coordinate geometry to two equivalent La2+ and three Ni1+ atoms. In the second H1- site, H1- is bonded in a tetrahedral geometry to four Ni1+ atoms. In the third H1- site, H1- is bonded in a 2-coordinate geometry to two equivalent La2+ and two equivalent Ni1+ atoms.}, doi = {10.17188/1199652}, url = {https://www.osti.gov/biblio/1199652}, journal = {}, number = , volume = , place = {United States}, year = {2020}, month = {7} } Copy to clipboard Dataset: View Dataset https://doi.org/10.17188/1199652 Save / Share: Export Metadata Endnote RIS CSV / Excel XML JSON Save to My Library You must Sign In or Create an Account in order to save documents to your library. Facebook Twitter Email Print More share options LinkedIn Pinterest Tumblr Similar records in OSTI.GOV collections: Materials Data on La2Mg(NiH4)2 by Materials Project Dataset MgLa2(NiH4)2 crystallizes in the monoclinic P2_1/c space group. The structure is three-dimensional. there are two inequivalent Mg2+ sites. In the first Mg2+ site, Mg2+ is bonded in a 6-coordinate geometry to six H1- atoms. There are a spread of Mg–H bond distances ranging from 1.93–2.33 Å. In the second Mg2+ site, Mg2+ is bonded in a 7-coordinate geometry to seven H1- atoms. There are a spread of Mg–H bond distances ranging from 1.94–2.22 Å. There are four inequivalent La2+ sites. In the first La2+ site, La2+ is bonded in a 10-coordinate geometry to ten H1- atoms. There are a spread more » of La–H bond distances ranging from 2.31–2.73 Å. In the second La2+ site, La2+ is bonded in a 10-coordinate geometry to ten H1- atoms. There are a spread of La–H bond distances ranging from 2.37–2.97 Å. In the third La2+ site, La2+ is bonded in a 9-coordinate geometry to nine H1- atoms. There are a spread of La–H bond distances ranging from 2.31–2.68 Å. In the fourth La2+ site, La2+ is bonded in a 9-coordinate geometry to nine H1- atoms. There are a spread of La–H bond distances ranging from 2.37–3.02 Å. There are four inequivalent Ni1+ sites. In the first Ni1+ site, Ni1+ is bonded to four H1- atoms to form corner-sharing NiH4 tetrahedra. There are a spread of Ni–H bond distances ranging from 1.55–1.66 Å. In the second Ni1+ site, Ni1+ is bonded in a rectangular see-saw-like geometry to four H1- atoms. There are a spread of Ni–H bond distances ranging from 1.54–1.63 Å. In the third Ni1+ site, Ni1+ is bonded to four H1- atoms to form corner-sharing NiH4 tetrahedra. There are a spread of Ni–H bond distances ranging from 1.56–1.69 Å. In the fourth Ni1+ site, Ni1+ is bonded in a rectangular see-saw-like geometry to four H1- atoms. There are a spread of Ni–H bond distances ranging from 1.56–1.62 Å. There are sixteen inequivalent H1- sites. In the first H1- site, H1- is bonded to one Mg2+, two La2+, and one Ni1+ atom to form a mixture of distorted edge and corner-sharing HLa2MgNi tetrahedra. In the second H1- site, H1- is bonded to one Mg2+, two La2+, and one Ni1+ atom to form a mixture of distorted edge and corner-sharing HLa2MgNi tetrahedra. In the third H1- site, H1- is bonded in a 1-coordinate geometry to one Mg2+, three La2+, and one Ni1+ atom. In the fourth H1- site, H1- is bonded in a 2-coordinate geometry to three La2+ and two Ni1+ atoms. In the fifth H1- site, H1- is bonded to two equivalent Mg2+ and two La2+ atoms to form a mixture of edge and corner-sharing HLa2Mg2 tetrahedra. In the sixth H1- site, H1- is bonded to two equivalent Mg2+ and two La2+ atoms to form HLa2Mg2 tetrahedra that share corners with seven HLa2MgNi tetrahedra and edges with two HLa3Ni tetrahedra. In the seventh H1- site, H1- is bonded to two equivalent La2+ and two Ni1+ atoms to form a mixture of distorted edge and corner-sharing HLa2Ni2 tetrahedra. In the eighth H1- site, H1- is bonded to two La2+ and two Ni1+ atoms to form distorted corner-sharing HLa2Ni2 tetrahedra. In the ninth H1- site, H1- is bonded to one Mg2+, two La2+, and one Ni1+ atom to form a mixture of distorted edge and corner-sharing HLa2MgNi tetrahedra. In the tenth H1- site, H1- is bonded to one Mg2+, two La2+, and one Ni1+ atom to form a mixture of distorted edge and corner-sharing HLa2MgNi tetrahedra. In the eleventh H1- site, H1- is bonded to three La2+ and one Ni1+ atom to form distorted HLa3Ni tetrahedra that share corners with eleven HLa2MgNi tetrahedra and edges with two HLa3Ni tetrahedra. In the twelfth H1- site, H1- is bonded in a 2-coordinate geometry to one Mg2+, two La2+, and one Ni1+ atom. In the thirteenth H1- site, H1- is bonded to three La2+ and one Ni1+ atom to form a mixture of distorted edge and corner-sharing HLa3Ni tetrahedra. In the fourteenth H1- site, H1- is bonded to one Mg2+, two La2+, and one Ni1+ atom to form a mixture of distorted edge and corner-sharing HLa2MgNi tetrahedra. In the fifteenth H1- site, H1- is bonded in a distorted single-bond geometry to one Mg2+ and two La2+ atoms. In the sixteenth H1- site, H1- is bonded in a distorted single-bond geometry to one Mg2+, four La2+, and one Ni1+ atom. « less https://doi.org/10.17188/1311657 View Dataset Materials Data on LaMg2NiH7 by Materials Project Dataset LaMg2NiH7 crystallizes in the monoclinic P2_1/c space group. The structure is three-dimensional. there are four inequivalent Mg2+ sites. In the first Mg2+ site, Mg2+ is bonded in a 5-coordinate geometry to five H1- atoms. There are a spread of Mg–H bond distances ranging from 1.95–2.30 Å. In the second Mg2+ site, Mg2+ is bonded to six H1- atoms to form distorted MgH6 pentagonal pyramids that share corners with two equivalent MgH6 pentagonal pyramids and corners with three equivalent NiH4 tetrahedra. There are a spread of Mg–H bond distances ranging from 1.89–2.17 Å. In the third Mg2+ site, Mg2+ is bonded more » in a 6-coordinate geometry to six H1- atoms. There are a spread of Mg–H bond distances ranging from 1.96–2.38 Å. In the fourth Mg2+ site, Mg2+ is bonded to six H1- atoms to form distorted MgH6 pentagonal pyramids that share corners with two equivalent MgH6 pentagonal pyramids and corners with three equivalent NiH4 tetrahedra. There are a spread of Mg–H bond distances ranging from 1.90–2.18 Å. There are two inequivalent La2+ sites. In the first La2+ site, La2+ is bonded in a 12-coordinate geometry to twelve H1- atoms. There are a spread of La–H bond distances ranging from 2.32–2.76 Å. In the second La2+ site, La2+ is bonded in a 12-coordinate geometry to twelve H1- atoms. There are a spread of La–H bond distances ranging from 2.31–2.88 Å. There are two inequivalent Ni1+ sites. In the first Ni1+ site, Ni1+ is bonded to four H1- atoms to form NiH4 tetrahedra that share corners with three equivalent MgH6 pentagonal pyramids. There is one shorter (1.57 Å) and three longer (1.58 Å) Ni–H bond length. In the second Ni1+ site, Ni1+ is bonded to four H1- atoms to form NiH4 tetrahedra that share corners with three equivalent MgH6 pentagonal pyramids. There are a spread of Ni–H bond distances ranging from 1.56–1.60 Å. There are fourteen inequivalent H1- sites. In the first H1- site, H1- is bonded in a 2-coordinate geometry to one Mg2+, two La2+, and one Ni1+ atom. In the second H1- site, H1- is bonded in a 2-coordinate geometry to one Mg2+, two equivalent La2+, and one Ni1+ atom. In the third H1- site, H1- is bonded to two Mg2+, one La2+, and one Ni1+ atom to form distorted corner-sharing HLaMg2Ni trigonal pyramids. In the fourth H1- site, H1- is bonded in a distorted trigonal non-coplanar geometry to two equivalent Mg2+, one La2+, and one Ni1+ atom. In the fifth H1- site, H1- is bonded in a 1-coordinate geometry to two equivalent Mg2+, two La2+, and one Ni1+ atom. In the sixth H1- site, H1- is bonded in a 2-coordinate geometry to one Mg2+, two equivalent La2+, and one Ni1+ atom. In the seventh H1- site, H1- is bonded to two Mg2+, one La2+, and one Ni1+ atom to form distorted corner-sharing HLaMg2Ni trigonal pyramids. In the eighth H1- site, H1- is bonded in a 3-coordinate geometry to two equivalent Mg2+, one La2+, and one Ni1+ atom. In the ninth H1- site, H1- is bonded in a distorted water-like geometry to two Mg2+ and two equivalent La2+ atoms. In the tenth H1- site, H1- is bonded to two Mg2+ and two La2+ atoms to form distorted HLa2Mg2 tetrahedra that share corners with two equivalent HLa2Mg2 tetrahedra and corners with four HLaMg2Ni trigonal pyramids. In the eleventh H1- site, H1- is bonded in a distorted water-like geometry to two Mg2+ and two equivalent La2+ atoms. In the twelfth H1- site, H1- is bonded to two Mg2+ and two La2+ atoms to form HLa2Mg2 tetrahedra that share corners with two equivalent HLa2Mg2 tetrahedra and corners with four HLaMg2Ni trigonal pyramids. In the thirteenth H1- site, H1- is bonded in a distorted trigonal planar geometry to one Mg2+ and two La2+ atoms. In the fourteenth H1- site, H1- is bonded in a distorted trigonal planar geometry to one Mg2+ and two La2+ atoms. « less https://doi.org/10.17188/1285252 View Dataset Materials Data on LaFe5H7 by Materials Project Dataset LaFe5H7 crystallizes in the hexagonal P6_3mc space group. The structure is three-dimensional. La is bonded to twelve H atoms to form LaH12 cuboctahedra that share corners with six equivalent LaH12 cuboctahedra, corners with six equivalent FeH4 trigonal pyramids, edges with three equivalent FeH4 tetrahedra, edges with six equivalent FeH4 trigonal pyramids, and faces with two equivalent LaH12 cuboctahedra. There are a spread of La–H bond distances ranging from 2.48–2.84 Å. There are three inequivalent Fe sites. In the first Fe site, Fe is bonded to four H atoms to form FeH4 trigonal pyramids that share corners with two equivalent LaH12 more » cuboctahedra, corners with two equivalent FeH4 tetrahedra, corners with four equivalent FeH4 trigonal pyramids, and edges with two equivalent LaH12 cuboctahedra. There is two shorter (1.73 Å) and two longer (1.74 Å) Fe–H bond length. In the second Fe site, Fe is bonded in a 3-coordinate geometry to four H atoms. There is three shorter (1.71 Å) and one longer (2.12 Å) Fe–H bond length. In the third Fe site, Fe is bonded to four H atoms to form FeH4 tetrahedra that share corners with six equivalent FeH4 trigonal pyramids and edges with three equivalent LaH12 cuboctahedra. There is three shorter (1.71 Å) and one longer (1.83 Å) Fe–H bond length. There are three inequivalent H sites. In the first H site, H is bonded to two equivalent La and two equivalent Fe atoms to form distorted HLa2Fe2 tetrahedra that share corners with eight equivalent HLa2Fe2 tetrahedra, corners with two equivalent HFe5 trigonal bipyramids, and edges with two equivalent HLa2Fe2 tetrahedra. In the second H site, H is bonded to five Fe atoms to form corner-sharing HFe5 trigonal bipyramids. In the third H site, H is bonded in a 3-coordinate geometry to two equivalent La and three Fe atoms. « less https://doi.org/10.17188/1272955 View Dataset Materials Data on LaFe5H12 by Materials Project Dataset LaFe5H12 crystallizes in the hexagonal P6/mmm space group. The structure is three-dimensional. La2+ is bonded to twelve equivalent H1- atoms to form LaH12 cuboctahedra that share edges with six equivalent FeH6 pentagonal pyramids. All La–H bond lengths are 2.40 Å. There are two inequivalent Fe2+ sites. In the first Fe2+ site, Fe2+ is bonded in a body-centered cubic geometry to eight equivalent H1- atoms. All Fe–H bond lengths are 1.80 Å. In the second Fe2+ site, Fe2+ is bonded to six equivalent H1- atoms to form distorted FeH6 pentagonal pyramids that share edges with three equivalent LaH12 cuboctahedra. All Fe–H more » bond lengths are 1.64 Å. H1- is bonded to one La2+ and three Fe2+ atoms to form a mixture of distorted edge and corner-sharing HLaFe3 tetrahedra. « less https://doi.org/10.17188/1272957 View Dataset Materials Data on NdMgNi4H7 by Materials Project Dataset MgNdNi4H7 crystallizes in the cubic F-43m space group. The structure is three-dimensional. Mg is bonded to six equivalent H atoms to form MgH6 octahedra that share corners with twelve equivalent NiH4 tetrahedra and faces with four equivalent NdH12 cuboctahedra. All Mg–H bond lengths are 1.98 Å. Nd is bonded to twelve equivalent H atoms to form NdH12 cuboctahedra that share corners with twelve equivalent NdH12 cuboctahedra, edges with twelve equivalent NiH4 tetrahedra, and faces with four equivalent MgH6 octahedra. All Nd–H bond lengths are 2.71 Å. Ni is bonded to four H atoms to form NiH4 tetrahedra that share corners more » with three equivalent MgH6 octahedra, corners with six equivalent NiH4 tetrahedra, and edges with three equivalent NdH12 cuboctahedra. The corner-sharing octahedral tilt angles are 57°. There is three shorter (1.63 Å) and one longer (1.64 Å) Ni–H bond length. There are two inequivalent H sites. In the first H site, H is bonded in a distorted trigonal planar geometry to one Mg, two equivalent Nd, and two equivalent Ni atoms. In the second H site, H is bonded in a tetrahedral geometry to four equivalent Ni atoms. « less https://doi.org/10.17188/1752346 View Dataset Similar Records
https://www.osti.gov/biblio/1199652
When Will BI Head Downstream? Over the past year, the business intelligence landscape has transformed drastically. Formerly, this market was comprised of a vast collection of solution providers, but it has evolved to just four major players -- IBM, SAP, Oracle and Microsoft. These BI titans have expanded through acquisition, snatching up the BI solutions provided by Cognos, Business Objects, Hyperion and ProClarity, while also growing organically, all in an attempt to increase their footprint in the enterprise applications space. When Will BI Head Downstream? Over the past year, the business intelligence (BI) landscape has transformed drastically. Formerly, this market was comprised of a vast collection of solution providers, but it has evolved to just four major players — IBM, SAP, Oracle and Microsoft. These BI titans have expanded through acquisition, snatching up the BI solutions provided by Cognos, Business Objects, Hyperion and ProClarity, while also growing organically, all in an attempt to increase their footprint in the enterprise applications space. Wrong Direction for SMBs The rapid expansion of these vendors has led them to focus on integrating platforms rather than creating new tools, which has resulted in complex and expensive solutions and stagnant innovation. This shift has not proven problematic for large enterprises that possess the required resources to support these BI solutions, as they have large IT departments full of technology-savvy employees, not to mention sizable budgets to invest in the adoption of these expensive solutions. Furthermore, these enterprises will, in fact, benefit from the end-to-end BI packages that result from the BI powerhouses’ integrated offerings and homogeneous platforms. However, what happens when small or medium-sized businesses look for BI solutions? SMBs usually do not have the same available resources to dedicate to aggregating and analyzing data. Due to complexity and cost, small businesses cannot afford to support these complete, end-to-end packages. In fact, many SMBs do not even need all the functionalities of these packages, but they cannot afford to sacrifice the benefits of a BI solution altogether, namely, the ability to manage and leverage their information assets. Needs Unmet Organizations face the challenge of increasing loads of data, and traditional spreadsheet reports are not providing the quick and easy information access that is required for them to complete their job effectively. The majority of organizations have a variety of software applications that constitute their data infrastructure, and this data is often locked within the silos of these independent applications, making it difficult to report on combined data and have a holistic view of the business. Many large enterprises have invested in developing data extraction and data warehouses to collect data from their disparate sources, but small businesses often cannot afford to overcome this technology hurdle. For example, a large enterprise may use Oracle E-Business or SAP as its enterprise resource planning (ERP) solution, Siebel as its customer relationship management (CRM) solution, and various custom-built applications to satisfy their unique needs. Off the Shelf On the other hand, a small organization may have QuickBooks to manage its finances, Salesforce as its CRM and a host of Excel spreadsheets to meet their own, distinct needs. For these SMBs, seamlessly accessing data from all these data sources is the crux of the BI data challenge. Currently, of the big four vendors, Microsoft is the closest to providing a solution to overcome this obstacle. Microsoft Excel has become the most pervasive BI tool to address the needs of small businesses. Microsoft has wisely leveraged Excel as the front-end to deliver its extensive BI offerings, by tying it to the more sophisticated stack of BI technologies it has acquired and developed. Despite this progress, Microsoft has not yet mastered the solution, opening the window of opportunity for innovation outside the walls of the big four BI vendors to fill the void created by the recent consolidation. Niche BI vendors are taking the reins on providing new tools, offering cost-effective and user-friendly tools to help small businesses leverage their information assets. Simultaneously, application providers such as QuickBooks and Salesforce, which are heavily relied upon by small businesses, are making their data easier to access; outside vendors can now create pre-built data connectors to these applications, a capability that ultimately enhances the opportunity for niche BI vendors to provide innovative, effective solutions for small businesses. BI for the Masses For example, data visualization tools, such as dashboards, provide an inexpensive and easy-to-use solution that aggregates and analyzes data. This type of niche tool provides a visual representation of data, or graphical user interface (GUI). The visual representation is customizable to fit the needs of the variety of workers it serves. All users — those with advanced analytic roles, to those collecting and entering the data — can access and understand the information that is pertinent to them, thus, bringing BI to the masses. This type of niche BI offering exhibits the innovation sparked by the BI market consolidation. No Clear Leader No one can deny that the BI landscape is maturing and expanding, but there is yet to be any one solution to deliver on the same scale as Salesforce.com did for CRM, or Intuit for business finances; in short, none of the BI vendors have yet ignited a mass adoption at all the levels of the corporation. However, the niche BI vendors have seized this opportunity to innovate and provide cost-effective and user-friendly solutions. While many fear the stagnant innovation within the “BI powerhouses,” they need not worry, as these innovative providers are looking to meet the needs of SMBs and bring BI to every business and each employee. Shadan Malik is president and CEO of iDashboards , a business intelligence dashboard software firm based in Troy, Mich. He holds two patents in the area of data visualization for dashboards, and he authored the first book on dashboard best practices,
https://www.crmbuyer.com/story/when-will-bi-head-downstream-63586.html
Gerald Harris (black trunks) vs. Mike Bronzoulis The industry pioneer in UFC, Bellator and all things MMA (aka Ultimate Fighting). MMA news, interviews, pictures, videos and more since 1997. Recommended Hotels for you: Popular Top Hits SEARCH SEARCH Search Results Go www.sherdog.com What are you looking for? Go NEWS ▼ FEATURES ▼ FIGHT FINDER ▼ PODCASTS ▼ VIDEOS RANKINGS ▼ FORUM ▼ BOXING ▼ MORE ▼ FIGHT ODDS UFC NEWS ONE NEWS PFL NEWS BELLATOR NEWS WOMEN'S MMA NEWS PREVIEWS OPINION INTERVIEWS UFC EVENTS BELLATOR EVENTS PFL EVENTS ONE CHAMPIONSHIP EVENTS FULL CALENDAR FIGHT FINDER GUIDE SHILLAN & DUFFY PODCAST THE SHEEHAN SHOW FIGHT BUSINESS PODCAST AFTER THE BELL DIVISIONAL RANKINGS POUND-FOR-POUND RANKINGS WOMEN'S POUND-FOR-POUND RANKINGS UFC DISCUSSION WORLDWIDE MMA DISCUSSION OFF TOPIC DISCUSSION PHOTOSHOPS BOXING NEWS BOXING DISCUSSION KICKBOXING AND MUAY THAI BARE KNUCKLE BOXING GRAPPLING PICTURES HOW TO WATCH CONTACT + NEWS UFC NEWS ONE NEWS PFL NEWS BELLATOR NEWS WOMEN'S MMA NEWS + FEATURES PREVIEWS OPINION INTERVIEWS + FIGHT FINDER UFC EVENTS BELLATOR EVENTS PFL EVENTS ONE CHAMPIONSHIP EVENTS FULL CALENDAR FIGHT FINDER GUIDE + PODCASTS SHILLAN & DUFFY PODCAST THE SHEEHAN SHOW FIGHT BUSINESS PODCAST AFTER THE BELL VIDEOS + RANKINGS DIVISIONAL RANKINGS POUND-FOR-POUND RANKINGS WOMEN'S POUND-FOR-POUND RANKINGS + FORUM UFC DISCUSSION WORLDWIDE MMA DISCUSSION OFF TOPIC DISCUSSION PHOTOSHOPS + BOXING BOXING NEWS BOXING DISCUSSION KICKBOXING AND MUAY THAI BARE KNUCKLE BOXING GRAPPLING + MORE PICTURES HOW TO WATCH CONTACT FIGHT ODDS MORE FROM OUR CHANNELS FIGHTER PICTURES Facebook Twitter Reddit WhatsApp Email Gerald Harris (black trunks) vs. Mike Bronzoulis Credit: Andy Hemingway Picture by: Andy Hemingway Add this picture to your site: « Back to "Gerald "Hurricane" Harris" Picture Gallery Subscribe to our Newsletter * indicates required Email Address * Latest News ALL UFC BELLATOR PFL ONE Aljamain Sterling Admits He Accepted UFC 292 Title Defense ‘Against My Will’ Video: Conor McGregor, Michael Chandler Scuffle on ‘The Ultimate Fighter 31’ Conan Silveira Discusses Alexandre Pantoja’s Title Fight, Kayla Harrison’s PFL Status Deiveson Figueiredo: Dominick Cruz Targeted Opponent for Bantamweight Debut Alistair Overeem Announces Decision to Stop Fighting: ‘This is Not My Thing Anymore’ Valentine Woodburn Replaces Injured Tresean Gore, Faces Bo Nickal at UFC 290 Aljamain Sterling Admits He Accepted UFC 292 Title Defense ‘Against My Will’ Video: Conor McGregor, Michael Chandler Scuffle on ‘The Ultimate Fighter 31’ Conan Silveira Discusses Alexandre Pantoja’s Title Fight, Kayla Harrison’s PFL Status Deiveson Figueiredo: Dominick Cruz Targeted Opponent for Bantamweight Debut Valentine Woodburn Replaces Injured Tresean Gore, Faces Bo Nickal at UFC 290 Sean Brady Reveals Septic Bursitis Forced Exit from UFC 290 Bellator’s Cris Lencioni Out of ICU, Faces Uncertain Road to Recovery Seven Preliminary Bouts Announced for Bellator 298 in South Dakota James Gonzalez Replaces Cris Lencioni, Meets James Gallagher at Bellator 298 Irish Favorites Added to Bellator 299 Lineup in Dublin Leandro Higo vs. Nikita Mikhailov Among 5 Fights Added to Bellator 298 Billing Bellator Veteran Cris Lencioni in ICU After Suffering Cardiac Arrest During Training Conan Silveira Discusses Alexandre Pantoja’s Title Fight, Kayla Harrison’s PFL Status PFL Sets 10-Bout Lineup for First 2023 Playoffs Event on Aug. 4 2022 PFL Finalist Steven Ray Announces Retirement for Second Time PFL 6 Salaries: Shane Burgos, Four Others Earn Six-Figure Paydays PFL Suspends Natan Schulte, Raush Manfio for Lackluster Fight; Postseason Updated Playoff-Bound Olivier Aubin-Mercier, Sadibou Sy Shine in PFL Regular-Season Finale Seo Hee Ham, Stamp Fairtex to Vie for Interim Title at One Fight Night 14 on Sept. 1 Regian Eersel Demolishes Challenger, Kade Ruotolo Retains at ONE Fight Night 11 ONE on Prime Video 11 ‘Eersel vs. Menshikov’ Play-by-Play & Results Demetrious Johnson Outfoxes Adriano Moraes in ONE on Prime Video 10 Headliner ONE on Prime Video 10 ‘Johnson vs. Moraes 3’ Play-by-Play & Results ONE on Prime Video 10 Weigh-in Results: Trio of Title Fights Get Green Light EVENTS / FIGHTS UFC BELLATOR PFL ONE MORE Jul 08 2023 UFC 290 Volkanovski vs. Rodriguez Jul 15 2023 UFC on ESPN 49 Holm vs. Bueno Silva Jul 22 2023 UFC Fight Night 224 Aspinall vs. Tybura Jul 29 2023 UFC 291 Poirier vs. Gaethje 2 Aug 05 2023 UFC on ESPN 50 Sandhagen vs. Nurmagomedov Jul 29 2023 Bellator MMA x Rizin Pitbull vs. McKee Aug 11 2023 Bellator 298 Storley vs. Ward Sep 23 2023 Bellator 299 Eblen vs. Edwards Jul 08 2023 Professional Fighters League PFL Europe 2: 2023 Regular Season Aug 04 2023 Professional Fighters League PFL 7: 2023 Playoffs Aug 18 2023 Professional Fighters League PFL 8: 2023 Playoffs Aug 23 2023 Professional Fighters League PFL 9: 2023 Playoffs Sep 30 2023 Professional Fighters League PFL Europe 3: 2023 Playoffs Jul 14 2023 One Championship One on Prime Video 12: Kryklia vs. Xhaja Aug 04 2023 One Championship One on Prime Video 13: Allazov vs. Grigorian Sep 01 2023 One Championship One on Prime Video 14: Stamp vs. Ham + MORE UFC FIGHTS + MORE BELLATOR FIGHTS + MORE PFL FIGHTS + MORE ONE FIGHTS POLL How did you like the Strickland-Magomedov main event of UFC Vegas 76? Wildly entertaining; everything I look for in a main event for a major promotion! Decently entertaining, but not a big fight or better than other fights on the card. Fairly dull; Magomedov only had a single round of cardio and wasn't a serious foe. It sucked Wildly entertaining; everything I look for in a main event for a major promotion! 23% Decently entertaining, but not a big fight or better than other fights on the card. 40% Fairly dull; Magomedov only had a single round of cardio and wasn't a serious foe. 27% It sucked 10% TOTAL: 640 VOTES {firstname} { "nickname" }{lastname} {firstname} { "nickname" }{lastname} {name} - {title} FIGHT FINDER TOP TRENDING FIGHTERS Rickson Gracie Ilia Topuria Olivier Aubin-Mercier Conor McGregor MORE FIGHTERS... Sadibou Sy | Abusupiyan Magomedov | Clay Collard | Solomon Renfro | Damir Ismagulov | Rinat Fakhretdinov | Yoshiaki Yatsu + FIND MORE ✓ 感谢分享 AddToAny 更多… RESOURCES About Us Contact Us Advertising AdChoices Privacy Policy Terms & Conditions Sherdog is a property of Evolve Media (Australia) PTY LTD . © 2023 All Rights Reserved. | Affiliate Disclosure: Evolve Media (Australia) PTY LTD, and its owned and operated subsidiaries may receive a small commission from the proceeds of any product(s) sold through affiliate and direct partner links. X monitoring_string = "5eb5a0f65cbe346d74f978e14db1b00d"
https://www.sherdog.com/pictures/gallery/fighter/f_17903/171047/
Press Briefing by Mike McCurry | The American Presidency Project Press Briefing by Mike McCurry The Briefing Room 2:25 P.M. EST MR. MCCURRY: Let me do a couple of announcements. The first one that I have -- David is going to do a chore for me so we can get underway here. Item the first, the President of the United States of America will travel to Lansing, Michigan, on Thursday, March 6, to address the Michigan State Legislature. This is one of several trips you've heard the President say he will take in the course of the coming year. The Vice President will be out, too, to address in appropriate state settings the challenges that exist for all levels of government as we deal with reforming education and reforming welfare. The President, as he did with the Maryland State Legislature, will specifically talk about welfare reform, the important role the states play, certainly the very interesting experience in Michigan with that subject. And he'll also talk about the federal aspects that exist as we reform welfare as we know it. And then, obviously, the President will continue to press his argument about reforming education, the things that we need to do to have world-class standards for quality in America's schools, picking up on some of the same themes that you heard him address earlier today in front of the Business Council. Q: How are you picking the states, Mike? Q: Starts with M. (Laughter.) MR. MCCURRY: There's a lot that goes into it. It's a complicated process -- and places that are fun to go, interesting settings for the speech and interesting people to talk to. And certainly, the Governor is an interesting person as well. Q: In other words, you have no idea why we're going there. (Laughter.) MR. MCCURRY: Because it's an interesting state, it's a great state. I lived in Lansing one time in my life. That's not the reason we're going. (Laughter.) Okay, now, moving on -- I just want you to know in case you did not know that the President's National Security Advisor and the Deputy Secretary of State are in Haiti today. Sandy Berger and Strobe Talbott went down there for a day of meetings with President Preval, other senior Haitian officials. There aims, to review the important progress that Haiti has made in consolidating and strengthening its democracy and encourage them to make continued efforts at reform, to do more to limit violence, to work on the progress that we've seen in Haiti, since Haiti's liberation from the de facto regime. Have a full day of meetings down there. Maybe David can tell you more about that if you are interested. Item the third. I'm going to break an embargo, sort of. Some of you know that the Centers for Disease Control is releasing at 4:00 p.m. today some very important statistics about AIDS, and I'm going to share with you a short statement from the President. We have it in written in form as well. The President is encouraged by today's report from the Centers for Disease Control on an historic reduction in the number of Americans dying from AIDS, and further evidence that this very terrible epidemic, in the President's words, "is beginning to yield to our sustained national public health investment in AIDS research, prevention and care." The President in his statement says, "In these last four years, we have steadily increased our national commitment to fighting HIV and AIDS. We have increased funding for the programs by more than 50 percent, developed the first-ever national AIDS strategy, accelerated approval of successful new AIDS drugs by the Food and Drug Administration, strengthened and focused the Office of AIDS Research at the National Institutes of Health and created a White House Office on National AIDS Policy. And we have made good progress. But it is also clear that the AIDS epidemic is not over. We must continue to press ahead if we are to meet our ultimate goal to end this epidemic to find a cure for those who are living with HIV and a vaccine to protect everyone from this virus." Q: Mike, the numbers of death are down, but are the numbers of those contracting HIV or those with AIDS, are they down? MR. MCCURRY: The report addresses some of that. That is, as I say, embargoed. The CDC's numbers are embargoed until 4:00 p.m. We can talk a little bit more about that at that time. Q: And related to that, there's been a push over the past couple of weeks to get the federal government to endorse some sort of needle exchange. Where is the White House on that? MR. MCCURRY: Secretary Shalala has been looking at some of the data coming in on the needle exchange program. I should really leave it in her province to address that. That's ultimately a call that has to be made on public health policy grounds. They're looking at the results of some of the experimentation that has occurred in local jurisdictions. Q: How do you read the polling on the fundraising business? Is this something -- MR. JOHNSON: So you already have this, Terry, you don't need it? Q: We'd like to hear the American version. We have what the Russians say about it. MR. JOHNSON: President Yeltsin spoke today beginning about noon Eastern Standard Time, for about 20 minutes -- Clinton and Yeltsin. Q: Start again. MR. JOHNSON: The President of the United States of America and the President of the Russian Federation, Mr. Yeltsin, spoke today at about noon Eastern Standard Time. Their conversation lasted about 20 minutes. As some of you know, they used consecutive translation. This is part of a continuing pattern of consultations that the United States and the Russian Federation have had as we lead up to the summit in Helsinki. They followed up on some of the issues that were discussed when Secretary Albright was in Moscow last week, and when Prime Minister Chernomyrdin was here in Washington for the Gore-Chernomyrdin Commission meetings earlier in the month. They agreed on basically a three-part agenda for the Helsinki summit. The first item is going to be European security and the efforts of the United States and its allies and the Russian Federation to create a new security architecture for Europe, which reflects the realities of the post-Cold War world. They're going to spend some time on the second item, and that is arms control, and our efforts to lower the level of armaments, particular nuclear arms; and third, on economic issues, and they're going to concentrate there on the economic interaction between the United States and the Russian Federation and our efforts to support their reform process and their economy as it moves forward. We're going to have expert teams from the United States traveling to Moscow over the course of the next few weeks in advance of the summit on all three of those agenda items, and their work there will help prepare for the summit in Helsinki and we believe make it a very successful venture. The President and President Yeltsin both look forward to meeting with each other and they closed off with that. Q: David, do you expect President Clinton, by the time he gets to Helsinki, to be able to offer Yeltsin a specific START III proposal with some numbers as to a lower limit of nuclear weapons? MR. JOHNSON: I know that as our expert teams travel to Moscow, arms control, and particularly nuclear arms control is one of the items on the agenda. I don't think I'm in a position to forecast where we're going to be on that at the time, but we certainly hope to move that process forward in Helsinki. Q: Can you tell us how much work is being done at least at this end? MR. JOHNSON: Well, I can tell you that an arms control team will be going soon in order to try to work out some things with the Russians in order to move this process forward. Q: Did they talk today about NATO expansion? MR. JOHNSON: They talked about European security; NATO expansion was mentioned, but this was basically a reasonably abbreviated call to agree on the agenda and to talk about the teams that are going to be going forward. Q: Anything at all following up on Yeltsin's comments and some of the hints of new flexibility, perhaps? MR. JOHNSON: No, it wasn't an opportunity or it wasn't taken as an opportunity to negotiate on these specific issues; more to agree on this being the agenda that we need to move forward on for the summit. Q: But, David, do you have an understanding of what this compromise that Yeltsin suggested might be accepted at Helsinki consists of? What kind of compromise is he talking about? MR. JOHNSON: I know that when our teams get there next week -- not necessarily next week on this issue, but during the course of the next few weeks, one of the things they're going to be talking about is how we move forward on the NATO-Russian charter and how we move forward on the other issues related to NATO expansion. But this was not a detailed conversation about those issues, and I don't think it's going to be productive to try to move that forward here. Q: David, is Yeltsin expected to attend the G-7 in Denver? MR. JOHNSON: He's expected to attend the Denver summit as far as I'm aware, yes. Q: Can you say what support you're offering on their economic reforms, more specifically than simply the word "support"? MR. JOHNSON: Not at this point. I think that as the agenda item gets further developed during the expert team meetings, we might be able to talk about that a little further. But I can't -- MR. JOHNSON: I can't help you with that today. Q: Who initiated the call? MR. JOHNSON: I believe we did, but let me make sure. MR. MCCURRY: If I'm not mistaken, I think in the President's letter to President Yeltsin, delivered by Secretary Albright, there was also a suggestion that they touch base by phone sometime sooner. That was one of the outcomes of that conversation. And obviously, on the question of what type of discussions we are having with the Russian Federation, remember that those are discussions between NATO and the Russian Federation, and Secretary General Solana has been instrumental in presenting on behalf of the Alliance many of the ideas we have for the development of a newly defined relationship between NATO and the Russian Federation. Q: Can you address this polling on the fundraising question? Is it something -- do you think the polling looks good and is this something the White House can weather quickly, or long-term, or how? MR. MCCURRY: You know, I didn't look at it that carefully. Are you talking about the CNN-USA Today poll? As a general proposition, the President believes that the American people are interested in seeing progress on things like balancing the budget, reforming our welfare system, having world-class standards on education and protecting Americans from crime in neighborhoods -- issues that he has been addressing each and every one of the past several days. That's what he was elected to do, he believes, by the American people. And I think that as long as the American people understand that that's what he gets up, comes here and works on each and every day, they will be generally satisfied with his performance. And that's the best way to interpret, I think, that poll. Q: Mike, what is the White House reaction to Mr. Greenspan's remarks on the stock market? And is the administration prepared to take any action should there be -- when there is a substantial drop in the stock market? MR. MCCURRY: We leave it up to the Chairman of the Federal Reserve to move the market, and we don't attempt to do it here, so we decline to have any specific comment on his remarks. I think they spoke -- he certainly spoke for himself, but he's an astute observer of national economic trends. And the President appreciates the opportunity he has from time to time to share views with him. Q: Mike, you didn't include campaign finance reform in that list of tasks that the President gets up every morning to perform. MR. MCCURRY: Campaign finance reform is indeed one of them. He continues to address that, has sessions working on that. I expect that he will have some further things to say on that next week, as a matter of fact, and that is a very high priority, because it addresses while it's -- going back to the question, it's not indicated as a subject of high concern or interest on the part of the American people, it is a subject of high interest to the President himself and it's one that he believes it's important to continue to work on. Q: But so far all he's done on that is just a lot of exhortations. MR. MCCURRY: Well, that's not accurate. He has worked closely with those who are sponsors of bipartisan legislation in both the House and the Senate, to discuss with them how we can advance that legislation. There's been a great deal of work done by the President and by the staff here at the White House, working with congressional staffs to plan the best way to advance that legislation and the best way to move it forward. I think it's a lot more than the bully pulpit. Q: Well, is he prepared to use some hardball tactics to tie campaign finance reform to some of the Republican priorities? MR. MCCURRY: I think he wants to, working with the sponsors of the legislation, find the best way to take this important opportunity to advance that very important legislation. This will be an ongoing effort in the course of the coming weeks because there's nothing that's currently pending on either the floor of the House or the Senate. But it's one that we will work with members to advance. Q: In view of the admission by that abortion rights official that he lied in certain aspects of the partial birth abortion controversy, that's caused a stir up on the Hill, whereby several Democratic senators are beginning to say they may change their votes the next time around. So if such a bill came up to the President for signature again, if it were passed, would he veto it this time? MR. MCCURRY: Well, remember, the President's goal on this subject has been what he told Congress he wanted to see happen in his most recent correspondence with the Hill on the subject. He said he does not believe that the procedure is always used in circumstances that meet the President's own standards, which is that there should be exception only for cases in which the serious adverse health consequences to a woman are indicated. But the President indicated the procedure may well be used in those situations, but as a general proposition he does not support use of the practice, certainly not as an elective practice. So he indicated at the time he corresponded last with Congress that he would sign legislation banning that procedure if it had that exception. That continues to be his position, and we would hope that as any possible legislation moves, it would take into account the President very strong feelings on that need for a narrowly defined exception. Q: Did the President indicate any personal reaction to Mr. Fitzsimmons' statement saying that he lied about the statistics? MR. MCCURRY: Not that he shared with me. Q: Would this make him more inclined, though, then, to see some sort of restrictions put on when it can be performed? MR. MCCURRY: I don't know that the statements by -- I don't know that his statements affected the President's thinking on the subjects. One, the President had thought about a lot as he had to consider the legislation passed by Congress, as he had to exercise a right to veto that legislation. He's pretty well developed his own thinking about how we limit this procedure and why it should be limited, given that it needs to have one specific exception for health consequences that are adverse to a woman. Q: What kind of timetable does the President have in mind for this announcement that he mentioned yesterday regarding the CPI, and is he talking about an alternative to Senator Lott's proposal, or accepting Senator Lott's proposal? MR. MCCURRY: I don't know that he has a specific timetable in mind. I do believe that he thinks it's important working with the bipartisan congressional leadership to do those things that he has identified in the past to assure that, first, we do have cost of living adjustments that allow Americans to see the value of benefits protected and allow them to see some of the tax incidents that would otherwise be indicated by inflation put under some measurable limit. But he also has the goal of making sure that any cost of living adjustment is as accurate as possible. And I think sharing the sentiment that Senator Lott expressed, he does believe that that should be based on broad technical agreement from experts on what the right measure of inflation is. Now, how you get to the process that you make that measurement is something that we've had good conversations with Senator Lott and others on the Hill about. We haven't had any conversations with Senator Lott that we haven't had with Democratic leaders on Capitol Hill. They will all have to come together as they look at that question and as they think of how they find the right process for addressing it. Now, the idea of a commission has been suggested by Senator Lott, there may be others with other ideas, too. We intend to pursue those in the discussions that we have in coming days. Q: How recently has he spoken with Senator Lott about this? MR. MCCURRY: I don't know when he last spoke to him, but I know that some members of our staff have been in fairly recent direct contact with the Senator and his staff. Q: But is the President going to make some announcement? He used the phrase "not too distant future" about this subject. MR. MCCURRY: Well, I think I did a good job of not defining "not too distant future," but it's one that is clearly that we've been working on and having conversations with people on the Hill about. Q: Mike, is the White House willing to provide the Senate Intelligence Committee with the full FBI background report on Tony Lake? MR. MCCURRY: The White House is more than willing to work with Senator Shelby and members of the staff to satisfy any concerns they have. And specifically with regard to any background work that has been done, we will work closely with the staff and address their concerns, make sure that they feel they have information that they need to satisfy any questions that they might have. Q: Well, let me try it a different way. Is the White House irreparably adverse to providing this full report to the committee? MR. MCCURRY: Well, we're interested in satisfying concerns that senators may have, and there may be a number of ways to do that. We'll work in an amicable fashion with Senator Shelby and his staff to satisfy those concerns. There may be a number of ways to do that, and my understanding is that we have good conversations underway with his staff to resolve. Q: Do you think it's a legitimate request by Shelby for the full report? MR. MCCURRY: I believe that it's legitimate for senators to exercise their advice and consent role, and if they have concerns we attempt to address them in the course of a nomination proceeding. Q: Mike, the DNC has apparently completed an internal review of its campaign collection procedures and is going to implement even newer solicitation procedures tomorrow. Have they shared this review with the White House, and do you have an you sort advance thoughts on how well they did? MR. MCCURRY: I know that they have indicated to us that they plan to complete that review and make it public, I believe, tomorrow. But my understanding was that we probably would not get a briefing on it until later in the day today. So I'd leave it to them to make the announcement. Q: Have any of the five budget task forces been assembled yet? MR. MCCURRY: John Hilley, who's the President's Director of Legislative Affairs -- newly empowered with an even bigger and better title than that, I think -- has been on the Hill, and there has been considerable progress on structuring those five working groups. We probably will leave it to those who are working with on the Hill to talk about those more. But they're in formation and I think have got a good idea now of how they're going to proceed, who's going to participate, what the specific agenda items are going to be. I suspect there will be more to say on that in coming days. Q: Is the President continuing the practice of inviting big money contributors to the White House as overnight guests? MR. MCCURRY: I haven't seen any here recently. Q: Does that mean that he has stopped, I mean, that he has decided not to invite them? MR. MCCURRY: No, it just means that there haven't been any here recently. Q: What do you mean by "recently," Mike? MR. MCCURRY: I'd have to check. We released to you the names of everyone who stayed through calendar year 1996. I don't have a list of those who stayed, if any, in 1997. Q: So do you assume that the practice has stopped? MR. MCCURRY: That would imply that he's made some conscious decision to end the practice, and I think he addressed himself to why he thinks it's an appropriate practice yesterday. Q: Mike, Senator Archer held a news conference today at which he said that the FY'98 budget would have triggers that cut off the tax cut provisions on December 31st, 2000. Is that an accurate characterization of the budget? MR. MCCURRY: The accurate characterization of the budget is the formal submission of the proposal that we made and the language therein. We're now working on a technical question of how you write legislative language that would implement some aspects of the trigger-on, trigger-off proceedings, and my understanding from several of the experts who tried to educate me on this is that it's a very highly technical matter that is best briefed by tax experts at Treasury or elsewhere. Q: Do you dispute what he said? He's saying, regardless of whether it was in the budget, or not, and you were, in fact, deliberately vague in the budget's mention itself -- do you dispute what he saying, that you'd cut them off at the end of 2000? MR. MCCURRY: No, our view is that there is no need for the provision anyhow, because as projected by the Office of Management and Budget, the budget is in surplus at the year 2002, but we have made it clear to Congress that we will work with them on developing the correct mechanism for alternative scenarios, and we think we can do that in a fashion that irons out any disagreements. The important thing is, the President has a proposal for targeted tax relief that fits within the structure of a balanced budget proposal. The President's confident that the budget that he's presented will balance by the year 2002, and also achieve the tax relief that he's proposed. Q: Mike, there's no need for what provision? MR. MCCURRY: The trigger provision. Q: But, Mike, if I can follow on that, the legislation that the administration sent up to the Hill, which technically is what it is that the President is proposing, would take four of his tax breaks and end them in 2000. So how could they be permanent? MR. MCCURRY: That's not under a scenario that the President foresees, and we are working with the Congress on legislative language that will address alternative scenarios. Q: Archer also asked the President to take a second look at his budget plan. Will he or Franklin Raines be taking a second look to see -- MR. MCCURRY: We've got a very good, credible balanced budget proposal, and the important thing is for Congress to take a look at the President's proposal. It's in some ways encouraging that Chairman Archer is doing exactly that and they're looking for the right ways to address certain aspects of the President's tax proposals and picking up on the earlier question, one of the five working groups that's trying to find some areas where we can develop common approaches with Congress is in the area of taxation. So there's more work to be done within that context on exactly these kinds of issues. Q: On Mexico certification, is that tomorrow? MR. MCCURRY: That's not clear to me. The State Department has not forwarded to the President any recommendations at this point, and the President will want to have discussions with his advisors, there will be others here who will want to meet and work through those issues, and I don't rule it out for tomorrow, but it's not necessarily tomorrow. Q: How seriously do you take the critics from Colombia and Mexico against the principle? MR. MCCURRY: We're aware of those criticisms, but we also have U.S. law that the President's responsible for enforcing. The specific determinations on certification are delegated to the Secretary of State, and the Secretary of State will forward her recommendations to the White House and we will follow our law. Q: Are you expecting that recommendation to come over today? MR. MCCURRY: That's not clear. But in any event, the President will not likely turn his attention to it until tomorrow. Q: Is he going to announce Colombia and Mexico at the same time? MR. MCCURRY: That's traditionally done, but I don't want to speculate on announcements until they're reviewed by the President. Q: Mike, how does he respond to the complaints from Senator Feinstein, Gramm, Gephardt, some of the others on the Hill on this issue, and how does he plan to address those concerns? MR. MCCURRY: Well, depending on -- after carefully looking at the law, looking at the Secretary's recommendations and doing what the President believes is right, if he has some disagreement with those members he'll defend the decision that he makes. Q: Are those valid concerns, though, that they're -- MR. MCCURRY: Well, I think they're motivated by the same thing the President is motivated by, which is a desire to see maximum effort done to control the flow of illegal drugs into the United States. And I think that encouraging the best possible cooperation from the Mexican government is a goal that we share with those members. Q: On a related topic, do you have any insight into the American who was kidnapped and murdered and found in Colombia? Was that seen as a warning of -- MR. MCCURRY: I don't have any information with me here. I know that they've addressed that at the State Department and I think briefed on it yesterday. Q: Do you anticipate the decision, no matter what it is, would not affect the President's trip to Mexico City? MR. MCCURRY: I don't believe that the President's decision would likely affect the President's planned travel to Mexico. Q: Mike, this morning the trustees of the President's legal defense fund put out their report on the second half of the year. The outstanding legal bills now total $2.25 million and the contributions for the period total only about $62,000. MR. MCCURRY: I believe that the President is painfully aware of those facts. Q: How big a burden is this on the First Family and how are they ever going to pay off these bills? MR. MCCURRY: Well, I refer you to the President when he's addressed that question in the past. He said he's young and vigorous and expects to be an employable ex-President and he expects to honor his obligation to pay those bills. He said that in the past and that remains his view. Q: Secretary Cuomo is on the Hill testifying about affordable housing rescue plans and that's part of the President's budget. What are the key points that the President wanted Cuomo to put out to Congress today? MR. MCCURRY: Whichever ones he's making. Q: Mike, this question may strike you as naive, but since Harold Ickes got his $125,000 salary paid by the taxpayer, why should he be spending apparently the bulk of his time doing things like negotiating with consultants, arranging the Democratic fundraising and running the campaign? Wasn't he essentially working for the campaign and for the DNC? MR. MCCURRY: Well, if you're familiar with Harold and his long hours of work here, I think you'd be mischaracterizing the work he did. He had a large range of assignments as Deputy White House Chief of Staff, some of them involved the supervision of the President's political efforts. But he also had a large volume of additional duties. I wouldn't characterize his work here based on only those documents you've seen as a result of our disclosure. Q: Did the Counsel's Office ever have to review, make a formal review of what percentage of time he spent on political duties versus official duties? And is that an appropriate mix? MR. MCCURRY: That's not required by the law because the only requirement we have, which is a voluntary one, not in statute, is that folks at the White House devote a 40-hour work week to the taxpayers. And there is no question in anyone's mind here, I hope, that Harold at least satisfied that obligation. But he also had -- you can do political work here at the White House, there's nothing that restricts that. The restrictions pertain to the use of government resources in connection with political work. Q: Mike, I believe the President reacted to the shooting in Fayetteville when it happened, the verdict came down and the former paratrooper was found guilty. Did the President catch the verdict? Did he have a reaction to it? And did he have any thoughts about the Army probe? MR. MCCURRY: Have not had a chance to talk to him about that. I don't know whether he had a reaction or not. Q: Mike, the President in his news conference mentioned a need to get to the bottom of Gulf War illnesses. The Pentagon today has indicated that there are -- it's discovered that more documents from its chemical and biological weapons log are missing, and the National Commander of the American Legion has a release out calling for an independent commission with subpoena power to get to the bottom of it. How would you assess that? MR. MCCURRY: The President has a lot of faith and confidence in his advisory commission, as he said yesterday. They've done a lot of work; in fact, it's arguable that the President's effort, stimulated by the First Lady's interest and her own discussion with a number of veterans and their families, the effort to put that commission in place is what has really triggered the effort, as the President said, to leave no stone unturned in looking at what happened during the previous administration. That continues to be our view, that commission continues to work. The President gave them an additional mandate to look at some of the questions related to the discovery of documents yesterday, as you know, and the President has full faith and confidence that the advisory commission will be able to produce the kinds of answers, or at least get the --if not the answers, at least be able to establish what documentary record ought to exist in the work that they're doing. Q: Does the President believe that they're hampered at all by a lack of subpoena power? MR. MCCURRY: I'm not aware that there has been any issue in which documents that the commission has obtained were not obtainable, but I would really refer you over to them and let them answer that question. Q: Just getting back for a moment to the question of partial-birth abortions, if, in fact, a bill comes up again the way it did the last time without the health exception that the President is demanding, would he veto it again? MR. MCCURRY: You know the President's strong feelings on that, and you can imagine what his action would be. But we believe for those who are truly concerned about ending the practice as an elective practice or ending it in circumstances in which it's not indicated, that there would be a willingness on the part of those members pursuing this matter on the Hill to accommodate the President's very deeply felt concerns about serious health consequences for a mother. And if they address those satisfactorily, the President would look forward to signing legislation rather than having to exercise a veto. Q: Mike, just to follow on that, if I recall, did he not in his veto announcement cite statistics and the statistics that this doctor had -- does he not feel ill-served about the fact that the stats may have been -- MR. MCCURRY: If it was clear -- we cited five statistics in particular. The five women who stood with him in the room as he exercised the veto. The number is not as significant as the principle. If it's important for the life of a mother or for her health, which would be seriously and adversely affected if the procedure was not available, then it's important to have that exception available. Q: Mike, back to Mr. Ickes. When the administration first came in, the archivist put out a note telling everyone to preserve their documents for the library for historical records. Did he violate any rules by taking this stack of documents with him outside? MR. MCCURRY: He did not. The governing act is the Presidential Records Act. It allows individuals to retain personal records, and there's a very complete description that's available of what personal records constitute. The White House Legal Counsel has reviewed those documents that were disclosed, and is of the opinion that he properly had custody of those documents. Q: A couple of things on tobacco. Number one, does the President plan to do anything tomorrow to mark the beginning of the FDA regulations? And, second, although Governor Allen has apparently countermanded his State Attorney General's declaration that he wasn't going to enforce the I.D. regulations, do his statements cause any sort of concern as to whether or not the regulations are going to be enforced? MR. MCCURRY: Well, a couple things. First question, the President will have an opportunity tomorrow to mark the first effective day of his proposed regulations. They do go into effect tomorrow. The President will be joined by Secretary Shalala and Dr. David Kessler, who I think will be serving his last day as Administrator of the FDA. And the President will talk about the importance of restricting access and advertising of tobacco as it pertains to kids. The President's public health goal here is very clear, which is to reduce tobacco smoking by children. And we believe a very effective set of regulations aimed at exactly that purpose. We expect cooperation by local authorities in administering the federal law, although it's ultimately the federal government's task to enforce the regulations that go into effect tomorrow. But we believe that state and local governments will certainly see the importance of addressing the public health priorities that the President has defined -- curbing tobacco use by kids. The regulations have been very carefully drawn up with a lot of input from local public health authorities and from local jurisdictions. And we'll be able to address any concerns that states have. We would, of course, welcome any decision by the state of Virginia to assist in the effort to enforce these federal regulations. Q: Mike, speaking of Dr. Kessler, might he be close to naming Dr. Kessler's successor? MR. MCCURRY: No, in fact, tomorrow Dr. Michael Friedman, who has been the lead deputy of the FDA and is an acknowledged expert on many areas of public health that the administration has to address, will take up his position, I believe, as Acting Director. And the search for a replacement goes on. They're looking for someone of excellent reputation, someone who can continue the very fine and courageous service that Dr. Kessler has rendered to the country. Q: Mike, speaking of health appointments, does the President plan to leave the post of Surgeon General vacant? MR. MCCURRY: Not necessarily. There has been a search underway for a candidate for Surgeon General. There are still some issues that are being addressed and conversations we're having with the Department of Health and Human Services on the subject. But I wouldn't rule out the possibility that he would send forward a candidate for Surgeon General. Q: What kind of issues? MR. MCCURRY: The question of how best to structure the administration's pursuit of public health policy goals. Q: Mike, in preparing for G-7 summit, is Ickes also going to be Clinton's policy Sherpa, or is his role merely confined for the logistics of organizing the summit? MR. MCCURRY: He has given his extraordinary ability in organizing large events. You know, he was also principally responsible for supervising the work done on our national convention and also the Inauguration itself. So his familiarity with large events of consequence is I think well-known. But we have a very meticulous policy process in place that has worked well for United States participation in G-7 summits and involves the National Security Council, the National Economic Council. We have policy people and then others in our government who participate in a lot of the sessions that worked up to the G-7. Secretary Rubin, as you know, was just at a G-7 finance ministers meeting recently, so the policy process would be the one that we've used in the past. Q: On Gulf War, I've been told that U.S. policy would have been to go ahead with blowing up the depot even if there was firm CIA knowledge that there was chemical weapons, that the decision was made to go ahead anyway with it. Can you look into that? MR. MCCURRY: I'm not going to attempt to look into that. If you look at the briefing transcripts over at the Pentagon from Tuesday and presumably from today, too, you will see that they spent probably well over an hour on exactly that subject Tuesday, and I would refer you to what they've already said there. Q: On the question on the list of names of overnight guests released on Tuesday, in the spirit of disclosure, can the White House also release the dates that were associated with those days? MR. MCCURRY: I'll check and see. It's, as a practical matter, a little hard to do. A lot of people, particularly their closest friends, stayed on a number of occasions and stayed multiple times, and sometimes stayed for more than one night at a time. Typically, if they had family up, for example, they would stay for two or three days, or longer sometimes. But if you're interested in a particular person, we'll see if we can help you in identifying dates. Q: Can we get the number of people who stayed and the number of nights they stayed? MR. MCCURRY: I'll work with Ann Lewis and see what we can provide. MR. MCCURRY: I don't know the answer to that. If you can call Ann Lewis, she might be able to help you. Q: Getting back to the Cuomo on the Hill, how was he received? MR. MCCURRY: I'm not familiar with his testimony on the Hill, so you will have to -- we can check for you. We assume that he got the very warm and encouraging reception that he deserves. Q: Can you provide any specifics for what the President and the First Lady will be doing with Chelsea in New York for her birthday this coming weekend -- what shows, ballet, whatever? MR. MCCURRY: No. Look, it's a family occasion and it's a private outing for the family. They're going to go up, they're going to take in some shows, probably have some meals and have some fun. I think I'll leave it at that. Q: Back to the budget for a second. Republican leaders yesterday said that they plan to do a budget resolution of their own in consultation with the White House and try to get those broad outlines, broad numbers done by the middle of March. Does that process meet with the President's expectations about how to craft a bipartisan budget and get it done by Thanksgiving? MR. MCCURRY: I think the President is satisfied that the Republican leadership is working toward the same goal that he's working towards -- a balanced budget that would achieve something historic -- balancing the budget by the year 2002, there will be different ways that the two branches of government will go about getting that done, but at the end of the day they will come together and they'll come together and get the job done, and he believes that. Q: Is the White House prepared to participate in the process of crafting a resolution by mid-March? MR. MCCURRY: They write the resolution on Capitol Hill, so we don't directly participate. But in a sense, we've already given them a good head start on writing a resolution by giving them a very credible balanced budget proposal. Q: Actually, what they were describing yesterday was a process in which they would reach out by committee to the available Cabinet Secretaries and get them to provide very direct input. MR. MCCURRY: That's exactly how the budget process works. Interestingly, it's how it's supposed to work. In previous years, it hasn't worked because there has been a standoff between the two branches of government. What you're seeing is a return to regular order in the implementation of the budget act schedule for consideration, which has not always been Congress's disposition and not always been there ability to meet the statutory-imposed deadlines. So we're encouraged by what we're seeing. They're dealing with the President's budget seriously. They're seriously considering the President's proposals. There is engagement on a range of issues that are related to balance the budget. But no one disputes the President's determination -- we don't dispute their determination -- to arrive at the goal. We've got some differences on how we're going to do it, but we believe we can work those out. Q: Along that line, do you think the latest of the blue dog proposal might pose a possible middle ground? It has means testing in it for Medicare. It also has a CPI provision in it. MR. MCCURRY: It's got a lot of interesting ideas in it, and produced by a lot of people whose ideas we take very seriously, but it becomes one of those documents now in the mix of consideration as we work together with the legislative branch to get the job done. Q: On the topic of the Golden Venture detainees released from prison yesterday, why did it take the President so long to order their release? MR. MCCURRY: He took the time necessary to make the decision correctly and appropriately. Q: -- softening in his position on asylum seekers? MR. MCCURRY: No, as our statement at the time indicated, it did not. Q: I have a question from the home office. How does the President feel about -- MR. MCCURRY: Which home office is that? Q: The home office of my news organization. How does the President feel about McDonald's lowering the price of a Big Mac to 55 cents? MR. MCCURRY: He hasn't had one in such a long time that I doubt that he's got any particular point of view on that. MR. MCCURRY: He went and got a cup of coffee in Hawaii, but that was the first time in probably a couple of years that he had been. Q: -- but what is the U.S. government's position on the Israeli decision to go ahead with building that new settlement at Har Homa in East Jerusalem? MR. MCCURRY: You really want me to do that one? Let me -- it's one that I will not attempt to do without visual aids. Our view is that -- our focus now has to be one building confidence and trust between the parties, between the Israelis and the Palestinians. That's the way for them to cement their relationship. That's the way for them to create the momentum that the President called on in the aftermath of the Hebron agreement. The Israeli's government's decision on Har Homa is not a step that will build confidence. Frankly, we would have preferred that the decision not have been taken. THE PRESS: Thank you. MR. MCCURRY: Boy I tell, if I had tried that at the State Department, we would have been here for another hour. END 3:09 P.M. EST William J. Clinton, Press Briefing by Mike McCurry Online by Gerhard Peters and John T. Woolley, The American Presidency Project https://www.presidency.ucsb.edu/node/270359 Filed Under Categories Press Office Press Briefings
