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Cuyahoga, OH 1900 Federal Census ftp://ftp.us-census.org/pub/usgenweb/census/oh/cuyahoga/1900/ (File 9 of 12 for ED:212 - Collinwood Twp and Village) This Census was transcribed by Kenneth E. Stafford and and proofread by Elaine Rericka for the USGenWeb Census Project http://www.us-census.org Copyright (c) 2003 by Kenneth E. Stafford <[email protected]> ========================================================================== USGENWEB (US-CENSUS) NOTICE: These electronic pages may NOT be reproduced in any format for profit or presentation by any other organization. Non-commercial organizations desiring to use this material must obtain the consent of the transcriber prior to use. <[email protected]> Individuals desiring to use this material in their own research may do so. ========================================================================== Formatted by USGenWeb Census Project File Manager, Connie Burkett All of the above information must remain when copied or downloaded. ========================================================================== Census Year 1900 Microfilm Roll #T623-1260 State OHIO County Cuyahoga ==================================================================================================================================================================================================================================================================================================================================================================== CENSUS YEAR: 1900 STATE: OH COUNTY: Cuyahoga DISTRICT: Collinwood Township INCORP-PLACE: Collinwood Village MICROFILM#: T623-1260 ENUM/DISTR: 212 ENUMERATOR: E A Wisuell ==================================================================================================================================================================================================================================================================================================================================================================== BIRTH BIRTH S-M #YRS # #CHILD BIRTH FATHER MOTHER YEAR #YRS NATUR- MONTHS #MO AT CAN CAN SPEAK O-R O-F FARM #FARM PG# LN# STREET HS# DW# FM# LAST NAME FIRST NAME RELATION RACE SEX MONTH YEAR AGE W-D MAR CHILD LIVING PLACE BIRTHPL BIRTHPL IMMI US ALIZED OCCUPATION UNEMPL SCHOOL READ WRITE ENG? HOME MORT HOME SCH REMARKS (1) (2) (3) (3) (4) (5) (6) (7) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) ==================================================================================================================================================================================================================================================================================================================================================================== 90A 1 Putman 189 541 564 Lintz Anna Wife W F Dec 1870 29 M 7 1 1 Germany Germany Germany 1873 27 . . . . Yes Yes Yes . . . . Enumerated June 20, 1900. 90A 2 Putman 189 541 564 Lintz Elmer Son W M Aug 1897 2 S . . . Ohio Ohio Germany . . . . . . . . . . . . . . 90A 3 Putman 177 542 565 McNemar Alfred F Head W M Oct 1849 50 M 16 . . West Virginia West Virginia West Virginia . . . RR Conductor 0 . Yes Yes Yes O F H . . 