https://www.presidency.ucsb.edu/documents/press-briefing-mike-mccurry-551
Designs | Free Full-Text | A New Off-Board Electrical Vehicle Battery Charger: Topology, Analysis and Design The extensive use of electric vehicles (EVs) can reduce concerns about climate change and fossil fuel shortages. One of the main obstacles to accepting EVs is the limitation of charging stations, which consists of high-charge batteries and high-energy charging infrastructure. A new transformer-less topology for boost dc-dc converters with higher power density and lower switch stress is proposed in this paper, which may be a suitable candidate for high-power fast-charging battery chargers of EVs. Throughout this paper, two operating modes of the proposed converter, continuous current mode (CCM) and discontinuous current mode (DCM), are analyzed in detail. Additionally, critical inductances and design considerations for the proposed converter are calculated. Finally, real-time verifications based on hardware-in-loop (HiL) simulation are carried out to assess the correctness of the proposed theoretical concepts. A New Off-Board Electrical Vehicle Battery Charger: Topology, Analysis and Design Meysam Gheisarnejad 2 , Mahdieh S. Sadabadi 3 and Mohammad-Hassan Khooban 2,* 1 2 Department of Electrical and Computer Engineering, Aarhus University, 8200 Aarhus, Denmark 3 Department of Automatic Control and Systems Engineering, University of Sheffield, Sheffield S1 3JD, UK * Author to whom correspondence should be addressed. Designs 2021 , 5 (3), 51; https://doi.org/10.3390/designs5030051 Received: 16 May 2021 / Revised: 3 July 2021 / Accepted: 26 July 2021 / Published: 3 August 2021 Abstract : The extensive use of electric vehicles (EVs) can reduce concerns about climate change and fossil fuel shortages. One of the main obstacles to accepting EVs is the limitation of charging stations, which consists of high-charge batteries and high-energy charging infrastructure. A new transformer-less topology for boost dc-dc converters with higher power density and lower switch stress is proposed in this paper, which may be a suitable candidate for high-power fast-charging battery chargers of EVs. Throughout this paper, two operating modes of the proposed converter, continuous current mode (CCM) and discontinuous current mode (DCM), are analyzed in detail. Additionally, critical inductances and design considerations for the proposed converter are calculated. Finally, real-time verifications based on hardware-in-loop (HiL) simulation are carried out to assess the correctness of the proposed theoretical concepts. Keywords: electric vehicle ; battery charger ; boost converter ; off-board charger 1. Introduction Environmental considerations, the problem of air pollution, the reduction of fossil energy levels, and their cost are the most critical concerns facing governments [ 1 , 2 ]. The use of EVs can solve some of these problems. In some cases, these vehicles can inject electricity into the grid (vehicle-to-grid (V2G) technology) and thus play an essential role in decommissioning [ 3 ]. Battery chargers, the cable between vehicle and charger, feeder, material type and cost, connector, transformer, condition of the ground surface, and peak voltage control are among the challenges facing EVs [ 4 , 5 ]. Electric car battery charging systems can be divided into two groups: on-board and off-board [ 6 ]. On-board systems, which are themselves subdivided into subcategories of AC level 1 and AC level 2, are installed on electric cars. The ability to connect to the distribution power system directly, no need to build a charging station, and its cost are the advantages of this category. However, the need to install a battery charging system in each car, increasing the cost of the car production, low power, and duration time of battery charging are the disadvantages of this type of charging system. Charging of EVs in off-board systems is carried out by charging stations [ 7 ]. In other words, the equipment related to the charging section of EVs, except for the battery, is only at the charging station. Therefore, the cost of producing electric cars is reduced compared to on-board ones. On the other hand, the power density and efficiency are improved compared to on-board systems, and the charging time is significantly reduced. This type of electric vehicle charging system, also known as DC fast charger (level 3), is classified into two types: ac-connected and dc-connected [ 8 ]. In ac-connected systems, power is supplied from the grid by a transformer, and other equipment is transferred to ac-bus by an ac/dc converter and a dc/dc converter for each output port. Ac-connected systems are categorized into two categories: extreme fast charging stations and grid-facing ac/dc converters. Dc-connected systems provide the required energy of dc-bus by a transformer and an ac/dc converter. In these systems, dc/dc converters offer the possibility of connecting EVs. In both systems, energy storage systems and renewable energy sources may be used in some applications. In general, dc-connected systems have high efficiency, simple control, and fewer conversion steps compared to ac-connected ones while ac-connected systems have more straightforward protection and more standard measuring equipment. Dc-connected systems are installed in two types: isolated and non-isolated. If the isolation of the charging system is provided by the transformers before the ac/dc converter, it can use non-isolated converters. Although the bidirectional non-isolated boost converters have higher efficiency and easier control systems than most unidirectional non-isolated converters, the simple structure in unidirectional converters has driven research. For EV charging applications, depending on the battery voltage, a unidirectional boost converter can be a suitable and straightforward choice. The power of this type of converter is limited via the current passing through the switches and the inductor size for low current ripple. Various techniques have been introduced to increase the capability of this type of converter. One of the essential techniques for this type of converter is the switched-capacitor (SC) technique [ 9 , 10 ]. In the SC technique, adequate voltage gains, high density, and higher efficiency are provided for this technique. However, the stresses among the semiconductors have limited its use. The interleaving technique is also one of the other techniques introduced. In this technique, several converters can be located in series-parallel to each other to provide more suitable conditions on the output side [ 11 , 12 ]. In [ 11 ], an interleaved boost dc-dc converter with three-phase legs is introduced. Simple structure, convenient performance, and high power density are its advantages. In [ 13 ], the proposed converter in [ 11 ] was extended to six phase legs. In [ 14 ], a three-phase interleaved boost converter under discontinuous current mode (DCM) has been designed while its small inductor size causes the ability to change the direction of the inductor current and provides zero-voltage switching conditions. In [ 15 ], an interleaved boost converter in DCM utilized partial power concepts, and low voltage rates for switches and reduced losses are introduced. The drawback of this structure is the need for a lot of hardware equipment and inner dc-bus balancing. The voltage-lift technique is another popular method for non-isolated boost converters [ 16 , 17 ]. In this technique, the voltage is increased step by step, using the energy storage feature in the inductor and capacitor. Losses of semiconductor elements are the most critical drawback of this technique. In this paper, a new topology for a non-isolated boost dc-dc converter is proposed for the EV charger. First, the topology of the proposed converter is analyzed in detail. Next, the critical inductances are calculated to determine its operating condition, especially for designing for DCM operating as in [ 15 ]. Then, the designing considerations are carried out for choosing better switches, and a comparison between some literature is presented. Real-time examinations are presented to verify the theoretical concepts. Finally, some concluding remarks are given. 2. The Proposed Converter Topology Analysis The proposed converter topology is shown in Figure 1 . As observed from this figure, the proposed structure consists of two power electronic switches, two inductors, three capacitors, and three diodes. The switching of the proposed topology is carried out by the PWM technique, where their turning on/off switches are complementary. High voltage gain and high-frequency transformer-less are the proposed topology’s advantages, whereas its hard switching condition are the main drawback. The proposed converter voltage gain is carried out using the energy storage (inductors and capacitors) element feature. To simplify the analysis, it is assumed that: (a) the converter is in steady state, so the output voltage V o is constant, (b) the capacitors are large enough and therefore their voltage in each switching period remains unchanged, (c) all switches and diodes are ideal, (d) equivalent series resistance(ESR) ESR is neglected, and (e) the isolation of the system is carried out before the converter. In the following, equations of the current and voltage of each element in CCM and DCM are discussed. 2.1. Analysis of the Proposed Converter in CCM In the time interval of T o n , the switch of S 1 is turned on and the switch of S 2 is turned off. Then, the inductor L 1 is connected to the input voltage source ( V i ) and its through pass current is increased to its maximum value ( I L P 1 ) from its minimum value ( I L ) . During this time interval, the diode of D 2 is reversely biased and the diodes D 1 and D o are forward biased. In this time interval, the stored energy of the inductor L 2 is decreased to its minimum value ( I L V 2 ) from its maximum value L P 2 ) . The equivalent circuit of the proposed topology is shown in Figure 2 a. This time interval of T o f f begins when the switch of S 1 is turned off and the switch of S 2 is turned on. In this situation, the diodes of D 2 and o are turned on and the diode of D 1 is turned off. So, the inductor L 2 is connected to V i ; therefore, its stored energy is increased. Additionally, the stored energy of the capacitor C o is increased, then it is charged. The equivalent circuit of the proposed topology is shown in Figure 2 b. Some key waveforms of the proposed topology in CCM are illustrated in Figure 3 a. Here, some critical relations of the proposed converter are illustrated. The first index shows the component number and second part is used for time intervals, whereas 1 and 2 show T o n and T o f f in CCM, respectively, and 1, 2, 3, and 4 show ( t 0 , t 1 ) , ( t 1 , t 2 ) , ( t 2 , t 3 ) , and ( t 3 , t 4 ) at DCM, respectively. By applying the Kirchhoff voltage law (KVL) to the circuit of Figure 2 a, the following equation is obtained: V L 1 , 1 = V i = L 1 d i L 1 , 1 d t , (1) Additionally, the equation below can be determined by Figure 2 b: V L 1 , 2 = V C 1 = L 1 d i L 1 , 2 d t , (2) The equation below is also written for the inductor L 2 : V L 2 , 1 = − V C 2 , 1 = L 2 d i L 2 , 1 d t , (3) V L 2 , 2 = V i = L 2 d i L 2 , 2 d t , (4) By considering T = T o n + T o f f and D = T o n / T , the voltage gain of the proposed converter in CCM can be extracted by substitution (1) and (2) into voltage balance law for on inductor as follows: V o V i = 2 − D 1 − D , (5) Finally, D is obtained from (5) as follows: D = 2 V i − V o V i − V o , (6) The voltage and current relation of semiconductors and current ripples of inductors in CCM are shown in Table 1 . 2.2. Analysis of the Proposed Converter in DCM At ( t 0 , t 1 ) , the switch S 1 is turned on and the switch S 2 is turned off. Additionally, the diodes D 1 and D o are on and the diode D 2 is off. Then, the inductor L 1 is connected to V i and its stored energy is increased. Another side, the inductor L 2 is the load path, and its stored energy is decreased. Therefore, the inductor current is reached to the minimum value. The equivalent circuit of the proposed topology is shown in Figure 4 a. The time interval of ( t 1 , t 2 ) begins when the diode D o is turned off, whereas the switch S 1 is turned on and the switch S 2 is turned off. In this condition, the diode D 2 is on. So, the discharge current of the capacitor C o provides the load current and its stored energy is decreased. The equivalent circuit of the proposed topology is shown in Figure 4 b. At ( t 2 , t 3 ) , the switch S 1 is turned off and the switch S 2 is turned on. Additionally, the diodes D 2 and D o are on and the diode D 1 is off. Then, the inductor is connected to V i and its stored energy is increased. The store energy of the inductor L 1 is decreased due to its location at the load path. Therefore, the current thorough pass L 1 is reached to its minimum value. The equivalent circuit of the proposed topology is shown in Figure 4 c. At ( t 3 , t 4 ) , the switch is still turned off and the switch S 2 is turned on. Meanwhile, the diode D 2 is on, whereas the diode of D o is turned off and the diode D 1 is turned on. During this time interval, the inductor L 2 is connected to V i and is charged. Additionally, the load current is provided by the capacitor C o . The equivalent circuit of the proposed topology is shown in Figure 4 d. Figure 3 b shows some key waveforms of the proposed topology in DCM. By applying KVL on Figure 4 a,b, we have: V L 1 , 2 = V i = L 1 d i L 1 d t , (7) Additionally, the following equation can be written for the inductor L 1 : V L 1 , 3 = V i + V C 1 , 3 − V o = L 1 d i L 1 , 3 d t , (8) V L 1 , 4 = 0 , (9) From Figure 4 , the equation below also results for the inductor L 2 : V L 2 , 1 = V i + V C 2 , 1 − V o = L 2 d i L 1 , 1 d t , (10) V L 2 , 2 = 0 , (11) V L 2 , 4 = V i = L 2 d i L 2 , 4 d t , By applying the voltage balance law for the inductor L 2 and replacing (7) to (9) into it, and considering D = ( t 0 , t 2 ) / T as the duty cycle in DCM, the voltage gain of the proposed converter in DCM is calculated as follows: V o V i = 1 + 1 + D 2 R L f , Therefore, one obtains that: D = V o ( 2 V i − V o ) L f R V i 2 , Table 1 shows the voltage and current of the semiconductors and the ripple current of the inductors in this operating mode briefly. 3. Critical Inductance Calculation In a dc-dc converter, the CCM and DCM are determined based on the values of the inductors, and the critical inductance determines the boundary between the CCM and DCM. If the inductance value of the inductors is greater than the critical inductance value, the converter will operate in CCM, and if the inductance value of the inductors is less than the critical inductance value, the converter will operate in DCM. By replacing critical conditions into (7), the following equation is obtained: I L P 1 = V i L 1 D T + I L V 1 , (15) The equation below can be written for the capacitor: 1 T ∫ 0 T i C o d t = 0 , (16) The current of the capacitor C o is equal to: i C o , 1 = − I o , (17) i C o , 2 = i L 1 , 2 − I o , (18) Assuming a new time-off set for T o f f , the current of the inductor L 1 is equal to the following: i L 1 , 2 = 2 V i − V o 2 L t + I L P 1 , (19) By replacing (18) and (17) into (16) and considering (19), the equation below is resulted: I L P 1 = I o 1 − D V o − 2 V i 4 L f ( − D ) , The above equation can be written as: I L P ] , Substitution of the above relation into (15) yields to: I L V 1 = I o [ 1 1 − D − D ( 1 − R 2 L f ( 2 − D ) ] , The critical inductance of L 1 can be extracted form (22) as follows: L C 1 = V V o V o V o − i L 1 = L 2 , we have: L C 2 = L C 1 , (24) 4. Design Considerations The peak current flow switch (PCFS) plays a vital role in designing and selecting the type of switch, and finally, the converter price, and it can be minimized by proper selection of the inductor values. Next, the peak current of switches are extracted in CCM and DCM. 4.1. Switches Current in CCM According to Figure 2 a,b, the peak current passing through the switches are equal to: P 1 = I L P 1 + i C 1 , i S P 2 = I L P i C 2 , (26) By considering (21) and assuming L 1 = L 2 , it has resulted: i S P 1 = i S P 2 + i C 1 , (27) By considering L 1 = L C 1 and L 2 = L C 2 into (27), the maximum peak current of the switches are determined as follows: P 1 , max C C M = i S P 2 , max C C M = V o ( V o − V i ) + i C 1 , From the above equation, it can be concluded that the peak current passing through the switches depends on the values of D , L and R . Additionally, the maximum peak current of switches can be selected for L 1 C 1 and L 2 = L C 2 . 4.2. Switches Current in DCM According to Figure 5 , PCFSs are obtained as follows: i S P 1 D C M S P 2 D C M = V i D 2 L 1 f , (29) By replacing (22) into the above relation, PCFSs are rewritten as follows: i S P 1 D C M = i S P 2 , min D C M = V o ( 2 V i − ) L 1 R f , (30) From the above relation, it can be seen that the minimum PCFSs in DCM also have an inverse relation with D , R and inductors values and they are obtained by considering L 1 = L C 1 and L 2 C 2 . The maximum PCFSs are obtained for L 1 < L C 1 and L 2 < L C 2 . Figure 5 shows the relative between the peak current of switches and inductors values. It is obvious that the peak current of switches in DCM is higher than CCM ones. Comparing (28) and (30), it has resulted: i 1 , min D C M = i S P 2 , max C C M = i S P 2 D C M = i S P 2 , max C C M , (31) 4.3. Switches Voltage Stress From Figure 2 and Figure 4 , the voltage stress of switched-off can be calculated as follows: 1 = V i − V C 1 , V S 2 = V i + V C 2 5. Efficiency Analysis I L 1 = I L 2 = 1 − D 2 − D I i , Thus, the inductors losses are obtained as follows: P L r L 1 L f a c W t f e − ) , P L 2 = r L 2 I L 2 2 K f α c − D 2 − D I i 3 , After neglecting turn off state losses in the diodes and defining Q r r as reverse recovery energy of diode, the diode losses are as follows: P D 1 = V F 1 , a v e r D I D 0.25 Q r r V D f , D 2 = V F I D 2 , a v e r D I D 0.25 r V D f P D o V F I D o a v r D o 2 + 0.25 Q r r V D f , The RMS current values of C 1 and C 2 are obtained as follows: Considering , the RMS value of capacitor current is as follows: − D I i 6 , (45) The capacitors losses are obtained as follows: P C 1 = r C 1 I C 1 2 , (46) 2 = r C 2 I C 2 2 , P C o = r C o I C o (48) The switches RMS current and their losses are equal to: I S 1 = 1 T ∫ 0 D T ( 5 − 2 D 3 ( 2 − D i ) 2 d t = 5 − 2 D 3 ( 2 − D ) I i D , Thus, the total loss and efficiency are equal to: s s × 100 , (54) 6. Comparison The comparison results of different converters avilable in the literature and the proposed converter are presented in Table 2 . As shown in Table 2 , the comparison is made in terms of the number of active and passive elements and the voltage gain in CCM. In terms of the number of active elements, the proposed converter topology has more switches than the ones proposed in [ 16 ] and [ 17 ]. Moreover, the proposed converter has fewer diodes than the topology in [ 18 , 19 , 20 ], and has the same number of diodes as the ones in [ 9 , 10 , 16 , 17 ]. Although the number of inductors of the proposed converter is less than [ 9 , 17 ], its number is equal to [ 10 , 16 , 18 , 19 , 20 ]. As a result, the size of the proposed converter may be smaller than the others. In terms of the number of capacitors, the proposed converter has the same number of capacitors compared to [ 9 , 16 ], and has less than [ 17 , 19 ], and more than [ 10 , 18 ]. Figure 6 a,b show the changes in the maximum normalized voltage stress of the switch and the maximum normalized voltage stress of the diode, respectively. Except for [ 10 ], which has a fixed graph in both analyzes, the values of the maximum normalized voltage stress of the switch and the maximum normalized voltage stress of the diode change varied for different amounts of voltage gain (M). From Figure 6 a, the maximum normalized voltage stress of the switch in the proposed converter is almost equal to [ 9 ], while compared to [ 10 , 16 , 18 , 19 , 20 ], the value of the maximum normalized voltage stress of the switch is lower. It is worth noting that the maximum normalized voltage stress of the switch in the proposed converter is more than [ 17 ]. The maximum normalized voltage stress of the diode at lower yields is better than the converters studied (see Figure 6 b). The maximum normalized voltage stress of the diode in the proposed converter is better than [ 16 , 18 , 19 , 20 ], while the value of this parameter is higher compared to [ 9 , 10 , 17 ]. 7. Experimental Results Assuming that the switches and diodes are ideal and considering the parameters presented in Table 3 , the correctness of the stated theoretical concepts and relations are examined. Based on the suggested converter topology described in Section 2 , a hardware-in-loop (HiL) simulating setup is configured based on the OPAL-RT real-time simulator as depicted in Figure 7 . Since the HiL is developed in a real-time platform, this simulation is a more practical validation setup than an off-line MATLAB simulation for the verification of system responses to unusual events. First, the operating of the proposed converter in critical condition is carried out. Then, CCM and DCM results are recorded for the proposed converter. It should be noted that the recorded time period of the results shown is selected to show the performance of the converter in steady-state. To analyze the performance of the proposed dc-dc boost converter, the operating mode of the converter must first be determined. According to (23) and Table 3 , the value of critical inductances for L 1 and L 2 are equal to 256 μ H . If L 1 = L 2 > L C 1 = L C 2 , the converter will be in CCM; otherwise, it will be in DCM. The operation of the proposed converter will be in critical mode for L 1 = L 2 = L C 1 = L C 2 . The experimental results are recorded by choosing L 1 = L 2 = L C 1 = L C 2 = 256 μ H . The switch’s current waveforms are illustrated in Figure 8 a,b. As one can observe from these figures, the maximum peak current of switches is 15 A . Additionally, the output voltage in this mode is equal to 209 V . Figure 9 shows the experimental results in CCM. As shown in Figure 9 a,b, the maximum peak current of the inductors is 2.7 A ; hence, the inductor size can be reduced. It can be noted that Δ i L 1 = Δ i L 2 = 1 A . The switches’ current waveforms are shown in Figure 9 c,d, while their maximum values are 13 A according to (25) to (28). The output voltage is almost equal to 209 V , reconfirming the theoretical calculation (see Figure 9 e). Considering the presented parameters in Table 3 into (34) and (52), powder core inductor ( r L 1 = r L 2 = 0.08 Ω ; K = 0.00551 ; α = 1.23 ; β = 2.12 ; W t f e = 34.6 ; B a c = 0.0527 ), electrolytic capacitor ( r C 1 = r C 2 = 0.015 Ω ; r C o = 0.02 Ω ), N-channel MOSFET ( Type : STW 45 NM 5 0 F ; r D S − , P C 1 = P C 2 = 1.6 W , P C o = 0.01 W and P S 1 = P S 2 = 6.0543 W . Thus, the calculated efficiency is 93.1 % . The results in DCM are depicted in Figure 10 . The inductors’ currents are illustrated in Figure 10 a,b. As shown in these figures, their variation proves the theorical relations and their maximum values are 14 A . The switch current also reached 17 A (see Figure 10 c–e shows the output voltage value, which is equal to 295 V . 8. Conclusions In this paper, a new topology of a non-isolated boost dc-dc converter is proposed for the off-board EV charger. High voltage gain and high-frequency transformer-less are the main advantages of the proposed topology. Throughout this paper, the operation of the proposed converter was analyzed at CCM and DCM in detail. Additionally, the critical inductance calculations were carried out, and the designing considerations were extracted for choosing proper switches. Then, the proposed converter was compared with the existing topologies in the literature. The validity of the correctness of the theoretical concepts was verified through HiL setup based on the OPAL-RT simulator. As discussed in Section 2 , the output voltage increased to 210 V and 295 V at CCM and DCM, respectively, by D = 50 % , V i = 70 V and f = 30.5 kHz with the calculated efficiency equal to 93.1 % . Additionally, the maximum peak current of switches reached 15 A , 13 A and 17 A at critical mode, CCM and DCM, respectively. Therefore, the proposed topology can be a suitable appliance as an EV charger. Author Contributions F.M.S., Methodology; M.G., Software; M.S.S., Supervision; M.-H.K.; Validation. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. Conflicts of Interest The authors declare no conflict of interest. References Iyer, V.M.; Gulur, S.; Gohil, G.; Bhattacharya, S. An Approach Towards Extreme Fast Charging Station Power Delivery for Electric Vehicles with Partial Power Processing. IEEE Trans. Ind. Electron. 2019 , 67 , 8076–8087. [ Google Scholar ] [ CrossRef ] Ucer, E.; Koyuncu, I.; Kisacikoglu, M.C.; Yavuz, M.; Meintz, A.; Rames, C. Modeling and Analysis of a Fast Charging Station and Evaluation of Service Quality for Electric Vehicles. IEEE Trans. Transp. Electron. 2019 , 5 , 215–225. [ Google Scholar ] [ CrossRef ] Rafiei, M.; Boudjadar, J.; Khooban, M.-H. Energy Management of a Zero-Emission Ferry Boat With a Fuel-Cell-Based Hybrid Energy System: Feasibility Assessment. IEEE Trans. Ind. Electron. 2021 , 68 , 1739–1748. [ Google Scholar ] [ CrossRef ] Tu, H.; Feng, H.; Srdic, S.; Lukic, S. Extreme Fast Charging of Electric Vehicles: A Technology Overview. IEEE Trans. Transp. Electron. 2019 , 5 , 861–878. [ Google Scholar ] [ CrossRef ] Khooban, M.-H. An Optimal Non-Integer Model Predictive Virtual Inertia Control in Inverter-Based Modern AC Power Grids-Based V2G Technology. IEEE Trans. Energy Convers. 2021 , 36 , 1336–1346. [ Google Scholar ] [ CrossRef ] Metwly, M.Y.; Abdel-Majeed, M.S.; Abdel-Khalik, A.S.; Hamdy, R.A.; Hamad, M.S.; Ahmed, S. A Review of Integrated On-Board EV Battery Chargers: Advanced Topologies, Recent Developments and Optimal Selection of FSCW Slot/Pole Combination. IEEE Access 2020 , 8 , 85216–85242. [ Google Scholar ] [ CrossRef ] Srdic, S.; Lukic, S. Toward extreme fast charging: Challenges and opportunities in directly connecting to medium-voltage line. IEEE Electrif. Mag. 2019 , 7 , 22–31. [ Google Scholar ] [ CrossRef ] Yilmaz, M.; Krein, P.T. Review of battery charger topologies, charging power levels, and infrastructure for plug-in electric and hybrid vehicles. IEEE Trans. Power Electron. 2013 , 28 , 2151–2169. [ Google Scholar ] [ CrossRef ] Banaei, M.R.; Sani, S.G. Analysis and implementation of a new sepic-based single-switch buck-boost dc-dc converter with continuous input current. IEEE Trans. Power Electron. 2018 , 33 , 10317–10325. [ Google Scholar ] [ CrossRef ] Shahir, F.M.; Babaei, E.; Farsadi, M. Extended topology for boost dc-dc converter. IEEE Trans. Power Electron. 2019 , 34 , 2375–2384. [ Google Scholar ] [ CrossRef ] Aggeler, D.; Canales, F.; Zelaya-De La Parra, H.; Coccia, A.; Butcher, N.; Apeldoorn, O. Ultra-Fast Dc-Charge Infrastructures for Ev-Mobility and Future smart Grids. In Proceedings of the IEEE PES Innovative Smart Grid Technologies Conference Europe (ISGT Europe), Gothenburg, Sweden, 11–13 October 2010; pp. 1–8. [ Google Scholar ] Garcia, O.; Zumel, P.; de Castro, A.; Cobos, A. Automotive dc-dc bidirectional converter made with many interleaved buck stages. IEEE Trans. Power Electron. 2006 , 21 , 578–586. [ Google Scholar ] [ CrossRef ] Kang, T.; Kim, C.; Suh, Y.; Park, H.; Kang, B.; Kim, D. A design and control of bi-directional non-isolated dc-dc converter for rapid electric vehicle charging system. In Proceedings of the Twenty-Seventh Annual IEEE Applied Power Electronics Conference and Exposition (APEC), Orlando, FL, USA, 5–9 February 2012; pp. 14–21. [ Google Scholar ] Zhang, J.; Lai, J.; Kim, R.; Yu, W. High-power density design of a soft-switching high-power bidirectional dc-dc converter. IEEE Trans. Power Electron. 2007 , 22 , 1145–1153. [ Google Scholar ] [ CrossRef ] Christen, D.; Jauch, F.; Biel, J. Ultra-fast charging station for electric vehicles with integrated split grid storage. In Proceedings of the 17th European Conference on Power Electronics and Applications (EPE’15 ECCE-Europe), Geneva, Switzerland, 8–10 September 2015; pp. 1–11. [ Google Scholar ] Shahir, F.M.; Babaei, E.; Farsadi, M. Voltage-lift technique based non-isolated boost dc-dc converter: Analysis and design. IEEE Trans. Power Electron. 2018 , 33 , 5917–5926. [ Google Scholar ] [ CrossRef ] Salvador, M.A.; Lazzarin, T.B.; Coelho, R.F. High step-up dc-dc converter with active switched-inductor and passive switched-capacitor networks. IEEE Trans. Ind. Electron. 2018 , 65 , 5644–5654. [ Google Scholar ] [ CrossRef ] Shahir, F.M.; Babaei, E.; Farsadi, M. Analysis and design of voltage-lift technique based non-isolated boost dc-dc converter. IET Power Electron. 2018 , 11 , 1083–1091. [ Google Scholar ] [ CrossRef ] Zhou, L.; Zhu, B.; Lou, Q.; Chen, S. Interleaved non-isolated high step-up dc/dc converter based on the diode-capacitor multiplier. IET Power Electron. 2014 , 7 , 390–397. [ Google Scholar ] [ CrossRef ] Pan, C.T.; Chuang, C.F.; Chu, C.C. A novel transformer-less adapt-able voltage quadrupler dc converter with low switch voltage stress. IEEE Trans. Power Electron. 2014 , 29 , 4787–4796. [ Google Scholar ] [ CrossRef ] Figure 1. The proposed topology for the boost dc-dc converter. Figure 1. The proposed topology for the boost dc-dc converter. Figure 2. The equivalent circuit of the proposed topology in CCM; ( a ) at T o n , ( b ) at T o f f . Figure 2. Figure 3. Some key waveforms of the proposed topology; ( a ) at CCM, ( b ) at DCM. Figure 3. Some key waveforms of the proposed topology; ( a ) at CCM, ( b ) at DCM. Figure 4. The equivalent circuit of the proposed topology in DCM; ( a ) at Figure 5. The relation between the value of the inductances and PCFS. Figure 5. The relation between the value of the inductances and PCFS. Figure 6. The maximum normalized voltage stress for ( a ) switch and ( b ) diode. Figure 6. The maximum normalized voltage stress for ( a ) switch and ( b ) diode. Figure 7. Photograph of the OPAL-RT setup adopted for the HiL verification. Figure 9. The results in CCM, ( a Table 1. Comparison between proposed converter and the existing topologies. Table 1. Comparison between proposed converter and the existing topologies. Elements/Time Interval CCM DCM T o n T o f f t 0 − t 1 t 1 − t 2 t 2 − t 3 t 3 − t 4 D 1 i C 1 + I o + i C o V L 1 − V C 1 i C 1 + I o + i C o i C 1 + I o + i C o V L 1 − V C 1 i C 1 + I o + i C o D 2 V L 2 + V C 2 I o + i C o − i C 2 V L 2 + V C 2 I o + i C o − i C 2 I o + i C o − i C 2 I o + i C o − i C 2 D o I o + i C o I o + i C o V i − V o I o + i C o V i − V o S 1 i L 1 + i C 1 V i − V L 1 i L 1 + i C 1 V i − V L 1 V i S 2 V i − V L 2 I i − i L 1 V i − V L 2 V i I i − i L 1 I i − i D 1 Δ i L 1 | V i L 1 T o n | = | − V C 1 L 1 T o f f | | V i L 1 Δ t | = | − V i + V C 1 , 3 − V o L 1 Δ t | Δ i L 2 | V C 2 , 1 L 2 T o n | = | V i L 2 T o f f | | − V i + V C 2 , 1 − V o L 2 Δ t | = | V i L 2 Δ t | Table 2. Comparison between proposed converter and the existing topologies. Table 2. Comparison between proposed converter and the existing topologies. Table 3. Parameters for the proposed converter topology. Table 3. Parameters for the proposed converter topology.
https://www.mdpi.com/2411-9660/5/3/51/htm
(PDF) Understanding SNAP Recipient Characteristics to Guide Equitable Expansion of Nutrition Incentive Programs in Diverse Food Retail Settings PDF | Structural barriers, such as food costs, reduce access to healthy foods for populations with limited income, including those benefitting from the... | Find, read and cite all the research you need on ResearchGate Understanding SNAP Recipient Characteristics to Guide Equitable Expansion of Nutrition Incentive Programs in Diverse Food Retail Settings April 2022 International Journal of Environmental Research and Public Health19(9):4977 DOI: 10.3390/ijerph19094977 License CC BY 4.0 Authors: <here is a image f2f62089ad6ff61c-d19572ff1996375a> Lauren Vargo Lauren Vargo <here is a image f2f62089ad6ff61c-d19572ff1996375a> Timothy H. Ciesielski Timothy H. Ciesielski <here is a image f2f62089ad6ff61c-d19572ff1996375a> Milen Embaye Milen Embaye <here is a image f2f62089ad6ff61c-d19572ff1996375a> Ana Bird Ana Bird Abstract and Figures Structural barriers, such as food costs, reduce access to healthy foods for populations with limited income, including those benefitting from the Supplemental Nutrition Assistance Program (SNAP). Nutrition incentive programs seek to address this barrier. Evaluations of SNAP-based incentive programming often focus on one setting (i.e., either farmers’ markets or grocery stores). We examined use patterns, characteristics, and preferences among 253 SNAP consumers with access to incentive programming at both a farmers’ market and a grocery store located within five miles of their home. Cross-sectional survey data were collected in 2019 in two Ohio cities. Despite geographic access, 45% of those surveyed were not using the incentive program; most non-users (80.5%) were unaware of the program. Program users compared to non-users had higher household incomes (p < 0.001) and knew more people using the program (p < 0.001). Grocery stores were the most common setting of use (59%); 29% used at farmers’ markets; 11% used in both settings. User characteristics varied by store setting based on demographics, program experience, fruit and vegetable purchasing and consumption patterns, and social dynamics related to use. Our findings support comprehensive awareness-raising efforts and tailored implementation of incentive programming that attends to diverse segments of SNAP consumers to promote equity in program reach. <here is a image 4a11666e36261ae0-08d3f8e7245c5690> Study design and inclusion flow chart for the recruitment of snap consumers into a cross-sectional survey in 2019. … <here is a image bc78433d4b0e70e7-97f599ff21b8b8be> Participant characteristics that differ among nutrition incentive program users and non-users in Ohio, 2019. … <here is a image 54c395990e21b4cc-99e426200e111d0b> Characteristics that differ by nutrition incentive program setting of use: grocery store, farmers' market, or both (at p < 0.1). … <here is a image e8c27c40e3c16c3b-5ce398c5652bd507> Cont. … Figures - available via license: Creative Commons Attribution 4.0 International Available via license: CC BY 4.0 Citation: Vargo, L.; Ciesielski, T.H.; Embaye, M.; Bird, A.; Freedman, D.A. Understanding SNAP Recipient Characteristics to Guide Equitable Expansion of Nutrition Incentive Programs in Diverse Food Retail Settings. Int. J. Environ. Res. Public Health 2022 , 19 , 4977.https:// doi.org/10.3390/ijerph19094977 Academic Editors: Chelsea R. Singleton and Bailey Houghtaling Received: 28 January 2022 Accepted: 15 April 2022 Published: 20 April 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). InternationalJournalof Environmental Research and Public Health Article Understanding SNAP Recipient Characteristics to Guide Equitable Expansion of Nutrition Incentive Programs in Diverse Food Retail Settings Lauren Vargo 1 , Timothy H. Ciesielski 1, Milen Embaye 1, Ana Bird 2and Darcy A. Freedman 1,* 1 Mary Ann Swetland Center for Environmental Health Research, Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; [email protected] (L.V.); [email protected] (T.H.C.); [email protected] (M.E.) 2 Produce Perks Midwest, Cincinnati, OH 45241, USA; [email protected] * Correspondence: [email protected] Abstract: Structural barriers, such as food costs, reduce access to healthy foods for populations with limited income, including those benefitting from the Supplemental Nutrition Assistance Program (SNAP). Nutrition incentive programs seek to address this barrier.Evaluations of SNAP-based incentive programming often focus on one setting (i.e., either farmers’ markets or grocery stores). We examined use patterns, characteristics, and preferences among 253 SNAP consumers with access to incentive programming at both a farmers’ market and a grocery store located within five miles of their home.Cross-sectional survey data were collected in 2019 in two Ohio cities.Despite geographic access, 45% of those surveyed were not using the incentive program; most non-users (80.5%) were unaware of the program. Program users compared to non-users had higher household incomes ( p < 0.001 ) and knew more people using the program ( p< 0.001). Grocery stores were the most common setting of use (59%); 29% used at farmers’ markets; 11% used in both settings. User characteristics varied by store setting based on demographics, program experience, fruit and vegetable purchasing and consumption patterns, and social dynamics related to use.Our findings support comprehensive awareness-raising efforts and tailored implementation of incentive programming that attends to diverse segments of SNAP consumers to promote equity in program reach. Keywords: nutrition incentives; supplemental nutrition assistance program; health disparities; health equity; food security; food purchasing 1. Introduction Food insecurity is a persistent and pressing public health inequity in the U.S., with 10.5% of households affected nationally in 2019; trends did not improve throughout 2020 during the COVID-19 pandemic when food assistance benefits were increased [ 1 , 2 ]. The Supplemental Nutrition Assistance Program (SNAP) is a federal food assistance program that provides income-eligible individuals and families with monthly benefits to purchase food, aiming to supplement limited food budgets and improve food security [ 1 , 3 ]. Even with these financial supplements, people receiving SNAP face structural barriers to achiev- ing a healthy diet, citing the lack of affordability of healthy foods as the top barrier [ 4 ]. While SNAP is estimated to reduce the probability of being food insecure among recipients [ 5, 6] , recipients report having poorer diet quality and higher rates of diet-related diseases when compared to income-eligible non-recipients [ 7 , 8 ]. People receiving SNAP also report pe- riods of food insecurity and a decline in diet quality throughout the month as financial resources are spent [ 7 ] and often have nutrient deficiencies that can be directly addressed through increased intake of fruits and vegetables [ 9]. The Food Insecurity Nutrition Incentive (FINI) Program, now known as the Gus Schumacher Nutrition Incentive Program (GusNIP), was established in the U.S. in the Int. J. Environ. Res. PublicHealth 2022 , 19 , 4977. https://doi.org/10.3390/ijerph19094977https://www.mdpi.com/journal/ijerph Int. J. Environ. Res. PublicHealth 2022 , 19 , 49772 of 13 2014 Farm Bill to provide financial incentives to SNAP recipients for purchasing fruits and vegetables [ 10 ]. Evaluations of SNAP-based nutrition incentive programs found they increase spending on fruits and vegetables and are associated with reductions in food insecurity and improvements in diet quality [ 11 , 12 ]. However, the reach of the program is limited in many communities; more implementation research is needed to increase the number of people who are benefiting from the program [ 13]. Ohio is a rich context for examining implementation of SNAP-based nutrition incentive programming. Ohio’s nutrition incentive program, Produce Perks, has evolved over the past decade from single-site operations at farmers’ markets into a statewide, networked, multi-food retail setting program [ 14 ].Like the approach in Ohio,national nutrition incentive programming initially focused on farmers’ markets. However, evaluation of the Healthy Incentives Pilot (HIP) in 2012 found that less than 1% of SNAP households shopped at farmers’ markets during any given month [ 15 ], a trend that persisted as of 2019 [ 16 ]. In contrast, about 40% of SNAP benefits are spent at a supermarket or grocery store [ 16 ]. Accordingly, there are growing efforts to diversify and expand program operations in grocery stores across the U.S. [ 11 , 12 ]. This allows implementation to occur in multiple food retail settings within a community, promoting choice and nutrition equity among SNAP recipients [ 17]. Most extant research is focused on the potential impacts of incentive program im- plementation at either farmers’ markets [ 18 – 21 ] or grocery stores [ 11 , 12 ]. Little is known about factors influencing decisions to use SNAP-based incentive programs when they are available at multiple food retail settings in one community, such as a farmers’ market and a grocery store.In this research, we address this gap by taking a holistic view to examine use patterns, characteristics, and preferences among SNAP recipients with access to nutrition incentive programming at both a farmers’ market and a grocery store located within five miles of their home.The study is guided by an established nutritious food access framework allowing for examination of economic, spatial–temporal, service delivery, social, and personal factors that may shape incentive program use [ 22 ]. Overall, our goal was to inform future research and interventions that promote equitable program access in similar urban contexts. 2. Materials and Methods 2.1. Study Description Our study was conducted by a collaborative team that included an academic research center and a statewide non-profit organization that supports implementation of Ohio’s nutrition incentive program.We performed a cross-sectional survey from July–October 2019 in two cities in Ohio: Akron and Cleveland.In 2019, the populations of Akron and Cleveland were about 198,000 and 385,000, respectively, and both cities resided in counties that had over 13% of persons living in poverty [ 23 ].These cities met study eligibility requirements, including: (1) having a grocery store operating and offering Produce Perks year-round for a minimum of six months prior to data collection, (2) having a farmers’ market operating and offering Produce Perks year-round for a minimum of six months prior to data collection, and (3) the grocery store and farmers’ market being located within three miles of one another.Our goal was to recruit participants with comparable and reasonable geospatial access to Produce Perks in both retail settings in their community to allow for examination of other potential access barriers per the nutritious food access framework [ 22 ].Accordingly, we drew a buffer around the centroid of both the farmers’ markets and grocery store in each city using ArcGIS to represent the Euclidean distance of five miles [ 24 ]. We recruited people receiving SNAP who lived within this five-mile buffer. In 2015, we observed that SNAP recipients in Cleveland traveled a median distance of 2.3 miles when they shopped at a farmers’ market [ 25 ].Thus, by choosing sites that were no more than 3 miles apart and drawing 5-mile eligibility circles around these sites, we ensured that travel distance to either option was reasonable. The Case Western Reserve University Institutional Review Board reviewed and approved the study protocol (20190723). Int. J. Environ. Res. PublicHealth 2022 , 19 , 49773 of 13 2.2. Study Participants We conducted participant recruitment by partnering with the statewide non-profit organization that manages nutrition incentive programming and the statewide social services agency that operates SNAP benefits.The research team worked with these partners to distribute two targeted mailers to SNAP recipients within the study boundaries in both cities.The mailers sent by the county-based social service agencies included:(1) a promotional flyer about Produce Perks with the location and details of a grocery store and year-round farmers’ market located near their home, information about how to use the incentive program, and resources to find more information about Produce Perks; and (2) a study recruitment flyer listing basic eligibility criteria and information for the SNAP recipient to contact the research team if interested in learning more about the study. Additional recruitment efforts included in-person tabling at all four promoted farmers’ market and grocery store sites throughout the data collection period and distribution of recruitment flyers to local organizations, community events, apartment buildings, and food pantries. We used a six-item screener to determine eligibility for this cross-sectional survey. Screener questions were asked by a trained research assistant in person or over the phone. Individuals were eligible if they were: (1) currently receiving SNAP benefits; (2) residing within the defined study boundaries; (3) responsible for at least half of the food shopping for their household; (4) ≥ 18 years of age; (5) English-speaking; and (6) the only member of their household enrolled in the study.To determine whether a potential participant resided within the defined study boundaries, they were asked to provide their home address, which was then entered into ArcGIS to confirm that it was within the study boundaries. If a participant did not want to provide an address or the address provided was outside of the study boundaries, they were not eligible for the study.Those who were eligible were offered more information on the study, as well as an opportunity to provide consent. We screened 412 people for eligibility, of whom 145 (35.2%) were screened at the in-person events and 267 (64.8%) were screened by phone (Figure 1). Most of those screened were eligible for the study (99.3% of those screened in person and 91.4% of those screened on the phone). We invited 388 people who were eligible to participate and 253 completed the survey (65.2%).About one-third of those eligible did not complete the survey, whether they were screened in person (32.6%) or by phone (36.1%). Prior to completing the survey, study participants provided informed consent in writing (if in person) or verbally (if over the phone). 2.3. Data Collection We developed a structured survey guide for this study (full survey available in Supplementary S1). Food security was measured using the USDA’s U.S. Household Food Security Survey Module: Six-Item Short Form [ 26 ]. Items from the Behavioral Risk Factor Surveillance System (BRFSS) Questionnaire were used to assess health status, fruit and vegetable intake, and demographics [ 27 ]. All other questions were derived from the United States Department of Agriculture (USDA) Economic Research Service Current Population Survey (CPS) Food Security Questionnaire [ 28 ] or previously conducted studies [ 27 , 29 ]. Overall, the survey contained questions that assessed five domains of nutritious food access: economic, spatial temporal, service delivery, social, and personal [ 22 ]. The full list of variables is enumerated in Table S1 and we list some here to explain the approach.In terms of Economic variables, we collected information on annual household income, the amount of monthly SNAP allowance, and the number of people supported by that SNAP allowance. Spatial Temporal variables included: distance to the preferred food shopping store, transportation options/strategies, and frequency of shopping. The Service variables focused on the quality and variety of produce offerings at grocery stores and farmers’ markets, while the Social variables quantified the frequency of Produce Perks and farmers’ market use among friends and family of the participants. Finally, the Personal variables assessed several individual characteristics, perceptions, and skills, including education Int. J. Environ. Res. PublicHealth 2022 , 19 , 49774 of 13 level, food security, home ownership, frequency of produce consumption, and confidence preparing fruits and vegetables. Int. J. Environ. Res. Public Health 2022 , 19 , x FOR PEER REVIEW 4 of 13 Figure 1. Study design and inclusion flow chart for the recruitment of snap consumers into a cross- sectional survey in 2019. 2.3. Data Collection We developed a structured survey guide fo r this study (full survey available in Supplementary S1). Food security was measured using the USDA’s U.S. Household Food Security Survey Module: Six-Item Short Form [26]. Items from the Behavioral Risk Factor Surveillance System (BRFSS) Questionnaire we re used to assess health status,fruit and vegetable intake, and demographics [27]. All other questions were derived from the United States Department of Agriculture (USDA) Economic Research Service Current Population Survey (CPS) Food Security Questionnaire [28] or previously conducted studies [27,29]. Overall, the survey contained questions that assessed five domains of Eligibility screening 100% (Total Screened = 412) Completed the Survey 67.4% (97) + 63.9% (156) Total Surveyed = 65.2% (n = 253) Produce Perks Non-Users 44.6% (n =113) Asked survey questions and a multiple-choice question about why they have not used the Produce Perks program Produce Perks Users 55.3% (n = 140) Asked survey questions and a multiple-choice question about why they use the Produce Perks program and details about where they use the program Screened By-Phone 64.8% (n = 267) Targeted mailers were sent to SNAP householdsby the county SNAP Office and flyers were posted within the community. Participants emailed or called, and then were screened b y p hone. ScreenedIn-Person 35.2% (n = 145) Research team members tabled at grocery stores, farmer’s markets and community centers. Participants were screened on-site. Eligible and Invited 99.3% (n = 144) Eligible and Invited 91.4% (n = 244) Not Eligible 0.7% (n = 1) Not Eligible 8.6% ( n = 23 ) Uses at Farmers’ Market Only 29.3% (n = 41) Uses at Both Locations 10.7% (n = 15) Uses at Retail Stores Only 59.3% (n = 83) Missin g information on use sites 0.7% ( n = 1 ) Lost to follow up 32.6% (n = 47) Lost to follow up 36.1% (n = 88) Figure 1. Study design and inclusion flow chart for the recruitment of snap consumers into a cross-sectional survey in 2019. All surveys were conducted by phone and were administered by seven trained re- search assistants. Data were entered directly into REDCap as the survey was being con- ducted. Surveys took about 30 min.Participants were compensated with a $20 gift card for their time. Int. J. Environ. Res. PublicHealth 2022 , 19 , 49775 of 13 2.4. Data Analysis Our primary analytic approach was designed to identify the factors that differ with respect to Produce Perks use status and use location.Program users were compared to non-users, and then users were compared by the setting of their use (grocery store only, farmers’ market only, or both locations).Variables that differed by Produce Perks use status were identified by the Wilcoxon–Mann–Whitney test, the chi-squared test, or Fisher’s exact test as appropriate. Variables that differed by location of use were identified by the Kruskal– Wallis test or Fisher’s exact test as appropriate. The non-parametric tests (Wilcoxon–Mann– Whitney, Fisher’s exact, and Kruskal–Wallis) were used when the assumptions needed for parametric tests were unreasonable to make (e.g., normal distribution or sufficient cell size). Statistical significance was set at p< 0.1 to reflect the importance of type II errors in this exploratory research setting. In other words, this is hypothesis-generating exploratory research, and in this setting the learning cost of false negatives outweighs the cost of false positives [ 30 ]. The variables analyzed here were organized according to the five domains of the Multi-Component Nutritious Food Access (NFA) Framework [ 22 ], as described above (i.e., economic, service delivery, spatial–temporal, social, and personal).The distance between a participants’ reported home address and preferred store address was calculated using Google Maps. Statistical analyses were conducted using SAS 9.4 (SAS Institute; Cary, NC, USA). 3. Results 3.1. Demographics of Study Participants A total of 253 SNAP recipients completed the cross-sectional survey (Table 1 ). Most participants self-identified as female (81.4%), Black (68.4%), and between the ages of 40 and 79 years old (76.6%).While all participants were currently receiving SNAP, the majority (65.6%) reported receiving SNAP for at least five years.Transportation for food shopping varied among participants, with 46.6% driving their own car and 53.4% relying on other options for transportation. On self-report, 30.8% of the participants described their general health status as “fair,” while 8.3% said their health was “poor.” Just over half (55.3%) reported using the Produce Perks nutrition incentive program at least once.Among those, most reported use at a grocery store (59.3%) compared to a farmers’ market (29.3%) or use at both sites (10.7%) (see Figure 1). A full list of descriptive responses is presented in Table S1. Table 1. Characteristics of the cross-sectional survey participants: 253 SNAP recipients from Cleve- land and Akron, Ohio, with access to nutrition incentive programming near their home in 2019. Characteristicsn %Characteristicsn% GenderNumber of children in the household Female206 81.4017167.6 Male45 17.814216.6 Other1 0.4 ≥ 240 15.8 Declined to respond10.4 Transportation for shopping Race Drive your own car11846.6 White6726.5Depend on other options13553.4 Black173 68.4 Self-reported general health status Other13 5.1Excellent2610.3 Age in years Very good4718.6 <4050 19.8Good8132.0 40–5996 37.9Fair7830.8 Int. J. Environ. Res. PublicHealth 2022 , 19 , 49776 of 13 Table 1. Cont. Characteristicsn %Characteristicsn% 60–7998 38.7Poor218.3 >804 1.6 Farmers’ market use in the past year Missing5 2.0Yes144 56.9 Level of Education No109 43.1 Some high school or less239.1 Length of time receiving SNAP (years) High school graduate10541.5<1104.0 Some college or more12549.41–23212.7 Annual Household Income 3–444 17.4 <10,00087 34.4 ≥ 5166 65.6 ≥ 10,00016665.6Do not know/not sure10.4 Number of people in the householdEver used Produce Perks 1137 54.2Yes14055.3 ≥ 2116 45.8No11344.7 3.2. Rationale for Program Use When asked why they did not use Produce Perks, 80.5% of the non-users reported that they did not know the incentive program existed. Less frequently cited reasons for not using the program included: confusion about how the program works (8.8%), inconvenient store location (6.2%), transportation hurdles (3.5%), and high food prices at participating stores (2.7%). No participants indicated that their lack of incentive program use was due to a distaste for fruits and vegetables or that their store lacked the produce they wanted. Among the 90 people who did not know about the program until they participated in the study, 76.7% said that they were very likely to use the program in the next 6 months. The 140 users were asked what motivated them to use the Produce Perks program. The most common motivations for using the incentive program included:the program helps you save money (74%), it allows you to buy more fruits and vegetables (61%), and it is easy to use (14%). 3.3. Produce Perks User Profiles Multiple variables across four of the five domains of access differed between Produce Perks users and non-users at p< 0.1 (Table 2 ):economic, spatial–temporal, social, and personal. In terms of economic factors, Produce Perks users had higher median incomes than non-users ( p < 0.001). Produce Perks users supported more people with their SNAP ( p = 0.005) and received more monthly SNAP benefits ( p= 0.039). With respect to spatial temporal factors, users lived closer to their preferred store ( p= 0.020) and perceived purchasing fruits and vegetables as more convenient ( p= 0.005) than non-users (i.e., a lower score reflects higher perceived convenience). Produce Perks users were also more likely to have purchased or received food from a farmers’ market ( p= 0.034), specialty store ( p = 0.038 ), or mobile pantry/free fruit and vegetable drop-off ( p = 0.044) in the past year. Additionally, Produce Perks users were more likely to have a car for shopping ( p = 0.051 ) and were less likely to use somebody else’s car for shopping ( p= 0.048).Regarding social factors, users reported that more of their friends or family had used Produce Perks ( p < 0.001 ) and had shopped at a farmers’ market ( p= 0.054) in the last 6 months. In terms of personal factors, Produce Perks users had more children in their household ( p= 0.034). though the median number of children across both groups was less than one. They were also less likely to have moved in the last 12 months ( p= 0.050) and had higher educational attainment ( p= 0.061). Finally, when food security was analyzed as a dichotomous variable (i.e., a six-point USDA food security score >1, indicating low or very low food security), Int. J. Environ. Res. PublicHealth 2022 , 19 , 49777 of 13 Produce Perks users were less likely to report experience of food insecurity ( p= 0.044) in the past year. Overall, the strongest statistical findings and likely predictors of Produce Perks use were having a higher income and knowing more people who use the incentive program . Table 2. Participant characteristics that differ among nutrition incentive program users and non-users in Ohio, 2019. Nutrition Incentive Program Non-Users (n = 113) Nutrition Incentive Program Users (n = 140) p -Value for Difference Economic DomainMedianIQR a MedianIQR a Annual income in dollars10,0008400, 13,60012,0009950, 18,000 <0.001 b Number of people supported by your SNAP11, 211, 3 0.005 b Amount of SNAP money received last month17260.5, 193.5192110, 317.5 0.039 b Spatial Temporal DomainMedianIQR a MedianIQR a It is not convenient to buy fruits and vegetables (1 = strongly disagree, 5 = strongly agree) 21, 211, 2 0.005 b Distance to preferred store3.31.4, 4.82.20.8, 4.1 0.020 b In the last year I obtained food from a: Frequency%Frequency % Farmers’ market5649.68862.90.034 c Specialty store (e.g., ethnic store, bakery, meat market, seafood market, green grocer) 5346.98460.00.038 c Mobile pantry/free fruit and vegetable drop off1815.93726.40.044 c How do you usually get to your food store/market/pantry Have a car4539.87352.10.051 c Use someone else’s car1513.385.7 0.048 d Social DomainMedianIQR a MedianIQR a Think about friends, family, or people you know, about how many have used Produce Perks over the past 6 months? (1 = none, 5 = all) 11, 221, 3<0.001 a Think about friends, family, or people you know, about how many have shopped at your farmers’ market over the past 6 months? (1 = none, 5 = all) 2 (Mean: 2.5) 2, 3 2 (Mean: 2.2) 2, 30.054 a Personal DomainMedianIQR a MedianIQR a Number of children in your household 0 (Mean: 0.5) 0, 1 0 (Mean: 0.8) 0, 10.034 a Frequency%Frequency % Food insecurity (USDA six-item food security score > 1, indicating low or very low food security) 7062.06949.30.044 c Moved in the last 12 months2219.51510.70.050 c Education Some high school or less1513.385.7 0.061 b High school graduate4842.55740.7 Some college or more5044.37553.6 Total number of people in your household 1 (Mean:1.8) 1, 2 1 (Mean:2.2) 1, 3 0.086 b a Interquartile range. b Wilcoxon–Mann–Whitney test (non-parametric analog of the t -test, assumes ordinal rather than normally distributed interval). c Chi-squared test. d Fisher’s exact test (non-parametric analog of the chi-squared test). Int. J. Environ. Res. PublicHealth 2022 , 19 , 49778 of 13 When Produce Perks users were compared by their setting of use, several variables differed between the three Produce Perks use types at p < 0.1 (Table 3): grocery store only, farmers’ market only, and both.Those who used Produce Perks at a grocery store only ( n = 83 ) had been using the program for the shortest amount of time ( p< 0.001) and had the lowest education levels ( p= 0.025). This group reported purchasing fruits and vegetables less frequently ( p< 0.001) and they had less confidence in their ability to prepare fresh greens ( p = 0.008) as well as root vegetables ( p= 0.018). Additionally, grocery store-only Produce Perks users made more frequent trips to their primary store ( p= 0.009), knew of more friends and family shopping at the same grocery store ( p = 0.054), and had fewer adults in their household ( p= 0.067). They also reported that they ate beans ( p= 0.062) and other vegetables (i.e., beyond beans, dark green or orange vegetables) less frequently ( p= 0.007). Finally, the grocery store-only users reported a similar variety of fruits and vegetables at their primary store compared to the farmers’ market, while the two groups who utilized farmers’ markets reported a greater variety at their farmers’ markets compared to their primary store ( p< 0.001). Those using Produce Perks at farmers’ markets only (n = 41) were older ( p= 0.033), had used Produce Perks for the longest amount of time ( p < 0.001), and were also less likely to be Black ( p = 0.056).The group who used Produce Perks at both retail stores and farmers’ markets was the smallest group (n = 15). Users of Produce Perks at both grocery stores and farmers’ markets were redeeming the largest amounts of Produce Perks incentive money ( p= 0.030). This group was the youngest ( p= 0.038), most educated ( p= 0.025), and had the highest levels of confidence in preparing fresh green vegetables ( p = 0.008). There were no significant differences in food security across the three user types, when specifying food security as a dichotomous variable ( p= 0.703). Table 3. Characteristics that differ by nutrition incentive program setting of use:grocery store, farmers’ market, or both (at p< 0.1). Nutrition Incentive Program Users Grocery Store Only (n = 83) Farmers’ Market Only (n = 41) Both (n = 15) p -Value for Difference MedianIQR aMedianIQR a MedianIQR a Economic Domain Over the past 6 months, about how much Produce Perks did you receive from the location of first use? 2010, 502010, 5010020, 200 0.030 b Service Domain How does the variety of fresh fruits and vegetables at your primary store compare to the variety of fresh fruits and vegetables at the farmers’ market? (1 = much greater variety, 5 = much less variety) 32, 443, 543, 5 <0.001 b Spatial Temporal Domain Number of visits per month to your primary store42, 832, 423, 4 0.009 b Social Domain Think about friends, family, or people you know, about how many shopped at the promoted store offering Produce Perks over the past 6 months? (1 = none, 5 = all) 32, 522, 32.52, 4 0.054 b Think about friends, family, or people you know, about how many have shopped at your farmers’ market over the past 6 months? (1 = none, 5 = all) 22, 321, 32.52, 4 0.091 b Int. J. Environ. Res. PublicHealth 2022 , 19 , 49779 of 13 Table 3. Cont. Nutrition Incentive Program Users Grocery Store Only (n = 83) Farmers’ Market Only (n = 41) Both (n = 15) p -Value for Difference MedianIQR aMedianIQR a MedianIQR a Personal Domain Number of months since first Produce Perks use31, 7132, 3083, 36 <0.001 b How often do you purchase fruits and vegetables when you go to your primary store? (1 = never, 5 = always) 43, 554, 555, 5 <0.001 b Number of times per month ate “other” vegetables (beyond beans, dark green or orange vegetables) 126, 28208, 303015, 30 0.007 b Confidence in preparing fresh green vegetables (1 = not at all confident, 5 = extremely confident) 44, 554, 555, 5 0.008 b Confidence in preparing root vegetables (1 = not at all confident, 5 = extremely confident) 44, 554, 554, 5 0.018 b Education Frequency % Frequency%Frequency % 0.025 b Some high school or less89.600.000.0 High school graduate3845.81638.1320.0 Some college or more3744.62661.91280.0 MedianIQR aMedianIQR a MedianIQR a Age in years5637, 626047, 695342, 57 0.038 b Frequency %Frequency %Frequency% Black,race63 75.9 23 54.8 1066.70.056 c MedianIQR aMedianIQR a MedianIQR a Number of times per month ate beans32, 442, 543, 8 0.062 b Number of adults in your household 1 (Mean:1.3) 1, 1 1 (Mean:1.6) 1, 2 1 (Mean:1.6) 1, 2 0.067 b Number of times per month cooked meals made from scratch or using whole foods 168, 302012, 302820, 30 0.076 b a Interquartile range. b Kruskal–Wallis (non-parametric analog of ANOVA, assumes ordinal rather than normally distributed interval). cFisher’s exact test (non-parametric analog of the chi-squared test). 4. Discussion The results of this cross-sectional research add to the field by offering a holistic view of nutrition incentive use and non-use among people receiving SNAP with access to programming in both farmers’ market and grocery store settings near their residence. Our results offer insights that could be used to expand the dietary and food security benefits of nutrition incentive programming. Three key lessons learned from our research include: (1) insufficient awareness of nutrition incentive programming was a critical yet modifiable impediment to its use; (2) multi-setting approaches are needed to engage diverse audiences of SNAP recipients in nutrition incentive programming; and (3) synergistic strategies are needed to reach those who may benefit the most from nutrition incentives. Despite having geographic access, 44.6% of the participants reported that they had not used the SNAP-based nutrition incentive program in the past year.The overwhelming response as to why SNAP recipients had not tried the program was because they did not know it existed. However, when informed about the incentive program, most participants indicated that they were very likely to use it in the next six months. These findings highlight the importance of conducting dissemination research to explore how best to promote SNAP-based nutrition incentive programming to reach diverse groups by testing the impact of different messengers (e.g., trusted peers, nutrition educators, other influencers), Int. J. Environ. Res. PublicHealth 2022 , 19 , 497710 of 13 channels of communications (e.g., word of mouth, social media, print), and messages. Our findings provide evidence for dissemination efforts that leverage social networks to raise awareness about SNAP-based incentive programs, an approach that has been effective in other research [ 31]. Additionally, our findings reinforce the importance of implementing SNAP-based incentive programs in multiple settings within a community to align with different food shopping routines of SNAP consumers.Much of the prior research on SNAP-based in- centive programming focused on farmers’ market settings demonstrating several benefits, such as improvements in spending flexibility among households, fruit and vegetable pur- chasing and consumption, and opportunities for social connectivity [ 13 , 18 – 21 ].In our study, incentive program users at farmers’ markets reported utilizing the program for the longest amount of time and were more likely to be older and White, which is consistent with research on farmers’ market shoppers in the U.S. [ 32 ]. Singleton and colleagues, for instance, found that non-Hispanic Black shoppers reported shopping at farmers’ markets less frequently and for fewer years than non-Hispanic Whites [
https://www.researchgate.net/publication/360106230_Understanding_SNAP_Recipient_Characteristics_to_Guide_Equitable_Expansion_of_Nutrition_Incentive_Programs_in_Diverse_Food_Retail_Settings
Pharmaceutics | Free Full-Text | Instillation of Ophthalmic Formulation Containing Nilvadipine Nanocrystals Attenuates Lens Opacification in Shumiya Cataract Rats We developed ophthalmic formulations based on nilvadipine (NIL) nanocrystals (NIL-NP dispersions; mean particle size: 98 nm) by using bead mill treatment and investigated whether the instillation of NIL-NP dispersions delivers NIL to the lens and prevents lens opacification in hereditary cataractous Shumiya cataract rats (SCRs). Serious corneal stimulation was not detected in either human corneal epithelial cells or rats treated with NIL-NP dispersions. The NIL was directly delivered to the lens by the instillation of NIL-NP dispersions, and NIL content in the lenses of rats instilled with NIL-NP dispersions was significantly higher than that in the ophthalmic formulations based on NIL microcrystals (NIL-MP dispersions; mean particle size: 21 µm). Moreover, the supply of NIL prevented increases in Ca2+ content and calpain activity in the lenses of SCRs and delayed the onset of cataracts. In addition, the anti-cataract effect in the lens of rats instilled with NIL-NP dispersions was also significantly higher than that in NIL-MP dispersions. NIL-NPs could be used to prevent lens opacification. Instillation of Ophthalmic Formulation Containing Nilvadipine Nanocrystals Attenuates Lens Opacification in Shumiya Cataract Rats Ryoka Goto 1 , Shigehiro Yamada 1 , Hiroko Otake 1 , Yosuke Nakazawa 2 , Mikako Oka 3 , Naoki Yamamoto 4 , Hiroshi Sasaki 5 and Noriaki Nagai 1,* 1 Faculty of Pharmacy, Kindai University, Kowakae, Higashi-Osaka 577-8502, Osaka, Japan 2 Laboratory of Clinical Pharmacology, Yokohama University of Pharmacy, Yokohama 245-0066, Kanagawa, Japan 4 Center for Clinical Trial and Research Support, Fujita Health University, Research Promotion and Support Headquarters, Toyoake 470-1192, Aichi, Japan 5 Department of Ophthalmology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan * Author to whom correspondence should be addressed. Pharmaceutics 2021 , 13 (12), 1999; https://doi.org/10.3390/pharmaceutics13121999 Received: 28 October 2021 / Revised: 19 November 2021 / Accepted: 22 November 2021 / Published: 25 November 2021 (This article belongs to the Special Issue Nanotechnology-Enabled Strategies to Enhance Topical Bioavailability ) Abstract : We developed ophthalmic formulations based on nilvadipine (NIL) nanocrystals (NIL-NP dispersions; mean particle size: 98 nm) by using bead mill treatment and investigated whether the instillation of NIL-NP dispersions delivers NIL to the lens and prevents lens opacification in hereditary cataractous Shumiya cataract rats (SCRs). Serious corneal stimulation was not detected in either human corneal epithelial cells or rats treated with NIL-NP dispersions. The NIL was directly delivered to the lens by the instillation of NIL-NP dispersions, and NIL content in the lenses of rats instilled with NIL-NP dispersions was significantly higher than that in the ophthalmic formulations based on NIL microcrystals (NIL-MP dispersions; mean particle size: 21 µm). Moreover, the supply of NIL prevented increases in Ca 2+ content and calpain activity in the lenses of SCRs and delayed the onset of cataracts. In addition, the anti-cataract effect in the lens of rats instilled with NIL-NP dispersions was also significantly higher than that in NIL-MP dispersions. NIL-NPs could be used to prevent lens opacification. Keywords: nilvadipine ; cataract ; nanocrystals ; ophathalmic formulation ; Shumiya cataract rat Graphical Abstract 1. Introduction Cataracts lead to impaired vision via partial or complete opacification of the lens, resulting in blindness. The World Health Organization (WHO) showed that the number of visually impaired people in the world is estimated to be 314 million [ 1 ]. Although cataracts can be treated with the surgical replacement of the opacified lens, this surgery is not easily performed in developing countries. Therefore, due to a lack of access to eye care and complications associated with surgery, alternative treatments and treatment strategies using topical drugs, such as eye drops, are required to treat patients facing the threat of blindness. Increasing age, ultraviolet light, oxidative stress, lipid peroxidation, diabetes, the oxidation of lens proteins, genetic predispositions, and various toxic agents are known as risk factors for cataract formation [ 2 , 3 , 4 , 5 , 6 ]. Among them, changes in the intracellular calcium ion (Ca 2+ ) have long been known to be related to lens opacification, and the highest Ca 2+ concentrations were related to highly localized opacities [ 2 , 3 , 4 , 5 , 6 ]. Ca 2+ homeostasis has been reported to be important for lens transparency and structural integrity [ 7 , 8 ]. Moreover, increased Ca 2+ content in the lens and the subsequent stimulation of calpain activity cause the onset of cataracts [ 9 , 10 , 11 , 12 ]. In addition, the regulated low intracellular Ca 2+ level maintains the stability of the lens protein. Nilvadipine (NIL) is a second-generation dihydropyridine calcium (Ca) channel blocker and decreases the intracellular Ca 2+ levels by the inhibition of l -type Ca channels. The NIL was used to treat systemic hypertension and enhanced the vertebral blood flow more effectively than nicardipine and nifedipine [ 13 ]. Moreover, the l -type Ca channels, such as CaV 1.2 and 1.3 channels, are distributed and expressed in the epithelium and cortical fiber cells [ 14 ]. Intracellular Ca 2+ was decreased by the prevention of l -type Ca channels in mouse lens epithelial cells [ 14 ]. Thus, the NIL can prevent the development of opacification and maintain lens transparency by Ca 2+ regulation. However, traditional ophthalmic formulation (eye drops) cannot deliver an adequate drug level to the lens, and the ocular bioavailability (BA) is poor as the drugs are diluted by lacrimation and eliminate rapidly from the precorneal area by the tear turnover after instillation [ 15 ]. Therefore, delivering the required levels of NIL and maintaining the drug levels in targeting ocular tissue is important, and this challenge must be overcome for the desired pharmacological efficacy in the ophthalmic field [ 16 ]. Liposomes, dendrimers, nanocrystals, nanosuspensions, nanocarriers, microcapsules, micelles, gels, and implants are useful techniques in the ophthalmic field in terms of improving the drug delivery system (DDS), with increased ocular BA, targeted delivery, and controlled release used to overcome diffusion and penetration problems [ 17 , 18 , 19 , 20 , 21 ]. Particularly, the dispersions containing nanocrystals have been studied extensively as an ophthalmic DDS [ 17 , 18 , 19 , 20 , 21 ]. We also previously designed ophthalmic formulations based on the nanocrystals of fluorometholone, indomethacin, ketoprofen, and tranilast [ 22 , 23 , 24 , 25 ] and found that the instillation of dispersions containing a drug nanocrystal transfer into the intraocular field through the endocytosis pathway, such as caveolae-mediated endocytosis, clathrin-mediated endocytosis, and macropinocytosis, and the instillation of nanocrystals can enhance the ocular BA [ 26 ]. Therefore, nanotechnology based on nanocrystals may overcome the low ocular BA. In this study, experimental animal models were used for the design of ophthalmic formulations [ 27 , 28 , 29 ]. A Shumiya cataract rat (SCR) is a hereditary cataractous rat strain [ 30 ] and one of the experimental animal models for cataracts. The opacification in an SCR lens appears in the nucleus and its peripheral areas with ageing, and the prevalence of lens opacification is expressed in 66.7% of SCRs [ 30 ]. The Ca 2+ levels in cataractous lenses increase markedly with age compared with lenses of SCRs without cataracts, and the autolytic products of calpain are also caused in lenses of SCRs [ 31 , 32 , 33 ]. Thus, the SCR is a useful model for evaluating anti-cataract drugs. In this study, we attempted to develop ophthalmic formulations based on NIL nanocrystals (NIL-NP dispersions) and investigated whether the instillation of NIL-NP dispersions deliver the NIL to lens and prevent lens opacification in SCRs. 2. Materials and Methods 2.1. Animals Male SCRs aged 5 weeks were housed in accordance with the Pharmacy Committee Guidelines for the Care and Use of Laboratory Animals in Yokohama University of Pharmacy and transported to Kindai University at 5 weeks of age. They were housed with controlled lighting (7:00–19:00 light; 19:00–7:00 dark) at 25 °C, unlimited access to drinking water, and a CE-2 formulation diet (Clea Japan Inc., Tokyo, Japan). Twenty microliters of NIL ophthalmic formulations (0.6% NIL) were instilled with the right eye, and all experiments were performed in accordance with the guidelines for the Association for Research in Vision and Ophthalmology (ARVO) and the Pharmacy Committee Guidelines for the Care and Use of Laboratory Animals. Moreover, the experiments using animals were approved on 1 April 2019 (project identification code, KAPS-31-003) by Kindai University. 2.2. Chemicals NIL powder (NIL microcrystals, NIL-MPs), propyl p-hydroxybenzoate, Ca Test Kits, and d -mannitol were purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan), and Cell Count Reagent SF was obtained from Nacalai Tesque Inc. (Kyoto, Japan). Benzalkonium chloride (BAC) was provided from Kanto Chemical Co., Inc. (Tokyo, Japan), and pivalephrine (0.1%) was purchased from Santen Pharmaceutical Co., Ltd. (Osaka, Japan). The Bio-Rad Protein Assay Kit was provided by Bio-Rad Laboratories (Hercules, CA, USA), and 2-hydroxypropyl-β-cyclodextrin (HPβCD) was obtained from Nihon Shokuhin Kako Co., Ltd. (Tokyo, Japan). Fluorescein was provided from Alcon Japan Ltd. (Tokyo, Japan). An LPO Assay Kit (BIOXYTECH ® LPO-586™) was obtained from OXIS International, Inc. (Portland, OR, USA), and the SM-4-type methylcellulose (MC) was supplied by Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan). All other chemicals were of the highest purity commercially available. 2.3. Preparation of NIL-NP Dispersions Dispersions containing NIL-MPs (NIL-MP dispersions) were produced by mixing NIL powder and solution (vehicle) containing MC, BAC, d -mannitol, and HPβCD, and NIL-NP dispersions were prepared following our previous reports using a Bead Smash 12 (Wakenyaku Co. Ltd., Kyoto, Japan) and a Shake Master NEO BMS-M10N21 (Bio-Medical Science Co. Ltd., Tokyo, Japan) [ 23 , 33 ]. Briefly, NIL-MPs were added to powder based on d -mannitol and MC and milled in an agate mortar for 60 min. Afterwards, the mixture was crushed with 1 mm zirconia beads using a Bead Smash 12 at 3000 rpm for 30 s at 4 °C. Subsequently, the mixture was transferred to a tube containing saline with HPβCD and milled with 0.1 mm zirconia beads as follows: (I) 5500 rpm, 30 s × 30 times, 4 °C, by Bead Smash 12; (II) 1500 rpm, 1 h × 3 times, 4 °C, by Shake Master NEO. The compositions of NIL-MP and NIL-NP dispersions were as follows: 0.6% NIL, 1% MC, 0.001% BAC, 0.5% d -mannitol, and 0.5% HPβCD in saline. 2.4. Measurement of NIL NIL was measured by a HPLC method consisting of a LC-20AT Shimadzu pump, a DGU-20A Shimadzu degasser, an SIL-10AF auto sampler, a CTO-20A column oven, and an SPD-20A UV detector (HPLC, Shimadzu Corp., Kyoto, Japan). A quantity of 50 mM phosphate buffer/acetonitrile/methanol (50/25/25, v / v %) was applied as a mobile phase and flowed at 0.25 mL/min. An Inertsil ® ODS-3 column (2.1 × 50 mm) was used (GL Science Co., Inc., Tokyo, Japan), and the wavelength for detection was selected as 242 nm. In this study, 1 mg/mL propyl p-hydroxybenzoate was used as an internal standard. The measurement was performed at 35 °C using a column oven, and the samples (10 μL) were injected using a SIL-10AF. The measuring time was set at 16.5 min. 2.5. Characteristics of Ophthalmic Formulations Containing NIL Characteristics of ophthalmic formulations were measured following our previous reports [ 34 , 35 ]. A SALD-7100 laser diffraction particle size analyzer (Shimadzu Corp., Kyoto, Japan; refractive index 1.60-0.10i) and NANOSIGHT LM10 dynamic light scattering (QuantumDesign Japan, Tokyo, Japan) were used to measure the particle size distribution, and an atomic force microscope (AFM) image of NIL nanocrystals (NIL-NPs) was provided by an SPM-9700 scanning probe microscope (Shimadzu Corp., Kyoto, Japan). The NANOSIGHT LM10 was used to measure the number of NIL-NPs. The crystalline forms of NIL-MPs and NIL-NPs were analyzed by powder X-ray diffraction (XRD) using Mini Flex II (Rigaku Co., Tokyo, Japan). In addition, the melting points of the NIL-MPs and NIL-NPs were evaluated by thermogravimetry–differential thermal analysis (TG-DTA) measurements under a nitrogen atmosphere using a simultaneous DTG-60H TG-DTA apparatus (Shimadzu Corp., Kyoto, Japan). The viscosity and zeta potential of ophthalmic formulations containing NIL were evaluated using an SV-1A (A&D Company, Limited, Tokyo, Japan) and a Model 502 Zeta Potential Meter (Nihon Rufuto Co., Ltd., Tokyo, Japan), respectively. 2.6. Solubility of NIL in the Ophthalmic Formulations NIL dispersions were centrifuged at 1 × 10 5 × g using a MAX-XP Beckman Optima™ Ultracentrifuge (Beckman Coulter, Osaka, Japan), and soluble NIL was separated from non-solubilized NIL. Subsequently, the concentration of soluble NIL was measured by the HPLC method described above and is expressed as the solubility of NIL at 20 °C in this study [ 33 , 35 ]. 2.7. Dispersibility of NIL in the Ophthalmic Formulations Three milliliters of NIL ophthalmic formulations were added to a 5 mL test tube, and were incubated in a dark room at 20 °C. After one month, the NIL ophthalmic formulations were collected from the upper 90% of the test tube, and the concentrations of the collected samples were measured by the HPLC method described above and expressed as the dispersibility of NIL. In addition, the size distribution, the AFM image, and the number of NIL-NPs in the collected samples were measured using the NANOSIGHT LM10 and SPM-9700 described above [ 33 , 35 ]. 2.8. Corneal Stimulation of NIL Ophthalmic Formulations in Cultured Human Corneal Epithelial Cells Corneal stimulation was evaluated by human corneal epithelial cells (HCE-T cells, RIKEN BRC, Ibaraki, Japan). The 1 × 10 4 cells of HCE-T cells were seeded in 96-well microplates (IWAKI, Chiba, Japan) and cultured in Dulbecco’s modified Eagle’s medium (DMEM, Thermo Fisher Scientific, Waltham, MA, USA) with 10 mg/L gentamicin (Wako Pure Chemical Industries, Ltd., Osaka, Japan) and 10% ( v / v ) heat-inactivated fetal bovine serum in humidified air containing 5% CO 2 at 37 °C for 3 days. Subsequently, the HCE-T cells were treated for 2 min by the NIL ophthalmic formulations. Afterwards, the cells were washed with a phosphate buffer and incubated in a medium consisting of 100 µL DMEM and 10 µL Cell Count Reagent SF (Nacalai Tesque Inc., Kyoto, Japan) for 1 h, and Abs was measured at 450 nm according to the manufacturer’s instructions. The cell viability was analyzed as a ratio [Abs treatment /Abs non-treatment (Control) × 100] [ 35 ]. In an in vivo condition, residence time in the eye is 1–2 min after instillation, due to lachrymation [ 36 ]. Therefore, we chose a treatment time of 2 min. 2.9. Corneal Toxicity of NIL Ophthalmic Formulations in the Rats Seven-week-old Wistar rats were used to measure the in vivo corneal toxicity of the NIL ophthalmic formulations. Twenty microliters of NIL ophthalmic formulations (0.6% NIL) were repetitively instilled with the right eye three times a day (9:00, 15:00, and 21:00) for 2 months. The eyes were kept open for about 1 min to prevent the NIL ophthalmic formulations from being washed out. Afterwards, the 1% fluorescein was instilled to dye the wound on the cornea, which was observed using a TRC-50X Fundus camera (Topcon, Tokyo, Japan). The wound area in the image was calculated with Image J (National Institute of Health, Bethesda, MD, USA) [ 35 ]. 2.10. Measurement of NIL Content in the Lenses Twenty microliters of NIL ophthalmic formulations (0.6% NIL) were singly instilled with the right eye of 7-week-old Wistar rats, euthanized by injection of a lethal dose of sodium pentobarbital 0.5, 1, 2, 3, 6, and 24 h after instillation. The eyes were kept open for about 1 min to prevent the NIL ophthalmic formulations from being washed out. Afterwards, the lenses of rats were removed and homogenized in 300 µL of methanol. The homogenates were centrifuged at 20,400× g for 15 min at 4 °C, and the concentration of NIL in the supernatants was measured by the HPLC method described above. 2.11. Scheimpflug Slit Images in the SCR Twenty microliters of NIL ophthalmic formulations (0.6% NIL) were repetitively instilled in the right eye of 6-week-old SCRs for 6 weeks (once a day), and the changes in the transparency of the lenses of these SCRs were observed by an EAS-1000 equipped with a CCD camera (Nidek, Gamagori, Japan) following a previous study [ 37 ]. Briefly, the SCRs without anesthesia were dilated by an instillation of 0.1% pivalephrine and monitored by the EAS-1000. Afterwards, the total area (pixels) of the opacity of the lenses was analyzed by the EAS-1000-equipped software. The measurement conditions were as follows: thread level, flash level, and slit length were 100 threshold level, 100 Watt-seconds, and 4.2 mm, respectively. 2.12. Evaluation of Cataract-Related Factors Twenty microliters of NIL ophthalmic formulations (0.6% NIL) were repetitively instilled with the right eye of 6-week-old SCRs for 3 weeks (once a day), and these rats were euthanized by injections of a lethal dose of sodium pentobarbital 6 h after the last instillation. Afterwards, the lenses of the rats were removed and homogenized in phosphate-buffered saline (pH 7.4) on ice. The lens homogenates were centrifuged at 20,400× g for 30 min at 4 °C, and the supernatants were used for measurements of cararact-related factors, such as the nitric oxide (NO) level, the lipid peroxidation (LPO) level, Ca 2+ -ATPase activity, Ca 2+ content, and calpain activity. NO levels were measured by a flow-through spectrophotometer (NOD-10, Eicom, Kyoto, Japan) [ 29 ]. The NO 2 − and NO 3 − were separated on a reverse-phase separation column packed with polystyrene polymer (NO-PAK, 4.6 × 50 mm, Eicom, Kyoto, Japan) NO 2 − was mixed with Griess’ reagent to form a purple azo dye in a reaction coil, and the absorbance was measured at 540 nm. The amounts of NO reflect the level of NO 2 − metabolites, which is produced from NO. The LPO levels were determined by measuring the lipid peroxidation products 4-hydroxynonenal and malondialdehyde using an LPO Assay Kit according to the manufacturer’s instructions and are expressed as pmol/mg of protein [ 37 ]. The Ca 2+ -ATPase activity was calculated as follows [ 37 ]: the samples were incubated in Solution A (pH 7.4, water, 100 mM, HEPES, 200 mM KCl, 2 mM EGTA, 10 mM MgCl 2 , and 2 mM ATP) with or without 2.2 mM CaCl 2 for 1 h at 37 °C. Afterwards, the reaction was stopped by trichloroacetic acid and calculated as the difference in the Pi liberated from the ATP measured in the presence and absence of Ca 2+ to measure the absorbance of supernatants at 660 nm. In addition, the Ca Test Kit according to the methyl xylenol blue colorimetric method was used to measure the Ca 2+ content [ 38 ], and the Ca 2+ content was expressed as the µmol/mg wet weight. A Calpain Activity Fluorometric Assay Kit was used as the calpain activity, and Abs (505 nm) was measured according to the manufacturer’s instructions [ 39 ]. The protein levels in samples used to determine NO levels, LPO levels, and Ca 2+ -ATPase activity were determined according to the Bradford method using a Bio-Rad Protein Assay Kit. 2.13. Measurement of Blood Pressure (BP) Twenty microliters of NIL ophthalmic formulations (0.6% NIL) were repetitively instilled with the right eye of 6-week-old SCRs for 6 weeks (once a day). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using a noninvasive blood pressure analysis system, BP-98A (Softron, Tokyo, Japan) [ 34 ]. The blood pressure (BP) was measured 3 h after the instillation of NIL ophthalmic formulations. 2.14. Statistical Analysis Statistical analysis was performed using the Student’s t-test and ANOVA followed by Dunnett’s multiple comparison, and all values are expressed as the mean ± standard error (S.E.). p < 0.05 was considered a significant difference. 3. Results 3.1. Physical Properties of NIL-NP Dispersions Figure 1 shows the size frequencies of NIL particles in the NIL ophthalmic formulations. The mean particle size of NIL without bead mill treatment was 21 ± 1.6 µm, and the size was shifted to approximately 30–150 nm by the bead mill treatment. Figure 2 shows the peak patterns of XRD and the melting point of NIL in the NIL-MP and NIL-NP dispersions. Many diffraction peaks were detected in NIL treated with or without the bead mill, and the peak patterns of NIL-MPs and NIL-NPs were similar. Moreover, the diffractogram does not change with or without bead mill treatment. These results show that milled NIL has a crystalline arrangement, and the crystalline arrangement was not changed by the bead mill treatment. Figure 3 shows the solubility, zeta potential, and viscosity of NIL in the NIL-MP and NIL-NP dispersions. The solubility of NIL was not significantly changed by the bead mill treatment, since the solubility in the NIL-NPs without HPβCD was similar to the NIL-MPs without HPβCD. The addition of HPβCD enhanced the solubility of NIL, and the solubility in the NIL-MPs with HPβCD was 2.2-fold higher than the NIL-MPs without HPβCD. On the other hand, the solubility in the NIL-NPs with HPβCD was 2.8-fold higher than the NIL-NPs without HPβCD. Thus, the constants of the HPβCD-NIL inclusion complexes in the NIL-NPs were higher than those in the NIL-MPs. The drug solubility of the NIL-NP dispersions with HPβCD was 43.6 ± 0.6 µM, and 99.7% of the NIL in the dispersions was solid. The zeta potential in the NIL-MP and NIL-NP dispersions were −69 and −74 mV, respectively, and the zeta potential in the NIL-NP dispersions was similar to that in the NIL-MP dispersions. Moreover, no difference in viscosity was observed between the NIL-MP and NIL-NP dispersions. Figure 4 shows changes in particle size frequency, nanoparticle number, concentration, and aggregation, in the NIL of the NIL-MP and NIL-NP dispersions one month after preparation. No degradation of NIL was found in the NIL-MP or NIL-NP dispersions. In the NIL-MP dispersion, precipitation was observed one month after preparation, although aggregation and precipitation was not detected in any of the NIL-NP dispersions. In addition, the nano-size was maintained in the NIL-NP dispersions, and the particle number of the NIL-NP dispersions was not changed for one month. These results show that the NIL-NP dispersions maintained dispersibility for at least one month. 3.2. Drug Delivery to Lens by the Instillation of NIL-NP Dispersions Figure 5 A shows the cell viability of HCE-T cells treated with NIL-MP and NIL-NP dispersions. The cell viability of the HCE-T cells treated with NIL-NP dispersions was 89.8 ± 4.8%, and no significant decrease in the cell viability of the HCE-T cells treated with the vehicle or with NIL-MP and NIL-NP dispersions was observed, in comparison with the untreated group (control). Thus, no serious cell damage was observed in HCE-T cells treated with NIL-NP dispersions. Figure 5 B shows the corneal damage by the repetitive instillation of NIL-MP and NIL-NP dispersions using rats. No significant damage was observed in the groups treated with NIL-MP or NIL-NP dispersions. Over two months, no corneal wound caused by the repetitive instillation of the vehicle was observed. In addition, NIL-MP and NIL-NP dispersions also did not show any corneal wound. Figure 6 shows NIL content in the lens of rats instilled with NIL-MP and NIL-NP dispersions. The NIL was delivered to the lens by the instillation of NIL dispersions, and NIL content in the lenses of rats instilled with NIL-NP dispersions was significantly higher than that in the NIL-MP dispersions. In addition, NIL content in the right lens (instilled eye) was 9.1-fold higher than in the left lens (non-instilled eye) in the rats instilled with NIL-NP dispersions. 3.3. Delay Effect of NIL-NPs on the Onset of Lens Opacification in the SCR Figure 7 A,B show changes in lens opacification in the SCRs repetitively instilled with NIL-MP and NIL-NP dispersions using Scheimpflug slit images. The onset of lens opacification was started at 7 weeks of age, and mature cataracts were observed at 9 weeks of age. The repetitive instillation of NIL-MP dispersions delayed cataract development, and the onset of lens opacification started at 8 weeks of age. The repetitive instillation of NIL-NP dispersions also prevented the onset of opacification, and the preventive effect of cataract development was significantly higher than that in the non-instilled and NIL-MP-instilled SCRs. It is important to investigate whether the instillation of NIL-NP dispersions affect the BP. Therefore, we measured the changes in the BP of SCRs instilled with NIL-NP dispersions ( Figure 7 C). Both the SBP and DBP of SCRs repetitively instilled with NIL-NP dispersions were similar to those of non-instilled rats. Figure 8 shows the changes in cataract-related factors in the lenses of 9-week-old SCRs repetitively instilled with NIL-MP and NIL-NP dispersions. The NO levels, LPO levels, Ca 2+ content, and calpain activity in the 9-week-old SCRs with opaque lenses were significantly higher than those in the 6-week-old SCRs with transparent lenses, and the Ca 2+ -ATPase activity was lower in 9-week-old SCRs. The NO, LPO level, and Ca 2+ -ATPase activity of the non-instilled and NIL-instilled groups were similar. On the other hand, NIL-MP and NIL-NP dispersions attenuated the increase in Ca 2+ content and calpain activity. Moreover, the repetitive instillation of NIL-NP dispersions showed a high preventive effect in comparison with the NIL-MPs. The Ca 2+ content and calpain activity in the lenses of SCRs repetitively instilled with NIL-NP dispersions were 0.38-fold and 0.62-fold higher than those of SCRs instilled with NIL-MP dispersions. 4. Discussion The Ca 2+ levels in cataractous lenses are higher than those in transparent lenses, and the enhanced Ca 2+ concentration in a lens increases the calpain activity, resulting in the onset of cataract and lens opacification [ 9 , 10 , 11 , 12 ]. Thus, the influx and emission of tightly regulated Ca 2+ is critical for the homeostasis of function and the physiology in lenses. In this study, we designed ophthalmic formulations containing NIL nanocrystals (NIL-NP dispersions) and showed that the instillation of NIL-NP dispersions regulated Ca 2+ levels in the lens of SCRs, resulting in a delay of the onset of opacification and cataracts. The selection of additives is important for the production of ophthalmic formulations based on drug nanocrystals by the bead mill method. In the ophthalmic field, BAC was used as a preservative, and a range of BAC concentrations from 0.2 to 0.001% has been applied for the preparation of commercially available ophthalmic formulations (eye drops). On the other hand, high BAC levels cause corneal damage, and the prevention of corneal damage by BAC is important to develop ophthalmic formulations with efficacy and safety. We previously reported that d -mannitol attenuated BAC toxicity without diminishing the preservative effect, and the combination of BAC and d -mannitol was safe and useful as a prescription ophthalmic formulation [ 40 ]. Therefore, we selected additives of 0.001% BAC and 0.5% d -mannitol in this study. Moreover, it has been reported that the cohesion of nanoparticulate solids was prevented by adsorption to the surface of HPβCD [ 33 ] and that MC enhances the crushing efficiency in bead mill treatment and is essential for the production of nanoparticulate solids by the bead mill method [ 33 ]. Based on these findings, we used BAC, d -mannitol, HPβCD, and MC as additives. Bead mill treatment using these additives decreased the particle size of NIL, and the size was changed to approximately 30–150 nm from 1–100 µm ( Figure 1 ). It is known that the crystalline structure affects the characteristics of NIL. Therefore, we measured the crystalline structure in NIL particles treated with or without a bead mill ( Figure 2 ). Many peaks were presented at 10–30° in both NIL-MPs and NIL-NPs, and the XRD peak patterns in the NIL-NP dispersions were similar to those in the NIL-MP dispersions. In addition, we measured the changes in the TG-DTA curve of NIL treated with or without bead mill treatment. The melting point detected at 148 °C in the NIL-MPs and the peak in the NIL-NPs were also similar. Based on these results, it was suggested that the NIL-NPs maintained a crystalline form (not amorphous), and the crystalline structure was not changed by the bead mill treatment. Next, we determined the solubility, zeta potential, and viscosity in NIL-NP dispersions ( Figure 3 ). We used HPβCD to prevent the cohesion of nanoparticulate solids [ 33 ]. HPβCD can form an inclusion complex with a wide variety of solid compounds, and HPβCD complexation is widely used for the solubilization of a poor solution. However, HPβCD enhanced the solubility of the NIL-MP and NIL-NP dispersions, and the ratio of the HPβCD-NIL inclusion complexes of these dispersions were different. The constants of the HPβCD-NIL inclusion complexes in the NIL-NP dispersions were higher than those in the NIL-MP dispersions. On the other hand, almost all (99.7%) of the NIL was presented as solid nanoparticles in the NIL-NP dispersions. In contrast to these results, the solubility, zeta potential, and viscosity in the NIL-NP dispersions were similar to those in the NIL-MP dispersions. We also evaluated the dispersibility of NIL in the NIL-MP and NIL-NP dispersions ( Figure 4 ). The drug dispersibility of NIL in the NIL-NP dispersions was higher than that in the NIL-MP dispersions, and there was no observed aggregation, precipitation, or decomposition of NIL in the NIL ophthalmic formulations for one month. The evaluation of safety and toxicity is important for ophthalmic formulations. It has been reported that BAC and HPβCD induced cell toxicity; however, it is possible to suppress these stimulations by reducing the concentration [ 41 ]. Previous reports have shown that BAC and HPβCD levels less than 0.001% and 12.5% do not cause eye irritation in the eye membrane, respectively [ 41 ]. In addition, d -mannitol attenuates BAC toxicity [ 40 ], and there is a small amount of MC toxicity in the eye [ 33 ]. In this study, cell viability in the HCE-T cells treated with the vehicle showed 0.001% BAC, 0.5% d -mannitol, 0.5% HPβCD, and 1% MC was 91.7%. Moreover, cell viability in the HCE-T cells treated with NIL-MP and NIL-NP dispersions was 88.1% and 89.8%, respectively. In addition, no corneal damage was observed in rats repetitively instilled with NIL-MP or NIL-NP dispersions. These results show that the instillation of NIL-NP dispersions is safe for ocular surfaces. It is difficult to deliver drugs to a lens because the tear film barrier and corneal barrier restrict this kind of delivery [ 42 ]. We demonstrated whether the instillation of dispersions containing NIL nanocrystals is useful as a DDS for the lens. It is known that the drug is also detected in the non-instilled eye (left eye) when absorbed through the conjunctiva and nasolacrimal duct in the drug-instilled eye (right eye). In this study, the NIL was directly delivered to the lens by the instillation of NIL-NP dispersions, since the NIL levels in the lens of the instilled eye (right eye) were remarkable higher than those in the non-instilled eye (left eye) ( Figure 6 B). In addition, the NIL levels in the lens of rats instilled with NIL-NP dispersions were significantly higher than those in the NIL-MP dispersions ( Figure 6 A). Furthermore, the repetitive instillation of NIL-NP dispersions, in comparison with NIL-MP dispersions, attenuated the lens opacification of SCRs ( Figure 7 A,B). Since NIL is used to treat patients with hypertension, we measured the changes in BP after the instillation of NIL-NP dispersions. Such instillation had little effect on both SBP and DBP ( Figure 7 C,D). These results suggest that the ophthalmic formulations based on NIL nanocrystals are useful as a DDS for lenses and that NIL-NPs prevent cataract development in SCRs. SCRs also serve as a useful model for revealing the mechanism of cataract development and its preventive effect in SCR lenses. The overproduction of NO can cause the oxidative inhibition of Ca 2+ -ATPase via lipid peroxidation and increased Ca 2+ influx into the lens [ 43 ]. Afterwards, the enhanced Ca 2+ increased calpain activity [ 6 , 44 ], resulting in the proteolysis of cytoskeletal proteins and crystals [ 45 ]. These biochemical mechanisms develop lens opacification in SCRs. Therefore, we investigated the effect of NIL-NP dispersions on NO levels, LPO levels, Ca 2+ -ATPase activity, Ca 2+ content, and calpain activity in SCRs. The repetitive instillation of NIL-NP dispersions did not attenuate increases in NO or LPO levels or decreases in Ca 2+ -ATPase activity. In contrast to these results, the enhanced Ca 2+ content and calpain activity in the lenses of SCRs were inhibited by the NIL-NP dispersions, and the preventive effect in the NIL-NP dispersions was significantly higher than that in the NIL-MP dispersions. Taken together, we hypothesize that NIL-NP dispersions directly deliver NIL to lenses and that NIL attenuates these lens’ enhanced Ca 2+ content. Thereafter, calpain activity was inhibited by the NIL-NP dispersions, resulting in the delay of lens opacification ( Figure 9 ). On the other hand, the Ca 2+ and calpain activity between SCRs instilled with NIL-NP dispersions (Ca 2+ content 15.6 ± 0.18 µmol/mg wet weight, calpain activity 187 ± 16.1%, n = 8) were also significantly lower than that in non-instilled SCRs (Ca 2+ content 2.13 ± 0.19 µmol/mg wet weight, calpain activity 231 ± 10.8%, n = 8) in the 11-week-old SCRs with opaque lens. This result shows that the NIL have a longer effect but not strong enough to partially delay cataract formation. The cataract can be treated with a surgical procedure, however, this surgery is not easily performed in developing countries. From this background, the delay of cataract formation will improve the patient’s sight. In addition, we previously reported that the instillation of disulfiram (radical scavenger) and lanosterol (solubilization of crystallin aggregation) also prevent the onset of cataract [ 39 , 46 , 47 ]. The combination of NIL and other anti-cataract drugs with different preventive mechanisms may be effective in treatment of cataracts, resulting in providing an impact in cataract treatments. It is important to compare the NIL-NP dispersions and other advanced functional nano eye drops [ 48 , 49 ], and discuss the efficient maintenance of drug levels in targeting ocular tissue and management of the diseases occurring in the inner segments of the eye. In addition, further studies are needed to evaluate the mechanism of the ocular DDS in NIL-NP dispersions. We previously reported that drug nanoparticles in ophthalmic formulations are taken into the corneal epithelium by energy-dependent endocytosis, e.g., caveolae-mediated endocytosis, clathrin-mediated endocytosis, and micropinocytosis, resulting in an enhancement of transcorneal penetration [ 24 , 26 ]. Therefore, we are now planning to demonstrate whether energy-dependent endocytosis, by using its inhibitors, is related to transcorneal penetration and delivery to the lens of NIL-NPs. 5. Conclusions We prepared dispersions containing NIL nanocrystals and showed that the instillation of NIL-NP dispersions directly delivered NIL to the lens. Moreover, the supply of NIL by the instillation of NIL-NP dispersions delayed the progress of lens opacification in SCRs. These findings contribute to the development of therapy for cataracts. Author Contributions Conceptualization, N.N.; data curation, R.G., S.Y., H.O., Y.N. and N.Y.; formal analysis, S.Y., H.O., Y.N., M.O. and H.S.; funding acquisition, N.N.; investigation, R.G., S.Y., Y.N. and N.Y.; methodology, R.G., H.O., M.O., N.Y., H.S. and N.N.; supervision, N.N.; visualization, N.N.; writing—original draft, N.N.; writing—review and editing, N.N. All authors have read and agreed to the published version of the manuscript. Funding We gratefully acknowledge grant no. 21K06656 from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Institutional Review Board Statement The protocol was conducted according to the guidelines for the ARVO and Kindai University and approved by Kindai University (KAPS-31-003, 1 April 2019). Informed Consent Statement Not applicable. Data Availability Statement The data presented in this study are available upon request from the corresponding author. Acknowledgments Not applicable. Conflicts of Interest The authors declare that there are no conflicts of interest. References WHO. Vision 2020 the Right to Sight. Global Initiative for the Elimination of Avoidable Blindness. Available online: https://www.who.int/blindness/Vision2020_report.pdf (accessed on 1 November 2021). Garland, D. Role of site-specific, metal-catalyzed oxidation in lens aging and cataract: A hypothesis. Exp. Eye Res. 1990 , 50 , 677–682. [ Google Scholar ] [ CrossRef ] Rasi, V.; Costantini, S.; Moramarco, A.; Giordano, R.; Giustolisi, R.; Gabrieli, C.B. Inorganic element concentrations in cataractous human lenses. Ann. Ophthalmol. 1992 , 24 , 459–464. [ Google Scholar ] Ye, J.; Zadunaisky, J. Study of the Ca2 + /Na + exchange mechanism in vesicles isolated from apical membranes of lens epithelium of spiny dogfish ( Squalus acanthias ) and bovine eye. Exp. Eye Res. 1992 , 55 , 243–250. [ Google Scholar ] [ CrossRef ] Cekic, O.; Bardak, Y. Lenticular calcium, magnesium, and iron levels in diabetic rats and verapamil effect. Ophthalmic. Res. 1998 , 30 , 107–112. [ Google Scholar ] [ CrossRef ] Dilsiz, N.; Olcucu, A.; Atas, M. Determination of calcium, sodium, potassium and magnesium concentrations in human senile cataractous lenses. Cell Biochem. Funct. 2000 , 18 , 259–262. [ Google Scholar ] [ CrossRef ] Rhodes, J.D.; Sanderson, J. The mechanisms of calcium homeostasis and signalling in the lens. Exp. Eye Res. 2009 , 88 , 226–234. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Duncan, G.; Collison, D.J. Calcium signalling in ocular tissues: Functional activity of G-protein and tyrosine-kinase coupled receptors. Exp. Eye Res. 2002 , 75 , 377–389. [ Google Scholar ] [ CrossRef ] Shearer, T.R.; Ma, H.; Fukiage, C.; Azuma, M. Selenite nuclear cataract: Review of the model. Mol. Vis. 1997 , 23 , 8–17. [ Google Scholar ] Sanderson, J.; Marcantonio, J.M.; Duncan, G. A human lens model of cortical cataract: Ca2 + -induced protein loss, vimentin cleavage and opacification. Investig. Ophthalmol. Vis. Sci. 2000 , 41 , 2255–2261. [ Google Scholar ] Truscott, R.J.; Marcantonio, J.M.; Tomlinson, J.; Duncan, G. Calcium-induced opacification and proteolysis in the intact rat lens. Investig. Ophthalmol. Vis. Sci. 1990 , 31 , 2405–2411. [ Google Scholar ] Nakamura, Y.; Fukiage, C.; Shih, M.; Ma, H.; David, L.L.; Azuma, M.; Shearer, T.R. Contribution of calpain Lp82-induced proteolysis to experimental cataractogenesis in mice. Investig. Ophthalmol. Vis. Sci. 2000 , 41 , 1460–1466. [ Google Scholar ] Ohtsuka, M.; Ono, T.; Hiroi, J.; Esumi, K.; Kikuchi, H.; Kumada, S. Comparison of the Cardiovascular Effect of FR34235, a New Dihydropyridine, with Other Calcium Antagonists. J. Cardiovasc. Pharmacol. 1983 , 5 , 1074–1082. [ Google Scholar ] [ CrossRef ] [ PubMed ] Maddala, R.; Nagendran, T.; De Ridder, G.G.; Schey, K.L.; Rao, P.V. L-Type Calcium Channels Play a Critical Role in Maintaining Lens Transparency by Regulating Phosphorylation of Aquaporin-0 and Myosin Light Chain and Expression of Connexins. PLoS ONE 2013 , 8 , e64676. [ Google Scholar ] [ CrossRef ][ Green Version ] Urtti, A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv. Drug Deliv. Rev. 2006 , 58 , 1131–1135. [ Google Scholar ] [ CrossRef ] Mannermaa, E.; Vellonen, K.-S.; Urtti, A. Drug transport in corneal epithelium and blood–retina barrier: Emerging role of transporters in ocular pharmacokinetics. Adv. Drug Deliv. Rev. 2006 , 58 , 1136–1163. [ Google Scholar ] [ CrossRef ] Hagigit, T.; Abdulrazik, M.; Orucov, F.; Valamanesh, F.; Lambert, M.; Lambert, G.; Behar-Cohen, F.; Benita, S. Topical and intravitreous administration of cationic nanoemulsions to deliver antisense oligonucleotides directed towards VEGF KDR receptors to the eye. J. Control. Release 2010 , 145 , 297–305. [ Google Scholar ] [ CrossRef ] [ PubMed ] Gan, L.; Gan, Y.; Zhu, C.; Zhang, X.; Zhu, J. Novel microemulsion in situ electrolyte-triggered gelling system for ophthalmic delivery of lipophilic cyclosporine A: In vitro and in vivo results. Int. J. Pharm. 2009 , 365 , 143–149. [ Google Scholar ] [ CrossRef ] Sun, D.; Maeno, H.; Gujrati, M.; Schur, R.; Maeda, A.; Maeda, T.; Palczewski, K.; Lu, Z.-R. Self-Assembly of a Multifunctional Lipid with Core-Shell Dendrimer DNA Nanoparticles Enhanced Efficient Gene Delivery at Low Charge Ratios into RPE Cells. Macromol. Biosci. 2015 , 15 , 1663–1672. [ Google Scholar ] [ CrossRef ] Hironaka, K.; Inokuchi, Y.; Fujisawa, T.; Shimazaki, H.; Akane, M.; Tozuka, Y.; Tsuruma, K.; Shimazawa, M.; Hara, H.; Takeuchi, H. Edaravone-loaded liposomes for retinal protection against oxidative stress-induced retinal damage. Eur. J. Pharm. Biopharm. 2011 , 79 , 119–125. [ Google Scholar ] [ CrossRef ] Shen, J.; Wang, Y.; Ping, Q.; Xiao, Y.; Huang, X. Mucoadhesive effect of thiolated PEG stearate and its modified NLC for ocular drug delivery. J. Control. Release 2009 , 137 , 217–223. [ Google Scholar ] [ CrossRef ] Otake, H.; Goto, R.; Ogata, F.; Isaka, T.; Kawasaki, N.; Kobayakawa, S.; Matsunaga, T.; Nagai, N. Fixed-Combination Eye Drops Based on Fluorometholone Nanoparticles and Bromfenac/Levofloxacin Solution Improve Drug Corneal Penetration. Int. J. Nanomed. 2021 , 16 , 5343–5356. [ Google Scholar ] [ CrossRef ] Nagai, N.; Isaka, T.; Deguchi, S.; Minami, M.; Yamaguchi, M.; Otake, H.; Okamoto, N.; Nakazawa, Y. In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals. Int. J. Mol. Sci. 2020 , 21 , 7083. [ Google Scholar ] [ CrossRef ] Nagai, N.; Ogata, F.; Ishii, M.; Fukuoka, Y.; Otake, H.; Nakazawa, Y.; Kawasaki, N. Involvement of Endocytosis in the Transdermal Penetration Mechanism of Ketoprofen Nanoparticles. Int. J. Mol. Sci. 2018 , 19 , 2138. [ Google Scholar ] [ CrossRef ][ Green Version ] Nagai, N.; Minami, M.; Deguchi, S.; Otake, H.; Sasaki, H.; Yamamoto, N. An In Situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva. Front. Bioeng. Biotechnol. 2020 , 8 , 764. [ Google Scholar ] [ CrossRef ] [ PubMed ] Nagai, N.; Ogata, F.; Otake, H.; Nakazawa, Y.; Kawasaki, N. Energy-dependent endocytosis is responsible for drug transcorneal penetration following the instillation of ophthalmic formulations containing indomethacin nanoparticles. Int. J. Nanomed. 2019 , 14 , 1213–1227. [ Google Scholar ] [ CrossRef ][ Green Version ] Tripathi, B.J.; Tripathi, R.C.; Borisuth, N.S.; Dhaliwal, R.; Dhaliwal, D. Rodent models of congenital and hereditary cataract in man. Lens Eye Toxic. Res. 1991 , 8 , 373–413. [ Google Scholar ] [ PubMed ] Nagai, N.; Ito, Y. Excessive hydrogen peroxide enhances the attachment of amyloid β1–42 in the lens epithelium of UPL rats, a hereditary model for cataracts. Toxicology 2014 , 315 , 55–64. [ Google Scholar ] [ CrossRef ] [ PubMed ] Nagai, N.; Ito, Y. Adverse effects of excessive nitric oxide on cytochrome c oxidase in lenses of hereditary cataract UPL rats. Toxicology 2007 , 242 , 7–15. [ Google Scholar ] [ CrossRef ] Shumiya, S. Establishment of the hereditary cataract rat strain (SCR) and genetic analysis. Lab. Anim. Sci. 1995 , 45 , 671–673. [ Google Scholar ] Inomata, M.; Nomura, K.; Takehana, M.; Saido, T.C.; Kawashima, S.; Shumiya, S. Evidence for the involvement of calpain in cataractogenesis in Shumiya cataract rat (SCR). Biochim. Biophys. Acta Mol. Basis Dis. 1997 , 1362 , 11–23. [ Google Scholar ] [ CrossRef ][ Green Version ] Nagai, N.; Ito, Y.; Inomata, M.; Shumiya, S.; Tai, H.; Hataguchi, Y.; Nakagawa, K. Delay of Cataract Development in the Shumiya Cataract Rat by the Administration of Drinking Water Containing High Concentration of Magnesium Ion. Biol. Pharm. Bull. 2006 , 29 , 1234–1238. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Nagai, N.; Ito, Y.; Okamoto, N.; Shimomura, Y. A nanoparticle formulation reduces the corneal toxicity of indomethacin eye drops and enhances its corneal permeability. Toxicology 2014 , 319 , 53–62. [ Google Scholar ] [ CrossRef ] [ PubMed ] Deguchi, S.; Ogata, F.; Watanabe, M.; Otake, H.; Yamamoto, N.; Kawasaki, N.; Nagai, N. Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine. Pharmaceutics 2021 , 13 , 1404. [ Google Scholar ] [ CrossRef ] Minami, M.; Otake, H.; Nakazawa, Y.; Okamoto, N.; Yamamoto, N.; Sasaki, H.; Nagai, N. Balance of Drug Residence and Diffusion in Lacrimal Fluid Determine Ocular Bioavailability in In Situ Gels Incorporating Tranilast Nanoparticles. Pharmaceutics 2021 , 13 , 1425. [ Google Scholar ] [ CrossRef ] Le Bourlais, C.; Acar, L.; Zia, H.; Sado, P.A.; Needham, T.; Leverge, R. Ophthalmic drug delivery systems—Recent advances. Prog. Retin. Eye Res. 1998 , 17 , 33–58. [ Google Scholar ] [ CrossRef ] Nagai, N.; Ito, Y.; Takeuchi, N. Inhibitive effects of enhanced lipid peroxidation on Ca2 + -ATPase in lenses of hereditary cataract ICR/f rats. Toxicology 2008 , 247 , 139–144. [ Google Scholar ] [ CrossRef ] Nagai, N.; Ito, Y.; Takeuchi, N.; Usui, S.; Hirano, K. Comparison of the Mechanisms of Cataract Development Involving Differences in Ca2+ Regulation in Lenses among Three Hereditary Cataract Model Rats. Biol. Pharm. Bull. 2008 , 31 , 1990–1995. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Nagai, N.; Umachi, K.; Otake, H.; Oka, M.; Hiramatsu, N.; Sasaki, H.; Yamamoto, N. Ophthalmic in situ Gelling System Containing Lanosterol Nanoparticles Delays Collapse of Lens Structure in Shumiya Cataract Rats. Pharmaceutics 2020 , 12 , 629. [ Google Scholar ] [ CrossRef ] Nagai, N.; Yoshioka, C.; Tanino, T.; Ito, Y.; Okamoto, N.; Shimomura, Y. Decrease in Corneal Damage due to Benzalkonium Chloride by the Addition of Mannitol into Timolol Maleate Eye Drops. J. Oleo. Sci. 2015 , 64 , 743–750. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Jansen, T.; Xhonneux, B.; Mesens, J.; Borgers, M. Beta-cyclodextrins as vehicles in eye-drop formulations: An evaluation of their effects on rabbit corneal epithelium. Lens Eye Toxic. Res. 1990 , 7 , 459–468. [ Google Scholar ] [ PubMed ] Kambhampati, S.P.; Kannan, R.M. Dendrimer Nanoparticles for Ocular Drug Delivery. J. Ocul. Pharmacol. Ther. 2013 , 29 , 151–165. [ Google Scholar ] [ CrossRef ][ Green Version ] Duncan, G.; Bushell, A. Ion analyses of human cataractous lenses. Exp. Eye Res. 1975 , 20 , 223–230. [ Google Scholar ] [ CrossRef ] Spector, A. Oxidative stress-induced cataract: Mechanism of action. FASEB J. 1995 , 9 , 1173–1182. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Shearer, T.R.; David, L.L.; Anderson, R.S.; Azuma, M. Review of selenite cataract. Curr. Eye Res. 1992 , 11 , 357–369. [ Google Scholar ] [ CrossRef ] [ PubMed ] Nagai, N.; Fukuoka, Y.; Sato, K.; Otake, H.; Taga, A.; Oka, M.; Hiramatsu, N.; Yamamoto, N. The Intravitreal Injection of Lanosterol Nanoparticles Rescues Lens Structure Collapse at an Early Stage in Shumiya Cataract Rats. Int. J. Mol. Sci. 2020 , 21 , 1048. [ Google Scholar ] [ CrossRef ][ Green Version ] Nagai, N.; Ito, Y.; Takeuchi, N. Effect of Disulfiram Eye Drops on Lipid Peroxide Formation via Excessive Nitric Oxide in Lenses of Hereditary Cataract ICR/f Rats. Biol. Pharm. Bull. 2008 , 31 , 981–985. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Luo, L.-J.; Nguyen, D.D.; Lai, J.-Y. Dually functional hollow ceria nanoparticle platform for intraocular drug delivery: A push beyond the limits of static and dynamic ocular barriers toward glaucoma therapy. Biomaterials 2020 , 243 , 119961. [ Google Scholar ] [ CrossRef ] [ PubMed ] Luo, L.-J.; Nguyen, D.D.; Lai, J.-Y. Harnessing the tunable cavity of nanoceria for enhancing Y-27632-mediated alleviation of ocular hypertension. Theranostics 2021 , 11 , 5447–5463. [ Google Scholar ] [ CrossRef ] Figure 1. Size frequencies and AFM image of NIL particles treated with or without a bead mill. ( A , B ): particle size frequencies of NIL-MP ( A ) and NIL-NP ( B ) dispersions obtained by the SALD-7100. ( C ) particle size frequencies of NIL-NP dispersions obtained by the NANOSIGHT LM10. ( D ): AFM image of NIL-NP dispersions obtained by the SPM-9700. The bar shows 500 nm. The dispersions containing NIL-NPs were obtained by the bead mill treatment, and the size was approximately 30–150 nm. Figure 2. Analysis of crystalline structure and characteristics in NIL particles treated with or without a bead mill. ( A , B ): The powder X-ray diffraction patterns of NIL-MP ( A ) and NIL-NP ( B ) dispersions. ( C , D ): The TG-DTA curve of NIL-MP ( C ) and NIL-NP ( D ) dispersions. Many diffraction peaks were detected in the NIL-NPs. The peak patterns of the XRD in the NIL-NP dispersions were similar to those of the NIL-MPs, and the melting point of the NIL-NPs was not changed by the bead mill treatment. Figure 2. Analysis of crystalline structure and characteristics in NIL particles treated with or without a bead mill. ( A , B ): The powder X-ray diffraction patterns of NIL-MP ( A ) and NIL-NP ( B ) dispersions. ( C , D ): The TG-DTA curve of NIL-MP ( C ) and NIL-NP ( D ) dispersions. Many diffraction peaks were detected in the NIL-NPs. The peak patterns of the XRD in the NIL-NP dispersions were similar to those of the NIL-MPs, and the melting point of the NIL-NPs was not changed by the bead mill treatment. Figure 3. Changes in the drug solubility, zeta potential, and viscosity of the NIL dispersions treated with or without a bead mill. ( A) Solubility in the milled NIL dispersions with or without HPβCD. ( B ) Zeta potential of the NIL in the NIL-MP and NIL-NP dispersions. ( C ) Viscosity of NIL-MP and NIL-NP dispersions. n = 5–8. * p < 0.05, vs. NIL dispersions without HPβCD for each category. # p < 0.05, vs. NIL-MP dispersions for each category. The solubility of NIL was increased by the bead mill treatment, and the constants of the HPβCD-NIL inclusion complexes in the NIL-NPs were also higher than those in the NIL-MPs. The zeta potential and viscosity of the NIL-MP and NIL-NP dispersions were not different. Figure 3. Changes in the drug solubility, zeta potential, and viscosity of the NIL dispersions treated with or without a bead mill. ( A) Solubility in the milled NIL dispersions with or without HPβCD. ( B ) Zeta potential of the NIL in the NIL-MP and NIL-NP dispersions. ( C ) Viscosity of NIL-MP and NIL-NP dispersions. n = 5–8. * p < 0.05, vs. NIL dispersions without HPβCD for each category. # p < 0.05, vs. NIL-MP dispersions for each category. The solubility of NIL was increased by the bead mill treatment, and the constants of the HPβCD-NIL inclusion complexes in the NIL-NPs were also higher than those in the NIL-MPs. The zeta potential and viscosity of the NIL-MP and NIL-NP dispersions were not different. Figure 4. Drug stability of NIL-NP dispersions 1 month after preparation at 22 °C. ( A ) Particle size frequencies of NIL in NIL-NP dispersions. ( B ) AFM image of NIL in NIL-NP dispersions. ( C ) NIL concentration in NIL-NP dispersions. ( D ) Particle number of NIL in NIL-NP dispersions. ( E ) Representative image of NIL-MP and NIL-NP dispersions at Day 0 and 1 month after preparation. ( F ) Dispersibility of NIL-MP and NIL-NP dispersions 1 month after preparation. n = 6–12. * p < 0.05 vs. Day 0 for each category. The NIL-NP dispersions maintained dispersibility for at least 1 month. Figure 4. Drug stability of NIL-NP dispersions 1 month after preparation at 22 °C. ( A ) Particle size frequencies of NIL in NIL-NP dispersions. ( B ) AFM image of NIL in NIL-NP dispersions. ( C ) NIL concentration in NIL-NP dispersions. ( D ) Particle number of NIL in NIL-NP dispersions. ( E ) Representative image of NIL-MP and NIL-NP dispersions at Day 0 and 1 month after preparation. ( F ) Dispersibility of NIL-MP and NIL-NP dispersions 1 month after preparation. n = 6–12. * p < 0.05 vs. Day 0 for each category. The NIL-NP dispersions maintained dispersibility for at least 1 month. Figure 5. Corneal toxicity in the instillation of NIL-NP dispersions. ( A ) Effect of NIL treatment on cell viability in HCE-T cells. ( B ) Corneal image in rats repetitively instilled with NIL-NP dispersions. Twenty microliters of NIL ophthalmic formulations were repetitively instilled with the right eye three times a day for 2 months. n = 5. No significant damage was observed in the groups treated with NIL-MP or NIL-NP dispersions. Figure 5. Corneal toxicity in the instillation of NIL-NP dispersions. ( A ) Effect of NIL treatment on cell viability in HCE-T cells. ( B ) Corneal image in rats repetitively instilled with NIL-NP dispersions. Twenty microliters of NIL ophthalmic formulations were repetitively instilled with the right eye three times a day for 2 months. n = 5. No significant damage was observed in the groups treated with NIL-MP or NIL-NP dispersions. Figure 6. Changes in NIL content in the lens of rats instilled with NIL dispersions. ( A ) NIL content in the lens 0–6 h after the instillation of NIL dispersions. ( B ) NIL content in the lens of NIL-instilled (right) and non-NIL-instilled eye (left) 24 h after the instillation of NIL dispersions. n = 6–9. * p < 0.05 vs. NIL-MPs for each category. # p < 0.05 vs. the right eye for each category. The NIL levels in the lens of rats instilled with NIL-NP dispersions were significantly higher than those with the NIL-MP dispersions, and the NIL was directly delivered to the lens by the instillation of NIL-NP dispersions. Figure 6. Changes in NIL content in the lens of rats instilled with NIL dispersions. ( A ) NIL content in the lens 0–6 h after the instillation of NIL dispersions. ( B ) NIL content in the lens of NIL-instilled (right) and non-NIL-instilled eye (left) 24 h after the instillation of NIL dispersions. n = 6–9. * p < 0.05 vs. NIL-MPs for each category. # p < 0.05 vs. the right eye for each category. The NIL levels in the lens of rats instilled with NIL-NP dispersions were significantly higher than those with the NIL-MP dispersions, and the NIL was directly delivered to the lens by the instillation of NIL-NP dispersions. Figure 7. Changes in the opacity and BP in the SCRs repetitively instilled with NIL-NP dispersions. ( A , B ) Scheimpflug slit images ( A ) and opacity levels ( B ) in the SCRs repetitively instilled with NIL-NP dispersions. SBP ( C ) and DBP ( D ) profiles in the SCRs repetitively instilled with NIL-NP dispersions. The 6-week-old SCRs were repetitively instilled with NIL dispersions for 6 weeks (once a day). None: non-instilled SCRs. NIL-MPs: NIL-MP-instilled SCRs. NIL-NPs: NIL-NP-instilled SCRs. n = 4–11. * p < 0.05, vs. none for each group. The repetitive instillation of NIL-NP dispersions significantly delayed the onset of opacification in comparison with non-instilled and NIL-MP-instilled SCRs. On the other hand, NIL-NP dispersions did not affect the BP. Figure 8. Changes in NO levels ( A ), LPO levels ( B ), Ca 2+ -ATPase activity ( C ), Ca 2+ content ( D ), and calpain activity ( E ) in the lenses of 9-week-old SCRs repetitively instilled with NIL-NPs. The 6-week-old SCRs were repetitively instilled with NIL dispersions for 3 weeks (once a day). Control: non-instilled SCRs aged 6 weeks (transparent lens). None: non-instilled SCRs aged 9 weeks. MPs: NIL-MP-instilled SCRs aged 9 weeks. NPs: NIL-NP-instilled SCRs aged 9 weeks. n = 4–9. * p < 0.05, vs. control for each group. # p < 0.05, vs. none for each group. $ p < 0.05, vs. MPs for each group. The repetitive instillation of NIL-NP dispersions significantly prevented enhanced Ca 2+ content and calpain activity. Figure 8. Changes in NO levels ( A ), LPO levels ( B ), Ca 2+ -ATPase activity ( C ), Ca 2+ content ( D ), and calpain activity ( E ) in the lenses of 9-week-old SCRs repetitively instilled with NIL-NPs. The 6-week-old SCRs were repetitively instilled with NIL dispersions for 3 weeks (once a day). Control: non-instilled SCRs aged 6 weeks (transparent lens). None: non-instilled SCRs aged 9 weeks. MPs: NIL-MP-instilled SCRs aged 9 weeks. NPs: NIL-NP-instilled SCRs aged 9 weeks. n = 4–9. * p < 0.05, vs. control for each group. # p < 0.05, vs. none for each group. $ p < 0.05, vs. MPs for each group. The repetitive instillation of NIL-NP dispersions significantly prevented enhanced Ca 2+ content and calpain activity. Figure 9. Scheme for the anti-cataract effect following the instillation of NIL-NP dispersions in SCRs. Figure 9. Scheme for the anti-cataract effect following the instillation of NIL-NP dispersions in SCRs. Goto, Ryoka, Shigehiro Yamada, Hiroko Otake, Yosuke Nakazawa, Mikako Oka, Naoki Yamamoto, Hiroshi Sasaki, and Noriaki Nagai. 2021. "Instillation of Ophthalmic Formulation Containing Nilvadipine Nanocrystals Attenuates Lens Opacification in Shumiya Cataract Rats" Pharmaceutics13, no. 12: 1999. https://doi.org/10.3390/pharmaceutics13121999