90A 4 Putman 177 542 565 McNemar Anna Wife W F Aug 1860 39 M 16 0 0 Pennsylvania Germany Germany . . . . . . Yes Yes Yes . . . . . 90A 5 Putman 177 542 565 Sturgeon Harry Lodger W M Nov 1870 29 S . . . Michigan Pennsylvania New York . . . RR Brakeman 0 . Yes Yes Yes . . . . . 90A 6 Putman 169 543 566 Hammel Christian Head W M Feb 1854 46 M 24 . . Germany Germany Germany 1870 30 Na Car Repairer RR 0 . Yes Yes Yes O F H . . 90A 7 Putman 169 543 566 Hammel Magdalena Wife W F Sep 1851 48 M 24 6 5 Germany Germany Germany 1872 28 . . . . Yes Yes Yes . . . . . 90A 8 Putman 169 543 566 Hammel Rose Daughter W F Oct 1879 20 S . . . Ohio Germany Germany . . . Saleslady (Dry Goods) 0 . Yes Yes Yes . . . . . 90A 9 Putman 169 543 566 Hammel Frank Son W M May 1886 14 S . . . Ohio Germany Germany . . . at School . 7 Yes Yes Yes . . . . . 90A 10 Putman 169 543 566 Hammel Lee Son W M Apr 1892 8 S . . . Ohio Germany Germany . . . at School . 9 . . . . . . . . 90A 11 Putman 165 544 567 Nolan George E Head W M Nov 1861 38 M 11 . . Ohio Ohio Ireland . . . RR Conductor 0 . Yes Yes Yes O M H . . 90A 12 Putman 165 544 567 Nolan Stasia A Wife W F Sep 1871 28 M 11 2 1 Ohio Ireland Ireland . . . . . . Yes Yes Yes . . . . . 90A 13 Putman 165 544 567 Nolan Edwin J Son W M Mch 1893 7 S . . . Ohio Ohio Ohio . . . at School . 9 . . . . . . . . 90A 14 Putman 165 544 567 Nolan Zita D Niece W F Dec 1882 17 S . . . Ohio Ohio Ohio . . . at School . 9 Yes Yes Yes . . . . . 90A 15 Putman 165 544 567 Nolan Leo M Nephew W M Sep 1885 14 S . . . Ohio Ohio Ohio . . . at School . 9 Yes Yes Yes . . . . . 90A 16 Putman 115 545 568 Hales Charles Head W M Sep 1861 38 M 17 . . Ohio England England . . . Day Laborer RR 0 . Yes Yes Yes R . H . . 90A 17 Putman 115 545 568 Hales Jennie Wife W F Apr 1856 44 M 17 1 1 Ohio Ohio Ohio . . . . . . Yes Yes Yes . . . . . 90A 18 Putman 115 545 568 Hales Virgil D Son W M June 1896 3 S . . . Ohio Ohio Ohio . . . . . . . . . . . . . . 90A 19 Putman 115 545 568 Brudinger Frederick Lodger W M Dec 1863 36 S . . . Germany Germany Germany 1884 14 Na Locomotive Hostetler 0 . Yes Yes Yes . . . . Either years in US or year of immigration is wrong. 90A 20 Putman 164 546 569 Moulton William H Head W M Jan 1857 43 M 22 . . Iowa Massachusetts Ohio . . . Overnight Shipping 0 . Yes Yes Yes O F H . . 90A 21 Putman 164 546 569 Moulton Mary R Wife W F Apr 1858 42 M 22 1 1 Ohio Ohio Ohio . . . . . . Yes Yes Yes . . . . . 90A 22 Putman 164 546 569 Moulton Ruth G Daughter W F Jan 1883 17 S . . . Ohio Iowa Ohio . . . at School . 9 Yes Yes Yes . . . . . 90A 23 Putman 180 547 570 Tifft Charles S Head W M Feb 1869 31 M 8 . . Ohio New York New York . . . RR Brakeman 0 . Yes Yes Yes O F H . . 90A 24 Putman 180 547 570 Tifft Emma Wife W F Sep 1872 27 M 8 2 1 England England England 1873 27 . . . . Yes Yes Yes . . . . . 90A 25 Putman 180 547 570 Tifft Emma Daughter W F Mch 1896 4 S . . . Ohio Ohio England . . . . . . . . . . . . . . 90A 26 Putman 174 548 571 Allen Frank Head W M July 1845 54 M 27 . . New York New York New York . . . Locomotive Engineer 0 . Yes Yes Yes O F H . . 