https://www.mdpi.com/1999-4923/13/12/1999
Biosensors | Free Full-Text | The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease (COPD) is a common progressive disorder of the respiratory system which is currently the third leading cause of death worldwide. Exhaled breath analysis is a non-invasive method to study lung diseases, and electronic noses have been extensively used in breath research. Studies with electronic noses have proved that the pattern of exhaled volatile organic compounds is different in COPD. More recent investigations have reported that electronic noses could potentially distinguish different endotypes (i.e., neutrophilic vs. eosinophilic) and are able to detect microorganisms in the airways responsible for exacerbations. This article will review the published literature on electronic noses and COPD and help in identifying methodological, physiological, and disease-related factors which could affect the results. The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease by Simone Scarlata 1 , Panaiotis Finamore 2 , Martina Meszaros 3 , Silvano Dragonieri 4 and Andras Bikov 5,6,* 2 Unit of Geriatrics, Campus Bio Medico University and Teaching Hospital, 00128 Rome, Italy 3 Department of Pulmonology and Sleep Disorders Centre, University Hospital Zürich, 8091 Zurich, Switzerland 4 Respiratory and Sleep Medicine Unit, Policlinico University Hospital, University of Bari Aldo Moro, 70124 Bari, Italy 5 Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M23 9LT, UK 6 Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester M13 9NT, UK * Author to whom correspondence should be addressed. Biosensors 2020 , 10 (11), 171; https://doi.org/10.3390/bios10110171 Received: 13 October 2020 / Revised: 5 November 2020 / Accepted: 9 November 2020 / Published: 11 November 2020 (This article belongs to the Special Issue Electronic Noses for Biomedical Applications and Environmental Monitoring II ) Abstract Chronic obstructive pulmonary disease (COPD) is a common progressive disorder of the respiratory system which is currently the third leading cause of death worldwide. Exhaled breath analysis is a non-invasive method to study lung diseases, and electronic noses have been extensively used in breath research. Studies with electronic noses have proved that the pattern of exhaled volatile organic compounds is different in COPD. More recent investigations have reported that electronic noses could potentially distinguish different endotypes (i.e., neutrophilic vs. eosinophilic) and are able to detect microorganisms in the airways responsible for exacerbations. This article will review the published literature on electronic noses and COPD and help in identifying methodological, physiological, and disease-related factors which could affect the results. Keywords: COPD ; chronic obstructive pulmonary disease ; e-nose ; electronic nose ; VOCs ; volatile organic compounds 1. Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease (COPD) is a common disorder of the respiratory system which is characterised by a progressive airflow limitation caused by exposure to noxious particles, usually tobacco smoke, in susceptible individuals [ 1 ]. However, other factors, such as premature birth, frequent childhood infections, asthma, or passive smoking, could also contribute to COPD [ 1 ]. The disease may affect the large airways, respiratory bronchioles, and lung parenchyma, however the extent of the involvement of different lung regions may vary [ 2 ] ( Figure 1 ). Figure 1. The pathophysiology of chronic obstructive pulmonary disease. Large airway disease is characterised by mucus hypersecretion, ciliary and epithelial dysfunction, mucosal and submucosal inflammation, as well as enhanced bronchial blood flow. Patients may present with symptoms of chronic productive cough or chronic bronchitis. Most of these patients have small airway disease, which is characterised by airway inflammation, peribronchial fibrosis, and subsequent small airway narrowing. Parenchymal involvement is termed emphysema, and it is characterised by progressive loss of the lung tissue, impaired oxygen intake, and carbon dioxide removal. People with small airway disease and emphysema often complain of progressive shortness of breath. Although widely recognised as a progressive disease, the activity of disease varies largely between patients. Around half of patients have a rapid (≥50 mL/year loss) decline in forced expiratory volume in the first second (FEV 1 ), a marker quantifying airway obstruction [ 3 ], and around 30% are prone to acute exacerbations, major events leading to health deterioration and associated with high healthcare burden and mortality [ 4 ]. COPD is diagnosed based on medical history, symptoms, and lung function showing fixed airflow obstruction. Although the diagnosis, especially the differential diagnosis from other lung diseases (i.e., asthma, bronchiectasis), is sometimes difficult, in most cases it can be made based on simple and cheap pulmonary function tests. It is important to have reliable biomarkers which could differentiate patients with eosinophilic airway inflammation and reflect on disease activity (i.e., predict lung function decline and future exacerbations). This is essential clinical information, as inhaled corticosteroids (ICS) seem to be more effective in patients with raised airway eosinophils [ 5 ], as well as patients with a high exacerbation burden [ 6 ]. On the other hand, in some patients recurrent exacerbations are maintained by colonising bacteria and patients may benefit from prophylactic antibiotic treatment [ 7 ]. Hence, biomarkers reflecting on bacterial colonisation and specifying bacteria would have significant clinical value. Similar to stable disease, acute exacerbations are also heterogeneous and patients may benefit from tailored treatment depending on the inflammatory profile [ 8 ] and infectious cause [ 9 ]. Exhaled breath analysis is a widely used technique for investigating airway diseases. It is totally harmless, and therefore can be performed even in very frail patients and during acute breathlessness, such as in exacerbation. Therefore, it has a great yet not fully explored clinical potential to distinguish patients with different inflammatory endotypes and airway microbiology. One of the most important limiting factors is the lack of standardisation [ 10 ] and the effect of various endogenous (airway calibre, comorbidities, etc.) and exogenous factors (diet, smoking, pollution) which may limit their use. Traditionally, techniques assessing breath biomarkers are divided into methods investigating volatile and non-volatile particles [ 10 ] and the measurement of breath temperature [ 11 ]. In this review, we will focus on the measurement of volatile organic compounds (VOCs) using electronic noses in COPD. 2. The Role of Electronic Noses in Breath Research Exhaled breath contains thousands of VOCs usually in pico or nanomolar concentrations. The origin of these molecules is two-fold. Some of them are inhaled from the environment and exhaled later. Environmental molecules may also be absorbed in the human body, react with endogenous VOCs, or induce altered production of endogenous molecules. Another group of VOCs is released by the human body, including cells of the respiratory tract reflecting on their metabolism. The release of some of these endogenous volatile molecules is induced by inflammation and oxidative stress [ 12 ]. The precise detection and quantification of these molecules involves gas-chromatography mass-spectrometry (GC-MS). However, GC-MS is expensive, uses bulky equipment, and requires special expertise. Electronic noses are a relatively cheap and easy-to-use alternative to GC-MS [ 13 ]. These devices are composites of a sensor array and an in-built processor, and their function resembles that of biological olfaction receptors, as they are unspecific to single molecules and, upon activation by an odour, create a signal pattern. Electronic noses therefore cannot identify individual molecules but are able to compare and discriminate exhaled samples based on their molecular pattern, which is often called a “breathprint”. Because individual VOCs generating a “breathprint” are not characterised during the analysis, it is essential to exclude environmental factors leading to altered VOC levels. As a first step, subjects are asked to avoid consuming food and beverages, not to smoke, and to refrain from physical exercise prior to breath collection. It is good practice if these events are recorded in a clinical research form together with the last medication taken. This may help in identifying outliers in the final analysis. Exhaled breath should be collected in a standardised way, either by a single expiratory method or a multiple breath technique, with custom-made or commercially available sampling devices [ 10 ]. The breath sample could be collected directly into disposable collection bags (e.g., polyethylene, Nalophan, Tedlar, Mylar, etc.) or canisters made of inert material or pre-concentrated into adsorbent cartridges (e.g., Breath Biopsy Cartridges, Tenax GR ® ) [ 14 ]. The stability of VOCs declines within hours and strongly depends on the material of the collection bags [ 15 , 16 , 17 , 18 ], therefore an immediate analysis is suggested following collection. The advantage of Tenax tubes is that they allow transportation and delayed measurement. Although storage and transportation in sorbent tubes significantly affected the “breathprint”, it did not influence the discrimination potential of an electronic nose to differentiate asthma and health [ 19 ]. A novel method has been introduced lately to analyse the “breathprint” directly during a single expiratory manoeuvre [ 20 ]. Breath collection is followed by the electronic nose analysis. Various electronic noses have been used in the field of breath research, including those based on conducting polymer sensor arrays (i.e., Cyranose 320) [ 21 ], metal oxides (i.e., Aeonose, Spironose) [ 22 ], nanomaterials [ 23 ], quartz microbalance (i.e., BIONOTE) [ 24 ], as well as colorimetric sensors [ 25 ]. All these devices are made of sensors able to interact with VOCs and generate electrical signals, however the mechanism underpinning the interaction is specific to the used array (e.g., piezoelectric effect for quartz microbalance electronic nose or oxidation for metal oxide devices). There is a difference between these sensor systems in terms of the sensitivity and selectivity to different VOCs, the stability of the sensor signal, and the effect of environmental factors such as temperature and humidity [ 14 ]. These differences need to be taken into account when comparing data originating from different sensor systems. Finally, sensor signals are integrated into a “breathprint”, which can be analysed with complex discrimination techniques. The exhaled breath sampling and analysis is summarised in Figure 2 . Figure 2. Algorithm for the exhaled breath collection and analysis with electronic nose. A common technical challenge which may affect the electronic nose measurements is the temporal drift of the sensors, which means that the steady state of the sensor responses changes over the time of usage. This drift can be divided into short- and long-term components. For conducting polymer sensors, the failure of the detachment of VOCs from the sensors or inability to regain the baseline conformation may contribute to short-term drift, which means that electronic nose measurements may influence the subsequent ones [ 26 ]. The oxidation of the polymers contributes to the long-term drift [ 27 ]. Exposing Cyranose 320, a commercially available electronic nose based on a conducting polymer sensor array, to methanethiol for 8 days resulted in a considerable sensor drift [ 28 ]. It was shown that even for VOCs with a low concentration, the calibration of the entire array response could be re-established robustly with the use of carefully chosen calibrants [ 21 , 29 , 30 ]. Another analytical method to normalise drift in complex sensor arrays could be orthogonal partial least squares normalisation [ 31 ]. A study by Bos et al. reported a significant sensor drift over 1 year, and the authors suggested transformation into standardised residuals by linear regression to normalise this [ 32 ]. The reproducibility of quartz microbalance sensors has been investigated in healthy subjects and COPD patients simultaneously by Incalzi et al. [ 33 ]. The authors found that the reproducibility was better in healthy subjects than in COPD, concluding that the variability of the disease, rather than sensor drift, is responsible for the variation in data [ 33 ]. Sensor drift has been noticed for metal oxide sensors as well [ 34 ]. Jaeschke et al. explored various statistical methods, including linear discriminant analysis (LDA), partial least squares discriminant analysis (PLS-DA), and direct orthogonalisation, and found that PLS-DA was particularly useful for correction [ 34 ]. The humidity of exhaled breath samples may contribute to sensor drift for gold nanoparticle-based sensor systems [ 34 ]. A compensation method based on relative humidity sensors has been proposed to address this issue [ 34 ]. Instrumental drift has been reported even for GC-MS [ 35 ]. Rodriguez-Perez et al. applied filtering and additive, multiplicative, and multivariate drift corrections and was able to improve the classification of COPD subjects based on exhaled breath analysis [ 35 ]. For a detailed description of the electronic nose technology in breath research, we refer to previously published review articles [ 13 , 14 , 21 , 23 , 27 , 36 , 37 , 38 , 39 , 40 , 41 ]. Another important aspect is the data analysis, as it involves complex pattern recognition and comparative statistical methods [ 42 ]. Not surprisingly, the results may be very different based on which method is used [ 43 ]. There is no single, recommended statistical method to be used in breath analyses [ 10 ], however the European Respiratory Society’s statement recommended careful pre-processing, normalisation, and environmental correction as part of the analysis as well as the validation of the results by an independent cohort [ 10 ]. Smolinska et al. summarised the normalisation and pre-processing techniques for exhaled breath analysis [ 44 ] with a detailed description of their advantages and drawbacks. Environmental contamination removal can be achieved with an analysis of the alveolar gradient by sampling the environment together with the actual breath sample [ 20 ]. 3. Altered Production and Kinetics of Exhaled VOCs in COPD Patients with COPD are usually middle-aged and elderly, and they tend to lose skeletal muscle with the progression of their disease. Therefore, the exhaled levels of those volatile organic compounds which are affected by age and metabolism, such as isoprene, acetone, and alkanes [ 45 , 46 ] may be compromised not by the disease but by senescence. Isoprene and acetone are found in relatively high concentrations in exhaled breath compared to other VOCs, and therefore these can contribute to the unspecific E-nose pattern significantly. Having said this, the E-nose pattern was found to be related to age in previous studies [ 47 , 48 ]. However, other reports found no influence of age on electronic noses to discriminate people with obstructive airway disease from healthy controls [ 49 , 50 ]. Patients with COPD may have an altered lifestyle, including regular exercise and diet [ 51 ]. Indeed, a study by Gaida et al. reported that the differences in VOC profiles between two groups of COPD patients sampled in different German cities could be due to lifestyle-related factors [ 52 ], however environmental factors, such as air pollution, could also contribute [ 53 ]. A number of studies have reported altered exhaled VOC profile associated with the consumption of certain foods and beverages [ 54 , 55 , 56 ]. In addition, exercise could alter “breathprint”, likely due to increased metabolism and oxidative stress in the airways as well as increased cardiac output [ 57 , 58 , 59 ]. However, in patients with COPD, the liberation of VOCs may be compromised due to dynamic hyperinflation during exercise. A relationship between exercise tolerance and the profile of exhaled VOCs has been previously reported [ 60 ]. The effect of gender on the composition of the exhaled VOC profile is less evident [ 55 , 61 , 62 ]. As alterations in exhaled “breathprint” may be related to hormonal changes rather than biological gender [ 63 , 64 ], this has to be investigated in women with COPD separately, as in most cases the disease is diagnosed post-menopause. The release of blood-borne volatile compounds into exhaled breath depends on the alveolo-capillary barrier, which may be destroyed in patients with emphysema. This factor may need to be taken into account when interpreting VOC results. Emphysema could also lead to significant ventilation-perfusion heterogeneity and the collapse potential of the small airways. Therefore, even during normal exhalation, VOCs originating from peripheral airways may entrap, which could contribute to their ultimate concentration in exhaled breath. In line with this, certain VOCs have been associated with the extent of emphysema and low diffusion capacity, as well as airflow limitation in patients with COPD [ 65 ]. A relationship between airway calibre and “breathprint” obtained with an electronic nose has been shown by some [ 47 ], but not all [ 66 ] studies. Focusing on COPD, a significant correlation was reported between the lung function and electronic nose results obtained by the quartz microbalance sensor array [ 33 ]. COPD is characterised by airflow limitation, which could influence the levels of exhaled VOCs, especially if they are collected with an uncontrolled single expiratory manoeuvre. In addition, some VOCs such as ethanol may be released from the bronchial circulation, and their diffusion to the airway lumen is hampered in bronchial thickening [ 67 ]. This is further complicated during acute exacerbations, which are characterised by mucus hypersecretion (leading to a longer diffusion time from the bronchial circulation) and an increase in bronchial circulation (causing an increased release of VOCs) [ 2 ]. Theoretically, the exhalation flow rate may influence the concentrations of those exhaled VOCs which are produced in the airways [ 47 ]. In line with this, the levels of exhaled VOCs such as acetone [ 68 ], ethanol [ 54 ], isoprene [ 69 , 70 ], and pentane [ 69 ], as well as the whole “breathprint” [ 20 ], were influenced by exhalation flow, and different exhalation flow rates affected the utility of the electronic nose to diagnose lung cancer [ 47 ]. However, it is unclear how this affects the electronic nose results in COPD. As ventilation heterogeneity—more particularly, the opening and closing of the peripheral airways—may show inter-breath variability, and because of the expiratory flow dependency of exhaled VOC levels, the volume-targeted multiple breath collection method may be preferable to the single-exhalation technique in COPD ( Figure 3 ). Figure 3. The mechanisms of altered production of exhaled volatile organic compounds (VOCs) in COPD. The liberation of VOCs into exhaled breath and their entrapment into the airway lining fluid (ALF) is strongly affected by the temperature and acidity of the ALF. For instance, a significant relationship was reported between the “breathprint” obtained by the electronic nose and the pH of the exhaled breath condensate [ 59 ]. As the bronchial temperature [ 11 ] and acidity [ 71 ] may be different in COPD, this effect needs to be considered when interpreting the VOC results. Finally, the exhaled compounds may originate from within the gastrointestinal tract. In line with this, a previous study found that gastro-oesophageal reflux disease can affect the “breathprint” in COPD [ 72 ]. 4. Exhaled VOCs in Relation to Inflammation and Microbiome in COPD It is well known that the inflammatory response in COPD is largely neutrophilic, but can also involve eosinophils to a lesser extent [ 71 , 73 ]. The presence and activity of inflammatory cells differ among patients subgroups and may be related to diverse pathophysiological pathways within the disease [ 74 , 75 ]. Biomarkers which reflect the inflammatory endotype of patients with COPD can help in a more effective tailored therapy, since a better response to corticosteroids in COPD with a higher presence of eosinophils has been clearly shown [ 76 , 77 , 78 ]. Several studies have demonstrated that there is an association between exhaled VOCs and the presence of inflammatory cells in subjects affected by COPD [ 65 , 79 , 80 , 81 ]. Fens et al. showed that exhaled VOCs are associated with differential sputum cell counts and soluble sputum markers of activated neutrophils and eosinophils in mild and moderate COPD, suggesting the potential of “breathprint” as a non-invasive biomarker in relatively early stages of COPD [ 79 ]. Furthermore, studies with GC-MS reported numerous VOCs linked with sputum inflammatory cells [ 65 , 80 ]. In particular, Schleich et al. identified VOCs discriminating between eosinophil and neutrophil cell cultures, regardless of their activation status [ 80 ]. Interestingly, Basanta et al. detected other types of VOCs which were able to distinguish between patients with COPD and healthy controls as well as to discriminate among subgroups of clinical interest, such as smokers with COPD versus asymptomatic smokers, and COPD subjects with higher sputum eosinophils or those with frequent exacerbations [ 65 ]. Moreover, de Vries et al. analysed exhaled VOCs with an electronic nose, showing an adequate prediction of blood eosinophils and neutrophils count in a pooled cohort of patients with asthma and COPD, irrespective of their underlying disease [ 81 ]. These results are very similar to those in asthma, where the electronic nose response not only correlated with bronchoalveolar lavage eosinophils [ 82 ], but was able to discriminate the eosinophilic, neutrophilic, and paucigranulocytic sputum profile [ 83 ]. However, despite promising studies indicating a significant correlation between exhaled VOCs and the presence of inflammatory cells in blood or sputum, the validation of results is yet to be achieved. Numerous studies have compared the exhaled VOCs of COPD patients during exacerbations and stable disease [ 84 , 85 , 86 , 87 ]. Using GC-MS, Pizzini et al. discriminated patients with acute COPD exacerbation from individuals with stable COPD as well as healthy controls. Following the exclusion of VOCs associated with smoking and those with high environmental concentration, they built a model based on a limited number of VOCs. The performance of this VOC pattern was superior to the C-reactive protein levels in discriminating stable and exacerbated patients [ 84 ]. Similarly, Gaugg et al. [ 85 ] showed that a profile of certain VOCs identified by GC-MS was different between frequent and non-frequent exacerbators at clinical stability, suggesting the potential of using breathomics for subphenotyping patients with COPD. Van Velzen et al. recruited patients with COPD at their stable state and followed them up at exacerbation and recovery. Breath samples were analysed with GC-MS and a platform of four electronic noses. The electronic nose platform was able to discriminate exacerbations from stable state as well as recovery with a cross-validated accuracy of 0.75, a sensitivity of 0.79, and a specificity of 0.71, without finding significant differences between baseline and recovery [ 86 ]. These results highlight the merit of VOC analysis in the follow-up of patients with COPD, as mild to moderate exacerbations are often difficult to diagnose due to the natural variability of the disease [ 1 ]. Due to compromised immune system as well as frequent steroid use, the airways of patients with COPD are often colonised by bacteria and fungi. These are associated with unique VOC patterns [ 88 ]. Using Cyranose 320 and LDA, Shafiek et al. demonstrated that the e-nose discriminates COPD exacerbation triggered by infections from non-infective exacerbations with an accuracy of 0.75 [ 87 ] and exacerbations from pneumonia with an accuracy 0.86–0.88, a sensitivity of 0.85–0.91, and a specificity of 0.86–0.75, depending on the presence of potentially pathogen microorganisms [ 87 ], allowing a timely and tailored antibiotic treatment. This accuracy is in line with another study where an electronic nose could discriminate viral and bacterial infection-induced exacerbation with an area under the receiver operating characteristic (ROC) curve (AUROC) of 0.74 [ 89 ]. Analysing the breath samples of 37 patients with COPD with the Cyranose 320 device, Sibila et al. concluded that patients with bacterial colonisation have a different “breathprint” [ 90 ]. More particularly, principal component analysis followed by ROC analysis showed an excellent classification (AUROC of 0.94). This study highlights the possibility of using electronic noses to identify patients who may benefit from a preventive antibiotic treatment. 5. The Effect of Smoking on Exhaled VOCs in COPD Cigarette smoke is a mixture of more than 5000 chemical compounds, among which hundreds have toxic and/or carcinogenic effects [ 91 ]. A number of studies have shown that VOCs profiles are significantly influenced by smoking behaviour [ 49 , 52 , 53 , 92 , 93 ]. It must be recognised that the exhaled VOCs of current smokers can be influenced in two ways. First, VOCs may directly derive from the cigarette. In line with this, different exhaled compounds were identified and directly correlated with smoking status, smoking intensity, years of smoking, and depth of inhalation [ 94 ]. Moreover, strong differences were observed in the VOC composition of tobacco cigarette smokers and exhaled breath in the comparison with that of electronic cigarette smokers [ 95 ]. Such a direct influence on the exhaled VOC composition may be mitigated by asking patients to abstain from smoking for a certain period before sampling exhaled breath. It seems that a two-hour period may suffice to reduce the influence of smoking [ 38 ]. It is well known that cigarette smoke promotes oxidative stress in the human body by augmenting the number of free radicals [ 96 , 97 ]. This may result in a production of oxidative stress-related compounds which promote airway inflammation by activating neutrophils and eosinophils [ 98 ]. Very interestingly, electronic nose studies on patients with COPD showed no difference in VOCs profiles between current and ex-smokers [ 38 , 79 , 99 ], whereas in healthy controls, there were significant differences between current and non-smokers [ 38 , 93 ]. Similarly, a recent study by Rodriguez-Aguilar et al. showed no difference in the composition of exhaled breath obtained from patients with COPD who were divided into smoking-induced and household air pollution-induced groups [ 100 ]. Taken together, the aforementioned studies suggest that exhaled VOC-profile can be helpful in detecting COPD, irrespective from their smoking status. However, the difference between COPD and health has disappeared when COPD patients were compared to healthy, non-smoker volunteers [ 49 ]. It seems that smoking did not affect the discrimination potential of gold nanoparticles, carbon nanotube or colorimetric sensors [ 101 , 102 , 103 ]. Due to these discrepancies we suggest that smoking history should be taken into account when designing case-control studies. 6. The Effect of Medications on Exhaled VOCs in COPD Pharmaceutical agents in COPD include bronchodilators, inhaled and systemic corticosteroids, roflumilast, antibiotics, mucolytics and theophylline [ 1 ]. Surprisingly, the number of studies investigating the effect of medications on exhaled VOC pattern is low. Salbutamol is a short acting β2-receptor agonist. Gaugg and colleagues demonstrated that the levels of VOCs change after salbutamol inhalation in patients with chronic airway diseases ( n = 13 asthma, 37 COPD), but not after inhaling placebo [ 104 ]. Similarly, Scarlata et al. reported a quantitative reduction in exhaled VOCs following inhaled bronchodilator treatment [ 105 ]. In line with this, the levels of exhaled VOCs were related to urinary salbutamol levels in patients with asthma [ 106 ]. Lazar et al. demonstrated a change in exhaled “breathprint” following salbutamol inhalation and the change was not due to alterations in the airway calibre, but the nebulised aerosols [ 66 ]. Corticosteroids are immunosuppressive drugs and are used in both stable (inhaled) and exacerbated (systemic) disease. Comparing ICS user and non-user patients with COPD, Fens et al. did not find a significant difference in the “breathprint” [ 49 ]. In line with this, analysing the effect of ICS on the potential of electronic noses to discriminate COPD from health, van Berkel did not find a significant influence [ 107 ]. Contrarily, Scarlata et al. reported a qualitative modification of exhaled VOC pattern in patients on ICS [ 105 ]. When investigating patients with severe asthma, a significant relationship between the exhaled “breathprint” and urine corticosteroid levels was found [ 106 ]. Analysing the same cohort of subjects, the stability of the electronic nose “breathprint” was determined by the systemic corticosteroid use [ 108 ]. It is likely that theophylline, antibiotics, roflumilast, and mucolytics may all effect exhaled VOCs, however these have not been investigated before. 7. The Effect of Respiratory and Non-Respiratory Comorbidities Due to age, common aetiologies (i.e., smoking), and the direct effect of hypoxaemia and inflammation, COPD is often accompanied with comorbidities. These may individually affect the electronic nose results [ 14 ], but may also compromise electronic nose discrimination potential to detect COPD. For instance, obstructive sleep apnoea (OSA), which itself alters the levels of exhaled VOCs [ 109 ], also affects how precisely COPD can be detected with two different electronic noses [ 110 , 111 ]. Investigating 13 patients with OSA, 15 patients with COPD, and 13 patients with both diseases (overlap syndrome) with Cyranose 320 and LDA, Dragonieri et al. concluded that OSA was different from COPD patients and overlap syndrome, while there was no difference between the COPD and overlap groups [ 111 ]. In contrast, including patients with OSA in the control group, 25% of patients with COPD were inaccurately classified to the OSA group and 25% of the patients with OSA were incorrectly classified into the COPD group in the study by Scarlata et al., who used a quartz microbalance array and PLS-DA [ 110 ]. These two studies highlight that some components of the “breathprint” may not be disease-specific but may represent a common underlying mechanism (i.e., hypoxaemia). Likewise, the exhaled VOC levels may be different in cardiovascular diseases, such as heart failure and coronary artery disease [ 112 ], which frequently accompany COPD [ 113 ]. It is also true that COPD may compromise the diagnostic ability to detect other diseases, such as shown for lung cancer [ 114 ]. 8. Electronic Nose Studies in COPD As described above, the composition of exhaled VOCs in could be altered due to several endogenous and exogenous factors. This chapter summarises the published evidence for case-control studies ( Table 1 ). First of all, it has to be emphasised that the electronic nose signal in COPD seems to be stable, with a within-day reproducibility of 0.80 and an overall mean between-day reproducibility around 0.70 [ 33 , 49 , 115 ]. Table 1. Clinical studies conducted on electronic noses in patients with COPD. Most studies have reported a good (AUROC or cross-validation value ≥0.70) to an excellent discrimination performance (≥0.90) of electronic noses in COPD regardless of comparator. However, it seems that this performance strongly depends on the number of control groups tested [ 110 ]. Notably, most of the studies conducted on multiple groups are generally underpowered with small sample size. For these reasons, targeting the optimal population represents a major issue deserving further investigation. An external validation set is highly recommended to strengthen the reliability of the results [ 10 ]. In most one-to-one comparison analyses, electronic noses have shown a good diagnostic ability, being able to discriminate COPD from healthy controls [ 49 , 87 , 90 , 100 ] and other chronic conditions carrying respiratory symptoms usually requiring differential diagnosis with COPD (i.e., asthma, obstructive sleep apnoea, lung cancer, chronic heart failure, etc.). Using Cyranose 320 and LDA, Fens et al. were able to discriminate patients with COPD from non-COPD smokers with a cross-validation value of 0.66. Interestingly, patients with COPD were not different from non-smoker controls [ 49 ]. In contrast, using Cyranose 320 and LDA as well, Sibila et al. could distinguish patients with COPD from non-COPD control subjects (77% ever-smoker) with a much higher cross-validation value (0.83-0.88) [ 90 ]. Using the same device and classification method, the study by Shafiek et al. reported an accuracy of 72% in classifying patients with stable COPD and healthy controls [ 87 ]. In a very recent study using the same device, adding support vector machines models to canonical discriminant analysis, a cross-validation value of 1.00 was achieved for the comparison between patients with COPD and healthy subjects [ 100 ]. COPD can be discriminated from chronic heart failure with an externally validated accuracy of 0.69, a sensitivity of 0.63, and a specificity of 0.74 [ 119 ], independently from age, smoking habit, and comorbidities, which have an impact on the VOC pattern [ 120 ]. Likewise, Fens and colleagues obtained an externally validated accuracy of 0.95, a sensitivity of 0.91, and a specificity of 0.94 in discriminating COPD smokers and former smokers from asthmatic patients with LDA [ 99 ]. Interestingly, the difference in VOC pattern between COPD and asthma cannot be attributed to the type (i.e., reversible or not) or degree of airways obstruction, because the externally validated discriminative accuracy remained almost the same [ 99 ]; these results suggest that COPD has a specific VOC pattern production, independent from the degree of airway obstruction. Regardless of smoking, COPD can be discriminated from OSA with an accuracy of 0.75-0.80 [ 110 , 111 ] and a sensitivity and specificity of 0.75, while the presence of both diseases in the same patient (i.e., overlap syndrome) cannot be clearly distinguished by COPD [ 111 ]. Likewise, COPD can be discriminated from lung cancer [ 20 , 116 , 121 ]. In all these studies, the participants performed exhaled breath analysis apart from spirometry and observed some restrictions in eating, smoking, and taking medication before the test, limiting its applicability in clinical practice. A combination of a metal-oxide semiconductor e-nose with a spirometer (i.e., “SpiroNose”, AMC, Amsterdam; Comon-Invent BV, Delft, The Netherlands) has represented a paramount step in the applicability of e-nose in clinical practice, allowing real-time analysis and eliminating the VOC collection and storage step. The study of De Vries and colleagues has demonstrated that SpiroNose is able to discriminate COPD Global Initiative for Obstructive Lung Disease (GOLD) stages II-IV from healthy controls, asthma, and lung cancer with a AUROC of 0.80, 0.81, and 0.88 [ 20 ], respectively, without the need for restrictions before the test. Alpha-1 antitrypsin (AAT) deficiency is a relatively rare genetic cause for COPD. In a pilot study, an electronic nose was applied in the discrimination of 10 patients with AAT deficiency, 23 patients with COPD without AAT deficiency, and 10 healthy subjects. The authors concluded a good discriminative cross-validated accuracy based on LDA [ 118 ]. They also supplemented 11 AAT-deficient patients with human purified AAT and found a significant change in “breathprint”. This change could be either due to the direct effect of AAT on the exhaled VOC pattern or may represent immunological alterations due to the augmentation therapy [ 118 ]. The “breathprint” was associated with the exercise capacity of COPD patients, expressed by the six minute walking distance and the disease-specific prognostic index BODE (Body mass index, Obstruction, Dyspnea, and Exercise), and was be able to predict those patients with a steeper decline more accurately than GOLD classification with PLS-DA [ 60 ], helping clinicians tailor their interventions and follow up and also helping diagnose frail patients who could benefit from palliative care. Although the technique is promising and is cheaper and easier to use than GC-MS, electronic noses are still more expensive than the current diagnostic spirometry and they warrant some expertise. In addition, due to the unspecific nature of the signals, they cannot easily be interpreted in clinical practice. Therefore, their role alone would be limited in diagnostic and differential diagnostic settings. However, their combination with traditional spirometry has merit in identifying endotypes and differentiating COPD from asthma with fixed airway obstruction [ 20 , 49 , 81 ]. Airway sampling using invasive techniques, such as bronchoscopy is not always feasible in COPD, and even sputum induction hold risks for patients with very severe COPD [ 122 ]. Although endotyping and monitoring airway inflammation hold essential clinical value [ 5 ], the currently used surrogates, such as blood eosinophils, only weakly correlate with their percentages in sputum [ 123 ]. In addition, it has recently been suggested that temporal variation, rather than the baseline values of blood eosinophilia, better predicted treatment response to inhaled corticosteroids in COPD [ 124 ]. The monitoring of airway inflammation via electronic nose holds clinical potential, and future studies should focus on this. 9. Summary The composition of volatile organic compounds in exhaled breath may be different due to various endogenous (airway inflammation, altered kinetics) and environmental (smoking, medications) factors. This is reflected in the results of case-control studies comparing COPD to various control conditions. This review highlights the need for normalisation in technical (i.e., sensor drift, statistical methods), sampling-related (i.e., expiratory flow rate), and patient-related (i.e., diet, smoking, medication abstinence prior to sampling) factors to make the results more comparable. Although the technique is currently limited, we believe that, through the international standardisation of the method, this would be a valuable in the clinical assessment of the airway inflammation of patients with COPD. Author Contributions S.S. and P.F. drafted Section 6 and Section 8 , M.M. prepared Figures and Table 1 and contributed to Section 8 , S.D. drafted Section 4 and Section 5 , A.B. drafted Section 1 , Section 2 , Section 3 , Section 7 and Section 9 . The manuscript was critically reviewed and approved by all authors. The authors agree to be personally accountable for their own contributions. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. Acknowledgments Andras Bikov is supported by the NIHR Manchester BRC. The authors are grateful to Rhys Tudge for grammatical corrections. Conflicts of Interest The authors declare no conflict of interest. References Vogelmeier, C.F.; Criner, G.J.; Martinez, F.J.; Anzueto, A.; Barnes, P.J.; Bourbeau, J.; Celli, B.R.; Chen, R.; Decramer, M.; Fabbri, L.M.; et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary. Eur. Respir. J. 2017 , 49 , 1700214. [ Google Scholar ] [ CrossRef ] [ PubMed ] Barnes, P.J.; Burney, P.G.; Silverman, E.K.; Celli, B.R.; Vestbo, J.; Wedzicha, J.A.; Wouters, E.F. Chronic obstructive pulmonary disease. Nat. Rev. Dis. Primers 2015 , 1 , 15076. [ Google Scholar ] [ CrossRef ] [ PubMed ] Lange, P.; Celli, B.; Agusti, A.; Boje Jensen, G.; Divo, M.; Faner, R.; Guerra, S.; Marott, J.L.; Martinez, F.D.; Martinez-Camblor, P.; et al. Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. N. Engl. J. Med. 2015 , 373 , 111–122. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Hurst, J.R.; Vestbo, J.; Anzueto, A.; Locantore, N.; Mullerova, H.; Tal-Singer, R.; Miller, B.; Lomas, D.A.; Agusti, A.; Macnee, W.; et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N. Engl. J. Med. 2010 , 363 , 1128–1138. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Pascoe, S.; Locantore, N.; Dransfield, M.T.; Barnes, N.C.; Pavord, I.D. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: A secondary analysis of data from two parallel randomised controlled trials. Lancet. Respir. Med. 2015 , 3 , 435–442. [ Google Scholar ] [ CrossRef ] Calverley, P.M.A.; Tetzlaff, K.; Vogelmeier, C.; Fabbri, L.M.; Magnussen, H.; Wouters, E.F.M.; Mezzanotte, W.; Disse, B.; Finnigan, H.; Asijee, G.; et al. Eosinophilia, Frequent Exacerbations, and Steroid Response in Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2017 , 196 , 1219–1221. [ Google Scholar ] [ CrossRef ] Bafadhel, M.; Haldar, K.; Barker, B.; Patel, H.; Mistry, V.; Barer, M.R.; Pavord, I.D.; Brightling, C.E. Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD: Relationship with neutrophilic airway inflammation, exacerbation frequency, and lung function. Int. J. Chronic Obstr. Pulm. Dis. 2015 , 10 , 1075–1083. [ Google Scholar ] [ CrossRef ][ Green Version ] Bafadhel, M.; McKenna, S.; Terry, S.; Mistry, V.; Pancholi, M.; Venge, P.; Lomas, D.A.; Barer, M.R.; Johnston, S.L.; Pavord, I.D.; et al. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: A randomized placebo-controlled trial. Am. J. Respir. Crit. Care Med. 2012 , 186 , 48–55. [ Google Scholar ] [ CrossRef ][ Green Version ] Di Pasquale, M.; Aliberti, S.; Mantero, M.; Gramegna, A.; Blasi, F. Pharmacotherapeutic management of bronchial infections in adults: Non-cystic fibrosis bronchiectasis and chronic obstructive pulmonary disease. Expert Opin. Pharmacother. 2020 , 1–15. [ Google Scholar ] [ CrossRef ] Horváth, I.; Barnes, P.J.; Loukides, S.; Sterk, P.J.; Högman, M.; Olin, A.C.; Amann, A.; Antus, B.; Baraldi, E.; Bikov, A.; et al. A European Respiratory Society technical standard: Exhaled biomarkers in lung disease. Eur. Respir. J. 2017 , 49 . [ Google Scholar ] [ CrossRef ][ Green Version ] Lázár, Z.; Bikov, A.; Martinovszky, F.; Gálffy, G.; Losonczy, G.; Horváth, I. Exhaled breath temperature in patients with stable and exacerbated COPD. J. Breath Res. 2014 , 8 , 046002. [ Google Scholar ] [ CrossRef ] [ PubMed ] Haick, H.; Broza, Y.Y.; Mochalski, P.; Ruzsanyi, V.; Amann, A. Assessment, origin, and implementation of breath volatile cancer markers. Chem. Soc. Rev. 2014 , 43 , 1423–1449. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Montuschi, P.; Mores, N.; Trove, A.; Mondino, C.; Barnes, P.J. The electronic nose in respiratory medicine. Respir. Int. Rev. Thorac. Dis. 2013 , 85 , 72–84. [ Google Scholar ] [ CrossRef ] [ PubMed ] Bikov, A.; Lázár, Z.; Horvath, I. Established methodological issues in electronic nose research: How far are we from using these instruments in clinical settings of breath analysis? J. Breath Res. 2015 , 9 , 034001. [ Google Scholar ] [ CrossRef ] Agency, U.E.P. Sampling of Principal Organic Hazardous Constituents from Combustion Sources Using Tedlar Bags. Available online: https://www.epa.gov/hw-sw846/sw-846-test-method-0040-sampling-principal-organic-hazardous-constituents-combustion (accessed on 3 November 2020). Wzorek, B.; Mochalski, P.; Sliwka, I.; Amann, A. Application of GC-MS with a SPME and thermal desorption technique for determination of dimethylamine and trimethylamine in gaseous samples for medical diagnostic purposes. J. Breath Res. 2010 , 4 , 026002. [ Google Scholar ] [ CrossRef ] Beauchamp, J.; Herbig, J.; Gutmann, R.; Hansel, A. On the use of Tedlar(R) bags for breath-gas sampling and analysis. J. Breath Res. 2008 , 2 , 046001. [ Google Scholar ] [ CrossRef ] Mochalski, P.; Wzorek, B.; Sliwka, I.; Amann, A. Suitability of different polymer bags for storage of volatile sulphur compounds relevant to breath analysis. J. Chromatogr. B 2009 , 877 , 189–196. [ Google Scholar ] [ CrossRef ] Van der Schee, M.P.; Fens, N.; Brinkman, P.; Bos, L.D.; Angelo, M.D.; Nijsen, T.M.; Raabe, R.; Knobel, H.H.; Vink, T.J.; Sterk, P.J. Effect of transportation and storage using sorbent tubes of exhaled breath samples on diagnostic accuracy of electronic nose analysis. J. Breath Res. 2013 , 7 , 016002. [ Google Scholar ] [ CrossRef ] De Vries, R.; Brinkman, P.; van der Schee, M.P.; Fens, N.; Dijkers, E.; Bootsma, S.K.; de Jongh, F.H.; Sterk, P.J. Integration of electronic nose technology with spirometry: Validation of a new approach for exhaled breath analysis. J. Breath Res. 2015 , 9 , 046001. [ Google Scholar ] [ CrossRef ] Lewis, N.S. Comparisons between mammalian and artificial olfaction based on arrays of carbon black-polymer composite vapor detectors. Acc. Chem. Res. 2004 , 37 , 663–672. [ Google Scholar ] [ CrossRef ] Righettoni, M.; Amann, A.; Pratsinis, S.E. Breath analysis by nanostructured metal oxides as chemo-resistive gas sensors. Mater. Today 2014 , 18 , 163–171. [ Google Scholar ] [ CrossRef ] Broza, Y.Y.; Haick, H. Nanomaterial-based sensors for detection of disease by volatile organic compounds. Nanomedicine 2013 , 8 , 785–806. [ Google Scholar ] [ CrossRef ] [ PubMed ] Di Natale, C.; Macagnano, A.; Martinelli, E.; Paolesse, R.; D’Arcangelo, G.; Roscioni, C.; Finazzi-Agrò, A.; D’Amico, A. Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. Biosens. Bioelectron. 2003 , 18 , 1209–1218. [ Google Scholar ] [ CrossRef ] Mazzone, P.J.; Wang, X.-F.; Xu, Y.; Mekhail, T.; Beukemann, M.C.; Na, J.; Kemling, J.W.; Suslick, K.S.; Sasidhar, M. Exhaled breath analysis with a colorimetric sensor array for the identification and characterization of lung cancer. J. Thorac. Oncol. 2012 , 7 , 137. [ Google Scholar ] [ CrossRef ][ Green Version ] Knobloch, H.; Turner, C.; Spooner, A.; Chambers, M. Methodological variation in headspace analysis of liquid samples using electronic nose. Sens. Actuators B 2009 , 139 , 353–360. [ Google Scholar ] [ CrossRef ] James, D.; Scott, S.M.; Ali, Z.; O’Hare, W.T. Chemical Sensors for Electronic Nose Systems. Microchim. Acta 2005 , 149 , 1–17. [ Google Scholar ] [ CrossRef ] Nake, A.; Dubreuil, B.; Raynaud, C.; Talou, T. Outdoor in situ monitoring of volatile emissions from wastewater treatment plants with two portable technologies of electronic noses. Sens. Actuators B 2005 , 106 , 36–39. [ Google Scholar ] [ CrossRef ] Vaid, T.P.; Burl, M.C.; Lewis, N.S. Comparison of the performance of different discriminant algorithms in analyte discrimination tasks using an array of carbon black-polymer composite vapor detectors. Anal. Chem. 2001 , 73 , 321–331. [ Google Scholar ] [ CrossRef ] Sisk, B.C.; Lewis, N.S. Comparison of analytical methods and calibration methods for correction of detector response drift in arrays of carbon black-polymer composite vapor detectors. Sens. Actuators B 2005 , 104 , 249–268. [ Google Scholar ] [ CrossRef ] Bylesjö, M.; Eriksson, D.; Sjödin, A.; Jansson, S.; Moritz, T.; Trygg, J. Orthogonal projections to latent structures as a strategy for microarray data normalization. BMC Bioinform. 2007 , 8 , 207. [ Google Scholar ] [ CrossRef ][ Green Version ] Bos, L.D.; Schultz, M.J.; Sterk, P.J. Exhaled breath profiling for diagnosing acute respiratory distress syndrome. BMC Pulm. Med. 2014 , 14 , 72. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Incalzi, R.A.; Pennazza, G.; Scarlata, S.; Santonico, M.; Petriaggi, M.; Chiurco, D.; Pedone, C.; D’Amico, A. Reproducibility and respiratory function correlates of exhaled breath fingerprint in chronic obstructive pulmonary disease. PLoS ONE 2012 , 7 , e45396. [ Google Scholar ] [ CrossRef ] [ PubMed ] Jaeschke, C.; Glöckler, J.; Padilla, M.; Mitrovics, J.; Mizaikoff, B. An eNose-based method performing drift correction for online VOC detection under dry and humid conditions. Anal. Methods 2020 , 12 , 4724–4733. [ Google Scholar ] [ CrossRef ] Rodríguez-Pérez, R.; Cortés, R.; Guamán, A.; Pardo, A.; Torralba, Y.; Gómez, F.; Roca, J.; Barberà, J.A.; Cascante, M.; Marco, S. Instrumental drift removal in GC-MS data for breath analysis: The short-term and long-term temporal validation of putative biomarkers for COPD. J. Breath Res. 2018 , 12 , 036007. [ Google Scholar ] [ CrossRef ] Di Natale, C.; Paolesse, R.; D’Amico, A. Metalloporphyrins based artificial olfactory receptors. Sens. Actuators B 2007 , 121 , 238–246. [ Google Scholar ] [ CrossRef ] Van der Schee, M.P.; Paff, T.; Brinkman, P.; van Aalderen, W.M.C.; Haarman, E.G.; Sterk, P.J. Breathomics in Lung Disease. Chest J. 2015 , 147 , 224–231. [ Google Scholar ] [ CrossRef ] [ PubMed ] Fens, N.; Schee, M.; Brinkman, P.; Sterk, P. Exhaled breath analysis by electronic nose in airways disease. Established issues and key questions. Clin. Exp. Allergy 2013 , 43 , 705–715. [ Google Scholar ] [ CrossRef ] Di Natale, C.; Paolesse, R.; Martinelli, E.; Capuano, R. Solid-state gas sensors for breath analysis: A review. Anal. Chim. Acta 2014 , 824 , 1–17. [ Google Scholar ] [ CrossRef ] [ PubMed ] Dragonieri, S.; Pennazza, G.; Carratu, P.; Resta, O. Electronic Nose Technology in Respiratory Diseases. Lung 2017 , 195 , 157–165. [ Google Scholar ] [ CrossRef ] Scarlata, S.; Pennazza, G.; Santonico, M.; Pedone, C.; Antonelli Incalzi, R. Exhaled breath analysis by electronic nose in respiratory diseases. Expert Rev. Mol. Diagn. 2015 , 15 , 933–956. [ Google Scholar ] [ CrossRef ] Scott, S.M.; James, D.; Ali, Z. Data analysis for electronic nose systems. Microchim. Acta 2006 , 156 , 183–207. [ Google Scholar ] [ CrossRef ] Leopold, J.H.; Bos, L.D.; Sterk, P.J.; Schultz, M.J.; Fens, N.; Horvath, I.; Bikov, A.; Montuschi, P.; Di Natale, C.; Yates, D.H.; et al. Comparison of classification methods in breath analysis by electronic nose. J. Breath Res. 2015 , 9 , 046002. [ Google Scholar ] [ CrossRef ] [ PubMed ] Smolinska, A.; Hauschild, A.C.; Fijten, R.R.; Dallinga, J.W.; Baumbach, J.; van Schooten, F.J. Current breathomics—A review on data pre-processing techniques and machine learning in metabolomics breath analysis. J. Breath Res. 2014 , 8 , 027105. [ Google Scholar ] [ CrossRef ] [ PubMed ] Lechner, M.; Moser, B.; Niederseer, D.; Karlseder, A.; Holzknecht, B.; Fuchs, M.; Colvin, S.; Tilg, H.; Rieder, J. Gender and age specific differences in exhaled isoprene levels. Respir. Physiol. Neurobiol. 2006 , 154 , 478–483. [ Google Scholar ] [ CrossRef ] [ PubMed ] Phillips, M.; Greenberg, J.; Cataneo, R.N. Effect of age on the profile of alkanes in normal human breath. Free Radic. Res. 2000 , 33 , 57–63. [ Google Scholar ] [ CrossRef ] [ PubMed ] Bikov, A.; Hernadi, M.; Korosi, B.Z.; Kunos, L.; Zsamboki, G.; Sutto, Z.; Tarnoki, A.D.; Tarnoki, D.L.; Losonczy, G.; Horvath, I. Expiratory flow rate, breath hold and anatomic dead space influence electronic nose ability to detect lung cancer. BMC Pulm. Med. 2014 , 14 , 202. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Kunos, L.; Bikov, A.; Lazar, Z.; Korosi, B.Z.; Benedek, P.; Losonczy, G.; Horvath, I. Evening and morning exhaled volatile compound patterns are different in obstructive sleep apnoea assessed with electronic nose. Sleep Breath 2015 , 19 , 247–253. [ Google Scholar ] [ CrossRef ] Fens, N.; Zwinderman, A.H.; van der Schee, M.P.; de Nijs, S.B.; Dijkers, E.; Roldaan, A.C.; Cheung, D.; Bel, E.H.; Sterk, P.J. Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma. Am. J. Respir. Crit. Care Med. 2009 , 180 , 1076–1082. [ Google Scholar ] [ CrossRef ] Dragonieri, S.; Schot, R.; Mertens, B.J.; Le Cessie, S.; Gauw, S.A.; Spanevello, A.; Resta, O.; Willard, N.P.; Vink, T.J.; Rabe, K.F.; et al. An electronic nose in the discrimination of patients with asthma and controls. J. Allergy Clin. Immunol. 2007 , 120 , 856–862. [ Google Scholar ] [ CrossRef ][ Green Version ] Jones, R.C.; Hyland, M.E.; Hanney, K.; Erwin, J. A qualitative study of compliance with medication and lifestyle modification in Chronic Obstructive Pulmonary Disease (COPD). Prim. Care Respir. J. 2004 , 13 , 149–154. [ Google Scholar ] [ CrossRef ] Gaida, A.; Holz, O.; Nell, C.; Schuchardt, S.; Lavae-Mokhtari, B.; Kruse, L.; Boas, U.; Langejuergen, J.; Allers, M.; Zimmermann, S.; et al. A dual center study to compare breath volatile organic compounds from smokers and non-smokers with and without COPD. J. Breath Res. 2016 , 10 , 026006. [ Google Scholar ] [ CrossRef ] [ PubMed ] Filipiak, W.; Ruzsanyi, V.; Mochalski, P.; Filipiak, A.; Bajtarevic, A.; Ager, C.; Denz, H.; Hilbe, W.; Jamnig, H.; Hackl, M.; et al. Dependence of exhaled breath composition on exogenous factors, smoking habits and exposure to air pollutants. J. Breath Res. 2012 , 6 , 036008. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Bikov, A.; Paschalaki, K.; Logan-Sinclair, R.; Horváth, I.; Kharitonov, S.A.; Barnes, P.J.; Usmani, O.S.; Paredi, P. Standardised exhaled breath collection for the measurement of exhaled volatile organic compounds by proton transfer reaction mass spectrometry. BMC Pulm. Med. 2013 , 13 , 43. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Krilaviciute, A.; Leja, M.; Kopp-Schneider, A.; Barash, O.; Khatib, S.; Amal, H.; Broza, Y.Y.; Polaka, I.; Parshutin, S.; Rudule, A.; et al. Associations of diet and lifestyle factors with common volatile organic compounds in exhaled breath of average-risk individuals. J. Breath Res. 2019 , 13 , 026006. [ Google Scholar ] [ CrossRef ] [ PubMed ] Baranska, A.; Tigchelaar, E.; Smolinska, A.; Dallinga, J.W.; Moonen, E.J.; Dekens, J.A.; Wijmenga, C.; Zhernakova, A.; van Schooten, F.J. Profile of volatile organic compounds in exhaled breath changes as a result of gluten-free diet. J. Breath Res. 2013 , 7 , 037104. [ Google Scholar ] [ CrossRef ] [ PubMed ] Bikov, A.; Galffy, G.; Tamasi, L.; Bartusek, D.; Antus, B.; Losonczy, G.; Horvath, I. Exhaled breath condensate pH decreases during exercise-induced bronchoconstriction. Respirology 2014 , 19 , 563–569. [ Google Scholar ] [ CrossRef ] [ PubMed ] King, J.; Kupferthaler, A.; Unterkofler, K.; Koc, H.; Teschl, S.; Teschl, G.; Miekisch, W.; Schubert, J.; Hinterhuber, H.; Amann, A. Isoprene and acetone concentration profiles during exercise on an ergometer. J. Breath Res. 2009 , 3 , 027006. [ Google Scholar ] [ CrossRef ] [ PubMed ] Bikov, A.; Lazar, Z.; Schandl, K.; Antus, B.M.; Losonczy, G.; Horvath, I. Exercise changes volatiles in exhaled breath assessed by an electronic nose. Acta Physiol. Hung. 2011 , 98 , 321–328. [ Google Scholar ] [ CrossRef ] Finamore, P.; Pedone, C.; Scarlata, S.; Di Paolo, A.; Grasso, S.; Santonico, M.; Pennazza, G.; Antonelli Incalzi, R. Validation of exhaled volatile organic compounds analysis using electronic nose as index of COPD severity. Int. J. Chronic Obstr. Pulm. Dis. 2018 , 13 , 1441–1448. [ Google Scholar ] [ CrossRef ][ Green Version ] Nair, S.; Cope, K.; Risby, T.H.; Diehl, A.M. Obesity and female gender increase breath ethanol concentration: Potential implications for the pathogenesis of nonalcoholic steatohepatitis. Am. J. Gastroenterol. 2001 , 96 , 1200–1204. [ Google Scholar ] [ CrossRef ] Das, M.K.; Bishwal, S.C.; Das, A.; Dabral, D.; Varshney, A.; Badireddy, V.K.; Nanda, R. Investigation of gender-specific exhaled breath volatome in humans by GCxGC-TOF-MS. Anal. Chem. 2014 , 86 , 1229–1237. [ Google Scholar ] [ CrossRef ] [ PubMed ] Dragonieri, S.; Quaranta, V.N.; Carratu, P.; Ranieri, T.; Resta, O. The ovarian cycle may influence the exhaled volatile organic compound profile analyzed by an electronic nose. J. Breath Res. 2018 , 12 , 021002. [ Google Scholar ] [ CrossRef ] [ PubMed ] Bikov, A.; Pako, J.; Kovacs, D.; Tamasi, L.; Lazar, Z.; Rigo, J.; Losonczy, G.; Horvath, I. Exhaled breath volatile alterations in pregnancy assessed with electronic nose. Biomarkers 2011 , 16 , 476–484. [ Google Scholar ] [ CrossRef ] [ PubMed ] Basanta, M.; Ibrahim, B.; Dockry, R.; Douce, D.; Morris, M.; Singh, D.; Woodcock, A.; Fowler, S.J. Exhaled volatile organic compounds for phenotyping chronic obstructive pulmonary disease: A cross-sectional study. Respir. Res. 2012 , 13 , 72. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Lazar, Z.; Fens, N.; van der Maten, J.; van der Schee, M.P.; Wagener, A.H.; de Nijs, S.B.; Dijkers, E.; Sterk, P.J. Electronic nose breathprints are independent of acute changes in airway caliber in asthma. Sensors 2010 , 10 , 9127–9138. [ Google Scholar ] [ CrossRef ] [ PubMed ] Hlastala, M.P.; Powell, F.L.; Anderson, J.C. Airway exchange of highly soluble gases. J. Appl. Physiol. 2013 , 114 , 675–680. [ Google Scholar ] [ CrossRef ][ Green Version ] Boshier, P.R.; Priest, O.H.; Hanna, G.B.; Marczin, N. Influence of respiratory variables on the on-line detection of exhaled trace gases by PTR-MS. Thorax 2011 , 66 , 919–920. [ Google Scholar ] [ CrossRef ][ Green Version ] Larstad, M.A.; Toren, K.; Bake, B.; Olin, A.C. Determination of ethane, pentane and isoprene in exhaled air--effects of breath-holding, flow rate and purified air. Acta Physiol. 2007 , 189 , 87–98. [ Google Scholar ] [ CrossRef ] Thekedar, B.; Oeh, U.; Szymczak, W.; Hoeschen, C.; Paretzke, H.G. Influences of mixed expiratory sampling parameters on exhaled volatile organic compound concentrations. J. Breath Res. 2011 , 5 , 016001. [ Google Scholar ] [ CrossRef ] Barnes, P.J.; Chowdhury, B.; Kharitonov, S.A.; Magnussen, H.; Page, C.P.; Postma, D.; Saetta, M. Pulmonary biomarkers in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2006 , 174 , 6–14. [ Google Scholar ] [ CrossRef ] Timms, C.; Thomas, P.S.; Yates, D.H. Detection of gastro-oesophageal reflux disease (GORD) in patients with obstructive lung disease using exhaled breath profiling. J. Breath Res. 2012 , 6 , 016003. [ Google Scholar ] [ CrossRef ] [ PubMed ] Turato, G.; Zuin, R.; Miniati, M.; Baraldo, S.; Rea, F.; Beghé, B.; Monti, S.; Formichi, B.; Boschetto, P.; Harari, S.; et al. Airway inflammation in severe chronic obstructive pulmonary disease: Relationship with lung function and radiologic emphysema. Am. J. Respir. Crit. Care Med. 2002 , 166 , 105–110. [ Google Scholar ] [ CrossRef ] [ PubMed ] Louis, R.E.; Cataldo, D.; Buckley, M.G.; Sele, J.; Henket, M.; Lau, L.C.; Bartsch, P.; Walls, A.F.; Djukanovic, R. Evidence of mast-cell activation in a subset of patients with eosinophilic chronic obstructive pulmonary disease. Eur. Respir. J. 2002 , 20 , 325–331. [ Google Scholar ] [ CrossRef ] [ PubMed ] Snoeck-Stroband, J.B.; Lapperre, T.S.; Gosman, M.M.; Boezen, H.M.; Timens, W.; ten Hacken, N.H.; Sont, J.K.; Sterk, P.J.; Hiemstra, P.S. Chronic bronchitis sub-phenotype within COPD: Inflammation in sputum and biopsies. Eur. Respir. J. 2008 , 31 , 70–77. [ Google Scholar ] [ CrossRef ][ Green Version ] Brightling, C.E.; Monteiro, W.; Ward, R.; Parker, D.; Morgan, M.D.; Wardlaw, A.J.; Pavord, I.D. Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: A randomised controlled trial. Lancet 2000 , 356 , 1480–1485. [ Google Scholar ] [ CrossRef ] Leigh, R.; Pizzichini, M.M.; Morris, M.M.; Maltais, F.; Hargreave, F.E.; Pizzichini, E. Stable COPD: Predicting benefit from high-dose inhaled corticosteroid treatment. Eur. Respir. J. 2006 , 27 , 964–971. [ Google Scholar ] [ CrossRef ][ Green Version ] Siva, R.; Green, R.H.; Brightling, C.E.; Shelley, M.; Hargadon, B.; McKenna, S.; Monteiro, W.; Berry, M.; Parker, D.; Wardlaw, A.J.; et al. Eosinophilic airway inflammation and exacerbations of COPD: A randomised controlled trial. Eur. Respir. J. 2007 , 29 , 906–913. [ Google Scholar ] [ CrossRef ] Fens, N.; de Nijs, S.B.; Peters, S.; Dekker, T.; Knobel, H.H.; Vink, T.J.; Willard, N.P.; Zwinderman, A.H.; Krouwels, F.H.; Janssen, H.G.; et al. Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD. Eur. Respir. J. 2011 , 38 , 1301–1309. [ Google Scholar ] [ CrossRef ] Schleich, F.N.; Dallinga, J.W.; Henket, M.; Wouters, E.F.; Louis, R.; Van Schooten, F.J. Volatile organic compounds discriminate between eosinophilic and neutrophilic inflammation in vitro. J. Breath Res. 2016 , 10 , 016006. [ Google Scholar ] [ CrossRef ][ Green Version ] de Vries, R.; Dagelet, Y.W.F.; Spoor, P.; Snoey, E.; Jak, P.M.C.; Brinkman, P.; Dijkers, E.; Bootsma, S.K.; Elskamp, F.; de Jongh, F.H.C.; et al. Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label. Eur. Respir. J. 2018 , 51 . [ Google Scholar ] [ CrossRef ][ Green Version ] Fens, N.; van der Sluijs, K.F.; van de Pol, M.A.; Dijkhuis, A.; Smids, B.S.; van der Zee, J.S.; Lutter, R.; Zwinderman, A.H.; Sterk, P.J. Electronic nose identifies bronchoalveolar lavage fluid eosinophils in asthma. Am. J. Respir. Crit. Care Med. 2015 , 191 , 1086–1088. [ Google Scholar ] [ CrossRef ] [ PubMed ] Plaza, V.; Crespo, A.; Giner, J.; Merino, J.L.; Ramos-Barbón, D.; Mateus, E.F.; Torrego, A.; Cosio, B.G.; Agustí, A.; Sibila, O. Inflammatory Asthma Phenotype Discrimination Using an Electronic Nose Breath Analyzer. J. Investig. Allergol. Clin. Immunol. 2015 , 25 , 431–437. [ Google Scholar ] [ PubMed ] Pizzini, A.; Filipiak, W.; Wille, J.; Ager, C.; Wiesenhofer, H.; Kubinec, R.; Blaško, J.; Tschurtschenthaler, C.; Mayhew, C.A.; Weiss, G.; et al. Analysis of volatile organic compounds in the breath of patients with stable or acute exacerbation of chronic obstructive pulmonary disease. J. Breath Res. 2018 , 12 , 036002. [ Google Scholar ] [ CrossRef ] [ PubMed ] Gaugg, M.T.; Nussbaumer-Ochsner, Y.; Bregy, L.; Engler, A.; Stebler, N.; Gaisl, T.; Bruderer, T.; Nowak, N.; Sinues, P.; Zenobi, R.; et al. Real-Time Breath Analysis Reveals Specific Metabolic Signatures of COPD Exacerbations. Chest 2019 , 156 , 269–276. [ Google Scholar ] [ CrossRef ] Van Velzen, P.; Brinkman, P.; Knobel, H.H.; van den Berg, J.W.K.; Jonkers, R.E.; Loijmans, R.J.; Prins, J.M.; Sterk, P.J. Exhaled Breath Profiles Before, During and After Exacerbation of COPD: A Prospective Follow-Up Study. Copd 2019 , 16 , 330–337. [ Google Scholar ] [ CrossRef ][ Green Version ] Shafiek, H.; Fiorentino, F.; Merino, J.L.; López, C.; Oliver, A.; Segura, J.; de Paul, I.; Sibila, O.; Agustí, A.; Cosío, B.G. Using the Electronic Nose to Identify Airway Infection during COPD Exacerbations. PLoS ONE 2015 , 10 , e0135199. [ Google Scholar ] [ CrossRef ][ Green Version ] Bos, L.D.; Sterk, P.J.; Schultz, M.J. Volatile metabolites of pathogens: A systematic review. PLoS Pathog. 2013 , 9 , e1003311. [ Google Scholar ] [ CrossRef ][ Green Version ] Van Geffen, W.H.; Bruins, M.; Kerstjens, H.A. Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: A pilot study. J. Breath Res. 2016 , 10 , 036001. [ Google Scholar ] [ CrossRef ] Sibila, O.; Garcia-Bellmunt, L.; Giner, J.; Merino, J.L.; Suarez-Cuartin, G.; Torrego, A.; Solanes, I.; Castillo, D.; Valera, J.L.; Cosio, B.G.; et al. Identification of airway bacterial colonization by an electronic nose in Chronic Obstructive Pulmonary Disease. Respir. Med. 2014 , 108 , 1608–1614. [ Google Scholar ] [ CrossRef ][ Green Version ] Buszewski, B.; Ulanowska, A.; Ligor, T.; Denderz, N.; Amann, A. Analysis of exhaled breath from smokers, passive smokers and non-smokers by solid-phase microextraction gas chromatography/mass spectrometry. Biomed. Chromatogr. 2009 , 23 , 551–556. [ Google Scholar ] [ CrossRef ] Blanchet, L.; Smolinska, A.; Baranska, A.; Tigchelaar, E.; Swertz, M.; Zhernakova, A.; Dallinga, J.W.; Wijmenga, C.; van Schooten, F.J. Factors that influence the volatile organic compound content in human breath. J. Breath Res. 2017 , 11 , 016013. [ Google Scholar ] [ CrossRef ] [ PubMed ] Cheng, Z.J.; Warwick, G.; Yates, D.H.; Thomas, P.S. An electronic nose in the discrimination of breath from smokers and non-smokers: A model for toxin exposure. J. Breath Res. 2009 , 3 , 036003. [ Google Scholar ] [ CrossRef ] [ PubMed ] Chen, X.; Wang, F.; Lin, L.; Dong, H.; Huang, F.; Ghulam Muhammad, K.; Chen, L.; Gorlova, O.Y. Association of Smoking with Metabolic Volatile Organic Compounds in Exhaled Breath. Int. J. Mol. Sci. 2017 , 18 , 2235. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Marco, E.; Grimalt, J.O. A rapid method for the chromatographic analysis of volatile organic compounds in exhaled breath of tobacco cigarette and electronic cigarette smokers. J. Chromatogr. A 2015 , 1410 , 51–59. [ Google Scholar ] [ CrossRef ][ Green Version ] Gelvan, D.; Moreno, V.; Clopton, D.A.; Chen, Q.; Saltman, P. Sites and mechanisms of low-level oxidative stress in cultured cells. Biochem. Biophys. Res. Commun. 1995 , 206 , 421–428. [ Google Scholar ] [ CrossRef ] [ PubMed ] Seet, R.C.; Lee, C.Y.; Loke, W.M.; Huang, S.H.; Huang, H.; Looi, W.F.; Chew, E.S.; Quek, A.M.; Lim, E.C.; Halliwell, B. Biomarkers of oxidative damage in cigarette smokers: Which biomarkers might reflect acute versus chronic oxidative stress? Free Radic. Biol. Med. 2011 , 50 , 1787–1793. [ Google Scholar ] [ CrossRef ] Adcock, I.M.; Caramori, G.; Barnes, P.J. Chronic obstructive pulmonary disease and lung cancer: New molecular insights. Respiration 2011 , 81 , 265–284. [ Google Scholar ] [ CrossRef ] Fens, N.; Roldaan, A.C.; van der Schee, M.P.; Boksem, R.J.; Zwinderman, A.H.; Bel, E.H.; Sterk, P.J. External validation of exhaled breath profiling using an electronic nose in the discrimination of asthma with fixed airways obstruction and chronic obstructive pulmonary disease. Clin. Exp. Allergy 2011 , 41 , 1371–1378. [ Google Scholar ] [ CrossRef ] Rodríguez-Aguilar, M.; Díaz de León-Martínez, L.; Gorocica-Rosete, P.; Padilla, R.P.; Thirión-Romero, I.; Ornelas-Rebolledo, O.; Flores-Ramírez, R. Identification of breath-prints for the COPD detection associated with smoking and household air pollution by electronic nose. Respir. Med. 2020 , 163 , 105901. [ Google Scholar ] [ CrossRef ] Peng, G.; Tisch, U.; Adams, O.; Hakim, M.; Shehada, N.; Broza, Y.Y.; Billan, S.; Abdah-Bortnyak, R.; Kuten, A.; Haick, H. Diagnosing lung cancer in exhaled breath using gold nanoparticles. Nat. Nanotechnol. 2009 , 4 , 669–673. [ Google Scholar ] [ CrossRef ] Ionescu, R.; Broza, Y.; Shaltieli, H.; Sadeh, D.; Zilberman, Y.; Feng, X.; Glass-Marmor, L.; Lejbkowicz, I.; Mullen, K.; Miller, A.; et al. Detection of multiple sclerosis from exhaled breath using bilayers of polycyclic aromatic hydrocarbons and single-wall carbon nanotubes. ACS Chem. Neurosci. 2011 , 2 , 687–693. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Mazzone, P.J.; Hammel, J.; Dweik, R.; Na, J.; Czich, C.; Laskowski, D.; Mekhail, T. Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array. Thorax 2007 , 62 , 565–568. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Gaugg, M.T.; Engler, A.; Nussbaumer-Ochsner, Y.; Bregy, L.; Stöberl, A.S.; Gaisl, T.; Bruderer, T.; Zenobi, R.; Kohler, M.; Martinez-Lozano Sinues, P. Metabolic effects of inhaled salbutamol determined by exhaled breath analysis. J. Breath Res. 2017 , 11 , 046004. [ Google Scholar ] [ CrossRef ] [ PubMed ] Scarlata, S.; Finamore, P.; Santangelo, S.; Giannunzio, G.; Pennazza, G.; Grasso, S.; Santonico, M.; Incalzi, R.A. Cluster analysis on breath print of newly diagnosed COPD patients: Effects of therapy. J. Breath Res. 2018 , 12 , 036022. [ Google Scholar ] [ CrossRef ] [ PubMed ] Brinkman, P.; Ahmed, W.M.; Gómez, C.; Knobel, H.H.; Weda, H.; Vink, T.J.; Nijsen, T.M.; Wheelock, C.E.; Dahlen, S.E.; Montuschi, P.; et al. Exhaled volatile organic compounds as markers for medication use in asthma. Eur. Respir. J. 2020 , 55 . [ Google Scholar ] [ CrossRef ] Van Berkel, J.J.; Dallinga, J.W.; Möller, G.M.; Godschalk, R.W.; Moonen, E.J.; Wouters, E.F.; Van Schooten, F.J. A profile of volatile organic compounds in breath discriminates COPD patients from controls. Respir. Med. 2010 , 104 , 557–563. [ Google Scholar ] [ CrossRef ][ Green Version ] Brinkman, P.; Wagener, A.H.; Hekking, P.P.; Bansal, A.T.; Maitland-van der Zee, A.H.; Wang, Y.; Weda, H.; Knobel, H.H.; Vink, T.J.; Rattray, N.J.; et al. Identification and prospective stability of electronic nose (eNose)-derived inflammatory phenotypes in patients with severe asthma. J. Allergy Clin. Immunol. 2019 , 143 , 1811–1820.e1817. [ Google Scholar ] [ CrossRef ][ Green Version ] Bikov, A.; Hull, J.H.; Kunos, L. Exhaled breath analysis, a simple tool to study the pathophysiology of obstructive sleep apnoea. Sleep Med. Rev. 2016 , 27 , 1–8. [ Google Scholar ] [ CrossRef ] Scarlata, S.; Pennazza, G.; Santonico, M.; Santangelo, S.; Rossi Bartoli, I.; Rivera, C.; Vernile, C.; De Vincentis, A.; Antonelli Incalzi, R. Screening of Obstructive Sleep Apnea Syndrome by Electronic-Nose Analysis of Volatile Organic Compounds. Sci. Rep. 2017 , 7 , 11938. [ Google Scholar ] [ CrossRef ][ Green Version ] Dragonieri, S.; Quaranta, V.N.; Carratu, P.; Ranieri, T.; Resta, O. Exhaled breath profiling in patients with COPD and OSA overlap syndrome: A pilot study. J. Breath Res. 2016 , 10 , 041001. [ Google Scholar ] [ CrossRef ] Cikach, F.S., Jr.; Dweik, R.A. Cardiovascular biomarkers in exhaled breath. Prog. Cardiovasc. Dis. 2012 , 55 , 34–43. [ Google Scholar ] [ CrossRef ][ Green Version ] Bikov, A.; Horváth, A.; Tomisa, G.; Bártfai, L.; Bártfai, Z. Changes in the Burden of Comorbidities in Patients with COPD and Asthma-COPD Overlap According to the GOLD 2017 Recommendations. Lung 2018 , 196 , 591–599. [ Google Scholar ] [ CrossRef ] [ PubMed ] Krauss, E.; Haberer, J.; Barreto, G.; Degen, M.; Seeger, W.; Guenther, A. Recognition of breathprints of lung cancer and chronic obstructive pulmonary disease using the Aeonose( ® ) electronic nose. J. Breath Res. 2020 , 14 , 046004. [ Google Scholar ] [ CrossRef ] [ PubMed ] Bofan, M.; Mores, N.; Baron, M.; Dabrowska, M.; Valente, S.; Schmid, M.; Trové, A.; Conforto, S.; Zini, G.; Cattani, P.; et al. Within-day and between-day repeatability of measurements with an electronic nose in patients with COPD. J. Breath Res. 2013 , 7 , 017103. [ Google Scholar ] [ CrossRef ] [ PubMed ] Dragonieri, S.; Annema, J.T.; Schot, R.; van der Schee, M.P.; Spanevello, A.; Carratú, P.; Resta, O.; Rabe, K.F.; Sterk, P.J. An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. Lung Cancer 2009 , 64 , 166–170. [ Google Scholar ] [ CrossRef ] [ PubMed ] Hubers, A.J.; Brinkman, P.; Boksem, R.J.; Rhodius, R.J.; Witte, B.I.; Zwinderman, A.H.; Heideman, D.A.; Duin, S.; Koning, R.; Steenbergen, R.D.; et al. Combined sputum hypermethylation and eNose analysis for lung cancer diagnosis. J. Clin. Pathol. 2014 , 67 , 707–711. [ Google Scholar ] [ CrossRef ][ Green Version ] Hattesohl, A.D.; Jörres, R.A.; Dressel, H.; Schmid, S.; Vogelmeier, C.; Greulich, T.; Noeske, S.; Bals, R.; Koczulla, A.R. Discrimination between COPD patients with and without alpha 1-antitrypsin deficiency using an electronic nose. Respirology 2011 , 16 , 1258–1264. [ Google Scholar ] [ CrossRef ] Finamore, P.; Pedone, C.; Lelli, D.; Costanzo, L.; Bartoli, I.R.; De Vincentis, A.; Grasso, S.; Parente, F.R.; Pennazza, G.; Santonico, M.; et al. Analysis of volatile organic compounds: An innovative approach to heart failure characterization in older patients. J. Breath Res. 2018 , 12 , 026007. [ Google Scholar ] [ CrossRef ] Antonelli Incalzi, R.; Pennazza, G.; Scarlata, S.; Santonico, M.; Vernile, C.; Cortese, L.; Frezzotti, E.; Pedone, C.; D’Amico, A. Comorbidity modulates non invasive ventilation-induced changes in breath print of obstructive sleep apnea syndrome patients. Sleep Breath 2015 , 19 , 623–630. [ Google Scholar ] [ CrossRef ] Tirzïte, M.; Bukovskis, M.; Strazda, G.; Jurka, N.; Taivans, I. Detection of lung cancer with electronic nose and logistic regression analysis. J. Breath Res. 2018 , 13 , 016006. [ Google Scholar ] [ CrossRef ][ Green Version ] Bathoorn, E.; Liesker, J.; Postma, D.; Koëter, G.; van Oosterhout, A.J.; Kerstjens, H.A. Safety of sputum induction during exacerbations of COPD. Chest 2007 , 131 , 432–438. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Gao, J.; Zhang, M.; Zhou, L.; Yang, X.; Wu, H.; Zhang, J.; Wu, F. Correlation between fractional exhaled nitric oxide and sputum eosinophilia in exacerbations of COPD. Int. J. Chronic Obstr. Pulm. Dis. 2017 , 12 , 1287–1293. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Mathioudakis, A.G.; Bikov, A.; Foden, P.; Lahousse, L.; Brusselle, G.; Singh, D.; Vestbo, J. Change in blood eosinophils following treatment with inhaled corticosteroids may predict long-term clinical response in COPD. Eur. Respir. J. 2020 , 55 . [ Google Scholar ] [ CrossRef ] [ PubMed ] Figure 1. The pathophysiology of chronic obstructive pulmonary disease. Figure 2. Algorithm for the exhaled breath collection and analysis with electronic nose. Figure 3. The mechanisms of altered production of exhaled volatile organic compounds (VOCs) in COPD. Table 1. Clinical studies conducted on electronic noses in patients with COPD. Comparator Group Device Number of Subjects Classification Technique Sensitivity (%) Specificity (%) Cross-Validation Value (%) Remarks Reference Healthy Cyranose 320 N = 37 COPD N = 13 H LDA 83 76 79 COPD vs. H [ 90 ] Infection Cyranose 320 N = 74 ECOPD N = 19 ECOPD + P N = 50 COPD N = 30 H LDA 72 67 ND ECOPD vs. COPD [ 87 ] 88 75 ECOPD + P vs. COPD 91 75 ECOPD + P vs. ECOPD Aeonose N= 22 COPD + BI N = 21 COPD without BI N = 18 COPD + VI N = 25 COPD without VI ANN 73 76 ND COPD + VI vs. COPD without VI [ 89 ] 83 72 COPD + BI vs. COPD without BI Lung cancer Cyranose 320 N = 10 LC N = 10 COPD N = 10 H LDA ND ND 85 LC vs. COPD [ 116 ] 80 LC vs. H N = 20 LC N = 31 COPD ROC analysis based on principal components 80 48 ND Diagnostic accuracy increased when combined with sputum hypermethylation [ 117 ] Custom made colorimetric sensor N = 18 COPD N = 49 LC N = 21 H N = 15 IPF N = 20 SR N = 20 PAH Random forest method 73 72 ND LC [ 103 ] Smoking Cyranose 320 N = 88 COPD + S N = 28 COPD + HAP N = 178 H LDA + SVM 100 97.8 100 COPD vs. H [ 100 ] ND 98.1 100 COPD + S vs. H ND 97.5 100 COPD + HAP vs. H ND 2.5 75.7 COPD + S vs. COPD + HAP Asthma and lung cancer SpiroNose N = 31 COPD N = 37 A N = 31 LC N = 45 H LDA ND ND 78 COPD vs. H [ 20 ] ND ND 81 COPD vs. A ND ND 80 COPD vs. LC ND ND 87 A vs. H ND ND 68 A vs. LC ND ND 88 LC vs. H Asthma and Smoking Cyranose 320 N = 20 A N = 30 COPD N = 20 non-S N = 20 S LDA ND ND 96 A vs. COPD [ 49 ] ND ND 95 A vs. non-S ND ND 93 A vs. S ND ND 66 COPD vs. S ND ND NS COPD vs. non-S Asthma Cyranose 320 N = 40 COPD N = 60 A LDA 85 90 88 COPD vs. fixed A (N = 21) [ 99 ] 91 90 83 COPD vs. reversible A (N = 39) SpiroNose N = 115 COPD N = 206 A Not performed ND ND NS Five significant combined asthma and COPD clusters [ 81 ] OSA Cyranose 320 N = 15 COPD N = 13 OSA N = 13 OVS. LDA ND ND 96.2 OSA vs. OVS [ 111 ] ND ND 82.1 OSA vs. COPD ND ND 67.9 COPD vs. OVS Custom made QMB N = 20 COPD N = OSA + NH N = 20 OSA + H N = 20 O N = 56 H PLS-DA 44 93 ND [ 110 ] Alpha 1-antitripsin deficiency Cyranose 320 N = 10 COPD with AAT N = 23 COPD without AAT N = 10 H LDA ND ND 58 AAT vs. non-AAT [ 118 ] ND ND 68 non-AAT vs. H ND ND 62 AAT vs. H Congestive heart failure BIONOTE N = 103 COPD N = 89 CHF N = 117 H PLS-DA 80 82 ND CHF vs. H [ 119 ] 63 74 ND CHF vs. COPD A = asthma; AAT = alpha 1-antitripsin deficiency; ANN = artificial neural network; CHF = congestive heart failure; COPD = chronic obstructive pulmonary disease; COPD + BI = COPD with bacterial infection; COPD + HAP = COPD with household air pollution; COPD + S = COPD with smoking; COPD + VI = COPD with viral infection; ECOPD = exacerbation of COPD; ECOPD + P = exacerbation of COPD with pneumonia; H = healthy controls; IPF = idiopathic pulmonary fibrosis; LC = lung cancer; LDA = linear discriminant analysis; O = obese controls; OSA = obstructive sleep apnoea; OSA + H = hypoxic OSA; OSA + NH = non-hypoxic OSA; OVS = overlap syndrome; PAH = pulmonary arterial hypertension; PLS-DA = partial least square discriminant analysis; QMB = quartz microbalance; ROC = receiver operating characteristic; S = smoker; SR = sarcoidosis; SVM = support vector machines. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/ ). MDPI and ACS Style Scarlata, S.; Finamore, P.; Meszaros, M.; Dragonieri, S.; Bikov, A. The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease. Biosensors 2020, 10, 171. https://doi.org/10.3390/bios10110171 AMA Style Scarlata S, Finamore P, Meszaros M, Dragonieri S, Bikov A. The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease. Biosensors. 2020; 10(11):171. https://doi.org/10.3390/bios10110171 Chicago/Turabian Style Scarlata, Simone, Panaiotis Finamore, Martina Meszaros, Silvano Dragonieri, and Andras Bikov. 2020. "The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease" Biosensors10, no. 11: 171. https://doi.org/10.3390/bios10110171 Article Metrics
https://www.mdpi.com/2079-6374/10/11/171/htm
The role of thrombin in angiogenesis | Request PDF Request PDF | The role of thrombin in angiogenesis | The formation of vasculature is a key step during embryogenesis. The vasculature and the intravascular blood compartment, which uses the former as... | Find, read and cite all the research you need on ResearchGate The role of thrombin in angiogenesis Abstract ... Platelets, in addition to maintaining haemostasis, play a critical role in regulating angiogenesis by releasing factors that promote the growth of new vessels. Although thrombin is the most powerful platelet agonist and is generated in almost all physiopathological processes involved in the formation of new vessels (Moser, 2008) , the thrombin-dependent release of pro-and anti-angiogenic molecules is not clearly understood. Pioneering studies by Mohle et al. (1997) and Maloney et al. (1998) demonstrated that megakaryocytes and platelets synthesize and release VEGF upon stimulation with thrombin. ... Platelet-mediated angiogenesis is independent of VEGF and fully inhibited by aspirin Article May 2013 BRIT J PHARMACOL Julia Etulain Carlos Fondevila Soledad Negrotto Mirta Schattner Identification of unexplored substrates of the serine protease, thrombin, using N-terminomics strategy Dec 2019 INT J BIOL MACROMOL Sonali R. Bhagwat Krishnan Hajela Sumit Bhutada Amit Kumar The function and regulation of thrombin is a complex as well as an intriguing aspect of evolution and has captured the interest of many investigators over the years. The reported substrates of thrombin are coagulation factors V, VIII, XI, XIII, protein C and fibrinogen. However, these may not be all the substrate of thrombin and therefore its functional role(s), may not have been completely comprehended. The purpose of our study was to identify hitherto unreported substrates of thrombin from human plasma using a N-terminomics protease substrate identification method. We identified 54 putative substrates of thrombin of which 12 are already known and 42 are being reported for the first time. Amongst the proteins identified, recombinant siglec-6 and purified serum alpha-1-acid glycoprotein were validated by cleavage with thrombin. We have discussed the probable relevance of siglec-6 cleavage by thrombin in human placenta mostly because an upregulation in the expression of siglec-6 and thrombin has been reported in the placenta of preeclampsia patients. We also speculate the role of alpha-1-acid glycoprotein cleavage by thrombin in the acute phase as alpha-1-acid glycoprotein is known to be an inhibitor of platelet aggregation whereas thrombin is known to trigger platelet aggregation. Thrombosis with outflow obstruction delays thrombolysis and results in chronic wall thickening of rat veins Full-text available J VASC SURG Klaus See-Tho Edmund J Harris An in vivo model of acute deep venous thrombosis was developed in rats to assess the role of venous thrombosis and outflow obstruction in recanalization and development of secondary wall changes. The left femoral veins of male Sprague-Dawley rats were thrombosed either by means of proximal ligation (obstruction, group A, n = 38) or by means of temporary 24-hour occlusion with a microvascular clamp (unobstructed, group B, n = 20). Right femoral veins served as controls. The rats were killed at intervals over 5 weeks. Wall thickness was compared among groups by means of counting of cells on representative sections through the midvein area. Thrombi were indirectly quantitated with a radiolabeled fibrinogen assay in a parallel series of rats. Control veins showed no evidence of cellular or structural changes. Early thrombus extension was seen in group A (peak at day 4) followed by recanalization after 2 weeks. Group A veins had marked wall thickening (27 +/- 7 vs 6 +/- 2 cells, p < 0.01, peak at 10 days) consisting of smooth muscle-type, neointimal, and medial cellular proliferations. Within 2 to 3 weeks, local neovascular channels had grown to bypass the outflow obstruction, and resumption of normal cephalad flow was seen. At the same time neointimal proliferation regressed, but medial cellular growth persisted, resulting in chronic wall thickening (11 +/- 3 vs 5 +/- 1 cells, p < 0.01, after 21 days). In contrast, group B veins exhibited no thrombus extension, had significantly less wall thickening (13 +/- 2 vs 5 +/- 1 cells, p < 0.01, peak at 4 days), and did not induce growth of local collateral blood vessels. Within 2 weeks, group B veins regained normal appearance and resumed normal flow. Thrombosis of rat femoral veins without chronic obstruction results in rapid lysis of thrombus and transient proliferative changes. In contrast, thrombosis with chronic outflow obstruction results in delayed recanalization, early extension of thrombus, and development of vigorous and persistent proliferative cellular responses. Thrombus-induced chronic wall thickening may be an important factor in development of postthrombotic venous insufficiency. Henri Versteeg
https://www.researchgate.net/publication/23301137_The_role_of_thrombin_in_angiogenesis
Mutagenicity of ethyl carbamate to lacZ-transgenic mice | Request PDF Request PDF | Mutagenicity of ethyl carbamate to lacZ-transgenic mice | The mutagenicity of the rodent carcinogen ethyl carbamate (EC, urethane) has been assessed using the lacZ- transgenic mouse mutation assay (Muta... | Find, read and cite all the research you need on ResearchGate Article Mutagenicity of ethyl carbamate to lacZ-transgenic mice April 1998 Mutagenesis13(2):133-7 DOI: 10.1093/mutage/13.2.133 Source PubMed Authors: <here is a image f2f62089ad6ff61c-d19572ff1996375a> C V Williams C V Williams <here is a image f2f62089ad6ff61c-d19572ff1996375a> K Fletcher K Fletcher <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Helen Tinwell Bayer <here is a image f2f62089ad6ff61c-d19572ff1996375a> J Ashby J Ashby Abstract The mutagenicity of the rodent carcinogen ethyl carbamate (EC, urethane) has been assessed using the lacZ- transgenic mouse mutation assay (Muta Mouse). In two separate experiments a single i.p. dose of 900 mg/kg urethane followed by a 14-16 day expression period yielded statistically significant (approximately 2-fold) increases in mutation frequency (MF) in the lung and liver of the mice. In the second experiment MF in the spleen and bone marrow was also assessed and statistically significant increases in MF were observed in each case. Concomitantly conducted bone marrow micronucleus assays gave 15.8- and 8-fold increases respectively in the incidence of micronucleated polychromatic erythrocytes in the two studies. <here is a image 175d1bd4b7439d95-754927124da715c1> ... 12 In more recent in vivo studies using the-Muta TM Mouse and lacZ as a reporter gene, EC was found to have a 2-fold increase in mutant frequency (MF). 21 Although in vitro assays are more sensitive, in vivo genotoxicity assays are more relevant to in vivo systems, such as in the human. We were thus interested in using an in vivo model to identify the specific mutations induced by VC and EC and to obtain evidence to affirm that VC is a more potent mutagen than EC. ... ... Using Muta TM Mouse and lacZ as the reporter gene, previous studies reported about a 2-fold increase in MFs in the lung at 14 and 16 days after treatment with EC (900 mg/kg). 21 These findings confirmed that EC is mutagenic in the lungs of mice. Comparisons of EC and VC revealed that a VC dose of 30 mg/kg elicited a similar MF as that of an EC dose of 500 mg/kg (Table III, Fig. 3). ... In vivo mutagenicity of vinyl carbamate and ethyl carbamate in lung and small intestine of F 1 (Big Blue® × A/J) transgenic mice Article Full-text available Apr 2007 <here is a image f6f42c8bbd1fd81f-84116ec43d465a50> Lya G Soeteman-Hernández <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Poh-Gek Forkert Vinyl carbamate (VC) is a metabolite of ethyl carbamate (EC), a chemical found in alcoholic beverages and fermented foods. We undertook this study to: (i) evaluate the ability of both EC and VC to induce gene mutations in lung and various extrapulmonary tissues, and (ii) identify the type of mutations induced by the two compounds in various tissues. F1 (Big Blue x A/J) transgenic mice harboring the lambda cII transgene were used for identification and quantitation of mutations in vivo. Time-course studies in lung showed a plateau in mutant frequency (MF) 4 weeks after VC treatment, at which time mutations were fixed and were about 4-fold higher than in controls. Dose-dependent increases in MF were detected in the lung and small intestine (SI) after treatment with 15-75 mg/kg, i.p., of VC. VC was mutagenic in the lung and SI at doses of 45, 60 and 75 mg/kg. Sequencing of the cII gene in lung and SI showed that VC induced mainly A:T-->G:C transitions and A:T-->T:A transversions. EC was also mutagenic in the lung at 500 and 1,000 mg/kg and elicited mainly G:C-->A:T transitions. A VC dose of 60 mg/kg elicited a similar level of MF as an EC dose of 1,000 mg/kg. At 4 weeks after treatment, neither VC nor EC elicited mutations in the colon, bone marrow or kidney. These results demonstrated that VC and EC are mutagenic in vivo and affirm that VC is a more potent mutagen than EC. ... This difference in sensitivity between MN-RET and MN-PCE endpoints was attributed to the improved power afforded by scoring many more cells using the automated flow cytometric method in the MN-RET assay. Moreover, positive results for EC have been reported in numerous in vivo micronucleus tests conducted in peripheral blood and/or bone marrow from different rodent species (Wild, 1978;Westmoreland et al., 1991; Williams et al., 1998; Hamada et al., 2001;Tweats et al., 2007). ... Assessment of the Pig-a , micronucleus, and comet assay endpoints in rats treated by acute or repeated dosing protocols with procarbazine hydrochloride and ethyl carbamate: Integrated Study of Multiple Genotoxic Endpoints With Procarbazine Hydrochloride and Ethyl Carbamate Article Full-text available Sep 2018 Gaofeng Chen <here is a image a3d376e2333dea6e-85e61620ffd24808> Hairuo Wen Zhihui Mao Xue Wang The utility and sensitivity of the newly developed flow cytometric Pig‐a gene mutation assay have become a great concern recently. In this study, we have examined the feasibility of integrating the Pig‐a assay as well as micronucleus and Comet endpoints into acute and subchronic general toxicology studies. Male Sprague–Dawley rats were treated for 3 or 28 consecutive days by oral gavage with procarbazine hydrochloride (PCZ) or ethyl carbamate (EC) up to the maximum tolerated dose. The induction of CD59‐negative reticulocytes and erythrocytes, micronucleated reticulocytes in peripheral blood, micronucleated polychromatic erythrocytes in bone marrow, and Comet responses in peripheral blood, liver, kidney, and lung were evaluated at one, two, or more timepoints. Both PCZ and EC produced positive responses at most analyzed timepoints in all tissue types, both with the 3‐day and 28‐day treatment regimens. Furthermore, comparison of the magnitude of the genotoxicity responses indicated that the micronucleus and Comet endpoints generally produced greater responses with the higher dose, short‐term treatments in the 3‐day study, while the Pig‐a assay responded better to the cumulative effects of the lower dose, but repeated subchronic dosing in the 28‐day study. Collectively, these results indicate that integration of several in vivo genotoxicity endpoints into a single routine toxicology study is feasible and that the Pig‐a assay may be particularly suitable for integration into subchronic dose studies based on its ability to accumulate the mutations that result from repeated treatments. This characteristic may be especially important for assaying lower doses of relatively weak genotoxicants. Environ. Mol. Mutagen. 2018. ... In lungs of mice exposed to ethylcarbamate (900 mg/kg) for 14 days, significant changes were identified in transcripts encoding humoral immune response, antigen binding, TLRs, cytokines, cytokine receptors and genes involved in cell adhesion and migration (Fernando et al. 1996). Specifically, down-regulated expression of genes encoding TLR/IL1R signalling pathway was identified (Williams et al. 1998 ). ... From immunotoxicity to carcinogenicity: The effects of carbamate pesticides on the immune system Article Full-text available May 2016 ENVIRON SCI POLLUT R <here is a image 4efbe257f1f6233a-1eecb0bc55a8fb04> Ines Elbini <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Manel Jallouli <here is a image 451dc14ff7717939-831c4df86dda7096> Alya Annabi <here is a image b8f31d41bf02feb7-faeb80f6a65e5921> Montassar Lasram The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion. ... For example, the LIZ vector was employed to correlate the lymphoma-inducing potency of the compounds 1,3-butadiene [10,11], dimethylbenzoanthracene [12], benzene [13], and ethylnitrosourea [14] with significant increases in mutagenesis in the lymphoid system. Similar correlations between elevated mutagenicity in lymphoid tissues and development of malignant lymphomas were established for the mutagens benzo [a]pyrene [15], ethylnitrosourea [16] and ethyl carbamate [17] , using the lacZ or pUR288 vectors as the read-out systems. The combined results with all three shuttle vectors, LIZ, lacZ, and pUR288, suggested that the assessment of mutagenesis in lymphoid tissues may be of tremendous value, not the least because the ability to predict lymphoma development by means of a short-term assay may help to reduce the need for tumor induction studies in vivo. ... Inducible mutagenesis in TEPC 2372, a mouse plasmacytoma cell line that harbors the transgenic shuttle vector lambdaLIZ Article Feb 2001 MUTAT RES-FUND MOL M <here is a image 32b91eb776bb3d5e-fcca915995c3f292> Klaus Felix <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Alexander Kovalchuk S S Park Siegfried Janz The plasmacytoma cell line, TEPC 2372, was derived from a malignant plasma cell tumor that developed in the peritoneal cavity of a BALB/c mouse that harbored the transgenic shuttle vector for the assessment of mutagenesis in vivo, lambdaLIZ. TEPC 2372 was found to display the typical features of a BALB/c plasmacytoma. It consisted of pleomorphic plasma cells that secreted a monoclonal immunoglobulin (IgG2b/lambda), was initially dependent on the presence of IL-6 to grow in cell culture, contained a hyperdiploid chromosome complement with a tendency to undergo tetraploidization, and harbored a constitutively active c-myc gene by virtue of a T(6;15) chromosomal translocation. TEPC 2372 was further characterized by the ability to respond to in vitro exposure with 4-NQO (4-nitroquinoline-1-oxide), an oxidative model mutagen, with a vigorous dose-dependent increase in mutagenesis that peaked at a 7.85-fold elevation of mutant rates in lambdaLIZ when compared to background mutant rates in untreated controls. Cotreatment with 4-NQO and BSO (buthionine sulfoximine), a glutathione-depleting compound that causes endogenous oxidative stress, resulted in a 9.03-fold increase in the mutant frequency in lambdaLIZ. These results demonstrated that TEPC 2372, the malignant plasma cell counterpart of the lambdaLIZ-based in vivo mutagenesis assay, may be useful as an in vitro reference point for the further elucidation of oxidative mutagenesis in lymphoid tissues. ... In a typical study using CBA mice given 900 mg/kg (i.p. or oral), up to 30-fold increases in micronucleated polychromatic erythrocytes (PCEs) were observed relative to concurrent control values [8] ( Table 1). In addition, weak, but statistically significant, positive results have been detected in the Muta™ Mouse following single i.p. dosing with 900 mg/kg, where increases in mutant frequency in lung and liver (equivocal results in bone marrow and spleen) were seen [9] . Similar results have also been obtained in an evaluation of mutant frequencies of chemically induced tumours and normal tissues in lambda/cII transgenic mice treated with urethane [10]. ... Report of the IWGT working group on strategy/interpretation for regulatory in vivo tests. II. Identification of in vivo-only positive compounds in the bone marrow micronucleus test Article Mar 2007 MUTAT RES-FUND MOL M <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> David Tweats David H. Blakey R.H. Heflich <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Raymond R Tice A survey conducted as part of an International Workshop on Genotoxicity Testing (IWGT) has identified a number of compounds that appear to be more readily detected in vivo than in vitro. The reasons for this property varies from compound to compound and includes metabolic differences; the influence of gut flora; higher exposures in vivo compared to in vitro; effects on pharmacology, in particular folate depletion or receptor kinase inhibition. It is possible that at least some of these compounds are detectable in vitro if a specific in vitro test is chosen as part of the test battery, but the 'correct' choice of test may not always be obvious when testing a compound of unknown genotoxicity. It is noted that many of the compounds identified in this study interfere with cell cycle kinetics and this can result in either aneugenicity or chromosome breakage. A decision tree is outlined as a guide for the evaluation of compounds that appear to be genotoxic agents in vivo but not in vitro. The regulatory implications of these findings are discussed. ... Moreover, VC but not EC is mutagenic to Salmonella typhimurium strains TA 1535 and TA100 (Dahl et al., 1978(Dahl et al., , 1980Leithauser et al., 1990). However, more recent studies have identified the mutagenicity of EC, using the transgenic Muta Mouse and lacZ as the reporter gene (Williams et al., 1998) . Nevertheless, these findings indicated that VC has greater carcinogenic potential than EC, and further that the lung is an important and possibly a primary target tissue. ... Oxidation of Vinyl Carbamate and Formation of 1,N6-Ethenodeoxyadenosine in Murine Lung Article Jun 2007 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Poh-Gek Forkert <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Martin Kaufmann Gordon P Black Glenville Jones Vinyl carbamate (VC) is derived from ethyl carbamate, a carcinogen formed in fermentation of food and alcoholic products. We have undertaken studies to test the hypothesis that an epoxide generated from VC oxidation leads to formation of 1,N6-ethenodeoxyadenosine (epsilon dAS). We have developed approaches using liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry for identification and quantitation of epsilon dAS. Scanning and fragment ion analyses confirmed the identity of epsilon dAS based on the molecular ion [M + H]+ m/z 276 and the specific fragment ion m/z 160. Chemical oxidation of VC in reactions containing 2'-deoxyadenosine produced epsilon dAS with 1H NMR, chromatographic, and mass spectral characteristics identical to those of the authentic epsilon dAS, suggesting DNA alkylation by the VC epoxide. Subsequent studies evaluated formation of epsilon dAS in incubations of murine lung microsomes or recombinant CYP2E1 with VC. The formation of epsilon dAS in incubations of lung microsomes or recombinant CYP2E1 with VC was dependent on protein concentrations, CYP2E1 enzyme levels, and incubation time. The rates of epsilon dAS formation were highly correlated with VC concentrations. Peak rates were produced by lung microsomes and recombinant CYP2E1 at 3.0 and 2.5 mM VC, respectively. In inhibitory studies, incubations of VC were performed using lung microsomes from mice treated with the CYP2E1 inhibitor diallyl sulfone (100 mg/kg, p.o.). Results from these studies showed significantly decreased epsilon dAS formation in microsomes incubated with VC, with an inhibition of 70% at 3.0 mM. These findings suggested that CYP2E1 is a major enzyme mediating VC oxidation, leading to the formation of a metabolite that alkylates DNA to form the epsilon dAS adduct. Extrapolation of in vitro structural alerts for mutagenicity to the in vivo endpoint Article Oct 2018 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Rachael Tennant Sebastien J. Guense Steven J. Canipa <here is a image e48337fec034d124-1fadfebbf8754aa8> Richard V. Williams As part of the hazard and risk assessment of chemicals in man, it is important to assess the ability of a chemical to induce mutations in vivo. Because of the commonalities in the molecular initiating event, mutagenicity in vitro can correlate well to the in vivo endpoint for certain compound classes; however, the difficulty lies in identifying when this correlation holds true. In silico alerts for in vitro mutagenicity may therefore be used as the basis for alerts for mutagenicity in vivo where an expert assessment is carried out to establish the relevance of the correlation. Taking this into account, a data set of publicly available transgenic rodent gene mutation assay data, provided by the National Institute of Health Sciences of Japan, was processed in the expert system Derek Nexus against the in vitro mutagenicity endpoint. The resulting predictivity was expertly reviewed to assess the validity of the observed correlations in activity and mechanism of action between the two endpoints to identify suitable in vitro alerts for extension to the in vivo endpoint. In total, 20 alerts were extended to predict in vivo mutagenicity, which has significantly improved the coverage of this endpoint in Derek Nexus against the data set provided. Updating the Derek Nexus knowledge base in this way led to an increase in sensitivity for this data set against this endpoint from 9% to 66% while maintaining a good specificity of 89%. Environmental health criteria for transgenic animal mutagenicity assays Jan 2006 <here is a image af5f37bee32b2e7d-35c03c07c949bfed> Tao Chen <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Steve Dean <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> George Douglas U. Wahnschaffe The aim of this document is to introduce newcomers in this field to transgenic mutagenicity assays and to assess the possible role of these assays in toxicology testing and mechanistic research. A transgenic animal carries foreign DNA that is integrated into the chromosomal DNA of the animal and is present in all cells. In transgenic mutagenicity assays, the foreign DNA is an exogenous gene (transgene) injected into the nucleus of a fertilized rodent embryo. These reporter genes are transmitted by the germ cells and thus are present in all cells of the newborn rodent and can be used to detect mutation frequency. Part I of this document (Chapters 2-6) gives a short overview of in vivo genotoxicity testing. The methods employed in the design of transgenic animals are explained, giving details of the DNA construct and of the methods used for inserting the construct into the recipient animals. As examples, transgenic models - in particular the lacI model, commercially available as the Big Blue® mouse and Big Blue® rat, and the lacZ model, commercially available as the Muta™Mouse - are described, as well as more recently developed models, such as λcII, the gpt delta, lacZ plasmid and ΦX174. Study design is critical to the validity of a study for determining positive/negative mutagenicity of a test compound. The choice of the mutagenic target gene, species and tissue should be based on any prior knowledge of the pharmacological/toxicological parameters of the test agent. Since the selection of dose, dosing schedule and post-treatment sampling time varies for the optimal detection of mutation frequency for different tissues and agents, a protocol has been recommended that optimizes detection of all mutagens, regardless of potency or target tissue. A negative result obtained using a robust protocol should be considered as valid. Part II (Chapters 7-10) gives an overview of data published on chemicals tested using the lacI model and the lacZ model, compares these with data available with conventional systems and discusses the outcomes. These models were chosen because they are the only two systems with enough data available to allow comparisons and analyses to be made. The limited data available suggest that there is significant agreement with respect to the results obtained with the Muta™Mouse and the Big Blue® mouse or rat assay. Any observed differences between the Muta™Mouse and the Big Blue® mouse assay are likely to be attributable to the different experimental design used in the particular studies, rather than differences in the sensitivity of the transgenic reporter genes per se. The results of the transgenic mutation assays were compared with those of the mouse bone marrow micronucleus assay for 44 substances. Although the majority of the results were often similar, as many of the chemicals tested were potent carcinogens, the assays were complementary - that is, there was a significant improvement in the detection of carcinogens when both assays were used. The theoretical advantage of using two assays that detect different genotoxic end-points seems to be confirmed by this result. The ability of the transgenic animal assays to detect gene mutations in multiple tissues is also a distinct advantage. Although the mouse spot test is a standard genotoxicity test system according to Organisation for Economic Co-operation and Development (OECD) guidelines, this system has seldom been used for detection of somatic mutations in vivo in recent decades. The results of a comparison of both systems in this document showed that the transgenic mouse assay has several advantages over the mouse spot test and is a suitable test system to replace the mouse spot test for detection of gene but not chromosome mutations in vivo. Despite differences in the mutational properties of the various model mutagens, the responses of the exogenous loci (lacI, lacZ transgene) and the endogenous loci (Dlb-1, Hprt) were generally qualitatively similar following acute treatments. Several studies suggest that the lower somatic mutant frequency in the endogenous genes may provide enhanced sensitivity under such conditions. However, comparisons of transgenes and endogenous genes are difficult because of differences between the optimal experimental protocols for the different types of genes; in the neutral transgenes, sensitivity for the detection of mutations is increased with the longer administration times that are currently recommended. The limited data comparing unscheduled DNA synthesis (UDS) with lacI and lacZ suggest that transgenic animal assays exhibit superior predictivity compared with the UDS test, which measures DNA damage. Results from transgenic animal assays (lacI and lacZ) with over 50 chemicals agreed with results from in vitro data on gene mutation, chromosomal aberration and direct or indirect measures for DNA damage by these chemicals. A major advantage of the transgenic mouse/rat mutation assay compared with other in vivo mutagenicity tests is that mutagenic events in any organ can be detected. Therefore, an analysis was made to determine whether target organs in carcinogenicity studies can be predicted by transgenic mutation assays. In most cases, mutations were found in the target organs of the carcinogenicity studies. For several presumed genotoxic carcinogens, organs investigated in the transgenic mutagenicity assays, which were not target organs in carcinogenicity studies, were positive. As this has occurred for several compounds, it is unlikely to be explained by insufficient specificity with regard to target organs for carcinogenicity. Instead, it leads to the conclusion that genotoxicity is expressed in several organs in the body and that tumours do not develop in all these organs due to other factors. Carcinogens with a presumed non-genotoxic mode of action generally produce negative results in the transgenic animal assays. Very few data are available on substances that gave negative results in carcinogenicity assays on mice. However, for these few non-carcinogens, the results in transgenic mice were also negative. The available data suggest that the sensitivity and positive predictivity of the transgenic assays for carcinogenicity are high. Part III (Chapter 11) describes studies in which transgenic mutation assays (in particular, the lacI and lacZ model using cII and the gpt delta rodent system) have been used as mechanistic research tools. Due to the ease of sequencing the cII gene for mutational spectra, it is increasingly used instead of lacI and lacZ in the Muta™Mouse and Big Blue® models for sequencing studies. The gpt delta model is also used because of the ease of sequencing and, especially, because it detects deletions much larger than those detected by all but the lacZ plasmid assay. Spontaneous mutations have been studied in almost all transgenic animal mutagenicity assays: lacZ, lacI and CII, lacZ plasmid and gpt delta mice. In all systems, the predominant type of spontaneous mutation is G:C→A:T transitions, with most occurring at 5′-CpG sites, suggesting that the deamination of 5-methylcytosine is the main mechanism of mutagenesis. The frequency and nature of spontaneous mutations have been studied. The factors that affect the inferred mutation rate are site of integration of the transgene, age, tissue and strain. About half of all mutations arise during development (and half of these in utero). Several studies have examined the frequency and nature of spontaneous mutations versus age in multiple tissues and found that, with the exception of studies in the plasmid mouse, the spectrum of mutation types was similar with age and tissue type in adult animals. It did not vary with differences in gender or mouse genetic background. The mutation frequency in the male germline was consistently the lowest, remaining essentially unchanged in old age. Transgenic animal assays have been found to be useful tools in the examination of fundamental paradigms in genetic toxicology. Recent studies using these systems have addressed the issues of 1) dose-response relationship of genotoxic carcinogens and 2) the relationships among DNA adduct formation, mutation frequency and cancer in rodents. Further important application of these transgenic rodent assays has been in fundamental studies on the origin of mutations and the roles of various biological processes in preventing them. These studies have included studies of DNA repair mechanisms, carcinogenesis, ageing and inherited genetic conditions affecting these processes. While mutation spectra from DNA sequence data are not considered mandatory for the evaluation of gene mutation in vivo in the case of clear positive or negative results, they are useful for factors relating to the mechanism of mutagenesis. The ability to sequence induced mutations in transgenic reporter genes provides an investigator with important information regarding several aspects of mutation. Examples are given of studies that demonstrate how transgenic animal assays and subsequent spectral analysis can be used to examine different aspects of the activity of mutagenic agents: for example, 1) clonal correction and correction for ex vivo mutations, 2) premutagenic lesions, 3) tissue-specific responses, 4) evaluation of genotoxicants that do not interact with DNA, 5) determination of the active components of mixtures, 6) determinations of active metabolites and 7) investigations into the mechanisms of deletion mutations in vivo. Part IV (Chapters 12-14) evaluates the role and potential added value of transgenic mutation assays in toxicology and risk assessment. To date, transgenic mutagenicity assays have not been heavily used by industry in toxicological screening, in large part because an OECD Test Guideline has not yet been developed. Attempts at Organ-specific In Vivo Short-term Tests for Environmental Mutagens and Carcinogens in Rodent Liver and Stomach May 2013 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Chie Furihata The primary motivation for conducting short-term tests for environmental mutagens and carcinogens has been to predict mutagens and/or carcinogens and to assess any associated risks. Organ-specific in vivo short-term tests in rodents are valuable because chemical carcinogenesis is generally organ-specific. I have attempted to develop various organ-specificin vivo short-term tests mainly in rodent liver and stomach. Recently, our collaborative study group, Toxicogenomics/Japanese Environmental Mutagen Society·Mammalian Mutagenicity Study Group (JEMS·MMS), attempted to use gene expression profiling in in vivo short-term tests, conducted DNA microarrays to extract candidate marker genes, and later shifted to quantitative real-time PCR (qPCR) to profile the expression of selected genes. We successfully discriminated 8 genotoxic hepatocarcinogens from 4 non-genotoxic hepatocarcinogens by statistical analysis using principal component analysis (PCA) based on the gene expression profiles for 12 genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2, and Tubb2c) in mouse liver at 4 and 48 h following a single intraperitoneal administration of chemicals as determined by qPCR. More recently, we successfully performed a similar study in rat liver. Previously, my collaborators and I developed various organspecific in vivo short-term test methods, including UDS (unscheduled DNA synthesis); RDS (replicative DNA synthesis) using a liquid scintillation counter in rat glandular stomach, forestomach, colon, and liver and hairless mouse epidermis; DNA single-strand scission (DSS); and ornithine decarboxylase assay (ODC) in rat glandular stomach on 62 compounds. Developing short-term tests that are helpful for the risk assessment of human mutagens and carcinogens would contribute to the development of ideal prediction methods. Analysis of gene mutations and clastogenicity following short‐term treatment with azathioprine in Muta™Mouse Jan 1999 ENVIRON MOL MUTAGEN <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Catherine C Priestley Graeme E. Archer Emma J. Forster <here is a image c5137265df214342-00760474f5d144c1> Anthony M Lynch The mutagenicity and clastogenicity of the immunosuppressive drug azathioprine (AZA), a multitissue rodent carcinogen and IARC-classified human carcinogen, was investigated using transgenic lacZ mice (Muta™Mouse). Male animals (n = 5 per group) were dosed with AZA (10, 50, 100 mg/kg p.o. daily for 5 days), vehicle (n = 10), or the positive control, chlorambucil (15 mg/kg i.p., n = 3), and killed 24 hr or 25 days after the last treatment. Micronucleus assays were performed with bone marrow (24-hr samples) or peripheral blood (24-hr and 25-day samples) and DNA was extracted from bone marrow and liver for gene mutation analysis at the transgenic lacZ locus. AZA induced 5.3–111.3-fold increases in %MNPCE (P < 0.01) in bone marrow compared with vehicle control, accompanied by 4.4–5.6-fold increases in %MNRETs (P < 0.01) in peripheral blood. Chlorambucil caused a 14.5-fold increase in %MNRET and there was evidence of significant stem cell toxicity in both positive control and AZA treatment groups. By day 25, however, there was evidence of substantial recovery of the bone marrow as determined by the frequency of RET, and the %MNRET in all treatment groups was the same as the vehicle control. Analysis of lacZ MF showed 1.4–1.6-fold increases in AZA 24-hr bone marrow samples, increasing to ∼2.0-fold above concurrent controls by day 25 (medium dose P < 0.05, high dose P < 0.01). For liver, there was a 2-fold increase in MF (P < 0.05) in the 24-hr sample at the highest dose only, and increases of 1.3–1.5-fold by day 25 in the medium (P < 0.05) and high (P = 0.055) dose groups, respectively. The positive control, chlorambucil, induced 2–3-fold increases (P < 0.01) in mean MF in both bone marrow (25-day sample) and liver (24-hr and 25-day samples). These data confirm the clastogenicity of AZA in the mouse, and show that this compound induces gene mutations in bone marrow and liver, in vivo, at the highest dose and supports the view that AZA is a genotoxic carcinogen. Environ. Mol. Mutagen. 34:131–139, 1999 © 1999 Wiley-Liss, Inc. Discrimination of genotoxic and non-genotoxic hepatocarcinogens by statistical analysis based on gene expression profiling in the mouse liver as determined by quantitative real-time PCR Article May 2012 MUTAT RES-FUND MOL M Takashi Watanabe Takayoshi Suzuki <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Masakatsu Natsume <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Chie Furihata The general aim of the present study is to discriminate between mouse genotoxic and non-genotoxic hepatocarcinogens via selected gene expression patterns in the liver as analyzed by quantitative real-time PCR (qPCR) and statistical analysis. qPCR was conducted on liver samples from groups of 5 male, 9-week-old B6C3F(1) mice, at 4 and 48 h following a single intraperitoneal administration of chemicals. We quantified 35 genes selected from our previous DNA microarray studies using 12 different chemicals: 8 genotoxic hepatocarcinogens (2-acetylaminofluorene, 2,4-diaminotoluene, diisopropanolnitrosamine, 4-dimethylaminoazobenzene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N-nitrosomorpholine, quinoline and urethane) and 4 non-genotoxic hepatocarcinogens (1,4-dichlorobenzene, dichlorodiphenyltrichloroethane, di(2-ethylhexyl)phthalate and furan). A considerable number of genes exhibited significant changes in their gene expression ratios (experimental group/control group) analyzed statistically by the Dunnett's test and Welch's t-test. Finally, we distinguished between the genotoxic and non-genotoxic hepatocarcinogens by statistical analysis using principal component analysis (PCA) of the gene expression profiles for 7 genes (Btg2, Ccnf, Ccng1, Lpr1, Mbd1, Phlda3 and Tubb2c) at 4 h and for 12 genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2 and Tubb2c) at 48 h. Seven major biological processes were extracted from the ICH-Harmonised guidances on genotoxicity testing of pharmaceuticals: Evolution, reasoning and impact Article Jun 1999 MUTAT RES-FUND MOL M <here is a image bf7f36304ed42ad4-e08aa783f06f03a5> Lutz Müller Yasumoto Kikuchi Gregory Probst <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> David Tweats The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has convened an expert working group which consisted of the authors of this paper and their respective committees, consulting groups and task forces. Two ICH guidances regarding genotoxicity testing have been issued: S2A, `Guidance on Specific Aspects of Regulatory Genotoxicity Tests' and S2B, `Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals.' Together, these guidance documents now form the regulatory backbone for genotoxicity testing and assessment of pharmaceuticals in the European Union, Japan, and the USA. These guidances do not constitute a revolutionary new approach to genotoxicity testing and assessment, instead they are an evolution from preexisting regional guidelines, guidances and technical approaches. Both guidances describe a number of specific criteria as well as a general test philosophy in genotoxicity testing. Although these guidances were previously released within the participating regions in their respective regulatory communiqués, to ensure their wider distribution and better understanding, the texts of the guidances are reproduced here in their entirety (see Appendix A) and the background for the recommendations are described. The establishment of a standard battery for genotoxicity testing of pharmaceuticals was one of the most important issues of the harmonisation effort. This battery currently consists of: (i) a test for gene mutation in bacteria, (ii) an in vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma tk assay, (iii) an in vivo test for chromosomal damage using rodent hematopoietic cells. A major change in testing philosophy is the acceptance of the interchangeability of testing for chromosomal aberrations in mammalian cells and the mouse lymphoma tk assay. This agreement was reached on the basis of the extensive review of databases and newly generated experimental data which are in part described in this publication. The authors are fully aware of the fact that some of the recommendations given in these ICH guidances are transient in nature and that the dynamic qualities and ongoing evolution of genetic toxicology makes necessary a continuous maintenance process that would serve to update the guidance as necessary. Mechanisms of lung tumorigenesis by ethyl carbamate and vinyl carbamate DRUG METAB REV <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Poh-Gek Forkert Vinyl carbamate (VC) and ethyl carbamate (EC) induce the formation of lung tumors. The mechanism involves a two-step oxidation of EC to VC and VC to an epoxide, both of which are mediated mainly by CYP2E1. Interaction of the epoxide with DNA leads to the formation of DNA adducts, including 1,N(6)ethenodeoxyadenosine and 1,N(4)-ethenodeoxycytidine. The production of DNA adducts correlated with capacities for the bioactivation of VC, which are higher in the lungs of A/J than in C57BL/6 mice. Importantly, CYP2E1 is higher in the lungs of A/J than in C57BL/6 mice. Studies using F(1) (Big Blue x A/J) transgenic mice revealed the formation of mutations in the lambda cII gene after treatment with VC. Mutations induced by VC were mainly A:T-->G:C transitions and A:T-->T:A transversions, while mutations induced by EC were mainly G:C-->A:T transitions. An EC dose that was 17-fold higher than that for VC was required to produce a similar level of mutant frequency in the lung. Pretreatment of mice with the CYP2E1 inhibitor, diallyl sulfone, significantly inhibited the mutant frequencies induced by VC. Mutations in the endogeneous Kras2 gene were found in codon 61 of exon 2 and were identified as A:T transversions and A-->G transitions in the second base and A-->T transversions in the third base. These mutations were reduced by treatment of mice with diallyl sulfone before VC and coincided with a reduction in the number of lung tumors with Kras2 mutations. These findings affirmed that the metabolism of EC and VC is a prerequisite for, or at least substantially contributes to, initiation of the cascade of events leading to lung tumor formation. Mutagenicity of the human bladder carcinogen 4-aminobiphenyl to the bladder of Muta (TM) Mouse transgenic mice MUTAT RES-FUND MOL M K Fletcher <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Helen Tinwell J Ashby The human carcinogen 4-aminobiphenyl (4AB) was evaluated in the MutaMouse transgenic mouse mutation assay. A single oral dose of 75 mg/kg induced 6.9-, 1.8- and 2.2-fold increases in the mutation frequency (MF) in the bladder, liver and bone marrow, respectively. Ten daily oral doses of 10 mg/kg 4AB increased the MF in the bladder, liver and bone marrow by 13.7-, 4.8- 2.4-fold the control value, respectively. The repeat dosing protocol was therefore more sensitive than the single dose protocol. Assessment of DNA samples prepared from pooled liver homogenates clearly indicated the increase in MF observed in the individual liver samples obtained from both groups of 4AB-treated mice. Analysis of gene mutations and clastogenicity following short-term treatment with azathioprine in Muta(TM)Mouse C C Smith Graeme E. Archer Emma J. Forster <here is a image c5137265df214342-00760474f5d144c1> Anthony M Lynch The mutagenicity and clastogenicity of the immunosuppressive drug azathioprine (AZA), a multitissue rodent carcinogen and IARC-classified human carcinogen, was investigated using transgenic lacZ mice (Muta(TM)Mouse). Male animals (n = 5 per group) were dosed with AZA (10, 50, 100 mg/kg p.o. daily for 5 days), vehicle (n = 10), or the positive control, chlorambucil (15 mg/kg i.p., n = 3), and killed 24 hr or 25 days after the last treatment. Micronucleus assays were performed with bone marrow (24-hr samples) or peripheral blood (24-hr and 25-day samples) and DNA was extracted from bone marrow and liver for gene mutation analysis at the transgenic lacZ locus. AZA induced 5.3-111.3-fold increases in %MNPCE (P < 0.01) in bone marrow compared with vehicle control, accompanied by 4.4-5.6-fold increases in %MNRETs (P < 0.01) in peripheral blood. Chlorambucil caused a 14.5-fold increase in %MNRET and there was evidence of significant stem cell toxicity in both positive control and AZA treatment groups. By day 25, however, there was evidence of substantial recovery of the bone marrow as determined by the frequency of RET, and the %MNRET in all treatment groups was the same as the vehicle control. Analysis of lacZ MF showed 1.4-1.6-fold increases in AZA 24-hr bone marrow samples, increasing to ~2.0-fold above concurrent controls by day 25 (medium dose P < 0.05, high dose P < 0.01). For liver, there was a 2-fold increase in MF (P < 0.05) in the 24-hr sample at the highest dose only, and increases of 1.3-1.5-fold by day 25 in the medium (P < 0.05) and high (P = 0.055) dose groups, respectively. The positive control, chlorambucil, induced 2-3-fold increases (P < 0.01) in mean MF in both bone marrow (25-day sample) and liver (24-hr and 25-day samples). These data confirm the clastogenicity of AZA in the mouse, and show that this compound induces gene mutations in bone marrow and liver, in vivo, at the highest dose and supports the view that AZA is a genotoxic carcinogen. Recent advances in the protocols of transgenic mouse mutation assays Article MUTAT RES-FUND MOL M <here is a image a820f8d90f5e05c1-7ab710aa39df2dc1> Takehiko Nohmi Takayoshi Suzuki Ken-ichi Masumura Transgenic mutation assays were developed to detect gene mutations in multiple organs of mice or rats. The assays permit (1) quantitative measurements of mutation frequencies in all tissues/organs including germ cells and (2) molecular analysis of induced and spontaneous mutations by DNA sequencing analysis. The protocols of recently developed selections in the lambda phage-based transgenic mutation assays, i.e. cII, Spi(-) and 6-thioguanine selections, are described, and a data set of transgenic mutation assays, including those using Big Blue and Muta Mouse, is presented. Mutagenicity testing with transgenic mice. Part I: Comparison with the mouse bone marrow micronucleus test J Carcinog U. Wahnschaffe <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> A. Bitsch <here is a image 782960fd098111e1-f69aca298f63143a> Jonathan Kielhorn <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Inge Mangelsdorf As part of a larger literature study on transgenic animals in mutagenicity testing, test results from the transgenic mutagenicity assays (lacI model; commercially available as the Big Blue(R) mouse, and the lacZ model; commercially available as the Mutatrade markMouse), were compared with the results on the same substances in the more traditional mouse bone marrow micronucleus test. 39 substances were found which had been tested in the micronucleus assay and in the above transgenic mouse systems. Although, the transgenic animal mutation assay is not directly comparable with the micronucleus test, because different genetic endpoints are examined: chromosome aberration versus gene mutation, the results for the majority of substances were in agreement. Both test systems, the transgenic mouse assay and the mouse bone marrow micronucleus test, have advantages and they complement each other. However, the transgenic animal assay has some distinct advantages over the micronucleus test: it is not restricted to one target organ and detects systemic as well as local mutagenic effects. Detailed review of transgenic rodent mutation assays MUTAT RES-FUND MOL M <here is a image ac76ade45d70fcbd-d33739cddc739391> Iain B Lambert Timothy M Singer <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sherri Boucher <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> George Douglas Induced chromosomal and gene mutations play a role in carcinogenesis and may be involved in the production of birth defects and other disease conditions. While it is widely accepted that in vivo mutation assays are more relevant to the human condition than are in vitro assays, our ability to evaluate mutagenesis in vivo in a broad range of tissues has historically been quite limited. The development of transgenic rodent (TGR) mutation models has given us the ability to detect, quantify, and sequence mutations in a range of somatic and germ cells. This document provides a comprehensive review of the TGR mutation assay literature and assesses the potential use of these assays in a regulatory context. The information is arranged as follows. (1) TGR mutagenicity models and their use for the analysis of gene and chromosomal mutation are fully described. (2) The principles underlying current OECD tests for the assessment of genotoxicity in vitro and in vivo, and also nontransgenic assays available for assessment of gene mutation, are described. (3) All available information pertaining to the conduct of TGR assays and important parameters of assay performance have been tabulated and analyzed. (4) The performance of TGR assays, both in isolation and as part of a battery of in vitro and in vivo short-term genotoxicity tests, in predicting carcinogenicity is described. (5) Recommendations are made regarding the experimental parameters for TGR assays, and the use of TGR assays in a regulatory context. Use of primary cultures of adult rat hepatocytes on collagen gel-nylon mesh to evaluate carcinogen-induced unscheduled DNA synthesis Article Full-text available The procarcinogen, 2-acetylaminofluorene, the direct-acting carcinogen, methyl methanesulfonate, and two other hepatocarcinogens, thioacetamide and urethan, were tested for their ability to elicit unscheduled DNA synthesis in adult rat hepatocytes maintained in primary culture on collagen gel-nylon mesh. The carcinogens, dissolved in dimethyl sulfoxide were added to 6-hr or to 28-hr cultures along with [methyl-3H]thymidine (1 muCi/ml medium) in the presence of 10 mM hydroxyurea. Twelve hr later, the hepatocytes were harvested from the cultures with collagenase, and their DNA was purified on CsCl isopyknic gradients. Unscheduled DNA synthesis was measured as the increase in [methyl-3H]thymidine radioactivity incorporated per microgram DNA of the carcinogen-treated cultures as compared with that of control cultures. Both 2-acetylaminofluorene and methyl methanesulfonate demonstrated a concentration-dependent stimulation of unscheduled DNA synthesis in the 6-hr hepatocyte cultures. However, the response of the 28-hr cultures to these two carcinogens was absent unless the hepatocytes were preincubated for 22 hr in culture medium supplemented with 10(-5) M dexamethasone and 10(-6) M glucagon or in a more complete hormone-supplemented medium. Thioacetamide and urethan, on the other hand, failed to elicit a concentration-dependent unscheduled DNA synthesis under these conditions. The results obtained with this culture system are similar to those of other short-term tests for chemical carcinogenicity and support the potential use of the collagen gel-nylon mesh-hepatocyte primary culture as an in vitro screen for chemical carcinogens. Furthermore, this study suggests the importance of specific hormones in maintaining the capability for repair of DNA damage produced by carcinogenic and mutagenic chemicals in cultured hepatocytes. Summary report on the performance of bacterial mutation assays Article Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate Article
https://www.researchgate.net/publication/13711082_Mutagenicity_of_ethyl_carbamate_to_lacZ-transgenic_mice
Marine Drugs | Free Full-Text | Comparative Analyses of Metabolomic Fingerprints and Cytotoxic Activities of Soft Corals from the Colombian Caribbean Soft corals (Cnidaria, Anthozoa, Octocorallia) are a diverse group of marine invertebrates that inhabit various marine environments in tropical and subtropical areas. Several species are recognized as prolific sources of compounds with a wide array of biological activities. Recent advances in analytical techniques, supported by robust statistical analyses, have allowed the analysis and characterization of the metabolome present in a single living organism. In this study, a liquid chromatography-high resolution mass spectrometry metabolomic approach was applied to analyze the metabolite composition of 28 soft corals present in the Caribbean coast of Colombia. Multivariate data analysis was used to correlate the chemical fingerprints of soft corals with their cytotoxic activity against tumor cell lines for anticancer purpose. Some diterpenoids were identified as specific markers to discriminate between cytotoxic and non-cytotoxic crude extracts of soft corals against tumor cell lines. In the models generated from the comparative analysis of PLS-DA for tumor lines, A549 and SiHa, the diterpene 13-keto-1,11-dolabell-3(E),7(E),12(18)-triene yielded a high score in the variable importance in projection. These results highlight the potential of metabolomic approaches towards the identification of cytotoxic agents against cancer of marine origin. This workflow can be useful in several studies, mainly those that are time consuming, such as traditional bioprospecting of marine natural products. Comparative Analyses of Metabolomic Fingerprints and Cytotoxic Activities of Soft Corals from the Colombian Caribbean by Olivier P. Thomas 2,* , Carmenza Duque 3 , Edisson Tello 1,* 1 Bioprospecting Research Group and Bioscience Doctoral Program, Faculty of Engineering, Campus Puente del Común, Universidad de La Sabana, 250001 Chía, Colombia 2 Marine Biodiscovery, School of Chemistry and Ryan Institute, National University of Ireland Galway (NUI Galway), University Road, H91 TK33 Galway, Ireland 3 Departamento de Química, Universidad Nacional de Colombia, Carrera 30 # 45-03, 111321 Bogotá, Colombia 4 Departamento de Ciencias Biológicas y Ambientales, Universidad Jorge Tadeo Lozano, Carrera 4 # 22-61, 110311 Bogotá, Colombia * Authors to whom correspondence should be addressed. Mar. Drugs 2019 , 17 (1), 37; https://doi.org/10.3390/md17010037 Received: 16 June 2018 / Revised: 20 December 2018 / Accepted: 28 December 2018 / Published: 9 January 2019 Abstract : Soft corals (Cnidaria, Anthozoa, Octocorallia) are a diverse group of marine invertebrates that inhabit various marine environments in tropical and subtropical areas. Several species are recognized as prolific sources of compounds with a wide array of biological activities. Recent advances in analytical techniques, supported by robust statistical analyses, have allowed the analysis and characterization of the metabolome present in a single living organism. In this study, a liquid chromatography-high resolution mass spectrometry metabolomic approach was applied to analyze the metabolite composition of 28 soft corals present in the Caribbean coast of Colombia. Multivariate data analysis was used to correlate the chemical fingerprints of soft corals with their cytotoxic activity against tumor cell lines for anticancer purpose. Some diterpenoids were identified as specific markers to discriminate between cytotoxic and non-cytotoxic crude extracts of soft corals against tumor cell lines. In the models generated from the comparative analysis of PLS-DA for tumor lines, A549 and SiHa, the diterpene 13-keto-1,11-dolabell-3(E),7(E),12(18)-triene yielded a high score in the variable importance in projection. These results highlight the potential of metabolomic approaches towards the identification of cytotoxic agents against cancer of marine origin. This workflow can be useful in several studies, mainly those that are time consuming, such as traditional bioprospecting of marine natural products. ; soft-corals ; Pseudoplexaura flagellosa ; diterpenes ; cytotoxic activity ; LC-HRMSs Graphical Abstract 1. Introduction Oceans cover around 71% of the Earth surface and host a great diversity of species, to which the marine environments have exerted a driving force, leading to new adaptive strategies and the synthesis of new metabolites [ 1 ]. Sessile and soft-bodied invertebrates, such as soft orals (Cnidaria, Anthozoa), have evolved particular metabolic pathways, leading to the production of chemical compounds as mechanisms of defense [ 2 ]. To date, seven compounds based on natural products of marine origin have been approved by the Food and Drug Administration (FDA) as pharmaceuticals. Among these, four have been specifically developed for the treatment of cancer: Cytarabine (Cytosar-U ® , 1969 for the treatment of leukemia), eribulin mesylate (Halaven ® , 2010 for the treatment of metastatic breast cancer), brentuximab vedotin (Adcetris ® , 2011 for the treatment of anaplastic large T-cell lymphoma, and Hodgkin’s lymphoma), and trabectedin (Yondelis ® , 2015 for the treatment of soft tissue sarcoma and ovarian cancer) [ 3 ]. Considering that cancer is still a major health concern worldwide [ 4 ], it is necessary to find new and effective cytotoxic agents against cancer. In this context, marine organisms are still largely unexplored and are promising sources of bioactive compounds with potential cytotoxic activity. Chemical studies over the last 60 years have revealed that soft corals have developed an extraordinary ability to produce a large variety of compounds with unique chemical structures, usually associated with a broad range of biological activities [ 5 ]. Among some of the most interesting bioactive metabolites from soft corals are eleutherobin, originally isolated from the Australian soft coral, Eleutherobia sp., that exhibit anticancer properties [ 6 ] and the pseudopterosins from Caribbean Antillogorgia elisabethae that exhibit potent cytotoxic against five human cells lines (HeLa, PC-3, HCT116, MCF-7, and BJ), and anti-inflammatory and antimicrobial activity [ 7 , 8 , 9 , 10 , 11 ]. Due to the outstanding chemical diversity of soft corals, new tools that encompass the broad metabolome of a particular species belonging to this group will definitely open new opportunities to quickly target bioactive metabolites. Recent developments in analytical chemistry techniques, especially HPLC, MS, and NMR, have allowed the detection of thousands of metabolites with great sensitivity and specificity in a short time period [ 12 ]. Still, there is a prevailing question of whether metabolomic approaches could be used to quickly identify known or unknown metabolites as potential candidates for pharmaceutical applications [ 13 ]. Statistical analyses, such as multivariate data analyses, and particularly PCA (principal component analysis), group different samples through clustering or by determining outliers, whereas multivariate analysis methods allow the classification of the samples based on their cytotoxic activity against tumor cell lines. Thus, multivariate analyses can be used to correlate a set of metabolomic data to the results of a specific assay, making it possible to ascribe the metabolites that are likely involved in the detected cytotoxic activity against tumor cell lines [ 14 ]. The aim of this study was to establish a correlation between cytotoxic activity using three tumor lines, SiHa: Human cervical cancer, A549: Human lung adenocarcinoma, and PC3: Human prostatic carcinoma, and the chemical composition of 28 crude extracts from soft corals from the Colombian Caribbean. UPLC-HRMS (QToF) data were used to yield a metabolomic fingerprint of each crude extract based on terpenoids, [ 15 , 16 ], which are characteristic and well represented in these organisms and can be detected by the selected analytical method [ 17 ]. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was applied to the metabolomic data, considering that this analysis uses information in the Y matrix to decompose the X matrix into blocks of structured variation correlated and orthogonal to Y, respectively. In this investigation, OPLS-DA was used to discriminate the different extracts based on the metabolic fingerprints of all extracts and their cytotoxic activity against tumor cell lines, showing that extracts of Eunicea clavigera and Pseudoplexaura flagellosa were the extracts that mainly contributed to the separation. Additionally, partial least squares discriminant analysis (PLS-DA) was used to calculate the variable importance in projection (VIP) [ 18 ]. However, OPLS-DA can be used analogously to PLS-DA for discrimination, where the main benefit in interpretation using OPLS-DA compared to PLS-DA lies in the ability of OPLS-DA to separate predictive from non-predictive (orthogonal) variation [ 19 ]. Finally, the multivariate statistical analyzes established that a diterpenoid with a dolabellane type skeleton was responsible for the cytotoxic activity shown by the extracts against the SiHa and A549 cancer cell lines. 2. Results 2.1. Processing and Untargeted Data Acquisition A metabolomics workflow pathway was established for this research as is shown in Figure 1 . In that way, a fingerprint metabolomics approach was applied to 28 soft coral extracts belonging to five different genera ( Plexaura , Antillogorgia , Eunicea , Plexaurella , and Pseudoplexaura ) by UPLC-HRMS in the positive ion mode, leading to 18,290 features analyzed with Galaxy 4.0 software [ 20 ]. The Script used for data processing is described in the Supplementary Table S3 . The LC−MS data sets can be downloaded from the metabolomics repository, MetaboLights [ 21 ], with the reference study code, MTBLS777. Following this analysis, we established some quality criteria by which any variation of Quality Control (QC) samples around their mean (CVQC) > 30% was removed from the dataset; this reduced the matrix data from 18,290 to 12,060 features, representing a reduction of 34% of the total matrix. Following our metabolomic workflow, three data matrices were generated. These data sets had the same number of features, but differed in the classification groups, following the in vitro cytotoxic activity of the soft coral extracts against the three cancer cell lines evaluated, human cervical cancer (SiHa), human lung adenocarcinoma (A549), and human prostatic carcinoma (PC3). L929 fibroblasts (L929; ATCC ® CCL-1™) were used as the non-tumor cell line for toxicity control, however, the data obtained from L929 were not considered for the elaboration of the metabolomic matrix, due to the interest of this research. For this research, it was established that an extract is considered active if it exhibited an inhibition of the tumor cell lines ≥50% at 20 μg/mL, following the guidelines of the National Cancer Institute (NCI) [ 22 ]. Supplementary Table S2 shows the results of the cytotoxicity presented by each extract against the tumor cell line, where the extract of the species, Pseudoplexaura flagellosa (code G17Ef), presented a value of 66.8% against SiHa and 71.5% against A549. The extract of the species, Eunicea clavigera (code C17Ec), presented a value of 61.3% against SiHa and 57.5% against A549. In agreement with Figure 2 and Figure 3 and using the multivariate statistical analysis, PCA and OPLS-DA, it was visualized that these two extracts presented greater separation of the group of extracts that presented cytotoxic activity for the tumor cell lines of A549 and SiHa. 2.2. Statistical Analysis Using the data matrix (12,060 features), statistical analyses were run in the MetaboAnalyst platform [ 23 ]. PCA, orthogonal projection to latent structures discriminant analysis (OPLS-DA), and correlation analyses allowed the generation of variable importance in projection (VIP) scores. Figure 2 shows the results of the multivariate PCA considering their exposure to three different tumor lines, SiHa, A549, and PC3. From the unsupervised statistical analysis method using PCA, it was possible to determine that both Eunicea clavigera and Pseudoplexaura flagellosa ( Figure 2 a,b) were the extract of the species that mainly contributed to the separation from others that did not exhibit cytotoxicity against the cell lines, SiHa and A549. Therefore, this analysis suggests that both extracts might share some metabolites responsible for the detected cytotoxicity. Additionally, it was also found that the extract of Plexaura kuekenthali ( Figure 2 a) was also included in the group of separate species because it exhibited cytotoxicity against the cell line, SiHa. The PCA analysis for the extract of this species that exhibited cytotoxicity against the PC3 cell line did not show a clear separation that allowed identification of the clusters or outliers responsible for the observed cytotoxicity as seen in Figure 2 c. For better separation between classes in the hyperspace plot and visualization of the features responsible for the discrimination between bioactive and non-bioactive extracts as cytotoxic against tumor cell lines, the statistical method, OPLS-DA, was performed ( Figure 3 ). Regarding the OPLS-DA models observed in Figure 3 b,c, a clear separation is observed between the extract of the species that presented cytotoxicity from those that did not present. Additionally, in Figure 3 a,b, it can be observed that the extract of the species, Pseudoplexaura flagellosa and Eunicea clavigera , are closely related to each other again for the models using the SiHa and A549 tumor cell lines. To infer statistically significant discrimination ( p -value ≤ 0.05) between the two classes (cytotoxic and non-cytotoxic against tumor cell lines), a cross validation test was performed for the classification model with the three tumor cell lines, where the models were evaluated using both R2 and Q2 metrics. R2 values report the total amount of variance explained by the model in both the data (R2X) and independent variables (R2Y); the Q2 reports model accuracy and the ratio, Q2/R2, is a measure of cross-validation reproducibility, when the value is above 0.5 is considered with relevant associations [ 24 ]. The results showed values of Q2/R2 greater than 0.5 for the lines, A549 and SiHa, but not when the model was made with the tumor line of PC3 (see Table 1 ). These results show that for the first two cell lines, a good classification model was obtained, indicating the reliability of the models. Considering that the statistical analysis produced unreliable results for the model established with the PC3 tumor line, the subsequent analyzes will contemplate the data derived from the models when the lines of SiHa and A549 were used. To complement the PLS-DA analyses, the molecular formula of the compounds was generated using the Agilent formula generator platform (MFG). Features that significantly contributed to clustering and discrimination were selected according to a threshold value of VIP ≥ 2.0 and a p value < 0.05 [ 25 ]. According to the VIP analysis, 110 VIP were selected; Figure 4 shows the first 15 VIP for each cell line that mainly contributed to the separation of the extracts according to their cytotoxic potential. As shown in Figure 4 , the main feature that exhibited the greatest scores (SiHa score 3.1, A549 score 4.3) was M287T644, which was found in both models and seemed to be partly responsible for the separation. Other important features were M331T601 (SiHa score 3.0, A549 score 3.5) and M331T619 (SiHa score 3.2, A549 score 3.5). 2.3. Annotation, Dereplication, and Identification of the Feature M287T644 One of the great opportunities of metabolomics studies is the potential to identify new compounds by untargeted methods. A range of “dereplication” procedures are currently emerging to meet this challenge as key strategies for the identification of already known bioactive compounds and to improve the performance of natural product screening programs [ 27 ]. Here, we use a combinatorial approach for features selection with cytotoxic potential against tumor cell lines, using metabolomics analysis to establish the chemical profiles of soft coral extracts and dereplication using the AntiMarin ® data base to obtain a putative identification of the structures. By this way, we established that the characteristic, M287T644, corresponds to m / z of 287.2374 [M + H] + consistent with the molecular formula, C 20 H 30 O, which was found in the extract of Pseudoplexaura flagellosa . Comparison with the database allowed us to propose two possible compounds for this molecular formula, eduenone [ 28 ] and dolabellatrienone [ 29 ]. To more precisely identify this feature, the MS/MS data of m / z 287.2374 [M + H] + were recorded and analyzed using the MetFrag software [ 30 ]. The possibility that this feature corresponds to any of these two compounds, eduenone with a Diff of 0.59 ppm and dolabellatrienone with a Diff of 0.57 ppm, was confirmed. Considering that this feature was detected in the models made using the two tumor cell lines as one of the main features responsible for the separation of the group that presented cytotoxic activity, we decided to isolate the feature using repetitive HPLC-UV purifications. This compound was isolated as a yellowish oil with a molecular formula of C 20 H 30 O assigned based on HRESI-MS. The NMR spectroscopic features of this compound were indicative of a dolabellane compound similar to eduenone and dolabellatrienone. Some key 1 H NMR signals allowed a quick identification of this compound: The chemical signals of the olefinic methine group in H-3 δ H 5.24, dd, J = 11.4, 5.3 Hz, (eduenone: δ H 6.30, br s; dolabellatriene: δ H 5.24, dd, J = 11.2, 5.0 Hz), one cyclic-bearing methine in H-11 δ H 2.83, d, J = 11.8 Hz, (eduenone: δ H 2.99, br d, J = 12.0 Hz; dolabellatriene: δ H 2.83, br d, J = 12.2 Hz), and one methyl group located in H-15 δ H 1.23, s, (eduenone: δ H 1.14, s; dolabellatriene: δ H 1.23, s) were all consistent with the dolabellatriene. Therefore, based on the above results and the use of 1 H- 1 H COSY and HMBC spectra, the structure of this compound was established as shown in Figure 5 , a known dolabellane diterpenoid named 13-keto-1,11-dolabell-3( E ),7( E ),12(18)-triene previously isolated from Eunicea calyculata [ 31 ]. To evaluate the cytotoxicity of the compound, 13-keto-1,11-dolabell-3(E),7(E),12(18)-triene, two tumor cell lines, A549 and SiHa, were used in the MTT assay under five different concentrations, the dolabellatrienone exhibited values of IC 50 = 0.02 µg/mL against A549 and IC 50 = 0.03 µg/mL against SiHa. 3. Discussion In the search for bioactive substances, marine organisms, such as soft corals, have led to metabolites with significant cytotoxic activities against different cancer cell lines [ 32 ]. In that way, this work established a metabolomic workflow pathway ( Figure 2 ) that allowed correlation between the cytotoxic activities of 28 crude extracts from soft corals with their chemical composition. As seen in Figure 3 , the statistical analysis, OPLS-DA, which seeks for maximal variance between the latent components, showed discrimination between the extracts that presented potential cytotoxicity against the extracts with lower cytotoxic potential. In addition, the data of the selected features were found to contribute to the separation of the extracts that presented cytotoxic potential and was found to be in common for the two models that presented a significant statistical difference (SiHa and A549), as shown in Figure 4 . Considering this, it was decided to isolate the compound that corresponds to this feature from the extract identified as Pseudoplexaura flagellosa . This compound was identified by NMR and HRESI-MS analysis as 13-keto-1,11-dolabell-3( E ),7( E ),12(18)-triene C 20 H 30 O, m / z 287.2374 [M + H] + , a dolabellane compound previously isolated from Eunicea calyculata by Look and Fenical 1982 [ 31 ]. According with these metabolomics results, it is important to show some studies on compounds with dolabellane skeletons obtained from different marine organisms, which have shown cytotoxic potential against different tumor cell lines, scilicet: The compound, clavirolide G, isolated from the soft coral, Clavularia viridis , collected from the Xisha Islands in the South China Sea showed moderate cytotoxic activity against KB and HL-60 cells with IC 50 values of 5.12 μg/mL and 5.92 μg/mL, respectively [ 33 ]. The compounds, clavinflols A and B, from the Clavularia inflata collected in Green Island, exhibited cytotoxicity against human oral epidermoid carcinoma (KB) cells (ED 50 = 0.35 μg/mL) and showed selective activity towards human Hepa cells (ED 50 = 1.2 µg/mL), respectively [ 34 ]. The compound, casearimene A, isolated from the species, Casearia membranacea , showed marginal activity against the tumor cell line, A549 (ED 50 > 50 µg/mL) [ 35 ]. Also, five cytotoxic dolabellane diterpenes isolated in 2001 by Chang et al. from the Formosan soft coral, Clavularia inflata , showed moderate cytotoxicity against the A549 tumor cell line (ED 50 = 7.74 to 50 μg/mL). Additionally, the compound, 7-hydroperoxydolabella-4(16),8(17),11(12)-triene-3,13-dione, was the most promising (ED 50 = 0.57 μg/mL) [ 36 ]. The above studies demonstrated that diterpenes with a dolabellane skeleton have presented low and moderate cytotoxic activities against different tumor cell lines, as was presented against the tumor cell line, A549, which agrees with the results obtained in this research in which the compound, dolabellatrienone, exhibited values of IC 50 = 0.02 μg/mL against A549, IC 50 = 0.03 μg/mL against SiHa, and IC 50 = 64.95 μg/mL against L929. Finally, the main prospective application of this fingerprint metabolomic analysis in soft corals was aimed at the identification of potential metabolites with cytotoxic activity against cancer cell lines. This kind of metabolomic process can be useful in a several studies, mainly those that are time consuming, such as traditional bioprospecting of marine natural products; this takes around 1 to 3 years (depending on the sample and the metabolites), while the workflow established in this investigation took around four to six months to predict the presence and the identification of biologically active compounds (VIP) from soft coral extracts. 4. Materials and Methods 4.1. Materials Solvents used for extraction, methanol, and dichloromethane were purchased from Merck (Darmstadt, Germany). For the chromatographic and spectrometric analysis, Acetonitrile, methanol, and formic acid of LC-MS were purchased from Sigma Aldrich (Dublin, Ireland). For use in cell culture, D-MEM (Dulbecco’s Modified Eagle Medium) (1X) and RPMI 1640 (Roswell Park Memorial Institute, Darmstadt, Germany were made by Gibco / Invitrogen, Paisley, UK. Fetal bovine serum (FBS), brand Eurobio (Les Ulis, France). Trypticase soy broth (TSB) and trypticase soy agar (TSA) brand Scharlau Co (Barcelona, Spain), PC3 cell line (prostate cancer), extracted from prostatic adenocarcinoma of a Caucasian man (ATCC ® CRL1435™), SiHa cancer cervical cell line (ATCC ® HTB-35™), and A549 cancer lung cell line (ATCC ® CCL-185™), and L929 fibroblast (ATCC ® CCL-1 TM ). 4.2. Methods 4.2.1. Soft Coral Material Collection and Identification Twenty-eight samples of soft corals ( Supplementary Table S1 ) were collected at Santa Marta Bay, Colombia, in Punta Venado (N = 11° 16.26′ 87′′; W = 74° 12.24′ 58′′) at depths between 10 to 20 m. Small terminal fragments (of approximately 30 cm) were cut off the main soft coral colony with sharp scissors. Samples were air dried and then kept frozen until the moment of extraction at −80 °C. Soft corals were identified by morphological and sclerite analyses [ 37 , 38 , 39 ]. For sclerite preparations, a small distal fragment of each sample was treated with 5% sodium hypochlorite. Once the organic matter was removed, sclerites were washed with distilled water and centrifuged at least four times. A final wash with ethanol followed by oven drying yielded sclerite preparations. Analysis of the sclerites was performed by microscopy [ 39 , 40 ]. Vouchers of all samples are stored at the Invertebrate collection of Instituto de Ciencias Naturales at Universidad Nacional de Colombia (Bogotá, Colombia) ( Supplementary Table S1 ). 4.2.2. General Experimental Procedures UV measurements were obtained by the extraction of the diode array detector (DAD) signal in a PerkinElmer HPLC-DAD-ELSD FLEXAR LC(r) SYSTEM. High-resolution mass spectra (HRESIMS) were obtained with an Agilent 6540 mass spectrometer. Compound purification was carried out in a JASCO HPLC equipment, supplied with a PU4087 pump and a UV4070 UV/Vis detector using a preparative Phenyl-Hexyl OBD Column. 4.2.3. Soft Coral Extraction, Sample Preparation, and UPLC/MS Analyses The data acquisition was performed in an Agilent 6540 that generated a mass spectra zip file of 596 megabytes. Then, all data was preprocessed using the platform, Galaxy, which allows the automation of pipelines, ensuring reproducibility [ 20 ]. Afterwards, 1.0 g of dried powder from each soft coral was extracted at room temperature with a mixture of 1:1 DCM/MeOH, three times (30 mL) using an ultrasonic bath for 20 min. Debris were removed by centrifugation two times at 12,000× g for 5 min. Solvents were evaporated and dried extracts were passed through a C18 cartridge, eluting with MeOH to remove salts. Subsequently, the extracts were concentrated. The samples corresponding to the specie, Pseudoplexaura flagellosa (Gra 17) (one responsible for the separation according to OPLS-DA analysis), was purified by preparative RP-HPLC with a Phenyl-Hexyl OBD Column (XSelect CSH, 19 mm × 250 mm, 5 µm) and the optimization of gradient profiles was performed by selecting the mobile phase used for HPLC UV detection at λ 254 nm during 40 min. of acquisition time. Elution was done using water (A) and acetonitrile (B), both containing 0.1% formic acid with a gradient elution of 20%–50% B over 20 min, 50%–80% B over 10 min, 80%–100% B in 1 min, and holding for 5 min. 4.2.4. Metabolomic Procedure All samples used for metabolomics studies were analyzed using an Agilent 6540 mass spectrometer, which performs MS acquisition ( m / z 300–3000) at 10 spectra/sec in high resolution mode at a resolution of 35,000 and mass accuracy of 1 ppm. Electrospray Ionization (ESI) in positive and negative mode was used to ionize and detect compounds after chromatographic separations. General parameters of the MS1 mode source were gas flow of 12 L min −1 , gas temperature of 300 °C, voltage charge of 2000 V, fragmentor of 150 V, capillary voltage of 3500 V, nebulizer pressure of 30 psi, and octopole RF Peak of 700 V. The QC samples were analyzed intermittently during the analytical studies to assess the variance observed in the data. Chromatographic separation was achieved using a Phenyl-Hexyl HPLC column (150 mm × 3.0 mm, 1.9 µm Poroshell, Agilent Technologies, Santa Clara, CA, USA). The mobile phase consisted of (A) water with 0.1% formic acid to improve ionization and (B) methanol (MeOH) with 0.1% formic acid. The UPLC injection volume on each run was 1.0 μL. The UPLC run contained blanks. QC samples and pooled samples [ 41 ] were intercalated throughout the UPLC run to control for any acquisition-dependent variation. Samples were filtered using a 0.2 µm Whatman ® membrane filter with a pore size of 0.2 μm (Merck, Germany) prior to injection. Data were analyzed using the Agilent MassHunter Qualitative software (Version B.07.00). For formula generation, the Molecular Formula Generator algorithm (MFG) was used, which can automatically eliminate unlikely candidate compounds and rank the putative molecular formula according to their mass deviation, isotopic pattern accuracy, and elemental composition. 4.2.5. Statistical Analyses When analyzing large data sets from different samples, data variability can become a relevant complication: Hence, it might be to judge the quality of the data and assess their analytical variance. Hence, the use of a quality control (QC) allowed the minimization of this variability [ 42 ]. The QC samples contain the average of all metabolites within all the samples that were analyzed (0.1 µL of each octocoral extract was placed in a 1 mL vial), which were homogenized before the injection. QC samples were analyzed intermittently for the duration of the analytical study to assess the variance observed in the data throughout the sample preparation, data acquisition, and data pre-processing. Replicate injections should provide identical data for each injection, however, analytical variance is observed. Replicate QC injections can be used to measure this variance throughout the analytical study. We used a PCA to quickly assess the reproducibility of QC samples in an analytical run, and to determine the variance of the metabolite feature [ 43 ], pools were used and QC samples greater than 30% standard deviation were removed from the dataset [ 44 ]. An exploratory data analysis was first performed using PCA ( Supplementary Figure S1 ). Additionally, the obtained signals from the blank were considered as interference and were subtracted (sn threshold = 3) [ 45 ]. For an untargeted approach, UPLC-MS chromatograms in negative and positive ion mode were pre-treated using an open source, platform independent software called Galaxy [ 20 ]. With this software, it was possible to exclude noise from LC-MS profiles (Noise level 5.0 E3, all data points below this intensity level were ignored). Parameters for data processing included the centwave method, 15 ppm, mzwid 0.015, and minfrac 0.3. After exporting the processed data in tabular format (.cvs file), further analysis of the data matrix was performed by MetaboAnalyst version 3.0 [ 23 ]. After PCA analyses, a PLS-DA (partial least square-discriminant analysis) and OPLS-DA (orthogonal partial least-squares-discriminant analysis) were performed with MetaboAnalyst software. OPLS-DA is a powerful tool for the analysis of qualitative data structures, while the prediction results are equivalent to classification using standard PLS-DA [ 19 ]. The PLS approach is a robust regression technique used for investigations of the relationship between two data sets. In this experiment, a discriminant classification was carried out using a PLS-DA based on the PLS algorithm, in which the discriminating variable was the cytotoxic activity. The combined application of PCA and OPLS-DA to spectral datasets yields valuable insights on both general spectral trends (PCA) and group-predictive spectral features (PLS) [ 46 ]. 4.2.6. Cytotoxicity Assays Cell lines, human cervical cancer SiHa, human lung adenocarcinoma A549, human prostatic carcinoma PC3 and L929 fibroblasts, which was used as non-tumor cell line for toxicity control, were cultured in DMEM and RPMI 1640 media supplemented with 10% heat-inactivated fetal bovine serum (FBS) and penicillin-streptomycin (1%), at 37 °C in a 5% CO 2 humidified atmosphere, until 100% confluence was achieved [ 47 ]. The in vitro cytotoxicity of the soft corals extracts was evaluated using the MTT method, which is a colorimetric assay based on the capacity of mitochondrial succinate dehydrogenase enzymes in live cells to reduce the yellow, water-soluble substrate, 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), into an insoluble, colored formazan product, which is measured spectrophotometrically following Mosmann [ 48 ] with modifications proposed by Denizot and Lang [ 49 ]. Cells were allowed to attach in 96-well plates (4.0 × 10 4 cells/well) during 24 h. After 24 h, the medium was replaced with the extracts to be tested resuspended in DMSO (at a concentration of 2 mg/mL). Soft coral extracts were evaluated at a concentration of 20 µg/mL. The greatest DMSO concentration was 0.1%, which was not cytotoxic to any of the cell lines. Prior to the assay, the supernatant was removed and 100 μL of 12 mM MTT solution in sterile PBS was added to each well and incubated at 37 °C for 4 h. The solution was removed, and extracts in dimethyl sulfoxide (DMSO) were added to each well, followed by incubation at 37 °C for 15 min. Optical density at 595 nm was read in an iMarkTM Microplate Reader. Cells cultured without extracts and doxorubicin were used as controls [ 50 , 51 ]. All tests were performed in triplicate. The viability percentage was calculated with Equation (1) and the cell inhibition was calculated with Equation (2) [ 32 ]. (1) where Abs sample is the absorbance of the cells treated with the test extract and Abs control is the absorbance of cells not treated with the test extract. (2) Extract toxicity is demonstrated by the inhibition of cell growth and division. 4.2.7. Structure Elucidation Fraction SP-9 obtained from the extract of Pseudoplexaura flagellosa (Gra17) was purified and then analyzed by LC–MS to establish the m / z of this purified fraction, yielding a ( m / z of 287.2373). NMR spectra were acquired in an Agilent 600 MHz spectrometer equipped with a cryoprobe with pulse field gradient, and signals were referenced in ppm to the residual solvent signals (CDCl3 at 7.26 ppm, TMS at 0.00 ppm) ( Table S3 , NMR data of feature M287T644). 5. Conclusions In this work, metabolomics tools were successfully applied to compare the metabolomic profile of 28 extracts of soft corals. Data analyses using PCA, PLS-DA, and OPLS-DA were valuable to determine and highlight the potential cytotoxic metabolites from soft corals extracts. The Feature M287T644 was found as VIP in some extracts tested against SiHa and A549 cancer cell lines. Additionally, a dereplication process was important to putatively identify compounds suggested by statistical analyses as the main features explaining potential cytotoxicity in the tested extracts. The workflow established in this work led to the identification of the compounds 13-keto-1,11-dolabell-3( E ),7( E ),12(18)-triene as the main feature responsible for the separation of extracts with major cytotoxic potential, IC = 0.02 μg/mL against A549 and IC 50 = 0.03 μg/mL against SiHa cancer cell lines, being in agreement with that reported in the literature for dolabellane type compounds. Additionally, as shown in Table S2 , the G17 extract ( Pseudoplexaura flagellosa ) showed cytotoxic activity against the SiHa and A549 cell lines and was also cytotoxic against L929; however, the metabolite (VIP), C 20 H 30 O (13-keto-1,11-dolabell-3(E),7(E),12(18)-triene), isolated from this extract, which was the most responsible for the separation of the extracts of the soft corals that were classified as cytotoxic, did not reveal cytotoxicity against the normal cell line, L929, but presented moderate cytotoxicity against the cell line, A549. The application of this fingerprint metabolomic analysis in soft corals was aimed at identifying potential metabolites with cytotoxic activity against tumor cell lines. This approach can be useful in several studies, like traditional bioprospecting of marine natural products, which are time consuming. In that way, the workflow established in this investigation allows the prediction of the presence of biologically active compounds from soft coral extracts in short periods of times. Supplementary Materials The following are available online at https://www.mdpi.com/1660-3397/17/1/37/s1 , Figure S1: Principal component analysis (PCA); in the triangle the pools (QC) are shown. Table S1: Name of species of soft corals used in this research a Collection Code (ICN), assigned by Collection of the Institute of Natural Sciences of the National University of Colombia, (Bogotá, Colombia). Table S2: Percentage of cytotoxic activity against three cancerous cell lines. (1 if it is above 50% 0 if it is below). Table S3: Scrip using Galaxy software to UPLC-MS data extraction. Author Contributions L.S., O.P.T., C.D. and E.T. conceived and designed the experiments; L.S., M.P. and E.T. collected the biological material; M.P. identified the soft corals, L.S. and E.T. performed the chemical experiments; L.S. analyzed the data; L.S. and E.T. wrote the article; L.S., M.P., O.P.T. and E.T. edited and reviewed the article. All the authors have contributed to and approved the final manuscript. Funding Doctoral studies of L.S. were supported by grants by Colciencias Beca de Doctorado Nacional 647/2014 and Universidad de la Sabana. Universidad de la Sabana supported the Project INGPHD-5-2015 “Bioprospección de octocorales del Caribe Colombiano, como una fuente potencial de compuestos con actividad citotóxica”. Part of this project (Grant-Aid Agreement No.PBA/MB/16/01) was carried out with the support of the Marine Institute and was funded under the Marine Research Programme supported the Irish Government. Sergio Zapata Lopera from UTADEO, provided great help in obtaining, processing and measuring soft coral sclerites for soft coral identification purposes. Acknowledgments The authors acknowledge the Universidad de La Sabana for support towards the cytotoxic bioassays and Galway University towards NMR and MS equipment. We also thank Invertebrate collection of Instituto de Ciencias Naturales at Universidad Nacional de Colombia (Bogotá, Colombia) for curation of the octocoral samples and coded assigned. E.T. and L.S. would like to acknowledge L.D., D.X.H. and C.R. for the support in this project. Conflicts of Interest The authors declare no conflict of interest. References Blunt, J.; Copp, B.; Keyzers, R.; Munro, M.; Prinsep, M. Marine natural products. Nat. Prod. Rep. 2012 , 29 , 144–222. [ Google Scholar ] [ CrossRef ] [ PubMed ] Jiménez, J.; Marfil, A.; Francesch, C.; Cuevas, M.; Alvarez, A.; Albericio, F. Productos naturales de origen marino. Investig. Cienc. 2007 , 365 , 75–83. [ Google Scholar ] Dyshlovoy, S.; Honecker, F. Marine Compounds and Cancer: 2017 Updates. Mar. Drugs 2018 , 16 , 41. [ Google Scholar ] [ CrossRef ] [ PubMed ] Ruiz Torres, V.; Encinar, J.A.; Herranz López, M.; Pérez Sánchez, A.; Galiano, V.; Barrajón Catalán, E.; Micol, V. An updated review on marine anticancer compounds: The use of virtual screening for the discovery of small-molecule cancer drugs. Molecules 2017 , 22 , 1037. [ Google Scholar ] [ CrossRef ] [ PubMed ] Bennett, D. Growing Pains for Metabolomics. Scientist 2005 , 19 , 25–28. [ Google Scholar ] [ CrossRef ] Ojima, I.; Chakravarty, S.; Inoue, T.; Lin, S.; He, L.; Horwitz, S.B.; Kuduk, S.D.; Danishefsky, S.J. A common pharmacophore for cytotoxic natural products that stabilize microtubules. Proc. Natl. Acad. Sci. USA 1999 , 96 , 4256–4261. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Correa, H.; Valenzuela, A.L.; Ospina, L.F.; Duque, C. Anti-inflammatory effects of the gorgonian Pseudopterogorgia elisabethae collected at the Islands of Providencia and San Andrés (SW Caribbean). J. Inflamm. 2009 , 6 , 5. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Correa, H.; Aristizabal, F.; Duque, C.; Kerr, R. Cytotoxic and antimicrobial activity of pseudopterosins and seco-pseudopterosins isolated from the octocoral Pseudopterogorgia elisabethae of San Andrés and Providencia Islands (Southwest Caribbean Sea). Mar. Drugs 2011 , 9 , 334–343. [ Google Scholar ] [ CrossRef ] [ PubMed ] Correa, H. Estudios de Bioprospección del coral blando Pseudopterogorgia Elisabethae como Fuente de Sustancias con Actividad Biológica Fase IV. Ph.D. Thesis, National University of Colombia, Bogotá, Colombia, 2012. [ Google Scholar ] Marrero, J.; Rodríguez, A.D.; Baran, P.; Raptis, R.G. Ciereszkolide: Isolation and structure characterization of a novel rearranged cembrane from the caribbean sea plume Pseudopterogorgia kallos . Eur. J. Org. Chem. 2004 , 3909–3912. [ Google Scholar ] [ CrossRef ] Look, S.A.; Fenical, W.; Jacobst, R.S.; Clardyt, J.O.N. The pseudopterosins: Anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae . Proc. Natl. Acad. Sci. USA 1986 , 83 , 6238–6240. [ Google Scholar ] [ CrossRef ] [ PubMed ] Deng, L.; Gu, H.; Zhu, J.; Nagana Gowda, G.A.; Djukovic, D.; Chiorean, E.G.; Raftery, D. Combining NMR and LC/MS using backward variable elimination: Metabolomics analysis of colorectal cancer, polyps, and healthy controls. Anal. Chem. 2016 , 88 , 7975–7983. [ Google Scholar ] [ CrossRef ] [ PubMed ] Lindon, J.C.; Holmes, E.; Bollard, M.E.; Stanley, E.G.; Nicholson, J.K. Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis. Biomarkers 2004 , 9 , 1–31. [ Google Scholar ] [ CrossRef ] [ PubMed ] Tistaert, C.; Chataigné, G.; Dejaegher, B.; Rivière, C.; Hoai, N.N.; Van, M.C.; Quetin-leclercq, J.; Heyden, Y. Vander Multivariate data analysis to evaluate the fingerprint peaks responsible for the cytotoxic activity of Mallotus species. J. Chromatogr. B 2012 , 910 , 103–113. [ Google Scholar ] [ CrossRef ] [ PubMed ] Leal, M.C.; Madeira, C.; Brandão, C.A.; Puga, J.; Calado, R. Bioprospecting of marine invertebrates for new natural products—A chemical and zoogeographical perspective. Molecules 2012 , 17 , 9842–9854. [ Google Scholar ] [ CrossRef ] [ PubMed ] Wei, X.; Rodríguez, A.D.; Baran, P.; Raptis, R.G. Dolabellane-type diterpenoids with antiprotozoan activity from a southwestern Caribbean gorgonian octocoral of the genus Eunicea . J. Nat. Prod. 2010 , 73 , 925–934. [ Google Scholar ] [ CrossRef ] [ PubMed ] Maille, G.; Qin, C.; Siuzdak, G. Nonlinear Data Alignment for UPLC—MS and HPLC—MS Based Metabolomics: Quantitative Analysis of Endogenous and Exogenous Metabolites in Human Serum. Anal. Chem. 2006 , 78 , 3289–3295. [ Google Scholar ] [ CrossRef ] Szymanska, E.; Saccenti, E.; Smilde, A.K.; Westerhuis, J.A. Double-check: Validation of diagnostic statistics for PLS-DA models in metabolomics studies. Metabolomics 2012 , 14 . [ Google Scholar ] [ CrossRef ] [ PubMed ] Rantalainen, M.; Cloarec, O.; Nicholson, J.K.; Holmes, E.; Trygg, J. OPLS discriminant analysis: Combining the strengths of PLS-DA and SIMCA classification. J. Chemiometr. 2006 , 20 , 341–351. [ Google Scholar ] [ CrossRef ] Goecks, J.; Nekrutenko, A.; Taylor, J.; Afgan, E.; Ananda, G.; Baker, D.; Blankenberg, D.; Chakrabarty, R.; Coraor, N.; Goecks, J.; et al. Galaxy: A comprehensive approach for supporting accessible, reproducible and transparent computational research in the life sciences. Genome Biol. 2010 , 11 , 13. [ Google Scholar ] [ CrossRef ] Haug, K.; Salek, R.M.; Conesa, P.; Hastings, J.; De Matos, P.; Rijnbeek, M.; Mahendraker, T.; Williams, M.; Neumann, S.; Rocca-Serra, P.; et al. MetaboLights—An open-access general-purpose repository for metabolomics studies and associated meta-data. Nucleic Acids Res. 2013 , 41 , 781–786. [ Google Scholar ] [ CrossRef ] Hostettman, K. Methods in Plant Biochemistry. Assays for Bioactivity ; Academic Press: London, UK, 1991. [ Google Scholar ] Xia, J.; Psychogios, N.; Young, N.; Wishart, D.S. MetaboAnalyst: A web server for metabolomic data analysis and interpretation. Nucleic Acids Res. 2009 , 37 , 652–660. [ Google Scholar ] [ CrossRef ] [ PubMed ] Moltu, S.J.; Sachse, D.; Blakstad, E.W.; Strømmen, K.; Nakstad, B.; Almaas, A.N.; Westerberg, A.C.; Rønnestad, A.; Brække, K.; Veierød, M.B.; et al. Urinary metabolite profiles in premature infants show early postnatal metabolic adaptation and maturation. Nutrients 2014 , 6 , 1913–1930. [ Google Scholar ] [ CrossRef ] [ PubMed ] Chiu, C.Y.; Yeh, K.W.; Lin, G.; Chiang, M.H.; Yang, S.C.; Chao, W.J.; Yao, T.C.; Tsai, M.H.; Hua, M.C.; Liao, S.L.; et al. Metabolomics reveals dynamic metabolic changes associated with age in early childhood. PLoS ONE 2016 , 11 , e0149823. [ Google Scholar ] [ CrossRef ] [ PubMed ] Xia, J.; Sinelnikov, I.V.; Han, B.; Wishart, D.S. MetaboAnalyst 3.0—Making metabolomics more meaningful. Nucleic Acids Res. 2015 , 43 , W251–W257. [ Google Scholar ] [ CrossRef ] [ PubMed ] Hubert, J.; Nuzillard, J.M.; Renault, J.H. Dereplication strategies in natural product research: How many tools and methodologies behind the same concept? Phytochem. Rev. 2017 , 16 , 55–95. [ Google Scholar ] [ CrossRef ] National Center for Biotechnology Information Eduenone. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/10424127 (accessed on 25 September 2018). National Center for Biotechnology Information Dolabellatrienone. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/10469260 (accessed on 25 September 2018). Wolf, S.; Schmidt, S.; Müller Hannemann, M.; Neumann, S. In silico fragmentation for computer assisted identification of metabolite mass spectra. BMC Bioinform. 2010 , 1 , 43. [ Google Scholar ] [ CrossRef ] Look, S.A.; Fenical, W. New Bicyclic Diterpenoids from the Caribbean Gorgonian Octocoral Eunicea calyculata. J. Org. Chem. 1982 , 47 , 4129–4134. [ Google Scholar ] [ CrossRef ] Patel, S.; Gheewala, N.; Suthar, A.; Shah, A. In-Vitro cytotoxicity activity of Solanum Nigrum extract against Hela cell line and Vero cell line. Int. J. Pharm. Pharm. Sci. 2009 , 1 , 38–47. [ Google Scholar ] Gao, Y.; Xiao, W.; Liu, H.C.; Wang, J.R.; Yao, L.G.; Ouyang, P.K.; Wang, D.C.; Guo, Y.W. Clavirolide G, a new rare dolabellane-type diterpenoid from the Xisha soft coral Clavularia viridis . Chin. Chem. Lett. 2017 , 28 , 905–908. [ Google Scholar ] [ CrossRef ] Shen, Y.C.; Pan, Y.L.; Ko, C.L.; Kuo, Y.H.; Chen, C.Y. New dolabellanes from the Taiwanese soft coral clavularia inflata. J. Chin. Chem. Soc. 2003 , 50 , 471–476. [ Google Scholar ] [ CrossRef ] Chang, K.C.; Duh, C.Y.; Chen, I.S.; Tsai, I.L. A cytotoxic butenolide, two new dolabellane diterpenoids, a chroman and a benzoquinol derivative formosan Casearia membranacea . Planta Med. 2003 , 69 , 667–672. [ Google Scholar ] [ CrossRef ] [ PubMed ] Duh, C.Y.; Chia, M.C.; Wang, S.K.; Chen, H.J.; El-Gamal, A.A.H.; Dai, C.F. Cytotoxic dolabellane diterpenes from the Formosan soft coral Clavularia inflata . J. Nat. Prod. 2001 , 64 , 1028–1031. [ Google Scholar ] [ CrossRef ] [ PubMed ] Frederickm, M. Bayer the Shallow-Water Octocorallia of the West Indian Region: A Manual for Marine Biologists ; Smithsonian Institution: Washington, DC, USA, 1988. [ Google Scholar ] Sánchez, J.A.; Wirshing, H.H. A field key to the identification of tropical western Atlantic zooxanthellate octocorals (Octocorallia: Cnidaria). Caribb. J. Sci. 2005 , 41 , 508–522. [ Google Scholar ] Sánchez, J.A. Sistemática Filogenética del Género Eunicea Lamouroux, 1816 (Octocorallia: Gorgonacea: Plexauridae) con Aspectos Sobre la Historia Natural de Algunas Especies en el Caribe Colombiano. Master’s Thesis, Universidad Nacional de Colombia, Bogotá, Colombia, 1998. [ Google Scholar ] Sánchez, J.A.; Lasker, H.R. Patterns of morphological integration in marine modular organisms: Supra-module organization in branching octocoral colonies. R. Soc. 2003 , 270 , 2039–2044. [ Google Scholar ] [ CrossRef ] [ PubMed ] Sangster, T.; Major, H.; Plumb, R.; Wilson, A.; Wilson, I. A pragmatic and readily implemented quality control strategy for HPLC-MS and GC-MS-based metabonomic analysis. Analyst 2006 , 131 , 1075. [ Google Scholar ] [ CrossRef ] Godzien, J.; Alonso-Herranz, V.; Barbas, C.; Armitage, E.G. Controlling the quality of metabolomics data: New strategies to get the best out of the QC sample. Metabolomics 2015 , 11 , 518–528. [ Google Scholar ] [ CrossRef ] Dunn, W.; Broadhurst, D.; Edison, A.; Guillou, C.; Viant, M.; Bearden, D.; Beger, R. Quality assurance and quality control processes: Summary of a metabolomics community questionnaire. Metabolomics 2017 , 13 , 6. [ Google Scholar ] [ CrossRef ] Gorrochategui, E.; Jaumot, J.; Lacorte, S.; Tauler, R. Data analysis strategies for targeted and untargeted LC-MS metabolomic studies: Overview and workflow. TrAC Trends Anal. Chem. 2016 , 82 , 425–442. [ Google Scholar ] [ CrossRef ] Brown, M.; Dunn, W.B.; Dobson, P.; Patel, Y.; Winder, C.L.; Francis-McIntyre, S.; Begley, P.; Carroll, K.; Broadhurst, D.; Tseng, A.; et al. Mass spectrometry tools and metabolite-specific databases for molecular identification in metabolomics. Analyst 2009 , 134 , 1322. [ Google Scholar ] [ CrossRef ] Gromski, P.S.; Muhamadali, H.; Ellis, D.I.; Xu, Y.; Correa, E.; Turner, M.L.; Goodacre, R. A tutorial review: Metabolomics and partial least squares-discriminant análisis—A marriage of convenience or a shotgun wedding. Anal. Chim. Acta 2015 , 879 , 10–23. [ Google Scholar ] [ CrossRef ] Iwagawa, T.; Hashimoto, K.; Yokogawa, Y.; Okamura, H.; Nakatani, M.; Doe, M.; Morimoto, Y.; Takemura, K. Cytotoxic biscembranes from the soft coral Sarcophyton glaucum . J. Nat. Prod. 2009 , 72 , 946–949. [ Google Scholar ] [ CrossRef ] [ PubMed ] Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983 , 65 , 55–63. [ Google Scholar ] [ CrossRef ] Denizot, F.; Lang, R. Rapid colorimetric assay for cell growth and survival. J. Immunol. Methods 1986 , 89 , 271–277. [ Google Scholar ] [ CrossRef ] Al-Ghamdi, S.S. Time and dose dependent study of doxorubicin induced DU-145 cytotoxicity. Drug Metab. Lett. 2008 , 2 , 47–50. [ Google Scholar ] [ CrossRef ] [ PubMed ] Shaikh, K.S.; Pawar, A.; Aphale, S.R.; Moghe, A.S. Effect of vesicular encapsulation on in-vitro cytotoxicity of ciclopirox olamine. Int. J. Drug Deliv. 2012 , 4 , 139–146. [ Google Scholar ] [ CrossRef ] Figure 1. Metabolomic workflow pathway for 28 soft coral extracts. Data were processed with the Galaxy 4.0 software [ 20 ]. Metabolomic workflow included baseline correction, noise filtering, peak detection, peak alignment, normalization, deconvolution, and deisotoping. Figure 1. Metabolomic workflow pathway for 28 soft coral extracts. Data were processed with the Galaxy 4.0 software [ 20 ]. Metabolomic workflow included baseline correction, noise filtering, peak detection, peak alignment, normalization, deconvolution, and deisotoping. Figure 2. Principal component analysis score plot of metabolomics data from 28 extracts based on their cytotoxicity against three different cancer cell lines: ( a ) Human cervical cancer, SiHa, ( b ) human lung adenocarcinoma, A549, and ( c ) human prostatic carcinoma, PC3. Red dots indicate active extracts, and green dots represent extracts that were not active. An extract was considered active if it exhibited an inhibition of the tumor cell lines ≥50% at 20 μg/mL) [ 22 ]. The ellipses indicate confidence intervals of 95%. Figure 2. Principal component analysis score plot of metabolomics data from 28 extracts based on their cytotoxicity against three different cancer cell lines: ( a ) Human cervical cancer, SiHa, ( b ) human lung adenocarcinoma, A549, and ( c ) human prostatic carcinoma, PC3. Red dots indicate active extracts, and green dots represent extracts that were not active. An extract was considered active if it exhibited an inhibition of the tumor cell lines ≥50% at 20 μg/mL) [ 22 ]. The ellipses indicate confidence intervals of 95%. Figure 3. Supervised statistical analysis OPLS-DA score plots of metabolomic data of 28 soft coral extracts based on their cytotoxicity against three different cancer cell lines: ( a ) Human cervical cancer, SiHa, ( b ) human lung adenocarcinoma, A549, and ( c ) human prostatic carcinoma, PC3. Red dots indicate active extracts, and green dots represent extracts that were not active. An extract was considered active if it exhibited an inhibition of the tumor cell lines ≥ 50% at 20 μg/mL mL) [ 22 ]. The ellipses indicate confidence intervals of 95%. Figure 3. Supervised statistical analysis OPLS-DA score plots of metabolomic data of 28 soft coral extracts based on their cytotoxicity against three different cancer cell lines: ( a ) Human cervical cancer, SiHa, ( b ) human lung adenocarcinoma, A549, and ( c ) human prostatic carcinoma, PC3. Red dots indicate active extracts, and green dots represent extracts that were not active. An extract was considered active if it exhibited an inhibition of the tumor cell lines ≥ 50% at 20 μg/mL mL) [ 22 ]. The ellipses indicate confidence intervals of 95%. Figure 4. Results of the variable influence on projection (VIP) analyses to determine molecular features that contributed to extract clustering and discrimination in PLS-DA models against two cancer cell lines. Features were selected according to a threshold value of VIP ≥2.0 and a p value <0.05. The figures present the first 15 and most important features [ 26 ]. ( a ) SiHa; ( b ) A549. Figure 4. Results of the variable influence on projection (VIP) analyses to determine molecular features that contributed to extract clustering and discrimination in PLS-DA models against two cancer cell lines. Features were selected according to a threshold value of VIP ≥2.0 and a p value <0.05. The figures present the first 15 and most important features [ 26 ]. ( a ) SiHa; ( b ) A549. Figure 5. ( a ) MS spectrum of feature M287T644, isolated from the extract of Pseudoplexaura flagellosa ( b ) MS/MS spectrum of compound m / z : 287.2374 [M + H] + . ( c ). 1 H NMR spectrum of 13-keto-1,11-dolabell-3(E),7(E),12(18)-triene and chemical structure of C 20 H 30 O. Figure 5. ( a ) MS spectrum of feature M287T644, isolated from the extract of Pseudoplexaura flagellosa ( b ) MS/MS spectrum of compound m / z : 287.2374 [M + H] + . ( c ). 1 H NMR spectrum of 13-keto-1,11-dolabell-3(E),7(E),12(18)-triene and chemical structure of C 20 H 30 O. Table 1. Partial least squares-discriminant analysis (PLS-DA) parameters and permutation test for distinguishing between cytotoxic and non-cytototoxic groups from 28 extracts of soft corals tested against three cancer cell lines: SiHa: Human cervical cancer, A549: Human lung adenocarcinoma, PC3: Human prostatic carcinoma. Table 1. Partial least squares-discriminant analysis (PLS-DA) parameters and permutation test for distinguishing between cytotoxic and non-cytototoxic groups from 28 extracts of soft corals tested against three cancer cell lines: SiHa: Human cervical cancer, A549: Human lung adenocarcinoma, PC3: Human prostatic carcinoma. Parameters based on Q2 indicate the best classifier of PLS-DA analyses using a 10-fold cross-validation method. PLS-DA: partial least squares-discriminant analysis, Q2: predictive capability, R2: correlation coefficients.
https://www.mdpi.com/1660-3397/17/1/37
Browsing CEIG12 by Title Browsing CEIG12 by Title Management of 3D Geometry on Portable Devices  The mobile devices has evolutioned quickly in the recent years. The Games industry realized the great potential of these devices and made many developments whose requirements makes devices reach their hardware limits so ... Method of 3D Reconstruction using Silhouettes  Villen, J. D. Gomez ( The Eurographics Association , 2012 ) The present work has the aim of obtain the 3D model of simple objects by means of computer vision techniques. The method employed photographs taken around the object, then the silhouette is extracted and it is used to ... Modular Design of Graph Theory Based Software for Scientific Applications and Education  Sampedro, Frederic ; Puig, Anna ; Benseny, Antoni ( The Eurographics Association , 2012 ) This work describes a new software design approach in graph theory applications. Sometimes, while using or teaching applications related to this subject, one of the main drawbacks is to define the application-specific graph ... More Stable SPH-based Fluid Simulation  Perea, Juan J. ; Cordero, Juan M. ( The Eurographics Association , 2012 ) The simulation of fluid is a field largely discussed, from the viewpoint of engineering, in the so-called computational fluid dynamics (CFD). A problem that occurs repeatedly in the literature of CFD is the stability of ... Multi-resolution Myocardial Architecture Study  Poveda, F. ; Gil, D. ; Gurgui, T. ; Marti, E. ( The Eurographics Association , 2012 ) Myocardial complexity has lead to vivid controversy in the interpretation of the cardiac form and function over the years. This complexity has not been clarified yet even with the most recent computational reconstructions ... A New Approach to Explore Integral Field Spectroscopy Data  Romo, Celia ; Torres, Juan Carlos ; León, Alejandro J. ; Pérez, E. ( The Eurographics Association , 2012 ) Integral field spectroscopy (IFS) is a technique that is widely used in astronomy. It gives simultaneously the spectra of each spatial sampling element of a given field, generating a large amount of information that is ... Non-rigid 3D Faces Registration using Geodesic Distance Maps  Gurguí, T. ; Poveda, F. ; Martí, E. ( The Eurographics Association , 2012 ) 3D facial mesh registration is a key step in 3D facial analisys. This process calculates a mapping between faces in order to put in correspondence each point of both faces. In this poster we introduce a new approach for ... Point Cloud Visualization from Large-range Scanner in Android Devices  Pamos, Miguel Á. ; Segura, Rafael ( The Eurographics Association , 2012 ) In this work, we introduce a study of how to render a cloud of points extracted from a scanner based on LIDAR technology in an Android tablet Population Dynamics Visualization  Lozano, Miguel ; García-Fernández, Ignacio ; Orduña, Juan Manuel ( The Eurographics Association , 2012 ) In this work we present a graphic, interactive system to validate population dynamics models through hypothesis (simulation results) and radiocarbon samples selection and process. The goal of the graphical tool is to allow ... PrimeSense Sensors as a Low-cost Method for Motion Capture on Clinical Tests  Sanmartín, G. ; Flores, J. ; Arias, P. ; Cudeiro, J. ; Méndez, R. ( The Eurographics Association , 2012 ) Virtual Reality (VR) is the computer recreation of simulated environments that create on the user a sense of physical presence. VR provides the advantages of being highly flexible and controllable, allowing experts to ... A Procedural Modeling System for the Creation of Huge Models  Cubero, Francisco ; Mas, Albert ; Patow, Gustavo ( The Eurographics Association , 2012 ) This paper presents a new general purpose procedural geometrical modeling system. It is focused on providing flexibility, modularity and scalability. Furthermore, it is taylored to manage huge geometric models, with millions ... A Survey on Development Tools for Mobile Augmented Reality  Rovelo, Gustavo ; Abad, Francisco ; Camahort, Emilio ( The Eurographics Association , 2012 ) Augmented Reality (AR) applications have become more popular beyond the research laboratory due to recent technological breakthroughs in computer hardware and mobile devices. Users are starting to interact with virtual ... Teaching Tool for Self-learning and Self-evaluation of Human Anatomy Using 3D Models of Human Bones  Pamos, Miguel Á. ; Segura, Rafael ( The Eurographics Association , 2012 ) In this research, it's going to introduce the process we have applied by development an application intended to students of Physioteraphy Studies, The proccess is divided by three sub-process: scanning bones, processing ... Tracking for Virtual Environment using Kinect  Sánchez, M. García ; Salas, A. León ; Cantero, J. C. Torres ( The Eurographics Association , 2012 ) Los sistemas de tracking magnético suelen tener alcance limitado y presenta problemas de interferencias. En este trabajo proponemos utilizar los sensores de kinect para realizar el tracking en sistemas HMD. Uncertainty Visualization of Brain Fibers  Hermosilla, Pedro ; Brecheisen, Ralph ; Vázquez, Pere-Pau ; Vilanova, Anna ( The Eurographics Association , 2012 ) Diffuse Tensor Imaging (DTI) is an acquisition method based on Magnetic Resonance (MR) that provides information on the white matter fiber pathways in the living human brain. Such knowledge is crucial for understanding the ... Ventricular Puncture Trainer  Pandiella, Imanol Muñoz ; Monclús, Eva ; Brunet, Pere ; Conesa, Gerard ( The Eurographics Association , 2012 ) The learning process in neurosurgery is a large and difficult task based on experimentation, being ventriculostomy not an exception. We have developed a virtual reality system to help training novel surgeons on this kind ... Visual Language Generalization for Procedural Modeling of Buildings  Barroso, Santiago ; Patow, Gustavo ( The Eurographics Association , 2012 ) Procedural modeling has become the accepted standard for the creation of detailed large scenes, in particular urban landscapes. With the introduction of visual languages there has been a huge leap forward in terms of ... WebGL-based Visualization of Voxelized Brain Models  Torre, J. Cruz de la ; Ibáñez, J. Jiménez ; Estrella, A. M. López ; Miras, J. Ruiz de ( The Eurographics Association , 2012 ) This work presents our preliminary results on the interactive construction and visualization of voxelized brain models into Web platforms by using WebGL. Our voxel model is a non-usual level of detail (LOD) representation ...
https://diglib.eg.org/handle/10.2312/896/browse?order=ASC&rpp=20&sort_by=1&starts_with=M&type=title
The Oxford Oratory A sanctuary in the midst of the city The Oxford Oratory is a vibrant centre of Catholic life. Our church is open every day: join us for Mass, pop in for some quiet prayer, or come and discover more at one of our groups. Our historic church of St Aloysius has been a key feature in the lives of the city’s Catholics for 150 years, attracting people of all ages and from every walk of life. We use beauty to raise hearts and minds to God, faithful to the traditions of St Philip Neri and St John Henry Newman. Congratulations to Elizabeth who was received into the Church yesterday evening on the Feast of the Visitation. #oxfordoratory Congratulations to Livi, baptised on the vigil of Pentecost. “Therefore, Lord, we pray: graciously accept this oblation of our service, that of your whole family, which we make to you also for those to whom you have been pleased to give the new birth of water and the Holy Spirit, granting them forgiveness of all their sins; order our days in your peace, and command that we be delivered from eternal damnation and counted among the flock of those you have chosen. Through Christ our Lord. Amen.” #oxfordoratory Courtesy I recall how, as a child at school, we were sometimes made to learn poetry. At the time I hated it, and baulked at the idea of having to commit to memory The Ancient Mariner, and in fact, never did. But one poem which did touch me, was Belloc’s Courtesy. It began: Of Courtesy, it is much lessThan Courage of Heart or Holiness,Yet in my Walks it seems to meThat the Grace of God is in Courtesy. The poet goes on to tell us how, on one occasion he visited the ‘monks’ at Storrington in Sussex, and that ‘They took me straight into their Hall’where he ‘saw Three Pictures on a wall, And Courtesy was in them all.’ He then tells us the subject of those paintings: The first the Annunciation;The second the Visitation;The third the Consolation,Of God that was Our Lady’s Son. The first was of St. Gabriel;On Wings a-flame from Heaven he fell;And as he went upon one kneeHe shone with Heavenly Courtesy. Our Lady out of Nazareth rode —It was Her month of heavy load;Yet was her face both great and kind,For Courtesy was in Her Mind. The third it was our Little Lord,Whom all the Kings in arms adored;He was so small you could not seeHis large intent of Courtesy. Today is the feast of the Visitation, when we celebrate how our Lady made the long and uncomfortable journey to see her older kinswoman, Elizabeth, and her husband Zachariah, who lived in the hill country of Judah. Courtesy seems to me to be a perfect description of what this moment is all about. Imagine the cordial welcome extended to Mary by the older woman, solicitous for her health and how both women were eager to share with one another the joy of the forthcoming births of their sons. Our Lady had herself gone to visit her older cousin, not simply because she wanted to ‘be there’ for her, but because she wanted to share her own good news, which was not hers alone but for her people and, ultimately for the entire world. This is something Elizabeth seemed to know already! Her enthusiastic greeting is wonderful when she cries out ‘Oh that I should be visited by the Mother of my Lord’. Her unborn son joins in the greeting, kicking and letting his mother know that he too is part of this exciting thing that is happening. Elizabeth’s gracious words: ‘Blessed art thou among women and blessed is the fruit of thy womb’ have been enshrined in our prayer to the Virgin, incorporated with the Angelic Salutation: ‘Hail Mary, full of grace!’ And if today’s feast is about courtesy (so much more than stiff politeness or polished manners, but a warm and real concern for the wellbeing and interest of the other) then it is also about joy. Mary’s presence, together with that of her Divine Son, transformed the home of Elizabeth and Zachariah. ‘Elizabeth was filled with the Holy Spirit’ because of it. St Jose Maria puts it thus: ‘Mary brought joy to her cousin’s home, because she “brought” Christ’. Dame Julian liked to call Jesus ‘our courteous Lord,’ no doubt on account of his gracious dealings with us, flowing from his ‘large intent of Courtesy’! Julian writes in her Showings: And this is a supreme friendship of our courteous Lord, that he protects us so tenderly whilst we are in our sins; and furthermore he touches us most secretly, and shows us our sins by the sweet light of mercy and grace. But when we see ourselves so foul, then we believe that God may be angry with us because of our sins. Then we are moved by the Holy Spirit through contrition to prayer, and we desire with all our might an amendment of ourselves to appease God’s anger, until the time that we find rest of soul and ease of conscience. And then we hope that God has forgiven us our sin; and this is true. And then our courteous Lord shows himself to the soul, happily and with the gladdest countenance, welcoming it as a friend, as if it had been in pain and in prison, saying: My dear darling, I am glad that you have come to me in all your woe. I have always been with you, and now you see me loving, and we are made one in bliss. So sins are forgiven by grace and mercy, and our soul is honourably received in joy, as it will be when it comes into heaven, as often as it comes by the operation of grace of the Holy Spirit and the power of Christ’s Passion. These reflections are sent out each Wednesday to all those on our mailing list. Click here to sign up to our mailing list , and receive our Sunday E-newsletter and these reflections straight to your inbox. Even though we have just changed all the light bulbs, our church looks its best when we don’t need to use them. #oxfordoratory The flag goes up on feast days! #oxfordoratory Blessings with St Philip’s relic after Vespers on Thursday. #oxfordoratory Look down from heaven, Holy Father, from the loftiness of that mountain to the lowliness of this valley; from that harbour of quietness and tranquillity to this calamitous sea. And now that the darkness of this world hinders no more those benignant eyes of thine from looking clearly into all things, look down and visit, O most diligent keeper, this vineyard which thy right hand planted with so much labour, anxiety and peril. To thee then we fly; from thee we seek for aid; to thee we give our whole selves unreservedly. Thee we adopt for our patron and defender; undertake the cause of our salvation, protect thy clients. To thee we appeal as our leader; rule thine army fighting against the assaults of the devil. To thee, kindest of pilots, we give up the rudder of our lives; steer this little ship of thine, and, placed as thou art on high, keep us off all the rocks of evil desires, that with thee for our pilot and our guide, we may safely come to the port of eternal bliss. #oxfordoratory Our celebrations for St Philip began with First Vespers last night and continue with Masses today. Here St Philip’s relic and altar are incensed during Vespers. #oxfordoratory Our new longer term temporary digital organ was hoisted up to the gallery this week in time for First Vespers of Our Holy Father St Philip. Catch up on our YouTube channel if you missed it, and join us for the Solemn Mass at 6pm this Friday. #oxfordoratory Vessel of the Holy Spirit This year the novena in preparation for the feast of Our Holy Father St Philip corresponds almost exactly with the novena of novenas, the first novena, the nine days of prayer between the Ascension and Pentecost when we wait once more with the Apostles for the outpouring of the Holy Spirit. And this is most appropriate, as St Philip was, more than anything else, a man of the Spirit — as we say in his litany, he is the “vessel of the Holy Spirit”. The story of his life, which we read during the novena, really begins with his singular experience of the Spirit on the Vigil of Pentecost 1544 in the catacomb of St Sebastian when the Spirit descended like a ball of fire, entering his mouth and then into his heart. After that experience — Philip’s own Pentecost — his life would never be the same again. Behind his holiness of life, and his preaching, and his miracles, and his founding of our Institute, there is something fundamental we can learn from St Philip — conveniently for this time in the Church’s liturgical calendar, something about the Holy Spirit. St Philip’s life shows us what happens when we do not simply possess the Holy Spirit, but allow ourselves to be possessed by him. We all have the Holy Spirit dwelling in us — all of us who have been baptised and confirmed. He is in us as much as he was in St Philip Neri, as much as he was in the Apostles at Pentecost. But we are very good at closing ourselves to the Spirit — we, through our sins and our selfishness, our attachments and our self-will, block him out; we ignore his prompting and are deaf to his call, we partition him away into a little forgotten compartment in our souls. Or we make of him a very petty little thing indeed, our God — a God who always agrees with what we say, who wants us to do precisely what we want to do, and makes me right and everyone else wrong. But this is not the Holy Spirit whom we worship; this is not the awesome power of Almighty God, who hovered over the waters at creation, who raised Jesus from the dead, who came down on the Apostles and Our Lady in the Upper Room, who wonderfully penetrated the heart of St Philip, and who gives power and authority to the Church. The Holy Spirit blows where he wills; his ways are not always our ways; and if we give ourselves to him and allow him to possess us completely — as St Philip did — then we will find that he will do more for us than we ask or even imagine; do more through us and with us. St Philip wanted to be a layman — the Spirit called him to the priesthood; he wanted to be a martyr, the Spirit made him a martyr not of blood, but of charity; Philip wanted to preach the Gospel to the pagans in the Indies, the Holy Spirit had other plans. He wanted to be a humble, hidden servant of the Church, living at San Girolamo and doing what good he could, but the Spirit gave him the gift of preaching and teaching and working miracles and reading men’s hearts and winning souls, and brought him to the Vallicella, and through him founded the Congregation of the Oratory, spread, as it now is, across the world. St Philip loved to be unknown — the Holy Spirit moulded and fashioned and transformed him into one of the most popular saints, the Apostle of Rome. St Philip wanted to reform the hearts and souls of those men and women he met — the Spirit used him to reform the very heart of the Church herself. It is not enough to have the Holy Spirit — it is not enough even to think we are serving God or doing great things in his honour. We must allow ourselves to be led by the Spirit, formed and transformed by the Spirit. We must be prepared to give up our own desires and plans — even the good ones — and be taken over by the Holy Spirit to be used for his own purposes. If we do this, if we open up to the Spirit who dwells in our hearts, then the life of St Philip Neri, and indeed of all the saints, shows us that the Spirit will do great things for, in, and through us. St Philip, Vessel of the Holy Spirit and Sweetest of Fathers. Pray for us. These reflections are sent out each Wednesday to all those on our mailing list. Click here to sign up to our mailing list , and receive our Sunday E-newsletter and these reflections straight to your inbox. A Prayer of Our Holy Father St Philip: My Lord Jesus, I want to love you but you cannot trust me. If you do not help me, I will never do any good. I do not know you; I look for you but I do not find you. Come to me, O Lord. If I knew you, I would also know myself. If I have never loved you before, I want to love you truly now. I want to do your will alone; putting no trust in myself, I hope in you, O Lord. The Paschal Candle has been lit for Masses since the Easter Vigil to represent Christ’s presence among us, as with his disciples for forty days. After the Gospel of the Solemn Mass yesterday, it is extinguished to symbolise his ascension into heaven. #oxfordoratory Look up to heaven On Monday this week some of the Fathers and Brothers spent the day erecting and moving scaffolding — with all due health and safety measures observed — in order to change and improve the lighting on the sanctuary of our church. It is already a great boon for us to see more clearly the beautiful decoration which adorns that focal point of the whole building, as well as being a great help for the priest reading from the missal. Tomorrow as we celebrate the feast of the Ascension, our eyes are directed upwards once more as Our Risen Lord ascends to heaven and for a moment like the Apostles we gaze upwards as he is taken from our sight. How very much more clearly do we see when we make that effort to lift up our eyes towards the Lord. We not only contemplate his glory but from that vantage point are able to see all things in their fullness, seeing them from the perspective of heaven. Prayer, the lifting of the mind and heart to God, enables us to understand and to see clearly, all those other things of life in which we are otherwise immersed. That daily shifting our focus from the things of this world to the vantage point of heaven is that great encouragement for our daily striving for God, so that where Christ goes we too may follow him. It is often an effort for us to pull ourselves out of the daily round in order to lift up our heads and our hearts to the things of heaven, but if we are to have the desire for heaven to drive us on, it is essential that we always keep our goal before us. Not only in prayer, but all those things which form the way we see things must have heaven as their vantage point and aim. Monsignor Knox wrote: In all ages, in all countries, the world acts as a solvent to Catholic piety; breathes an air in which Catholic piety languishes. Man’s intellect always wants to approach things from the human side, from the side from which they can be known by man; shirks and burkes discussion of things from the side of reality, from the side which relates them to God. Man’s art and literary genius is constantly concerned with man at his most human level, his passions, his craven fears, the rebellion of his will against the order in which he lives. All that breathes a poison, for which writers who care about the truth as it is in God have to provide an antidote; they must fight, they must react, but still more they must see things, they must record things, from that higher standpoint which is God’s. You must, sometimes, give the lungs of your soul an airing on these heights, even if the atmosphere of it is more rare, is breathed with more effort, than the other. Or else, the miasma of the modern world will get you down, will weaken your resistance; you will be a prey to the germs of infidelity, to the infection of bad example. And you will forget your Friend. As the Church invites us then on the Ascension to gaze up towards heaven, to contemplate Our Lord, Risen and Ascended, it is perhaps a good time for us to think on the place we give to the things of heaven in our life each day — not only in terms of the time we give to heaven, but also in terms of what we strive for, on what really all our efforts are in fact based. And from our gazing upon heaven, we can then go on like the Apostles, down from that mountain and into the world — to teach the Good News and make disciples of all nations, keeping ever in mind that he whom we meet on those heights of prayer is with us always, even to the end of time. These reflections are sent out each Wednesday to all those on our mailing list. Click here to sign up to our mailing list , and receive our Sunday E-newsletter and these reflections straight to your inbox. Tuesday 16 May 2023 Q: How many Oratorians does it take to change a lightbulb?A: “Change”? Actually the real answer turns out to be three, plus one very helpful volunteer and a lot of scaffolding. The sanctuary lighting is all working at full brightness again! #oxfordoratory Monday 15 May 2023 Congratulations to David who was baptised on Saturday! #oxfordoratory Saturday 13 May 2023 One of this month’s relics on display is St Philip’s own copy of Jacapone da Todi’s “Laude”, which St Philip has written his name in. The story of how it was rediscovered in our church — only days before the first Fathers of the Oratory arrived here from Birmingham — is extraordinary. You might find it hard to believe, unless you heard it straight from the priest who found them, who is now the Bishop of Leeds. Read his account from his St Philip’s day sermon on our website: www.oxfordoratory.org.uk/blog/post/1335-solemnity-of-our-holy-father-saint-philip The novena to St Philip begins on Tuesday after the evening Mass. You will be able to place your own prayer intentions for the novena in St Philip’s chapel over the weekend. There will be Solemn Choral Vespers on Thursday 25 May at 6:30pm. We will welcome Fr Robert Ombres OP from Blackfriars to preach at the Solemn Mass for the feast day itself on Friday 26 May at 6pm. #oxfordoratory Friday 12 May 2023 May Music Sunday 7 MaySolemn Mass 11:005th Sunday of EasterMissa Simile est regnum caelorum LoboJubilate Deo universa terra PalestrinaCaro mea vere est cibus Guerrero Sunday 14 MaySolemn Mass 11:006th Sunday of EasterMissa Regina caeli PalestrinaBenedicite gentes PalestrinaPortio mea White Thursday 18 MaySolemn Mass 18:00The Ascension of the LordMissa Ascendens Christus VictoriaAscendit Deus PhilipsO Rex gloriae Marenzio Sunday 21 MaySolemn Mass 11:007th Sunday of EasterMissa Jam Christus astra ascenderat PalestrinaViri Galilaei PalestrinaEgo sum panis vivus Palestrina Thursday 25 MaySolemn Vespers 18:30Our Holy Father St Philip NeriDeus in adjutorium PadillaMagnificat primi toni VictoriaPangamus Nerio SewellO salutaris hostia LalouxTantum ergo WidorAlleluia GabrieliRespice de caelo Sewell Friday 26 MaySolemn Mass 18:00Our Holy Father St Philip NeriMissa Papae Marcelli PalestrinaIn spiritu humilitatis CroceJubilate Deo a8 G Gabrieli Sunday 28 MaySolemn Mass 11:00PentecostMissa De la Batalla GuerreroConfirma hoc deus LassusLoquebantur variis linguis Palestrina Wednesday 10 May 2023 Crowns come in different sizes One could not have missed the many images of crowns in the past week. On posters and flags, on shop advertisements and on the official emblem of the coronation of His Majesty the King. The whole world, it seems, was caught up in amazement at that moment when St Edward’s crown was placed on the King’s head, the only time it is ever worn, to be replaced by the Imperial State Crown, impressive in its size and its jewels. One could not help but feel a certain sympathy with them — perhaps especially Her Majesty the Queen — as they walked around gingerly with several pounds’ weight of crown on their heads, lest they take a tumble. A crown is a symbol not only of a regal inheritance, but of a sacred anointing and the leadership of a nation. It also shows that one is set apart from the rest, is chosen, is consecrated. Crowns are a familiar sight even in church. Our Lady’s statue is crowned, there are crowns above the cabinets in the Relic Chapel and they are even to be found, accompanied by palm branches, on the reliquaries placed on the High Altar on feast days. These crowns too stand for those set apart, who are chosen to bear the ultimate witness to the greatest truth. On Friday we keep the feast of Saints Nereus and Achilleus. Baptised by St Peter himself, these two soldiers having obeyed the cruel orders of their emperor out of fear alone, it is said, came quite suddenly to faith in Christ and in doing so were liberated. They were freed from their obedience to a tyrant to embrace obedience to Christ and in so doing were called to shed their blood in witness to their faith. Theirs is the story of so many brave Christians who saw eternal life as the greatest prize against which everything the world has to offer pales in comparison. St Philip had a great devotion to the saints. Their relics are enshrined at the Roman Oratory and the Venerable Cardinal Baronius was the Cardinal Priest of their ancient church, often frequented by St Philip. St Philip had a marvellous devotion to the saints and their relics. In his last years we are told he had the lives of the saints read to him daily and took great care to preserve the relics of the saints with devotion at the Vallicella. He saw in the lives of the saints a guide for the rest of us so that where they have gone we might follow. Earthly crowns fall on the heads of very few men. The crowns on our relic cabinets, on the altar reliquaries and paintings in the church are a reminder to us that there is a lasting crown in store for all of us, a crown of glory that will never fade and is given us by the Lord. It may not be that we have to win it by shedding our blood like Nereus and Achilleus, but rather through the long and arduous path of growing in holiness day by day. We are chosen and set apart, we are consecrated by our baptism to win the crown that is fitted for us. In the eyes of the world it rarely glitters, but it is more lasting than anything the world can dream up. And go for it we must. And we pray for our King Charles, that the golden crown set on his head a few days ago may always remind him of that crown of glory that awaits him, please God, after a life of service and virtue. May he be helped in seeking that crown by our prayers. These reflections are sent out each Wednesday to all those on our mailing list. Click here to sign up to our mailing list , and receive our Sunday E-newsletter and these reflections straight to your inbox. Saturday 6 May 2023 God save the King! Photo from our Coronation watch party today. #oxfordoratory Friday 5 May 2023 Where will you be watching tomorrow? Preparations are well underway for the Oratory Watch Party tomorrow after the 10:00am Mass. Why not join us? #oxfordoratory
https://www.oxfordoratory.org.uk/tour/blog/post/9864-now-we-see-as-in-a-mirror-dimly/blog/post/9796-the-oratory-prayer-book/blog/post/9974-9974/visiting-priests.php
Variation in antibiotic prescribing and its impact on recovery in patients with acute cough in primary care: prospective study in 13 countries | The BMJ Variation in antibiotic prescribing and its impact on recovery in patients with acute cough in primary care: prospective study in 13 countries doi: https://doi.org/10.1136/bmj.b2242 Cite this as: BMJ 2009;338:b2242 Article K Hood , director 2 , T Verheij , professor 3 , P Little , professor 4 , H Melbye , professor 5 , J Nuttall , senior trial manager 2 , M J Kelly , statistician 2 , S Mölstad , professor 6 , M Godycki-Cwirko , physician 7 , J Almirall , professor 8 , A Torres , professor 9 , D Gillespie , trainee statistician 2 , U Rautakorpi , senior medical officer 10 , S Coenen , postdoctoral fellow 11 12 , H Goossens , professor 13 Author affiliations 1 Department of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff CF14 4XN, Wales 2 South East Wales Trials Unit (SEWTU), Department of Primary Care and Public Health, School of Medicine, Cardiff University, Heath Park, Cardiff, Wales 3 University Medical Centre Utrecht, Julius Center for Health, Sciences and Primary Care, Universiteitsweg 100, Stratenum, 6th Floor, 6.111, 3584 CX Utrecht, Netherlands 4 University of Southampton, Southampton SO16 5ST 5 General Practice Research Unit, Institute of Community Medicine, University of Tromso, 9037 Tromso, Norway 6 Department of Medical and Health Sciences, Linkoping University, and Unit of Research and Development in Primary Care, S-55185 Jonkoping, Sweden 7 Department of Family and Community Medicine, Medical University of Lodz, U190-153 Lodz.Kopcinskiego 20, Poland 8 Unitat de Cures Intensives, Hospital de Mataro, Carretera de Cirera s/n, 08304 Mataro (Barcelona), Spain 9 Servei de Pneumologia i Al·lèrgia Respiratòria, Institut Clínic del Tòrax, Hospital Clínic de Barcelona, CIBERES 06/06/0028, Universitat de Barcelona, Spain 10 Finnish Office for Health Technology Assessment, FinOHTA, Stakes Tampere Satellite Office, Fin-Medi 3, Biokatu 10, 7. krs, 33520 Tampere, Finland 11 University of Antwerp-Campus Drie Eiken, Vaccine and Infectious Disease Institute, Centre for General Practice, Antwerp, Belgium 12 Research Foundation, Flanders, Brussels, Belgium. 13 University of Antwerp-Campus Drie Eiken, Vaccine and Infectious Disease Institute-Laboratory of Medical Microbiology, Antwerp, Belgium Correspondence to: C Butler [email protected] Accepted 13 February 2009 Abstract ObjectiveTo describe variation in antibiotic prescribing for acute cough in contrasting European settings and the impact on recovery. DesignCross sectional observational study with clinicians from 14 primary care research networks in 13 European countries who recorded symptoms on presentation and management. Patients followed up for 28 days with patient diaries. SettingPrimary care. ParticipantsAdults with a new or worsening cough or clinical presentation suggestive of lower respiratory tract infection. Main outcome measuresPrescribing of antibiotics by clinicians and total symptom severity scores over time. Results3402 patients were recruited (clinicians completed a case report form for 99% (3368) of participants and 80% (2714) returned a symptom diary). Mean symptom severity scores at presentation ranged from 19 (scale range 0 to 100) in networks based in Spain and Italy to 38 in the network based in Sweden. Antibiotic prescribing by networks ranged from 20% to nearly 90% (53% overall), with wide variation in classes of antibiotics prescribed. Amoxicillin was overall the most common antibiotic prescribed, but this ranged from 3% of antibiotics prescribed in the Norwegian network to 83% in the English network. While fluoroquinolones were not prescribed at all in three networks, they were prescribed for 18% in the Milan network. After adjustment for clinical presentation and demographics, considerable differences remained in antibiotic prescribing, ranging from Norway (odds ratio 0.18, 95% confidence interval 0.11 to 0.30) to Slovakia (11.2, 6.20 to 20.27) compared with the overall mean (proportion prescribed: 0.53). The rate of recovery was similar for patients who were and were not prescribed antibiotics (coefficient −0.01, P<0.01) once clinical presentation was taken into account. ConclusionsVariation in clinical presentation does not explain the considerable variation in antibiotic prescribing for acute cough in Europe. Variation in antibiotic prescribing is not associated with clinically important differences in recovery. Trial registrationClinicaltrials.govNCT00353951. Introduction Antibiotic resistance is a growing problem worldwide, with 10% of Streptococcus pneumoniaeisolates recorded as non-susceptible to penicillin in 30 countries in 2007.1There is wide variation in antibiotic prescribing for ambulant patients in Europe.2We do not know if this variation is explained by differences in presentation of illness or to which conditions it applies. Acute cough is one of the most common reasons for consulting. The proportion of European patients consulting in general practice with lower respiratory tract infection who are prescribed antibiotics ranges from about 27% in the Netherlands (for cough and bronchitis) to 75% in the United Kingdom.34Trial evidence suggests that most antibiotic prescriptions do not help these patients to get better any quicker, although the datasets are sometimes small and the impact of case mix at presentation is unclear.567Variation in antibiotic prescribing that does not improve outcomes for patients wastes resources, undermines self care for similar conditions in the future, puts patients at unnecessary risk of side effects, and increases selection of resistant organisms, and so represents an opportunity for improved care through greater standardisation. Higher levels of prescribing in certain settings, however, might be explained by differences in severity of illness and so variation might not always indicate inappropriate prescribing. We examined variation in antibiotic prescribing for acute cough in primary care in Europe and its impact on recovery, controlling for presentation. Methods Networks The Genomics to combat Resistance against Antibiotics in Community-acquired lower respiratory tract infections in Europe (GRACE) (www.grace-lrti.org) Network of Excellence recruited 14 primary care research networks (based in Antwerp, Helsinki, Rotenburg, Utrecht, Balatonfured, Milan, Tromso, Lodz, Bratislava, Barcelona, Mataro, Jonkoping, Cardiff, Southampton) in 13 countries (Belgium, Finland, Germany, Holland, Hungary, Italy, Norway, Poland, Slovakia, Spain (two networks), Sweden, UK (Wales and England)). Recruited networks had access to a minimum of 20 000 patients and had a track record of conducting research. A national network coordinator and a national network facilitator took responsibility for their network’s set up, recruitment, and data management. Study materials and procedures Study materials (protocol, patient diary, and case report form) and study procedures were developed with advice from all networks. The coordinators and facilitators undertook face to face training in study procedures, including entering data on to the GRACE online system (GOS), and cascaded training to all participating general practitioners. Study documents required by ethics review committees and participants (general practitioners and patients) were translated into local languages. Back translation by independent translators ensured accuracy. Inclusion criteria Eligible patients were aged 18 and over who were consulting with an illness where an acute or worsened cough was the main or dominant symptom or had a clinical presentation that suggested a lower respiratory tract infection with a duration of up to and including 28 days, were consulting for the first time within this illness episode, were seen within normal consulting hours, had not previously participated in the study, were able to fill out study materials, had provided written informed consent, and were considered immunocompetent. These broad inclusion criteria captured a wide range of patients with community acquired lower respiratory tract infection. Although almost all patients with this infection have a cough, the additional eligibility criterion of clinical presentation suggestive of lower respiratory tract infection was added to make those with infection but no cough also eligible. Recruitment of patients Participating general practitioners were asked to recruit consecutive eligible patients in October and November 2006 and from late January to March 2007. The scheduled two month gap enabled us to explore the effect of possible temporal variations in causes of cough during the winter. Data collection Clinicians (general practitioners and nurse practitioners) recorded aspects of patients’ history, symptoms, comorbidities (diabetes, chronic lung disease, and cardiovascular disease), clinical findings, and management, including antibiotic prescription and other treatments and investigations, on a case report form. They indicated the presence or absence of 14 symptoms (cough, phlegm production, shortness of breath, wheeze, coryza, fever during this illness, chest pain, muscle aching, headache, disturbed sleep, feeling generally unwell, interference with normal activities, confusion/disorientation, and diarrhoea) and then rated whether each of the symptoms constituted “no problem,” “mild problem,” “moderate problem,” or a “severe problem” for the patient. The colour of any sputum produced was recorded as clear, white, yellow, green, or bloodstained. Clinicians recorded the patient’s body temperature with a disposable thermometer (TempaDot, 3M Health Care) provided in each individual patient study pack. Patient reported follow-up Patients were given a symptom diary. They were asked to rate 13 symptoms each day until recovery (or for 28 days if symptoms were ongoing) on a seven point scale from “normal/not affected” to “as bad as it can be.” Patients rated the same symptoms as the clinicians apart from confusion/disorientation and diarrhoea. In addition they were asked to rate the impact of their illness on their social activities. There were questions about smoking and course of the illness, including subsequent management and contacts with the health service over the next 28 days. Data management All data from case report forms and patients’ diaries were entered via a remote secure data entry portal onto the GRACE online system that was compliant with regulatory guidelines. Central and internal monitoring and checking ensured the accuracy of data collection and entry. Patients were telephoned four to seven days after inclusion to provide them with the opportunity to ask questions and discuss any problems with diary completion. Sample size Sample size estimation was based on an estimate of a probability of 50% for certain events such as treatment decisions (50% is the most conservative estimate of probabilities in statistical terms; more common or more rare events would give more power). This required a total sample size of 270 per network to give 95% confidence intervals of 44 to 56 around detecting that 50% probability within each network. Though we had no information on the likely level of clustering of antibiotic prescribing within different networks, we considered that this conservative approach to estimation would give enough power for analyses between networks while accounting for clustering. Symptom scores The categories for clinicians to rate the severity of each symptom as “no problem,” “mild problem,” “moderate problem,” or “severe problem” were scored 1, 2, 3, and 4, respectively. Scores were calculated for patients with a minimum of 85% (that is, 12 out of 14 symptoms) of their symptoms recorded. This score was scaled to range between 0 and 100 so that it could be interpreted as a percentage of maximum symptom severity. We calculated patients’ self reported daily symptom severity scores from the diary data, with scores for 13 symptoms summed and scaled to range between 0 and 100 so that the symptom severity score for a given individual on a given day could be interpreted as a percentage of maximum possible symptom severity. This daily symptom severity score was used as the outcome variable in patient outcome model. Analysis Descriptives—Descriptive statistics by network and overall were calculated by using means and standard deviations (SD), medians (interquartile ranges), and proportions as appropriate. Presented SDs were inflated for clustering.8 Antibiotic prescribing—Differences in clinical presentation were controlled for by using 13 of the 14 symptoms recorded by clinicians (cough was excluded as it was present in 99.8% of cases), sputum type, temperature, age, and comorbidities. Antibiotic prescribing by networks was investigated by using a two level hierarchical logistic model9fitted to the data from the case report forms with patients nested within clinicians. The dependent variable was whether the clinician prescribed antibiotics or not, with patients who were given a prescription and advised to delay taking the antibiotics counted as receiving a prescription. Network was included as a fixed effect, with all networks being compared with the overall mean. The impact of smoking status and duration of illness before consulting was explored in the subset of patients with complete data (diary responders). Patients’ recovery—A three level hierarchical ARMA (1,1) model10was fitted to the logged daily symptom scores reported by patients (box). We controlled for differences in clinical presentation using the same variables as in the previous model, along with smoking status and duration of illness before consulting. We included the impact of differences in antibiotic management as both a main effect and an interaction with time (to allow for different recovery rates over time for those with and without antibiotics). ARMA model used to assess variation in outcome in relation to antibiotic prescribing An ARMA (1,1) model comprises an autoregressive part and a moving average part and expresses each observation as a combination of the two: X t =ε t +X t −1 +ε t −1 where X tis the symptom severity score at time t, ε tis the error term. This allows for each individual’s symptom severity scores and the related error term to be correlated with the previous day. Statistical analysis software—Descriptive analyses were performed with SPSS version 14.0 (Chicago, ILL). All modelling was performed in the R programming language and environment11using the lme412and nlme13packages. Results Patients A total of 3402 patients were recruited by 387 practitioners. Six networks included 270 patients or more, and all included over 100 (table 1). ⇓Four patients were later found to be ineligible and were excluded from further analysis. Case report forms were completed for 3368 (99%) and diary data were obtained from 2714 (80%) patients. Exclusion of patients with missing data reduced the case report form dataset to 3296 (97%) and the diary dataset to 2560 (75%) (fig 1) ⇓. Those who filled in the diary tended to be older than those who did not (median age 45 (interquartile range 33-58) v36 (27-48)). There were no significant differences in the proportions by sex. There was some variation in the response rates from each network, with patients from Eastern European networks being most likely to return the symptom diary. Those who did not fill in a diary were no more or less likely to have been prescribed antibiotics than the others. Fig 1Patient flow chart The median age of patients was 45.0 (interquartile range 35-58), 37% (1228) were men, 98% (3309) were seen at the office or surgery, 15% (515) had an existing respiratory condition, 8% (266) had a cardiovascular related illness, and 4% (138) had diabetes (table 1). ⇓The three most common presenting symptoms, other than cough (99.7%, 3358), were being generally unwell (80%, 2698), phlegm production (77%, 2592), and interference with normal activities (69%, 2335). The median number of symptoms recorded by a clinician was eight (6-9). Patients were unwell before the consultation for a median of five days (3-8). The average temperature was 36.8ºC (SD 1.59). Table 1 Countries, networks, general practitioners, practices, and included patients Antibiotic prescribing Antibiotics were prescribed for 53% (1776) of included patients for a median of seven days (6-7) (table 1). ⇑There were notable differences between networks in the unadjusted proportion of patients who were prescribed antibiotics. Clinicians from networks based in Bratislava, Milan, Balatonfured, Lodz, and Cardiff were more likely to prescribe antibiotics than the overall average. Amoxicillin accounted for 29% of prescriptions, ranging from 3% in Tromso to 83% in the Southampton network (fig 2) ⇓. Macrolides/lincosamides were prescribed for 26% of patients, ranging from 4% in Utrecht to 50%, 45%, and 38% in the Bratislava, Milan, and Lodz networks, respectively. Co-amoxiclav was prescribed for 15%, though this varied widely, from 0% in Jonkoping and Tromso to 47% in Barcelona (it was the most commonly prescribed antibiotic in both Barcelona and Mataro (43%)). Tetracyclines were prescribed for 14%. Three networks did not prescribe tetracyclines at all (Barcelona, Mataro, and Milan), and they were the first choice in three networks (Utrecht 72%, Jonkoping 56%, and Helsinki 51%). Cephalosporins were prescribed for 7% (ranging from 0% to 13%) and fluoroquinolones for 5%. Fluoroquinolones were most commonly prescribed in the Milan, Mataro, and Balatonfured networks (18%, 16%, and 13%, respectively) and were not prescribed at all in six networks (Southampton, Barcelona, Lodz, Jonkoping, Tromso, and Helsinki). Fig 2Choice of antibiotic by network Antibiotic prescribing by networks adjusted for clinical presentation Significant variation between networks remained after adjustment for clinical presentation, with antibiotic prescribing in 11 networks significantly different from the overall mean at the 5% level (table 2 ⇓). Figure 3 ⇓shows the unadjusted and adjusted odds ratios for antibiotic prescribing for all networks. Fig 3Unadjusted and adjusted odds ratios for antibiotic prescribing by network (both adjusted for clustering within clinician). All networks are compared with overall mean Table 2 Two level logistic regression model* of odds of being prescribed antibiotic in each network (3296 patients from 384 clinicians). Figures are odds ratios (95% confidence intervals) There were no significant differences between the two recruitment periods in overall rate of antibiotic prescribing. The model was also fitted to the subsample of patients with usable diary data to check the effect of duration of illness before consultation and smoking status on prescribing. Both variables were significantly associated with receiving a prescription for antibiotics, with a 2% increase in the odds of receiving an antibiotic for each additional day of illness before consulting (odds ratio 1.02, 95% confidence interval 1.01 to 1.04) and a 38% increase in the odds for smokers (1.38, 1.09 to 1.76). Adjustment for these factors, however, had no effect on the magnitude or significance of the variation between networks and therefore we have presented the model with the larger sample. Patients’ recovery There was considerable variation between networks in the rate of recovery after presentation, as shown by the median symptom trajectory plots (fig 4) ⇓. The median time to patients reporting feeling recovered (single item) was 11 days. The median time for patients’ symptom severity scores to drop to 0 was 15 days. Respiratory comorbidity was associated with initial higher symptom severity scores. Those who waited longer before presenting had higher initial symptom severity scores. Fig 4Unadjusted median symptom severity scores over time by network Open in new tab Download powerpoint Significant variation in outcome remained across networks after adjustment for clinical presentation, with two of the networks (Balatonfured and Mataro) reporting differences in patients’ reported symptom severity at baseline compared with the overall mean, three networks (Cardiff, Milan, and Jonkoping) reporting significantly slower recovery rates, and three networks (Mataro, Balatonfured, Antwerp) reporting significantly faster recovery. While there were significant differences in the symptom trajectories across the networks, differences were not large. Almost all the symptom trajectories converged after a week (fig 5) ⇓. Being prescribed antibiotics was associated with a faster reduction in symptom severity scores, as indicated by the significant interaction between prescribing antibiotics and day. This association, however, was small (table 3) ⇓. Fig 5Predicted recovery curves by network for those prescribed antibiotics from ARMA model Table 3 Estimates for ARMA (1,1) model*: symptom severity scores over time (65 541 observations in 2560 patients from 364 clinicians) The impact of antibiotic prescribing, while statistically significant, represents a tenth of a single percentage difference in symptom severity score (not presented), and therefore it is reasonable to consider it clinically unimportant. Such a small effect is entirely consistent with a placebo effect. Hospital admission Overall, 1.1% (28) of patients were admitted to hospital after inclusion. For individual networks this ranged from none to 4.3% (9). Discussion Main findings In this large prospective international comparative study of the management of acute cough among adults in primary care we found considerable variation in the 13 countries studied. Major differences in the decision whether or not to prescribe an antibiotic in these settings remained, even after we adjusted for clinical presentation (symptoms, duration of illness, smoking, age, comorbidity, and temperature). Patients included by networks based in Bratislava, Milan, Balatonfured, Lodz, and Cardiff were at least twice as likely to be prescribed antibiotics than the overall mean. Patients included by networks based in Tromso, Antwerp, and Jonkoping were at least four times less likely to be prescribed antibiotics than the overall mean. We also identified marked differences between networks in choice of antibiotic. For example, while amoxicillin was overall the most common antibiotic prescribed, this ranged from 3% in the Tromso network to 83% in Southampton. While fluoroquinolones were prescribed for 5% overall, they were prescribed for 18% of patients included in the Milan network. These differences might be attributable to different guidelines and habits in different countries. This will be further explored in a parallel qualitative study. There were two main findings regarding patients’ recovery. Firstly, there were significant differences between networks in both severity of symptoms on day one (intercept) and the recovery rate (slope). Differences in the recovery rate, however, were small (fig 5), and patients recovered at a similar rate regardless of network. Secondly, whether a patient was prescribed antibiotics or not was statistically associated with outcome. The magnitude of this association amounted to a difference of a tenth of a single per cent in the symptom severity score after seven days, which is not clinically relevant. Strengths and limitations We prospectively described antibiotic prescribing for a well defined population of patients in a large number of countries recruited at the same time. Recruitment was for two periods over a single winter, and findings by recruitment period were similar, suggesting local or temporal variations in cause were unlikely to have explained the observed differences. The clinicians who participated (and therefore their patients) were all affiliated to a research network and so might not have been representative. In general, research minded clinicians might be more likely to practice according to guidelines.14They would have been aware of our interest in exploring international differences in antibiotic prescribing, which might have led to an underestimation of the differences we found. Bias As the study spanned 13 European countries, there is no guarantee that perceptions of health and reporting of symptoms were consistent. We do not know how cultural differences influenced our results. We are exploring these issues in a parallel qualitative study with patients and clinicians in nine of the networks. Response bias was not relevant to data from the case report forms as there was a 99% completion rate. Completion rates for patients’ diaries ranged from 60% in the Cardiff network to almost 100% in the Bratislava network. The overall response rate to the diary was high (80%). Non-responders might have deteriorated more than responders, but given similar rates of antibiotic prescribing between the two groups and the generally benign natural clinical course of this condition this is unlikely. Ascertainment bias was minimised by a data collection protocol used by all networks. While every network followed this protocol, some networks implemented additional strategies to improve diary return rates. The impact of different intensities of contact with patients during follow-up is uncertain. Sample size This international study was adequately powered to explore antibiotic prescribing. Only a small number of patients were admitted to hospital, and there were no deaths. While this reflects the natural course of acute cough and the fact that it is managed almost exclusively in primary care, the low number of such complications made Europe-wide comparisons on admission to hospital impossible. For the analysis of recovery, the combination of the large number of data points per patient with the large number of patients made this analysis overpowered with some significant findings having little or no clinical relevance. Comparison with previous studies A study of antibiotic treatment for lower respiratory tract infection in France, Germany, Italy, Spain, and the UK over 10 years ago asked general practitioners to retrospectively describe their management of cases. Overall, community acquired pneumonia accounted for 18% of cases, making this a highly unusual sample. Retrospective data collection carries particular risks of selection bias and incomplete ascertainment of comparable clinical data. Overall, 83% were prescribed antibiotics.15 In a two country comparison, general practitioners in Spain and Denmark recorded their management of respiratory tract infections. Spanish general practitioners prescribed more antibiotics for patients with a presumed tonsillar and bronchi/lung infection focus. There was no adjustment for severity and duration of illness or smoking.16 Implications for practice and research Some interventions have been shown to successfully reduce inappropriate antibiotic prescribing in general practice,1718192021and prescribing fewer antibiotics at the general practice level is associated with local reductions in antibiotic resistance.22 We identified marked differences in whether and what antibiotics are prescribed for acute cough throughout Europe that remained after adjustment for clinical presentation based on the clinician’s assessment of symptoms, duration of illness, smoking, patient’s history (the presence of any comorbidities), age, and temperature. We also found that large differences in antibiotic prescribing did not translate to clinically important differences in patients’ recovery. Therefore management of acute cough is an issue that is appropriate for standardised international care pathways promoting conservative antibiotic prescribing. What is already known on this topic Acute cough is a major reason for antibiotic prescribing in primary care, with many prescriptions resulting in no clinical benefit There is considerable variation in antibiotic prescribing to ambulatory patients across Europe There are inadequate patient level data to determine whether this variation is justified by variation in clinical presentation. What this study adds Considerable variation in antibiotic prescribing for acute cough remains throughout Europe even after adjustment for illness severity, comorbidity, temperature, age, duration of illness before to consultation, and smoking status Recovery is not meaningfully influenced by variation in antibiotic prescribing Notes Cite this as: BMJ2009;338:b2242 Footnotes We acknowledge the entire GRACE team for their diligence, expertise, and enthusiasm. The GRACE team are: Zseraldina Arvai, Zuzana Bielicka, Francesco Blasi, Alicia Borras, Curt Brugman, Jo Coast, Mel Davies, Kristien Dirven, Peter Edwards, Iris Hering, Judit Holczerné, Helena Hupkova, Kristin Alise Jakobsen, Bernadette Kovaks, Chrisina Lannering, Frank Leus, Katherine Loens, Michael Moore, Magdalena Muras, Carol Pascoe, Tom Schaberg, Matteu Serra, Richard Smith, Jackie Swain, Paolo Tarsia, Kirsi Valve, Robert Veen, and Tricia Worby. We thank all the clinicians and patients who consented to be part of GRACE, without whom this study would not have been possible. Contributors: All authors contributed to either the conception and design or the analysis and interpretation of the data; contributed to drafting and revising the manuscript; and approved the final version of the manuscript. CCB is guarantor. Funding: This study was funded by 6th Framework Programme of the European Commission (LSHM-CT-2005-518226). The South East Wales Trials Unit is funded by the Wales Office for Research and Development. All authors declare that they are independent of the funders. Competing interests: None declared. Ethical approval: Ethic review committees in each country approved the study. References ↵ Grundmann H. EARSS annual report 2007 . Bilthoven, Netherlands: European Antimicrobial Resistance Surveillance System, 2007 :40. Goossens H, Ferech M, Vander Stichele R, Elseviers M. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 2005 ; 365 : 579 -87. ↵ Macfarlane J, Lewis SA, Macfarlane R, Holmes W. Contemporary use of antibiotics in 1089 adults presenting with acute lower respiratory tract illness in general practice in the UK: implications for developing management guidelines. Respir Med 1997 ; 91 : 427 -34. Akkerman AE, Kuyvenhoven MM, van der Wouden JC, Verheij TJM. Prescribing antibiotics for respiratory tract infections by GPs: management and prescriber characteristics. Br J Gen Pract 2005 ; 55 : 114 -8. Smucny J, Fahey T, Becker L, Glazier R, McIsaac W. Antibiotics for acute bronchitis. Cochrane Database Syst Rev 2000 ;(4):CD000245. Macfarlane J, Holmes W, Gard P, Macfarlane R, Rose D, Weston V, et al. Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community. Thorax 2001 ; 56 : 109 -14. OpenUrl Abstract / FREE Full Text Google Scholar ↵
https://www.bmj.com/content/338/bmj.b2242?ijkey=82a90ea59608468094e3d6dc8ca0535d18b320b9&keytype2=tf_ipsecsha
EVAR off-label use in Occlusive Arterial Disease - Clinical Trials Registry - ICH GCP The goal of this multi center prospective observational study is to evaluate the iliac patency rate during the time in patients treated with & quot;AFX (Endologix, Ir... Regulations GLOBAL » ICH GCP (De) ICH GCP (En) ICH GCP (Es) ICH GCP (Fr) ICH GCP (It) ICH GCP (Pt) ICH GCP (Ru) USA (FDA) UK (MHRA) AUSTRALIA (NHMRC) JAPAN (PMDA) EU (EMA) CRO List Clinical Trials US Clinical Trials Registry EU Clinical Trials Registry Pharmaceutical Companies Clinical Research Labs Service Companies Clinical Research Events Publications Researchers Jobs Publications News ICH GCP US Clinical Trials Registry Clinical Trial NCT05614856 Aorto-iliac Occlusion Treatment With ShorT Unibody aorTic Endograft - ASTUTE Study (ASTUTE) November 14, 2022 updated by: Roberto Silingardi, MD, Azienda Ospedaliero-Universitaria di Modena The goal of this multi center prospective observational study is to evaluate the iliac patency rate during the time in patients treated with "AFX (Endologix, Irvine Calif)" unibody stent-graft for aorto-iliac occlusive disease The main question it aims to answer is if The Unibody AFX (Endologix) endograft could be in a large and real-world cohort of patients effective solution for the less-invasive treatment of the aortoiliac occlusive disease (AIOD). Participants affected by AIOD with an indication of endovascular treatment will be prospectively enrolled and treated as our clinical practice. The requested follow-up did not differ from the one suggested by the most recent guidelines Study Overview Status Recruiting Conditions Occlusive Arterial Disease Intervention / Treatment Device: EVAR off-label use Detailed Description In the last two decades there was a general shift from conventional open surgery to endovascular mini-invasive interventions, particularly towards patients with iliac and aortic occlusive disease (AIOD). However, while iliac artery angioplasty and stenting increased 8.5 fold from 1996 to 2000, aorto-bifemoral bypass fell by only 15%1,2. Indeed, according to European Society of Vascular Surgery/European Society of cardiology guidelines, open surgery remains the preferred choice for the most complex lesions to address by in endovascular fashion (TransAtlantic Inter-Society Consensus [TASC II] type C and D lesions). The reason is the good long-term patency of aorto-bi-iliac or aorto-bifemoral bypass among endovascular devices. Surgery, however, is associated with a high burden of early and late morbidity and mortality, and this aggressive approach is limited by the patient's age and comorbidity. In 1991 the kissing stent technique emerged as an alternative for bilateral aortoiliac occlusive disease. Even if the reported technical success rates varied between 89% and 100% with a 1-year primary patency between 76% and 98%, outcomes may be worse in more complex lesions owing to radial size mismatch between stents and certain stent configurations within the distal aorta. In addition, heavy calcified or thrombus-filled aorta could increase technical complexity and risk of limb and life-threatening procedural complications such as dissections, aortic rupture, and peripherical embolizations. Covered stents may increase patency rates in extensive disease, as shown by The Covered vs Balloon Expandable Stent Trial (COBEST) and confirmed in various case series but did not address the problem of a potential radial size mismatch that can lead to re-circulation, turbulence, and stasis of blood, which in turn, may cause thrombus formation and intimal neohyperplasia. Another endovascular procedure for the treatment of AIOD is the CERAB technique. A CERAB is defined as an "endovascular reconstruction of the aortic bifurcation" using at least one covered stent-graft for the infrarenal aorta (flared proximally) and 2 stent-grafts deployed within the aortic stent and into the common iliac arteries. This particular configuration leads to the reduction of the radial mismatch, which is defined as the discrepancy between the stented lumen and the vessel lumen after stent placement and, as a result, to more favorable flow conditions. In addition, it protects against potentially fatal aortoiliac rupture during the dilatation of heavily calcified lesions. However, the radial mismatch is increased if the limbs are placed higher than the nonflared aortic stent. In addition, while the CERAB technique does recreate the aortic bifurcation, future crossover interventions may be more difficult. This is similar to most bifurcated aortic stent-grafts where the angle of engagement at the flow divider makes up-and-over access more challenging. Finally, dead space outside the proximal aortic stent can result in cases of aortic diameters > 20 mm. The aortic stent is then left protruding mal-opposed in a dilated aorta. Hence, this technique may not be indicated in the setting of even mild proximal aortic dilation. One potential alternative to treat the disease of both the distal aorta and the iliac arteries is the use of unibody stent-grafts. The AFX (Endologix) stent-graft is a unibody, low-profile endograft aimed to treat abdominal aortic aneurysms. The particular configuration of this device and its so-called anatomical fixation make it potentially an optimal solution to overcome the issue reported before inherent to AIOD treatment. This device presents a unique design with its long main body and two innate limbs and is designed to be deployed and sits on the native aortoiliac bifurcation and represents the only one-piece bifurcated endograft designed to use anatomical fixation for endograft stabilization. The AFX device consists of a main bifurcated body and a proximal aortic extension, which fix firmly to the aorta and provides sealing while reducing the possibility of stent's migration at the same time. The skeleton of the device is made of a cobalt-chromium alloy in a multilinked self-expanding unibody. External to the stent, the fabric is made of multilayer ePTFE material (STRATA). The stent is attached only to the proximal and distal ends at the proximal aortic extension and allows ePTFE to move independently and conform to abnormal surfaces, facilitating the sealing of the sac. According to published literature, the unibody device seems to represent a valid choice in the treatment of abdominal aortic aneurysms, but this particular device would seem to satisfactorily perform even in the treatment of occlusive pathologies and recently has become part of our clinical practice. Theoretical advantages of AFX (Endologix) are: Unibody design preserves aortic bifurcation, thanks to its anatomical fixation, as described previously. Unlike kissing stents (covered or uncovered), which can often protrude into the native aorta, disrupting flow and functionally raising the aortic bifurcation, a unibody device sits on and preserves the native bifurcation. This makes future "up-and-over" interventions to the lower extremities less technically challenging. Compared to CERAB, by using fewer stents in the narrow aorta, this technique has the added advantage of minimizing potential flow disturbances introduced by multiple covered stents. Graft fabric reduces neointimal hyperplasia: there is some evidence, including the randomized COBEST trial, that covered stents may be less likely to restenose or occlude than bare metal stents, particularly in TASC C and D lesions. This may be because the graft fabric represents a direct barrier to tissue ingrowth from neo-intimal hyperplasia. No limb competition in narrow bifurcation, thanks to its unibody design. Unibody stent-graft is protective in cases of potential ruptures, such as in heavily calcified lesions. Coverage of the entire diseased aorta may reduce atheroembolic risk. Using this covered graft and positioning it proximal and distal to the limits of disease effectively traps atherosclerotic material that could potentially embolize during device deployment, reducing atheroembolic risk. As with any new treatment alternative, this treatment strategy has limitations. Compared with the placement of kissing stents, or even the CERAB technique, the AFX (Endologix) device requires a larger profile sheath (17-Fr ipsilateral sheath, 9-Fr contralateral). Placing a stent-graft also has a higher potential for coverage of collateral vessels. The procedure is more time-consuming and requires a higher level of endovascular technical skill. Finally, while cost-effectiveness cannot be evaluated without robust efficacy data and will fluctuate based upon local differences in costs, use of the AFX (Endologix) unibody stent-graft is likely to be more expensive than kissing stent placement. The aim of the study is to evaluate the patency rates, safety, and efficacy of the AFX unibody stent-graft for the treatment of aortoiliac occlusive disease (AIOD), which may represent an additional technique in the endovascular treatment of this disease. The results will demonstrate whether the AFX (Endologix) stent graft is effective for the treatment of AIOD, in particular in more complex lesions (TASC C and D). The effectiveness will be evaluated in terms of patency (primary, assisted and secondary), technical success, clinical success, and quality of life improvement. Other objectives are the evaluation of procedure-related adverse events and re-interventions, as well as operative details. Nowadays, kissing stenting (KS) technique and the CERAB technique are considered the standard of care in the endovascular treatment of AIOD. However, patency rates and clinical success of the endovascular treatment, especially in the mid- and long- term, are still lower than the classic aorto-femoral bypass. Many aspects like the preservation of the aortic bifurcation, neointimal hyperplasia, limb competition, potential rupture, and atheroembolic risk are challenging problems that the endovascular surgeon has to face to improve the outcomes of the endovascular treatment. In vitro studies have investigated hemodynamic aspects15 but only three other groups have previously discussed their experience with this technique showing encouraging early- and mid-term results. Compared to other endovascular procedures, AFX (Endologix) unibody endograft shows many risks and disadvantages: It is a more invasive procedure with a larger introducer (19F+7F), which may need a surgical access The cost of the procedure is higher if compared to KS (but similar to CERAB) The endograft has a risk of fabric laceration with high calcium volume Very low chronic outward force (COF) of the Elgiloy stent Study Type Observational Enrollment (Anticipated) 100 Contacts and Locations This section provides the contact details for those conducting the study, and information on where this study is being conducted. Study Contact Name : Francesco Andreoli, MD Phone Number : +393405794971 Email : [email protected] Study Locations Italy Modena Baggiovara, Modena, Italy, 41126 Recruiting AOU di Modena Contact: Roberto Silingardi, Prof. Phone Number : +390593961225 Email : [email protected] Participation Criteria Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments. Eligibility Criteria Ages Eligible for Study 18 years and older (Adult, Older Adult) Accepts Healthy Volunteers N/A Genders Eligible for Study All Sampling Method Non-Probability Sample Study Population Patients affected by AIOD classified as TASC B, C or D involving aortic bifurcation and or the first 5mm of one of both common iliacs with indication to endovascular treatment enrolled at the Unit of Vascular Surgery of the Ospedale Civile di Baggiovara (Azienda Ospedaliero-Universitaria di Modena) and fulfilling the previous inclusion criteria. The Investigators (3 experts Vascular surgeons) will screen the patients for inclusion. Once the patient's eligibility will be stated, informed consent will be collected and the study could take place. Description Inclusion Criteria: Age >18; Both sex; Preoperative 2.5mm CTA available; Written informed consent; Patients affected by AIOD classified as TASC B (with aortic involvement) C or D involving aortic bifurcation and or the first 5mm of one of both common iliacs; Treated in the coordinator center or in one of the study's participating center's; With a calcium volume in target zone based on real lumen of less than 20% and absence of circumferential calcifications; Minimum follow-up requested: 3-months, 12-18 months and 5-years CTA; clinical and DUS examination at 6- and 12- and 36-months after the intervention and yearly thereafter. Exclusion Criteria: Age<18; No preoperative 2.5mm CTA available; Refused to sign the informed consent; Treated outside the coordinator centers or in one of the study's participating centers; Refusal to adhere to the requested follow-up; Patients affected by AIOD classified as TASC A or not involving aortic bifurcation or the first 5mm of one of both common iliacs; With a calcium volume in target zone based on real lumen of more than 20% and presence of circumferential calcifications; Study Plan This section provides details of the study plan, including how the study is designed and what the study is measuring. How is the study designed? Design Details Observational Models : Cohort Time Perspectives : Prospective Number of groups / cohorts 1 Cohorts and Interventions Group / Cohort Intervention / Treatment Treatment Group Patients affected by AIOD classified as TASC B, C or D involving aortic bifurcation and or the first 5mm of one of both common iliacs treated with the unibody endograft AFX (Endologix, Irvine, Calif) Device: EVAR off-label use Normally a femoral access was used, although a brachial approach can be useful for crossing total occlusions. For TASC B and C lesions, predilatation of the iliac lesions is advisable, while for TASC D it is mandatory. In case of total aortic occlusions, the procedure demands that recanalization of the distal aorta occurs as close as possible to the bifurcation.. The key technique is to recanalize from one common iliac artery into the opposing snaring the wire to create a femoral-femoral crossover. The femoral-femoral wire is then replaced with a MPA catheter; the SurePass wire attached to the contralateral limb is then passed through the catheter. The sheath can be placed within 5 cm of the aortic bifurcation, and the AFX can be delivered through the common iliac and aortic occlusion. Predilatation were performed with bilateral 6-8 mm x 150 mm balloons and or progressive dilatators. Other Names: Aorto-iliac recanalization with an abdominal aortic endograft What is the study measuring? Primary Outcome Measures Outcome Measure Measure Description Time Frame Patency rate Time Frame: through study completion, an average of 30 days (short), 1-year (mid) and 5-years (long)". short-, mid- and long-term patency rate (primary, assisted and secondary). Primary patency was defined as uninterrupted flow in the treated aortoiliac segment without occlusion or reintervention. Primary-assisted patency was defined as uninterrupted flow in the treated segment, allowing for reintervention for hemodynamically significant lesions in order to prevent occlusion. Secondary patency was defined as patency of the treated allowing for reintervention for occlusion. through study completion, an average of 30 days (short), 1-year (mid) and 5-years (long)". Secondary Outcome Measures Outcome Measure Measure Description Time Frame Technical success Time Frame: within 24 hours of procedure conclusion Technical success, defined as insertion of the endograft with flow into both iliac arteries at the conclusion of the procedure. within 24 hours of procedure conclusion Clinical Success Time Frame: through study completion, an average of 30 days (short), 1-year (mid) and 5-years (long)". clinical success was defined as freedom from device-related death, conversion to open repair and graft limb thrombosis through study completion, an average of 30 days (short), 1-year (mid) and 5-years (long)". Freedom from procedure related re-intervention and Adverse events Time Frame: through study completion, an average 2-years. Adverse events are defined as any systemic or local complication directly related to the procedure. Adverse events that occurred in the first 30-day were considered procedure-related, unless differently demonstrated. Re-intervention were defined as any open surgical or endovascular procedure performed two correct an adverse events related to the procedure and/or device through study completion, an average 2-years. Quality of life change Time Frame: through study completion, an average 2-years. Improvement of quality of life will be measured as improvement of claudication interval through study completion, an average 2-years. Rutherford scale change Time Frame: through study completion, an average 2-years. Rutherford scale measures the severity of peripheral artery disease from a range of category between 0 (asymptomatic) to 6 (severe gangrene) through study completion, an average 2-years. Cange of Ankle Brachial Index Time Frame: through study completion, an average 2-years. Ankle Brachial Index (ABI) measures the ratio to the pressure at the anke and at the arm. It measures the grade of lower limb ischemia and range from 1.2 (normal) to 0 (critical ischemia). through study completion, an average 2-years. Risk factor analysis Time Frame: through study completion, an average of 30 days (short), 1-year (mid) and 5-years (long)". Analysis of anatomical and preoperative factors afflicting the primary outcomes. through study completion, an average of 30 days (short), 1-year (mid) and 5-years (long)". Collaborators and Investigators This is where you will find people and organizations involved with this study. Sponsor Azienda Ospedaliero-Universitaria di Modena Collaborators Azienda Ospedaliero, Universitaria Pisana Careggi Hospital Arcispedale Santa Maria Nuova-IRCCS Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari Ospedale Policlinico San Martino Azienda Policlinico Umberto I S. Andrea Hospital Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo Azienda Ospedaliera Sant'Anna Publications and helpful links The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study. General Publications Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG; TASC II Working Group, Bell K, Caporusso J, Durand-Zaleski I, Komori K, Lammer J, Liapis C, Novo S, Razavi M, Robbs J, Schaper N, Shigematsu H, Sapoval M, White C, White J, Clement D, Creager M, Jaff M, Mohler E 3rd, Rutherford RB, Sheehan P, Sillesen H, Rosenfield K. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg. 2007;33 Suppl 1:S1-75. doi: 10.1016/j.ejvs.2006.09.024. Epub 2006 Nov 29. No abstract available. Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylor AR, Roffi M, Rother J, Sprynger M, Tendera M, Tepe G, Venermo M, Vlachopoulos C, Desormais I; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018 Mar 1;39(9):763-816. doi: 10.1093/eurheartj/ehx095. No abstract available. Grimme FA, Goverde PA, Van Oostayen JA, Zeebregts CJ, Reijnen MM. Covered stents for aortoiliac reconstruction of chronic occlusive lesions. J Cardiovasc Surg (Torino). 2012 Jun;53(3):279-89. Sabri SS, Choudhri A, Orgera G, Arslan B, Turba UC, Harthun NL, Hagspiel KD, Matsumoto AH, Angle JF. Outcomes of covered kissing stent placement compared with bare metal stent placement in the treatment of atherosclerotic occlusive disease at the aortic bifurcation. J Vasc Interv Radiol. 2010 Jul;21(7):995-1003. doi: 10.1016/j.jvir.2010.02.032. Epub 2010 Jun 11. Mwipatayi BP, Thomas S, Wong J, Temple SE, Vijayan V, Jackson M, Burrows SA; Covered Versus Balloon Expandable Stent Trial (COBEST) Co-investigators. A comparison of covered vs bare expandable stents for the treatment of aortoiliac occlusive disease. J Vasc Surg. 2011 Dec;54(6):1561-70. doi: 10.1016/j.jvs.2011.06.097. Epub 2011 Sep 9. Goverde PC, Grimme FA, Verbruggen PJ, Reijnen MM. Covered endovascular reconstruction of aortic bifurcation (CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease. J Cardiovasc Surg (Torino). 2013 Jun;54(3):383-7. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, Jones DN. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg. 1997 Sep;26(3):517-38. doi: 10.1016/s0741-5214(97)70045-4. Erratum In: J Vasc Surg 2001 Apr;33(4):805. Maldonado TS, Westin GG, Jazaeri O, Mewissen M, Reijnen MM, Dwivedi AJ, Garrett HE Jr, Dias Perera A, Shimshak T, Mantese V, Smolock CJ, Arthurs ZM. Treatment of Aortoiliac Occlusive Disease with the Endologix AFX Unibody Endograft. Eur J Vasc Endovasc Surg. 2016 Jul;52(1):64-74. doi: 10.1016/j.ejvs.2016.04.003. Epub 2016 May 6. Upchurch GR, Dimick JB, Wainess RM, Eliason JL, Henke PK, Cowan JA, Eagleton MJ, Srivastava SD, Stanley JC. Diffusion of new technology in health care: the case of aorto-iliac occlusive disease. Surgery. 2004 Oct;136(4):812-8. doi: 10.1016/j.surg.2004.06.019. Sharafuddin MJ, Hoballah JJ, Kresowik TF, Sharp WJ, Golzarian J, Sun S, Corson JD. Long-term outcome following stent reconstruction of the aortic bifurcation and the role of geometric determinants. Ann Vasc Surg. 2008 May-Jun;22(3):346-57. doi: 10.1016/j.avsg.2007.12.013. Epub 2008 Apr 14. Saratzis A, Salem M, Sabbagh C, Abisi S, Huasen B, Egun A, Nash J, Lau PF, Chaudhuri A, Dey R, Patrone L, Malina M, Davies R, Zayed H. Treatment of Aortoiliac Occlusive Disease With the Covered Endovascular Reconstruction of the Aortic Bifurcation (CERAB) Technique: Results of a UK Multicenter Study. J Endovasc Ther. 2021 Oct;28(5):737-745. doi: 10.1177/15266028211025028. Epub 2021 Jun 23. Reijnen MM. Update on covered endovascular reconstruction of the aortic bifurcation. Vascular. 2020 Jun;28(3):225-232. doi: 10.1177/1708538119896197. Epub 2020 Jan 2. Sirignano P, Silingardi R, Mansour W, Andreoli F, Migliari M, Speziale F. Unibody bifurcated aortic endograft: device description, review of the literature and future perspectives. Future Cardiol. 2021 Aug;17(5):793-804. doi: 10.2217/fca-2020-0119. Epub 2020 Nov 23. Silingardi R, Sirignano P, Andreoli F, Mansour W, Migliari M, Speziale F; LIVE Study Collaborators. Unibody Endograft Using AFX 2 for Less Invasive and Faster Endovascular Aortic Repair: Protocol for a Multicenter Nonrandomized Study. JMIR Res Protoc. 2020 Apr 6;9(4):e16959. doi: 10.2196/16959. Erratum In: JMIR Res Protoc. 2020 Jun 24;9(6):e20698. Kouvelos GN, Nana P, Bouris V, Peroulis M, Drakou A, Rousas N, Giannoukas A, Matsagkas MI. Initial Clinical Experience with the Endologix AFX Unibody Stent Graft System for Treating Patients with Abdominal Aortic Aneurysms: A Case Controlled Comparative Study. Vasc Specialist Int. 2017 Mar;33(1):16-21. doi: 10.5758/vsi.2017.33.1.16. Epub 2017 Mar 31. Chong A, Mirgolbabaee H, Sun Z, van de Velde L, Jansen S, Doyle B, Versluis M, Reijnen MMPJ, Groot Jebbink E. Hemodynamic Comparison of Stent-Grafts for the Treatment of Aortoiliac Occlusive Disease. J Endovasc Ther. 2021 Aug;28(4):623-635. doi: 10.1177/15266028211016431. Epub 2021 Jun 2. Van Haren RM, Goldstein LJ, Velazquez OC, Karmacharya J, Bornak A. Endovascular treatment of TransAtlantic Inter-Society Consensus D aortoiliac occlusive disease using unibody bifurcated endografts. J Vasc Surg. 2017 Feb;65(2):398-405. doi: 10.1016/j.jvs.2016.08.084. Epub 2016 Oct 17. Arnold A, Delaney CL, Wong YT, Wise N, Puckridge PJ. Reconstruction of the aorto-iliac segment in occlusive disease using the AFX unibody graft. ANZ J Surg. 2020 Dec;90(12):2496-2501. doi: 10.1111/ans.16236. Epub 2020 Aug 23. Georgakarakos E, Ioannidis G, Koutsoumpelis A, Papatheodorou N, Argyriou C, Spanos K, Giannoukas AD, Georgiadis GS. Tauhe AFX unibody bifurcated unibody aortic endograft for the treatment of abdominal aortic aneurysms: current evidence and future perspectives. Expert Rev Med Devices. 2020 Jan;17(1):5-15. doi: 10.1080/17434440.2020.1704254. Epub 2019 Dec 20. Study record dates These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website. Study Major Dates Study Start (Anticipated) December 1, 2022 Primary Completion (Anticipated) March 1, 2024 Study Completion (Anticipated) January 1, 2029 Study Registration Dates First Submitted October 31, 2022 First Submitted That Met QC Criteria November 4, 2022 First Posted (Actual) November 14, 2022 Study Record Updates Last Update Posted (Actual) November 17, 2022 Last Update Submitted That Met QC Criteria November 14, 2022 Last Verified November 1, 2022 More Information Terms related to this study Keywords EVAR AIOD Unibody endograft Additional Relevant MeSH Terms Cardiovascular Diseases Vascular Diseases Arterial Occlusive Diseases Other Study ID Numbers ASTUTE Plan for Individual participant data (IPD) Plan to Share Individual Participant Data (IPD)? Undecided Drug and device information, study documents Studies a U.S. FDA-regulated drug product No Studies a U.S. FDA-regulated device product Yes product manufactured in and exported from the U.S. Yes This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected] . As soon as a change is implemented on clinicaltrials.gov , this will be updated automatically on our website as well. Clinical Trials on Occlusive Arterial Disease NCT05929313 Recruiting Scoreflex TRIO - Scoring PTCA Catheter Coronary Arteriosclerosis NCT05923580 Not yet recruiting Group-based Cardiac Telerehabilitation and Its Effectiveness Coronary Artery Disease NCT05923489 Not yet recruiting Routine Angiography Follow-Up After Percutaneous Coronary Intervention in High-Risk Patients Coronary Artery Disease NCT05922137 Not yet recruiting Oriental Intervention for Enhanced Neurocognitive Health (ORIENT) Diet in Patients With Intracranial / Carotid Stenosis (ORIENT) Dementia | Cognitive Change | Cognitive Decline | Stenosis NCT05921266 Not yet recruiting Urolithin A Supplementation in Middle-aged Adults With Obesity Obesity | Cognitive Impairment | Vascular Dementia NCT05918380 Recruiting Project 3: ACHIEVE- CHD Coronary Heart Disease NCT05916898 Recruiting The Lower Silesia Shockwave Registry (LSSR) Safety Issues | Efficacy, Self NCT05916664 Recruiting Efficacy Study of Kinto Care Coaching for Dementia Family Caregivers Dementia | Alzheimer Disease | Lewy Body Disease | Frontotemporal Dementia | Vascular Dementia | Mixed Dementia NCT05916950 Not yet recruiting The THOR IDE Study (THOR) Peripheral Artery Disease | PAD | Peripheral Artery Stenosis | Peripheral Artery Calcification NCT05915468 Not yet recruiting Large De-NOVo Coronary artEry Disease Treated With Sirolimus Drug Eluting Balloon (LOVE DEB) Coronary Artery Disease Sponsors and Collaborators Assistance Publique - Hôpitaux de Paris Arbor Life Labs Cairo University Mayo Clinic University of the Sciences in Philadelphia the ministry of knowledge economy University Medical Center, Kazakhstan targomedGmbH National Cancer Institute (NCI) Assiut University Stockholm Spine Center AB Sanvello M.D. Anderson Cancer Center Osteovox Mälardalen University Pfizer Novartis Pharmaceuticals AstraZeneca GlaxoSmithKline GI Supply View Full List Medical Conditions Asthma Post-dural Puncture Headache Platelet Abnormality Adenosarcoma Locally Advanced Skin Squamous Cell Carcinoma Coronary Artery Disease Non-sedative Endoscopy HIV Infections Prostate Cancer Depression Graft Detachment Obesity Hypertension Pain Breast Cancer Stroke Land O' Lakes-supported Dairy Cooperatives Ketosis Prone Diabetes Stage 0 Chronic Lymphocytic Leukemia Pharmacokinetics of Fluorouracil Bolus (5-FU) View Full List Drug Interventions Cisplatin MK1903 TAK-733 Comparator: glipizide Dasatinib 100 MG + Quercetin (1250 MG) HMI-103 carboplatin Prednisone 50 mg LX3305 QD Bevacizumab Ferrous succinate Docetaxel Gemcitabine paclitaxel anlotinib 10mg + AP/PC low-volume preparation (10 mg bisacodyl plus 2L PEG-ELS) Phacolin eye drops Capecitabine Cyclophosphamide Dexamethasone View Full List CROs by country Contract Research Organizations in Argentina Contract Research Organizations in Bahamas Contract Research Organizations in Burundi Contract Research Organizations in Gabon Contract Research Organizations in Germany Contract Research Organizations in Guinea Contract Research Organizations in Japan Contract Research Organizations in Mauritania Contract Research Organizations in Montenegro Contract Research Organizations in Panama Contract Research Organizations in South Korea Contract Research Organizations in Sri Lanka Contract Research Organizations in Zambia CRO list by country CROs in Colombia Syneos Health Clinlogix PRA Health Sciences NAMSA SGS EGCP S.A. (Excellence in Good Clinical Practice) bioaccess Labcorp Drug Development PPD Coltrials SAS All CROs in Colombia Conditions Alphabetic (A-Z) By Category Rare Diseases Alphabetic (A-Z) Drug Interventions Alphabetic (A-Z) By Category Dietary Supplements Alphabetic (A-Z) By Category Sponsor/Collaborators Alphabetic (A-Z) By Category Locations Alphabetic (A-Z) By Category Regulations GLOBAL (ICH GCP) USA (FDA) UK (MHRA) AUSTRALIA (NHMRC) JAPAN (PMDA) EU (EMA) Resources CRO List Pharmaceutical Companies Clinical Research Labs Service Companies Jobs US Clinical Trials Registry EU Clinical Trials Registry Articles Publications News About us / Our mission Search trials Example: Heart Attack
https://ichgcp.net/clinical-trials-registry/NCT05614856
U.S. Census Bureau QuickFacts: Passaic County, New Jersey; United States; New Jersey; Hunterdon County, New Jersey; Somerset County, New Jersey; Camden County, New Jersey Frequently requested statistics for: Passaic County, New Jersey; United States; New Jersey; Hunterdon County, New Jersey; Somerset County, New Jersey; Camden County, New Jersey U.S. Census Bureau QuickFacts: Passaic County, New Jersey; United States; New Jersey; Hunterdon County, New Jersey; Somerset County, New Jersey; Camden County, New Jersey Please note that new Connecticut county level geographies are not availabe within the map. An official website of the United States government Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock A locked padlock ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites. What's New & FAQs QuickFacts Passaic County, New Jersey; United States; New Jersey; Hunterdon County, New Jersey; Somerset County, New Jersey; Camden County, New Jersey QuickFacts provides statistics for all states and counties, and for cities and towns with a population of 5,000 or more . -- Select a fact -- Population Estimates, July 1, 2022, (V2022) Population estimates base, April 1, 2020, (V2022) Population, percent change - April 1, 2020 (estimates base) to July 1, 2022, (V2022) Population, Census, April 1, 2020 Population, Census, April 1, 2010 Persons under 5 years, percent Persons under 18 years, percent Persons 65 years and over, percent Female persons, percent White alone, percent Black or African American alone, percent (a) American Indian and Alaska Native alone, percent (a) Asian alone, percent (a) Native Hawaiian and Other Pacific Islander alone, percent (a) Two or More Races, percent Hispanic or Latino, percent (b) White alone, not Hispanic or Latino, percent Veterans, 2017-2021 Foreign born persons, percent, 2017-2021 Housing units, July 1, 2022, (V2022) Owner-occupied housing unit rate, 2017-2021 Median value of owner-occupied housing units, 2017-2021 Median selected monthly owner costs -with a mortgage, 2017-2021 Median selected monthly owner costs -without a mortgage, 2017-2021 Median gross rent, 2017-2021 Building permits, 2022 Households, 2017-2021 Persons per household, 2017-2021 Living in same house 1 year ago, percent of persons age 1 year+, 2017-2021 Language other than English spoken at home, percent of persons age 5 years+, 2017-2021 Households with a computer, percent, 2017-2021 Households with a broadband Internet subscription, percent, 2017-2021 High school graduate or higher, percent of persons age 25 years+, 2017-2021 Bachelor's degree or higher, percent of persons age 25 years+, 2017-2021 With a disability, under age 65 years, percent, 2017-2021 Persons without health insurance, under age 65 years, percent In civilian labor force, total, percent of population age 16 years+, 2017-2021 In civilian labor force, female, percent of population age 16 years+, 2017-2021 Total accommodation and food services sales, 2017 ($1,000) (c) Total health care and social assistance receipts/revenue, 2017 ($1,000) (c) Total transportation and warehousing receipts/revenue, 2017 ($1,000) (c) Total retail sales, 2017 ($1,000) (c) Total retail sales per capita, 2017 (c) Mean travel time to work (minutes), workers age 16 years+, 2017-2021 Median household income (in 2021 dollars), 2017-2021 Per capita income in past 12 months (in 2021 dollars), 2017-2021 Persons in poverty, percent Total employer establishments, 2021 Total employment, 2021 Total annual payroll, 2021 ($1,000) Total employment, percent change, 2020-2021 Total nonemployer establishments, 2019 All employer firms, Reference year 2017 Men-owned employer firms, Reference year 2017 Women-owned employer firms, Reference year 2017 Minority-owned employer firms, Reference year 2017 Nonminority-owned employer firms, Reference year 2017 Veteran-owned employer firms, Reference year 2017 Nonveteran-owned employer firms, Reference year 2017 Population per square mile, 2020 Population per square mile, 2010 Land area in square miles, 2020 Land area in square miles, 2010 Clear   6 Table Map   Passaic County, New Jersey  United States  New Jersey  Hunterdon County, New Jersey  Somerset County, New Jersey  Camden County, New Jersey  More Print CSV Email Map TIGERweb Population Estimates, July 1, 2022, (V2022) - - - - - Populations below 5,000 are not in QuickFacts and therefore Not Selectable Selectable Not Selectable Value Notes   Estimates are not comparable to other geographic levels due to methodology differences that may exist between different data sources. Some estimates presented here come from sample data, and thus have sampling errors that may render some apparent differences between geographies statistically indistinguishable. ] Click the Quick Info  icon to the left of each row in TABLE view to learn about sampling error. In Vintage 2022, as a result of the formal request from the state, Connecticut transitioned from eight counties to nine planning regions. For more details, please see the Vintage 2022 release notes available here: Release Notes. The vintage year (e.g., V2022) refers to the final year of the series (2020 thru 2022). Different vintage years of estimates are not comparable. Users should exercise caution when comparing 2017-2021 ACS 5-year estimates to other ACS estimates. For more information, please visit the 2021 5-year ACS Comparison Guidance page. Fact Notes (a) Includes persons reporting only one race (c) Economic Census - Puerto Rico data are not comparable to U.S. Economic Census data (b) Hispanics may be of any race, so also are included in applicable race categories Value Flags - Either no or too few sample observations were available to compute an estimate, or a ratio of medians cannot be calculated because one or both of the median estimates falls in the lowest or upper interval of an open ended distribution. F Fewer than 25 firms D Suppressed to avoid disclosure of confidential information N Data for this geographic area cannot be displayed because the number of sample cases is too small. FN Footnote on this item in place of data X Not applicable S Suppressed; does not meet publication standards NA Not available Z Value greater than zero but less than half unit of measure shown QuickFacts data are derived from: Population Estimates, American Community Survey, Census of Population and Housing, Current Population Survey, Small Area Health Insurance Estimates, Small Area Income and Poverty Estimates, State and County Housing Unit Estimates, County Business Patterns, Nonemployer Statistics, Economic Census, Survey of Business Owners, Building Permits. Close Close Please Note! Close CONNECT WITH US Information Quality Data Linkage Infrastructure Data Protection and Privacy Policy Accessibility FOIA Inspector General No FEAR Act U.S. Department of Commerce USA.gov Measuring America's People, Places, and Economy  Is this page helpful? Yes No  Thank you for your feedback. Comments or suggestions?  Comments or suggestions? 255 characters maximum ⚠ 255 characters maximum reached NO THANKS SUBMIT
https://www.census.gov/quickfacts/fact/map/passaiccountynewjersey,US,NJ,hunterdoncountynewjersey,somersetcountynewjersey,camdencountynewjersey/PST045222
J. Compos. Sci. | Free Full-Text | Sustainable Composites from Waste Sulfur, Terpenoids, and Pozzolan Cements Sulfur cements have drawn significant attention as binders because sulfur is a byproduct of fossil fuel refining. Sulfur cements that can be formed by the vulcanization of elemental sulfur and plant-derived olefins such as terpenoids are particularly promising from a sustainability standpoint. A range of terpenoid–sulfur cements have shown compressional and flexural properties exceeding those of some commercial structural mineral cements. Pozzolans such as fly ash (FA), silica fume (SF), and ground granulated blast furnace slag (GGBFS) and abundant clay resources such as metakaolin (MK) are attractive fines for addition to binders. Herein, we report 10 composites prepared by a combination of sulfur, terpenoids (geraniol or citronellol), and these pozzolans. This study reveals the extent to which the addition of the pozzolan fines to the sulfur–terpenoid cements influences their mechanical properties and chemical resistance. The sulfur–terpenoid composites CitS and GerS were prepared by the reaction of 90 wt% sulfur and 10 wt% citronellol or geraniol oil, respectively. The density of the composites fell within the range of 1800–1900 kg/m3 and after 24 h submersion in water at room temperature, none of the materials absorbed more than 0.7 wt% water. The compressional strength of the as-prepared materials ranged from 9.1–23.2 MPa, and the percentage of compressional strength retained after acid challenge (submersion in 0.1 M H2SO4 for 24 h) ranged from 80–100%. Incorporating pozzolan fines into the already strong CitS (18.8 MPa) had negligible effects on its compressional strength within the statistical error of the measurement. CitS-SF and CitS-MK had slightly higher compressive strengths of 20.4 MPa and 23.2 MPa, respectively. CitS-GGBFS and CitS-FA resulted in slightly lower compressive strengths of 17.0 MPa and 15.8 MPa, respectively. In contrast, the compressional strength of initially softer GerS (11.7 MPa) benefited greatly after incorporating hard mineral fines. All GerS derivatives had higher compressive strengths than GerS, with GerS-MK having the highest compressive strength of 19.8 MPa. The compressional strengths of several of the composites compare favorably to those required by traditional mineral cements for residential building foundations (17 MPa), whereas such mineral products disintegrate upon similar acid challenge. Sustainable Composites from Waste Sulfur, Terpenoids, and Pozzolan Cements Authors to whom correspondence should be addressed. J. Compos. Sci. 2023 , 7 (1), 35; https://doi.org/10.3390/jcs7010035 Received: 29 October 2022 / Revised: 12 December 2022 / Accepted: 30 December 2022 / Published: 11 January 2023 (This article belongs to the Special Issue Recycled Polymer Composites: Futuristic Sustainable Material ) Abstract Sulfur cements have drawn significant attention as binders because sulfur is a byproduct of fossil fuel refining. Sulfur cements that can be formed by the vulcanization of elemental sulfur and plant-derived olefins such as terpenoids are particularly promising from a sustainability standpoint. A range of terpenoid–sulfur cements have shown compressional and flexural properties exceeding those of some commercial structural mineral cements. Pozzolans such as fly ash (FA), silica fume (SF), and ground granulated blast furnace slag (GGBFS) and abundant clay resources such as metakaolin (MK) are attractive fines for addition to binders. Herein, we report 10 composites prepared by a combination of sulfur, terpenoids (geraniol or citronellol), and these pozzolans. This study reveals the extent to which the addition of the pozzolan fines to the sulfur–terpenoid cements influences their mechanical properties and chemical resistance. The sulfur–terpenoid composites CitS and GerS were prepared by the reaction of 90 wt% sulfur and 10 wt% citronellol or geraniol oil, respectively. The density of the composites fell within the range of 1800–1900 kg/m 3 and after 24 h submersion in water at room temperature, none of the materials absorbed more than 0.7 wt% water. The compressional strength of the as-prepared materials ranged from 9.1–23.2 MPa, and the percentage of compressional strength retained after acid challenge (submersion in 0.1 M H 2 SO 4 for 24 h) ranged from 80–100%. Incorporating pozzolan fines into the already strong CitS (18.8 MPa) had negligible effects on its compressional strength within the statistical error of the measurement. CitS-SF and CitS-MK had slightly higher compressive strengths of 20.4 MPa and 23.2 MPa, respectively. CitS-GGBFS and CitS-FA resulted in slightly lower compressive strengths of 17.0 MPa and 15.8 MPa, respectively. In contrast, the compressional strength of initially softer GerS (11.7 MPa) benefited greatly after incorporating hard mineral fines. All GerS derivatives had higher compressive strengths than GerS, with GerS-MK having the highest compressive strength of 19.8 MPa. The compressional strengths of several of the composites compare favorably to those required by traditional mineral cements for residential building foundations (17 MPa), whereas such mineral products disintegrate upon similar acid challenge. Keywords: sustainable composite ; terpenoid ; sulfur ; hybrid organic–inorganic composite ; sulfur cement ; polymer cement 1. Introduction The modern infrastructure of human civilization—roads, bridges, houses, etc.—is largely built from cement and petrochemical products. The ecological toll of cement and plastic manufacturing is staggering [ 1 , 2 , 3 , 4 ]. There is a clear and pressing need to develop alternative structural goods that can be recycled or synthesized more sustainably, using renewably sourced or waste-product precursors [ 5 , 6 , 7 ]. The materials studied herein have the potential to serve as alternatives for ecologically less advantageous materials. Many terpenoid–sulfur cements have shown compressional and flexural properties surpassing those of some commercial structural mineral cements [ 8 , 9 , 10 , 11 ]. Terpenes and terpenoids are olefins that can be produced by a variety of plants, algae, and bacteria that have tremendous potential to replace petrochemical olefins and develop a greener economy [ 12 ]. In addition to naturally occurring plants, genetically engineered organisms have been designed to efficiently produce terpenoids [ 13 , 14 , 15 , 16 , 17 ], to the extent that techno-economic assessment suggests terpenoids are competitive with petrochemical olefins for some markets [ 18 , 19 ]. In durable structural materials, terpenoids have found use in more sustainable tars and bitumen for asphalt [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] and in sulfur cements/composite materials [ 8 , 9 , 10 ]. The sulfur used in sulfur cements is a byproduct of fossil fuel refining, which is annually produced in megaton quantities of unutilized material for valorization [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. Upon heating with olefins, sulfur undergoes a low-temperature (<200 °C) reaction to crosslink the olefins via a process known as inverse vulcanization ( Scheme 1 ) [ 31 , 38 ]. Whereas classic vulcanization is a process used for strengthening natural rubber, by reacting it with small amounts of sulfur and, thus, producing primarily materials, inverse vulcanization employs sulfur as the bulk component, so that more mineral-like strength profiles can be attained. The inverse vulcanization route is advantageous because it is both a simple and an up-to-100% atom-economical way of producing recyclable composites, which maintain favorable properties that are competitive with commercial materials [ 35 , 39 , 40 , 41 ]. As such, the inverse vulcanization process has been used to prepare high sulfur-content materials (HSMs) for a wide range of applications [ 34 , 35 , 36 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ] in lithium–sulfur batteries [ 50 , 51 , 54 , 55 , 56 ], infrared imaging [ 57 ], water purification [ 58 , 59 , 60 , 61 , 62 ], and fertilizers [ 46 , 63 , 64 ]. A wide range of sulfur cements has also been prepared by the inverse vulcanization of olefins [ 65 , 66 , 67 ]. In previous work, for example, we demonstrated that sulfur cements comprising fatty acids as the sustainable olefin source [ 7 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ] could be combined with pozzolanic fines from industrial waste such as fly ash (FA), silica fume (SF), or ground granulated blast-furnace slag (GGBFS) as well as abundant clay resources such as metakaolin (MK), to form a variety of durable composites. Mineral, industrial waste, and fiber fillers are all important for both extending composites and providing them with enhanced physical characteristics. Especially notable advances in these areas have been achieved in fiber-reinforced polymer materials [ 75 , 76 , 77 , 78 ]. Scheme 1. Heating elemental sulfur produces radicals that add to olefin π bonds to yield cross-linked high sulfur-content materials (HSMs) via a process known as inverse vulcanization. In the current work, it was of interest to evaluate the extent to which the addition of fines to sulfur–terpenoid cements influences their mechanical properties and chemical resistance. Sulfur–terpenoid cements comprising 90 wt% sulfur vulcanized with citronellol oil (CitS) or geraniol oil to yield (GerS) were used as the binders for these studies. The fines used for this study were FA, SF, GGBFS, and MK. Combination of the fines (10 wt%) with CitS binder yielded CitS-FA, CitS-SF, CitS-GGBFS, and CitS-MK, while combination with GerS binder produced composites GerS-FA, GerS-SF, GerS-GGBFS, and GerS-MK. The density, water uptake, and compressional strength before and after acid challenge were evaluated for the two binders alone as well as for the eight derivative composites. 2. Materials and Methods 2.1. Differential Scanning Calorimetry Differential scanning calorimetry (DSC) data were acquired using a Mettler Toledo (USA) DSC 3 STAR e System from −60 to 140 °C, with a heating rate of 5 °C min −1 under a flow of N 2 (200 mL min −1 ). Each DSC measurement was carried out over three heat–cool cycles to screen out thermal history. The data reported were taken from the third cycle of the experiment. The first cycle is used for removing solvent impurities. The melting and crystallization transitions as well as the glass-transition temperature were observed in the third cycle. 2.2. Compressional Measurements Compressional measurements were acquired on cylinders ( Figure 1 ) using a Mark-10 ES30 (USA) Manual Test Stand equipped with a Mark 10 M3-200 Force Gauge (USA) by a modified ASTM C39 standard. Terpenoid–sulfur composite materials were aged for 4 d prior to compressional strength testing. The four-day aging period was selected after assessing material properties over shorter and longer times for one set of samples, and the properties were leveled off after four days. Longer-term stability is not known for these materials. Figure 1. Representative photos of compressional cylinders of CitS-derived ( a ) and GerS-derived composites ( b ) before (upper row in each image) and after (lower row in each image) acid challenge. 2.3. Chemical Precursor Sources Terpenoids (Alfa Aesar, Ward Hill, MA, USA or Sigma-Aldrich, St. Louis, MO, USA) and elemental sulfur (99.5%, Alfa Aesar) were used without further purification. Fly ash (FA), silica fume (SF), and ground granulated blast-furnace slag (GGBFS) pozzolanic-cement components were purchased from Diversified Minerals, Inc., Oxnard, CA, USA, while metakaolin was manufactured by Opptipozz, Sandersville, GA, USA. 2.4. General Synthesis of Terpenoid–Sulfur Composites CAUTION: Heating elemental sulfur with organics can result in the formation of H 2 S gas. H 2 S is toxic, foul-smelling, and corrosive. This procedure follows the reported method [ 8 ]. A 180.0 g sample of elemental sulfur was added to a 2.5 L Erlenmeyer flask. The vessel was placed in a thermostat-controlled oil bath set to 180 °C and stirred with an overhead mechanical stirrer equipped with a stainless-steel stir rod and vane. Elemental sulfur was initially heated at 120 °C. Upon further heating, the viscosity of elemental sulfur increased, and a deep red color characteristic of polymeric sulfur radicals was observed. At this point, 20.0 g of citronellol for CitS or geraniol for GerS was added to the flask dropwise with rapid stirring for 35 min, over which time the color changed to a deep brown color. After cooling to room temperature, the materials were rigid brown to black solids that were readily remeltable and could be shaped into compressive test cylinders by pouring into silicone molds. A total of five independent samples were prepared for each measurement. 2.5. General Procedure for Addition of Fines to Binders CAUTION: Heating elemental sulfur with organics can result in the formation of H 2 S gas. H 2 S is toxic, foul-smelling, and corrosive. This procedure follows a reported method for adding fines to fatty acid–sulfur cements [ 37 ]. Approximately 27 g of the requisite binder was melted in a 125 mL Erlenmeyer flask equipped with a Teflon-coated magnetic stir bar. The flask was submerged in a thermostat-controlled oil bath set to 180 °C. Once the binder had fully melted, the corresponding pozzolan (10 wt%) was added with rapid stirring. After rapid stirring for 10 min, the mixture was removed from the heat, and cylinders for compressional analysis were prepared by pouring the molten mixture into silicone cylinder molds. 3. Results and Discussion 3.1. Component Properties and Preparation of Composites The binders for this study were terpenoid–sulfur cements prepared from the reaction of either geraniol oil or citronella oil with molten elemental sulfur at 180 °C for 35 min according to the reported procedure [ 8 ]. These particular terpenoids were selected for the current study because citronellol is a monounsaturated compound, whereas geraniol is a diunsaturated compound and, thus, is capable of additional crosslinking. The reaction of citronella oil or geraniol oil with 90 wt% sulfur, thus, led to CitS and GerS, respectively, as homogeneous brown solids ( Figure 1 ). These binders are remeltable to form a free-flowing brown liquid phase at temperatures above 120 °C. The thermal and morphological properties of CitS and GerS derived from differential scanning calorimetry (DSC) are summarized in Table 1 . The data in Table 1 are reported for the third heating cycle in each case, such that i) their thermal history effects can be removed and ii) their comparison to the reported data for other HSMs, which are also widely reported from the third heating cycle, is allowed. Table 1. Properties of terpenoid–sulfur cement binders and comparison to elemental sulfur (orthorhombic). The DSC data for all of the composites reflect the typical behavior observed in the third heating cycle of other high sulfur content materials (HSMs) [ 46 , 79 , 80 , 81 , 82 , 83 ]. The glass-transition temperature ( T g ) near −37 °C observable in the DSC thermogram is particularly notable, as it is the diagnostic for the polymeric sulfur domains and, thus, confirms that, as previously reported [ 8 ], the binders are covalently crosslinked network materials rather than physical blends of terpenoids with sulfur. The other features in the DSC thermograms correspond to a sulfur melting temperature ( T m ) near 118 °C, a monoclinic–orthorhombic crystal morphology transition near 106 °C, and cold crystallization features. Before adding fines, the binder crystallinity can be assessed by integrating thermal features according to Equation (1), reflecting the successful conversion of crystalline orthorhombic sulfur domains to amorphous polymeric sulfur domains in the structures [ 19 ]. Δ χ c = 1 − { Δ H m − Δ H c c Δ H m ( S ) − Δ H c c ( S ) } * 100 % (1) where Δ χ c , a dimensionless variable, is the change in the percentage of the crystallinity with respect to sulfur; Δ H m , in units of J/g, is the melting enthalpy of the binder material; Δ H c c , in units of J/g, is the cold crystallization enthalpy of the binder material; Δ H m ( S ) , in units of J/g, is the melting enthalpy of sulfur; and Δ H c c ( S ) , in units of J/g, is the cold crystallization enthalpy of sulfur. The pozzolans selected for the current study were fly ash (FA), silica fume (SF), and ground granulated blast-furnace slag (GGBFS) and the abundant clay resource metakaolin (MK). These materials were selected on the basis of their established utility as additives to more traditional mineral cements, affordability, abundance, thermal and chemical stability under planned composite preparation conditions, and, in the case of FS, SF, and GGBFS, classification as industrial waste products. Chemically, these fines are oxides or silicates of Ca, Si, Al, and Fe ( Table 2 ). The fineness moduli for these materials ( Table 2 ) were determined by weighing the particles passing through progressively finer ASTM-certified sieves (numbers 18, 30, 50, 100, and 200), according to the reported procedure [ 37 , 84 ]. Table 2. Fineness moduli ( F ) and compositions for pozzolans used in this study. The preparation of composites was effected by following a procedure from the literature for preparing composites of the same fines with an oleic acid–sulfur binder comprising 90 wt% sulfur [ 37 ]. Briefly, the binders were first melted down in an Erlenmeyer flask above its melting point of 120 °C. The requisite fine was then added with rapid mechanical stirring, and the stirring was continued for 10 min to ensure homogenization. Each molten composite mixture was poured into a series of cylindrical molds and allowed to set for four days, giving brown cylinders ( Figure 1 ). Scanning electron microscopy (SEM) imaging with element mapping by energy dispersive X-ray analysis (EDX) was undertaken to assess the distribution of the mineral components in the GerS-derived materials. SEM/EDX data previously reported for GerS showed a uniform, homogeneous distribution of S, C, and O in the absence of mineral additives. In the current case, the distribution of geraniol-derived C and of sulfur remained homogenously distributed in the composites, while well-dispersed particles high in Si and O content were also observed for the minerals ( Figure 2 ). Figure 2. SEM/EDX data for composites reveals the presence of mineral additive well-dispersed in the homogeneous GerS binder for the GerS-derived materials. 3.2. Physical and Mechanical Properties Several key metrics were assessed to evaluate the composites’ viability as structural materials. The density of the materials ( Table 3 ) is 1800–1900 kg/m 3 , thus meeting American Concrete Institute (ACI) standard ACI-213R and ASTM 169C guidelines for lightweight structural materials [ 85 , 86 ]. These densities are also similar to commercial composites such as fiber-reinforced resins (i.e., Lyondell Basell product BMC 940-21769, with a density = 1900 kg/m 3 ) and are slightly higher than the densities of composites made using ZOS 90 as the binder with FA (giving FAOS), SF (giving SFOS), GGBFS (giving GGBFSOS), and metakaolin (giving MKOS), with densities that range from 1600 to 1700 kg/m 3 . Table 3. Properties of composites and binders. Water uptake ( Table 3 ) is another critical metric for building applications due to the change in weight and strength of material after water absorption and the potential for product deterioration and failure resulting from cyclic freeze–thaw expansion and contraction. High sulfur-content materials (HSMs) generally have superior resistance to water absorption. The water uptake of the composites, as required under ASTM D570 by 24 h submersion at near room temperature, likewise confirmed that none of the materials absorb more than 0.7 wt% water, which is similar to the parent binder, despite the addition of 10 wt% of potentially hygroscopic mineral oxide/silicate fines. This observation is in line with the similar water-uptake values for the composites made using ZOS 90 as the binder. The low water uptake of sulfur cement–pozzolan composites stands in sharp contrast to the behavior of traditional mineral cements such as OPC, which absorb up to 28% water under identical testing conditions. The compressional strengths of the binders and terpenoid–sulfur-cement-derived composites are displayed in Figure 3 and are summarized in Table 1 along with the data for comparison to ZOS 90 and its derivative composites as well as metakaolin-based geopolymer cements. With the exception of GerS, the binders and derivative composites all exhibited compressional strength that was competitive with or exceeding that required (17 MPa) for cement foundations and footings for residential buildings (ACI specification 332.1R-06). The incorporation of fines into the already-strong CitS had a negligible impact on its compressional strength within the statistical error of the measurements. In contrast, and unsurprisingly, the compressional strength of the initially softer GerS benefited significantly from incorporating the hard mineral fines. The previously reported ZOS 90 -derived composites did not show such a predictable trend, with some of the composites showing improved compressional strength and others showing diminished compressional strength. Composites of fatty acid and sulfur, however, suffer from homogenization issues and have been shown to exhibit reactivity between the acidic fatty acid chains and some metal oxides. Such reactivity is not possible for the nonacidic terpenoids selected for the current study. Figure 3. Comparison of compressional strength before (blue bars) and after (green bars) exposure to 0.1 M H 2 SO 4 for 24 h. The compressive strength of the materials studied herein may also be compared to previously studied geopolymer cements with variable quantities of mineral additives. For example, a series of metakaolin geopolymer cements [ 87 ] was prepared including GCN x having x wt% calcium aluminate. These materials exhibited higher compressive strengths compared to the composites reported herein of the previously reported ZOS 90 and its derivative composites. These data reflect the superiority that purely mineral-based materials can hold over the HSM cements reported to date, despite some HSMs outperforming the ordinary Portland cement used in residential building contexts. Previous work has demonstrated that sulfur cements can exhibit some properties that are difficult for mineral products to attain, such as exceptional resistance to degradation by acid [ 88 ]. Whereas mineral cements such as OPC generally have very low resistance to acidic environments, some HSMs retain their full mechanical strength even after being submerged in acidic solutions for 24 h [ 41 ]. To assess the extent to which the current composites could withstand acid challenge, their compressional strengths were measured after the cylinders were submerged in 0.1 M H 2 SO 4 for 24 h, conditions under which OPC loses its structural and geometric integrity. The data from these analyses ( Table 3 and Figure 3 ) reveal that neither the binders nor the derivative composites exhibit any significant loss of compressional strength within the range of statistical error. 4. Conclusions Sulfur cements formed by inverse vulcanization of elemental sulfur and terpenoids show potential as sustainable alternatives for OPC and other traditional materials. Inverse vulcanization offers both a simple and highly atom-economical route for producing recyclable composites with favorable properties competitive with commercial materials. These properties include density, water uptake, compressive strength, and acid resistance. Adding pozzolans to CitS had fairly negligible effects on the compressive strength within standard error of measurements, so they could be used as fillers when economically advantageous, without any significant changes in application. The mechanical properties of GerS, however, benefited from the addition of pozzolans. Except for GerS, the compressional strength of the materials was similar or higher than required for cement foundations and footings for residential buildings (ACI specification 332.1R-06). The pozzolan–sulfur–terpenoid composites reported in this study, thus, hold potential as more sustainable alternatives for traditional cements and can be used in acid-contact contexts where ordinary Portland cement is susceptible to degradation. Work to build on the current study is underway to assess the influence of the quantity of the fines or other additives added to terpenoid–sulfur and other organic–sulfur cements, to explore the mechanical robustness of the composites over time, and to assess the influence of other chemical and physical strains on the long-term viability of the composites as cement surrogates. Author Contributions Conceptualization, R.C.S.; methodology, R.C.S.; formal analysis, K.A.T.; investigation, K.A.T.; resources, R.C.S. and A.G.T.; data curation, C.V.L., C.P.M. and K.A.T.; writing—original draft preparation, K.A.T. and R.C.S.; writing—review and editing, R.C.S., K.A.T., C.P.M. and C.V.L.; supervision, R.C.S. and A.G.T.; funding acquisition, R.C.S. All authors have read and agreed to the published version of the manuscript. Funding This research was funded by the National Science Foundation, grant number CHE-2203669. Data Availability Statement Data not available in the manuscript may be requested from the corresponding author ( [email protected] ). Conflicts of Interest The authors declare no conflict of interest. References Scrivener, K.L.; John, V.M.; Gartner, E.M. Eco-efficient cements: Potential economically viable solutions for a low-CO 2 cement-based materials industry. Cem. Concr. Res. 2018 , 114 , 2–26. [ Google Scholar ] [ CrossRef ] Jeong, J.; Choi, J. Adverse outcome pathways potentially related to hazard identification of microplastics based on toxicity mechanisms. Chemosphere 2019 , 231 , 249–255. [ Google Scholar ] [ CrossRef ] [ PubMed ] Cole, M.; Lindeque, P.; Halsband, C.; Galloway, T.S. Microplastics as contaminants in the marine environment: A review. Mar. Pollut. Bull. 2011 , 62 , 2588–2597. [ Google Scholar ] [ CrossRef ] Hidalgo-Ruz, V.; Gutow, L.; Thompson, R.C.; Thiel, M. Microplastics in marine environment review of methods for identification and quantification. Environ. Sci. Technol. 2012 , 46 , 3060–3075. [ Google Scholar ] [ CrossRef ] Lauer, M.K.; Smith, R.C. Recent advances in starch-based films towards food packaging applications: Physicochemical, mechanical, and functional properties. Compr. Rev. Food Sci. Food Saf. 2020 , 19 , 3031–3083. [ Google Scholar ] [ CrossRef ] [ PubMed ] Thiounn, T.; Smith, R.C. Advances and approaches for chemical recycling of plastic waste. J. Polym. Sci. 2020 , 58 , 1347–1364. [ Google Scholar ] [ CrossRef ][ Green Version ] Smith, A.D.; Smith, R.C.; Tennyson, A.G. Sulfur-Containing Polymers Prepared from Fatty Acid-Derived Monomers: Application of Atom-Economical Thiol-ene/Thiol-yne Click Reactions and Inverse Vulcanization Strategies. Sus. Chem. 2020 , 1 , 209–237. [ Google Scholar ] [ CrossRef ] Maladeniya, C.P.; Karunarathna, M.S.; Lauer, M.K.; Lopez, C.V.; Thiounn, T.; Smith, R.C. A Role for Terpenoid Cyclization in the Atom Economical Polymerization of Terpenoids with Sulfur to Yield Durable Composites. Mater. Adv. 2020 , 1 , 1665–1674. [ Google Scholar ] [ CrossRef ] Maladeniya, C.P.; Smith, R.C. Influence of Component Ratio on Thermal and Mechanical Properties of Terpenoid-Sulfur Composites. J. Compos. Sci. 2021 , 5 , 257. [ Google Scholar ] [ CrossRef ] Lauer, M.K.; Tennyson, A.G.; Smith, R.C. Green Synthesis of Thermoplastic Composites from a Terpenoid-Cellulose Ester. Acs Appl. Polym. Mater. 2020 , 2 , 3761–3765. [ Google Scholar ] [ CrossRef ] Lauer, M.K.; Tennyson, A.G.; Smith, R.C. Thermomorphological and mechanical properties of vulcanized octenyl succinate/terpenoid-derivatized corn starch composites. Mater. Adv. 2022 , 3 , 4186–4193. [ Google Scholar ] [ CrossRef ] Kristufek, S.L.; Wacker, K.T.; Timothy Tsao, Y.-Y.; Su, L.; Wooley, K.L. Monomer design strategies to create natural product-based polymer materials. Nat. Prod. Rep. 2017 , 34 , 433–459. [ Google Scholar ] [ CrossRef ] Bauman, N.; Ajjawi, I. Algal Microorganisms Engineered for Increased Productivity and Biomass. U.S. Patent 10,683,514, 16 June 2017. [ Google Scholar ] Kempinski, C.; Jiang, Z.; Bell, S.; Chappell, J. Metabolic Engineering of Higher Plants and Algae for Isoprenoid Production. Adv. Biochem. Eng./Biotechnol. 2015 , 148 , 161–199. [ Google Scholar ] [ CrossRef ] [ PubMed ] Heaps, N.; Molina, D.; Behnke, C. Terpenes and terpenoids in biofuel production in genetically engineered prokaryotes and eukaryotes. U.S. Patent 2010-US26445, 2010104763, 20100305, 2010. [ Google Scholar ] Arendt, P.; Pollier, J.; Callewaert, N.; Goossens, A. Synthetic biology for production of natural and new-to-nature terpenoids in photosynthetic organisms. Plant J. 2016 , 87 , 16–37. [ Google Scholar ] [ CrossRef ][ Green Version ] Putignani, L.; Massa, O.; Alisi, A. Engineered Escherichia coli as new source of flavonoids and terpenoids. Food Res. Int. 2013 , 54 , 1084–1095. [ Google Scholar ] [ CrossRef ] Sun, C.; Theodoropoulos, C.; Scrutton Nigel, S. Techno-economic assessment of microbial limonene production. Bioresour. Technol. 2020 , 300 , 122666. [ Google Scholar ] [ CrossRef ] Wu, W.; Maravelias, C.T. Synthesis and techno-economic assessment of microbial-based processes for terpenes production. Biotechnol. Biofuels 2018 , 11 , 294. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Wilbon, P.A.; Chu, F.; Tang, C. Progress in Renewable Polymers from Natural Terpenes, Terpenoids, and Rosin. Macromol. Rapid Commun. 2013 , 34 , 8–37. [ Google Scholar ] [ CrossRef ] Matsumura, A.; Yang, F.; Goto, H. Synthesis of a Terpene-Based New Chiral Inducer and Preparation of an Asymmetric Polymer. Polymers 2015 , 7 , 147–155. [ Google Scholar ] [ CrossRef ][ Green Version ] Nguyen, H.T.H.; Qi, P.; Rostagno, M.; Feteha, A.; Miller, S.A. The quest for high glass transition temperature bioplastics. J. Mater. Chem. A Mater. Energy Sustain. 2018 , 6 , 9298–9331. [ Google Scholar ] [ CrossRef ] Della Monica, F.; Kleij, A.W. From terpenes to sustainable and functional polymers. Polym. Chem. 2020 , 11 , 5109–5127. [ Google Scholar ] [ CrossRef ] Kamigaito, M.; Satoh, K. Sustainable Vinyl Polymers via Controlled Polymerization of Terpenes. Sustain. Polym. Biomass 2017 , 55–90. [ Google Scholar ] [ CrossRef ] Bruneau, C.; Fischmeister, C. Alkene metathesis for transformations of renewables. Top. Organomet. Chem. 2019 , 63 , 77–102. [ Google Scholar ] [ CrossRef ] Song, S.H. Influence of eco-friendly processing aids on silica-based rubber composites. Appl. Sci. 2020 , 10 , 7244. [ Google Scholar ] [ CrossRef ] Manoharan, P.; Naskar, K. Eco-friendly composites derived from naturally occurring molecules in promoting dispersion of nanosized silica particulates. Polym. Compos. 2019 , 40 , 871–883. [ Google Scholar ] [ CrossRef ] Wu, G.-M.; Kong, Z.-W.; Chen, J.; Huo, S.-P.; Liu, G.-F. Preparation and properties of waterborne polyurethane/epoxy resin composite coating from anionic terpene-based polyol dispersion. Prog. Org. Coat. 2014 , 77 , 315–321. [ Google Scholar ] [ CrossRef ] Lopez, C.V.; Smith, A.D.; Smith, R.C. High strength composites from low-value animal coproducts and industrial waste sulfur. Rsc Adv. 2022 , 12 , 1535–1542. [ Google Scholar ] [ CrossRef ] [ PubMed ] Lopez, C.V.; Karunarathna, M.S.; Lauer, M.K.; Maladeniya, C.P.; Thiounn, T.; Ackley, E.D.; Smith, R.C. High Strength, Acid-Resistant Composites from Canola, Sunflower, or Linseed Oils: Influence of Triglyceride Unsaturation on Material Properties. J. Poly. Sci. 2020 , 58 , 2259–2266. [ Google Scholar ] [ CrossRef ] Chung, W.J.; Griebel, J.J.; Kim, E.T.; Yoon, H.; Simmonds, A.G.; Ji, H.J.; Dirlam, P.T.; Glass, R.S.; Wie, J.J.; Nguyen, N.A.; et al. The use of elemental sulfur as an alternative feedstock for polymeric materials. Nat. Chem. 2013 , 5 , 518–524. [ Google Scholar ] [ CrossRef ] Zhang, Y.; Glass, R.S.; Char, K.; Pyun, J. Recent advances in the polymerization of elemental sulphur, inverse vulcanization and methods to obtain functional Chalcogenide Hybrid Inorganic/Organic Polymers (CHIPs). Polym. Chem. 2019 , 10 , 4078–4105. [ Google Scholar ] [ CrossRef ] Kleine, T.S.; Glass, R.S.; Lichtenberger, D.L.; MacKay, M.E.; Char, K.; Norwood, R.A.; Pyun, J. 100th Anniversary of Macromolecular Science Viewpoint: High Refractive Index Polymers from Elemental Sulfur for Infrared Thermal Imaging and Optics. Acs Macro Lett. 2020 , 9 , 245–259. [ Google Scholar ] [ CrossRef ] [ PubMed ] Yan, P.; Zhao, W.; Zhang, B.; Jiang, L.; Petcher, S.; Smith, J.A.; Parker, D.J.; Cooper, A.I.; Lei, J.; Hasell, T. Inverse vulcanized polymers with shape memory, enhanced mechanical properties, and vitrimer behavior. Angew. Chem. Int. Ed. 2020 , 59 , 13371–13378. [ Google Scholar ] [ CrossRef ] Worthington, M.J.H.; Kucera, R.L.; Chalker, J.M. Green chemistry and polymers made from sulfur. Green Chem. 2017 , 19 , 2748–2761. [ Google Scholar ] [ CrossRef ][ Green Version ] Chalker, J.M.; Worthington, M.J.H.; Lundquist, N.A.; Esdaile, L.J. Synthesis and Applications of Polymers Made by Inverse Vulcanization. Top. Curr. Chem. 2019 , 377 , 125–151. [ Google Scholar ] [ CrossRef ] Smith, A.D.; Smith, R.C.; Tennyson, A.G. Carbon-Negative Polymer Cements by Copolymerization of Waste Sulfur, Oleic Acid, and Pozzolan Cements. Sustain. Chem. Pharm. 2020 , 16 , 100249. [ Google Scholar ] [ CrossRef ] Thiounn, T.; Karunarathna, M.S.; Slann, L.M.; Lauer, M.K.; Smith, R.C. Sequential Crosslinking for Mechanical Property Development in High Sulfur Content Composites. J. Polym. Sci. 2020 , 58 , 2943–2950. [ Google Scholar ] [ CrossRef ] Lauer, M.K.; Karunarathna, M.S.; Tennyson, A.G.; Smith, R.C. Robust, remeltable and remarkably simple to prepare biomass-sulfur composites. Mater. Adv. 2020 , 1 , 2271–2278. [ Google Scholar ] [ CrossRef ] Lauer, M.K.; Karunarathna, M.S.; Tennyson, A.G.; Smith, R.C. Recyclable, Sustainable, and Stronger than Portland Cement: A Composite from Unseparated Biomass and Fossil Fuel Waste. Mater. Adv. 2020 , 1 , 590–594. [ Google Scholar ] [ CrossRef ] Lauer, M.K.; Estrada-Mendoza, T.A.; McMillen, C.D.; Chumanov, G.; Tennyson, A.G.; Smith, R.C. Durable Cellulose-Sulfur Composites Derived from Agricultural and Petrochemical Waste. Adv. Sustain. Syst. 2019 , 3 , 1900062. [ Google Scholar ] [ CrossRef ][ Green Version ] Zhang, B.; Gao, H.; Yan, P.; Petcher, S.; Hasell, T. Inverse vulcanization below the melting point of sulfur. Mater. Chem. Front. 2020 , 4 , 669–675. [ Google Scholar ] [ CrossRef ] Tonkin, S.J.; Gibson, C.T.; Campbell, J.A.; Lewis, D.A.; Karton, A.; Hasell, T.; Chalker, J.M. Chemically induced repair, adhesion, and recycling of polymers made by inverse vulcanization. Chem. Sci. 2020 , 11 , 5537–5546. [ Google Scholar ] [ CrossRef ] [ PubMed ] Wu, X.; Smith, J.A.; Petcher, S.; Zhang, B.; Parker, D.J.; Griffin, J.M.; Hasell, T. Catalytic inverse vulcanization. Nat. Commun. 2019 , 10 , 10035–10044. [ Google Scholar ] [ CrossRef ] [ PubMed ] Tikoalu, A.D.; Lundquist, N.A.; Chalker, J.M. Mercury Sorbents Made By Inverse Vulcanization of Sustainable Triglycerides: The Plant Oil Structure Influences the Rate of Mercury Removal from Water. Adv. Sustain. Syst. 2020 , 4 , 1900111. [ Google Scholar ] [ CrossRef ] Lundquist, N.A.; Tikoalu, A.D.; Worthington, M.J.H.; Shapter, R.; Tonkin, S.J.; Stojcevski, F.; Mann, M.; Gibson, C.T.; Gascooke, J.R.; Karton, A.; et al. Reactive Compression Molding Post-Inverse Vulcanization: A Method to Assemble, Recycle, and Repurpose Sulfur Polymers and Composites. Chem. A Eur. J. 2020 , 26 , 10035–10044. [ Google Scholar ] [ CrossRef ] [ PubMed ] Smith, J.A.; Green, S.J.; Petcher, S.; Parker, D.J.; Zhang, B.; Worthington, M.J.H.; Wu, X.; Kelly, C.A.; Baker, T.; Gibson, C.T.; et al. Crosslinker Copolymerization for Property Control in Inverse Vulcanization. Chem. A Eur. J. 2019 , 25 , 10433–10440. [ Google Scholar ] [ CrossRef ] [ PubMed ] Scheiger, J.M.; Direksilp, C.; Falkenstein, P.; Welle, A.; Koenig, M.; Heissler, S.; Matysik, J.; Levkin, P.A.; Theato, P. Inverse Vulcanization of Styrylethyltrimethoxysilane-Coated Surfaces, Particles, and Crosslinked Materials. Angew. Chem. Int. Ed. 2020 , 59 , 18639–18645. [ Google Scholar ] [ CrossRef ] Duarte, M.E.; Huber, B.; Theato, P.; Mutlu, H. The unrevealed potential of elemental sulfur for the synthesis of high sulfur content bio-based aliphatic polyesters. Polym. Chem. 2020 , 11 , 241–248. [ Google Scholar ] [ CrossRef ][ Green Version ] Nguyen, D.T.; Hoefling, A.; Yee, M.; Nguyen, G.T.H.; Theato, P.; Lee, Y.J.; Song, S.-W. Enabling High-Rate and Safe Lithium Ion-Sulfur Batteries by Effective Combination of Sulfur-Copolymer Cathode and Hard-Carbon Anode. ChemSusChem 2019 , 12 , 480–486. [ Google Scholar ] [ CrossRef ] Mutlu, H.; Theato, P.; Ceper Ezgi, B.; Ozmen Mehmet, M.; Li, X.; Yang, J.; Dong, W.; Theato, P.; Yang, J. Sulfur Chemistry in Polymer and Materials Science. Macromol. Rapid Commun. 2019 , 40 , e1800650. [ Google Scholar ] [ CrossRef ] Hoefling, A.; Nguyen, D.T.; Partovi-Azar, P.; Sebastiani, D.; Theato, P.; Song, S.-W.; Lee, Y.J. Mechanism for the Stable Performance of Sulfur-Copolymer Cathode in Lithium-Sulfur Battery Studied by Solid-State NMR Spectroscopy. Chem. Mater. 2018 , 30 , 2915–2923. [ Google Scholar ] [ CrossRef ] Hoefling, A.; Nguyen, D.T.; Lee, Y.J.; Song, S.-W.; Theato, P. A sulfur-eugenol allyl ether copolymer: A material synthesized via inverse vulcanization from renewable resources and its application in Li-S batteries. Mater. Chem. Front. 2017 , 1 , 1818–1822. [ Google Scholar ] [ CrossRef ] Chen, Z.; Droste, J.; Zhai, G.; Zhu, J.; Yang, J.; Hansen, M.R.; Zhuang, X. Sulfur-anchored azulene as a cathode material for Li-S batteries. Chem. Commun. 2019 , 55 , 9047–9050. [ Google Scholar ] [ CrossRef ] [ PubMed ] Zhao, F.; Li, Y.; Feng, W. Recent Advances in Applying Vulcanization/Inverse Vulcanization Methods to Achieve High-Performance Sulfur-Containing Polymer Cathode Materials for Li-S Batteries. Small Methods 2018 , 2 , 1800156. [ Google Scholar ] [ CrossRef ] Lopez, C.V.; Maladeniya, C.P.; Smith, R.C. Lithium-Sulfur Batteries: Advances and Trends. Electrochem 2020 , 1 , 226–259. [ Google Scholar ] [ CrossRef ] Griebel, J.J.; Namnabat, S.; Kim, E.T.; Himmelhuber, R.; Moronta, D.H.; Chung, W.J.; Simmonds, A.G.; Kim, K.-J.; van der Laan, J.; Nguyen, N.A.; et al. New Infrared Transmitting Material via Inverse Vulcanization of Elemental Sulfur to Prepare High Refractive Index Polymers. Adv. Mater. 2014 , 26 , 3014–3018. [ Google Scholar ] [ CrossRef ] [ PubMed ] Lin, H.-K.; Lai, Y.-S.; Liu, Y.-L. Cross-Linkable and Self-Foaming Polysulfide Materials for Repairable and Mercury Capture Applications. Acs Sustain. Chem. Eng. 2019 , 7 , 4515–4522. [ Google Scholar ] [ CrossRef ] Abraham, A.M.; Kumar, S.V.; Alhassan, S.M. Porous sulphur copolymer for gas-phase mercury removal and thermal insulation. Chem. Eng. J. 2018 , 332 , 1–7. [ Google Scholar ] [ CrossRef ] Parker, D.J.; Jones, H.A.; Petcher, S.; Cervini, L.; Griffin, J.M.; Akhtar, R.; Hasell, T. Low cost and renewable sulfur-polymers by inverse vulcanization, and their potential for mercury capture. J. Mater. Chem. A Mater. Energy Sustain. 2017 , 5 , 11682–11692. [ Google Scholar ] [ CrossRef ][ Green Version ] Akay, S.; Kayan, B.; Kalderis, D.; Arslan, M.; Yagci, Y.; Kiskan, B. Poly(benzoxazine-co-sulfur): An efficient sorbent for mercury removal from aqueous solution. J. Appl. Polym. Sci. 2017 , 134 , 45306. [ Google Scholar ] [ CrossRef ] Hasell, T.; Parker, D.J.; Jones, H.A.; McAllister, T.; Howdle, S.M. Porous inverse vulcanized polymers for mercury capture. Chem. Commun. 2016 , 52 , 5383–5386. [ Google Scholar ] [ CrossRef ] Valle, S.F.; Giroto, A.S.; Klaic, R.; Guimaraes, G.G.F.; Ribeiro, C. Sulfur fertilizer based on inverse vulcanization process with soybean oil. Polym. Degrad. Stab. 2019 , 162 , 102–105. [ Google Scholar ] [ CrossRef ] Mann, M.; Kruger, J.E.; Andari, F.; McErlean, J.; Gascooke, J.R.; Smith, J.A.; Worthington, M.J.H.; McKinley, C.C.C.; Campbell, J.A.; Lewis, D.A.; et al. Sulfur polymer composites as controlled-release fertilizers. Org. Biomol. Chem. 2019 , 17 , 1929–1936. [ Google Scholar ] [ CrossRef ] [ PubMed ] Thiounn, T.; Lauer, M.K.; Karunarathna, M.S.; Tennyson, A.G.; Smith, R.C. Copolymerization of a Bisphenol a Derivative and Elemental Sulfur by the RASP Process. Sus. Chem. 2020 , 1 , 183–197. [ Google Scholar ] [ CrossRef ] Thiounn, T.; Tennyson, A.G.; Smith, R.C. Durable, acid-resistant copolymers from industrial by-product sulfur and microbially-produced tyrosine. Rsc Adv. 2019 , 9 , 31460–31465. [ Google Scholar ] [ CrossRef ] [ PubMed ][ Green Version ] Thiounn, T.; Lauer, M.K.; Bedford, M.S.; Smith, R.C.; Tennyson, A.G. Thermally-healable network solids of sulfur-crosslinked poly(4-allyloxystyrene). Rsc Adv. 2018 , 8 , 39074–39082. [ Google Scholar ] [ CrossRef ][ Green Version ] Smith, A.D.; McMillin, C.D.; Smith, R.C.; Tennyson, A.G. Copolymers by Inverse Vulcanization of Sulfur with Pure or Technical Grade Unsaturated Fatty Acids. J. Poly. Sci. 2020 , 58 , 438–445. [ Google Scholar ] [ CrossRef ] Smith, A.D.; Thiounn, T.; Lyles, E.W.; Kibler, E.K.; Smith, R.C.; Tennyson, A.G. Combining agriculture and energy industry waste products to yield recyclable, thermally healable copolymers of elemental sulfur and oleic acid. J. Polym. Sci. Part A Polym. Chem. 2019 , 57 , 1704–1710. [ Google Scholar ] [ CrossRef ] Karunarathna, M.S.; Tennyson, A.G.; Smith, R.C. Facile new approach to high sulfur-content materials and preparation of sulfur-lignin copolymers. J. Mater. Chem. A Mater. Energy Sustain. 2020 , 8 , 548–553. [ Google Scholar ] [ CrossRef ] Karunarathna, M.S.; Smith, R.C. Valorization of Lignin as a Sustainable Component of Structural Materials and Composites: Advances from 2011 to 2019. Sustainability 2020 , 12 , 734–748. [ Google Scholar ] [ CrossRef ][ Green Version ] Karunarathna, M.S.; Lauer, M.K.; Tennyson, A.G.; Smith, R.C. Copolymerization of an aryl halide and elemental sulfur as a route to high sulfur content materials. Polym. Chem. 2020 , 11 , 1621–1628. [ Google Scholar ] [ CrossRef ] Karunarathna, M.S.; Lauer, M.K.; Smith, R.C. Facile route to an organosulfur composite from biomass-derived guaiacol and waste sulfur. J. Mater. Chem. A 2020 , 8 , 20318–20322. [ Google Scholar ] [ CrossRef ] Karunarathna, M.S.; Lauer, M.K.; Thiounn, T.; Smith, R.C.; Tennyson, A.G. Valorization of waste to yield recyclable composites of elemental sulfur and lignin. J. Mater. Chem. A Mater. Energy Sustain. 2019 , 7 , 15683–15690. [ Google Scholar ] [ CrossRef ] Vedernikov, A.; Minchenkov, K.; Gusev, S.; Sulimov, A.; Zhou, P.; Li, C.; Xian, G.; Akhatov, I.; Safonov, A. Effects of the Pre-Consolidated Materials Manufacturing Method on the Mechanical Properties of Pultruded Thermoplastic Composites. Polymers 2022 , 14 , 2246. [ Google Scholar ] [ CrossRef ] Minchenkov, K.; Vedernikov, A.; Kuzminova, Y.; Gusev, S.; Sulimov, A.; Gulyaev, A.; Kreslavskaya, A.; Prosyanoy, I.; Xian, G.; Akhatov, I.; et al. Effects of the quality of pre-consolidated materials on the mechanical properties and morphology of thermoplastic pultruded flat laminates. Compos. Commun. 2022 , 35 , 101281. [ Google Scholar ] [ CrossRef ] Vedernikov, A.; Tucci, F.; Carlone, P.; Gusev, S.; Konev, S.; Firsov, D.; Akhatov, I.; Safonov, A. Effects of pulling speed on structural performance of L-shaped pultruded profiles. Compos. Struct. 2021 , 255 , 112967. [ Google Scholar ] [ CrossRef ] Vedernikov, A.; Gemi, L.; Madenci, E.; Onuralp Özkılıç, Y.; Yazman, Ş.; Gusev, S.; Sulimov, A.; Bondareva, J.; Evlashin, S.; Konev, S.; et al. Effects of high pulling speeds on mechanical properties and morphology of pultruded GFRP composite flat laminates. Compos. Struct. 2022 , 301 , 116216. [ Google Scholar ] [ CrossRef ] Worthington, M.J.H.; Shearer, C.J.; Esdaile, L.J.; Campbell, J.A.; Gibson, C.T.; Legg, S.K.; Yin, Y.; Lundquist, N.A.; Gascooke, J.R.; Albuquerque, I.S.; et al. Sustainable Polysulfides for Oil Spill Remediation: Repurposing Industrial Waste for Environmental Benefit. Adv. Sustain. Syst. 2018 , 2 , 1800024. [ Google Scholar ] [ CrossRef ][ Green Version ] Worthington, M.J.H.; Kucera, R.L.; Albuquerque, I.S.; Gibson, C.T.; Sibley, A.; Slattery, A.D.; Campbell, J.A.; Alboaiji, S.F.K.; Muller, K.A.; Young, J.; et al. Laying Waste to Mercury: Inexpensive Sorbents Made from Sulfur and Recycled Cooking Oils. Chem. A Eur. J. 2017 , 23 , 16106. [ Google Scholar ] [ CrossRef ] Orme, K.; Fistrovich, A.H.; Jenkins, C.L. Tailoring Polysulfide Properties through Variations of Inverse Vulcanization. Macromolecules 2020 , 53 , 9353–9361. [ Google Scholar ] [ CrossRef ] Herrera, C.; Ysinga, K.J.; Jenkins, C.L. Polysulfides Synthesized from Renewable Garlic Components and Repurposed Sulfur Form Environmentally Friendly Adhesives. Acs Appl. Mater. Interfaces 2019 , 11 , 35312–35318. [ Google Scholar ] [ CrossRef ] Westerman, C.R.; Jenkins, C.L. Dynamic Sulfur Bonds Initiate Polymerization of Vinyl and Allyl Ethers at Mild Temperatures. Macromolecules 2018 , 51 , 7233–7238. [ Google Scholar ] [ CrossRef ] Lauer, M.K.; Sanders, Z.E.; Smith, A.D.; Smith, R.C. Morphological and mechanical characterization of high-strength sulfur composites prepared with variably-sized lignocellulose particles. Mater. Adv. 2021 , 2 , 7413–7422. [ Google Scholar ] [ CrossRef ] Holm, T. Lightweight Concrete and Aggregates ; ASTM 169C, Chapter 48; ASTM International: West Conshohocken, PA, USA, 2006. [ Google Scholar ] Akers, D.J.; Gruber, R.D.; Ramme, B.W.; Boyle, M.J.; Grygar, J.G.; Rowe, S.K.; Sheetz, S.R.; Snow, P.G.; Speck, J.F.; Sypher, W.X. Guide for Structural Lightweight Aggregate Concrete ; American Concrete Institute: Farmington Hills, MI, USA, 2003. [ Google Scholar ] Moudio, A.M.N.; Tchakouté, H.K.; Ngnintedem, D.L.V.; Andreola, F.; Kamseu, E.; Nanseu-Njiki, C.P.; Leonelli, C.; Rüscher, C.H. Influence of the synthetic calcium aluminate hydrate and the mixture of calcium aluminate and silicate hydrates on the compressive strengths and the microstructure of metakaolin-based geopolymer cements. Mater. Chem. Phys. 2021 , 264 , 124459. [ Google Scholar ] [ CrossRef ] Lauer, M.K.; Tennyson, A.G.; Smith, R.C. Inverse vulcanization of octenyl succinate-modified corn starch as a route to biopolymer-sulfur composites. Mater. Adv. 2021 , 2 , 2391–2397. [ Google Scholar ] [ CrossRef ] Scheme 1. Heating elemental sulfur produces radicals that add to olefin π bonds to yield cross-linked high sulfur-content materials (HSMs) via a process known as inverse vulcanization. Figure 1. Representative photos of compressional cylinders of CitS-derived ( a ) and GerS-derived composites ( b ) before (upper row in each image) and after (lower row in each image) acid challenge. Figure 2. SEM/EDX data for composites reveals the presence of mineral additive well-dispersed in the homogeneous GerS binder for the GerS-derived materials. Figure 3. Comparison of compressional strength before (blue bars) and after (green bars) exposure to 0.1 M H 2 SO 4 for 24 h. Table 1. Properties of terpenoid–sulfur cement binders and comparison to elemental sulfur (orthorhombic). Materials T g /°C T m /°C Δ H m [a] J/g Δ H cc [b] J/g Percentage Crystallinity [c] S 8 NA 119 45 NA 100 CitS NA 114 ND ND ND GerS −37 116 25 20 23 [a] Integrated heat of melting for the orthorhombic sulfur melt transition. [b] Integrated area for all cold crystallization transitions. [c] The reduction in the percentage of crystallinity of each of the samples was calculated with respect to sulfur (normalized to 100%). Table 2. Fineness moduli ( F ) and compositions for pozzolans used in this study. Materials Fineness Modulus Primary Constituents Silica Fume 3.78 SiO 2 Fly Ash 2.53 SiO 2 , CaO, Al 2 O 3 , Fe 3 O 2 Ground Granulated Blast-Furnace Slag 3.35 2CaO·SiO 2 , CaAl 2 Si 2 O 8 Metakaolin 4.63 Al 2 Si 2 O 7 Table 3. Properties of composites and binders. Compressional Strength [c] Materials Density [a] (kg/m 3 ) Water Uptake [b] (wt%) As-Prepared (MPa) After Acid (MPa) Retained Strength (% of As-Prepared) CitS 1800 0.1 ± 0.1 18.8 ± 2.3 15.8 ± 0.5 85 CitS-MK 1800 0.2 ± 0.01 20.4 ± 2.2 19.5 ± 0.4 95 CitS-SF 1800 0.7 ± 0.3 23.2 ± 3.2 18.7 ± 1.3 80 CitS-GGBFS 1800 0.2 ± 0.1 17.0 ± 0.4 16.7 ± 0.6 98 CitS-FA 1800 0.2 ± 0.3 15.8 ± 2.1 17.1 ± 1.2 108 GerS 1800 0.2 ± 0.2 11.7 ± 1.5 9.4 ± 2.1 80 GerS-MK 1800 0.1 ± 0.1 19.8 ± 2.3 23.2 ± 3.6 116 GerS-SF 1900 0.2 ± 0.2 16.4 ± 0.9 14.2 ± 1.3 87 GerS-GGBFS 1900 0.2 ± 0.1 19.4 ± 1.6 18.0 ± 3.1 93 GerS-FA 1900 0.2 ± 0.2 16.5 ± 0.7 16.5 ± 0.7 100 OPC [d] 1500 Up to 28% 17 decomposed 0 ZOS 90 1700 0.0 19.4 ± 1.8 ND ND FAOS 1700 0.0 20.6 ± 5.7 ND ND GGBFSOS 1700 0.0 8.50 ± 0.1 ND ND MKOS 1700 0.0 9.1 ± 1.2 ND ND PCOS 1600 0.1 22.0 ± 0.1 ND ND SFOS 1600 0.0 12.4 ± 4.4 ND ND GCN0 ND ND 49.50 ND ND GCN5 ND ND 57.17 ND ND GCN10 ND ND 63.59 ND ND GCN15 ND ND 38.79 ND ND GCN20 ND ND 35.05 ND ND [a] Density is reported as the average of three measurements on cylinders used for mechanical testing. [b] Water uptake was calculated by measuring the mass before and after the cylinder was submerged in deionized water for 24 h (average of three trials). [c] Average of three measurements with standard deviations. [d] Values for residential building-grade ordinary Portland cement for foundations and footings.
https://www.mdpi.com/2504-477X/7/1/35/html