90A 27 Putman 174 548 571 Allen Ella Wife W F Aug 1851 48 M 27 3 3 Ohio Ohio New York . . . . . . Yes Yes Yes . . . . . 90A 28 Putman 174 548 571 Allen May E Daughter W F Nov 1873 26 S . . . Ohio New York Ohio . . . . . . Yes Yes Yes . . . . . 90A 29 Putman 174 548 571 Allen Essie P Daughter W F Apr 1878 22 S . . . Ohio New York Ohio . . . . . . Yes Yes Yes . . . . . 90A 30 Putman 174 548 571 Allen Doris I Daughter W F Jan 1892 8 S . . . Ohio New York Ohio . . . at School . 9 . . . . . . . . 90A 31 Putman 184 549 572 Freeman Thomas Head W M Feb 1871 29 M 5 . . Ohio Ireland Ireland . . . RR Brakeman 0 . Yes Yes Yes R . H . . 90A 32 Putman 184 549 572 Freeman Sadie Wife W F July 1875 24 M 5 1 1 Pennsylvania Pennsylvania Pennsylvania . . . . . . Yes Yes Yes . . . . . 90A 33 Putman 184 549 572 Freeman Mary Daughter W F May 1899 1 S . . . Ohio Ohio Pennsylvania . . . . . . . . . . . . . . 90A 34 Putman 190 550 573 Merriman James Head W M Apr 1868 32 M 0 . . Ireland Ireland Ireland 1887 13 Na RR Brakeman 0 . Yes Yes Yes O F H . . 90A 35 Putman 190 550 573 Merriman Anna S Wife W F Feb 1868 32 M 0 1 1 Ohio Ireland Ireland . . . . . . Yes Yes Yes . . . . . 90A 36 Putman 190 550 573 Merriman Letitia Daughter W F May 1900 0/12 S . . . Ohio Ireland Ohio . . . . . . . . . . . . . . 90A 37 Putman 190 550 573 Mackim William Brother in Law W M May 1870 30 S . . . Ohio Ireland Ireland . . . Locomotive Engineer 0 . Yes Yes Yes . . . . . 90A 38 Putman 198 551 574 Bailey Alexander F Head W M Nov 1871 28 M 4 . . Ohio England England . . . Machinist RR 0 . Yes Yes Yes R . H . . 90A 39 Putman 198 551 574 Bailey Lillie M Wife W F Jan 1881 19 M 4 2 2 Ohio Canada (Eng) Canada (Eng) . . . . . . Yes Yes Yes . . . . . 90A 40 Putman 198 551 574 Bailey Alexander F Son W M Mch 1898 2 S . . . Ohio Ohio Ohio . . . . . . . . . . . . . . 90A 41 Putman 198 551 574 Bailey Irene C Daughter W F Feb 1900 2/12 S . . . Ohio Ohio Ohio . . . . . . . . . . . . . . 90A 42 Putman 202 552 575 Turner Robert G Head W M May 1869 31 M 5 . . England England England 1874 26 Na Clerk RR 0 . Yes Yes Yes R . H . . 90A 43 Putman 202 552 575 Turner Lena Wife W F Jan 1875 25 M 5 1 1 Ohio Germany Germany . . . . . . Yes Yes Yes . . . . . 90A 44 Putman 202 552 575 Turner Edna M Daughter W F Mch 1896 4 S . . . Ohio England Ohio . . . . . . . . . . . . . . 90A 45 Putman 210 553 576 Hagen Caroline Head W F Nov 1844 55 Wd . 5 5 Indiana New York New York . . . . . . Yes No Yes O M H . . 90A 46 Putman 210 553 576 Hagen Fred W Son W M Jan 1872 28 S . . . Michigan Ohio Indiana . . . Locomotive Fireman 0 . Yes Yes Yes . . . . . 90A 47 Putman 210 553 576 Hagen Edith Daughter W F Feb 1883 17 S . . . Ohio Ohio Indiana . . . Seamstress 6 . Yes Yes Yes . . . . . 90A 48 Putman 220 554 577 Colmorgen Frederick A Head W M Mch 1864 36 M 15 . . Germany Germany Germany 1873 27 Al Brakeman RR 0 . Yes Yes Yes R . H . . 90A 49 Putman 220 554 577 Colmorgen Minivera M Wife W F Jan 1867 32 M 15 2 2 Pennsylvania Pennsylvania Pennsylvania . . . . . . Yes Yes Yes . . . . . 90A 50 Putman 220 554 577 Colmorgen Charles Son W M Oct 1886 13 S . . . Pennsylvania Germany Pennsylvania . . . at School . 9 Yes Yes Yes . . . . . ==================================================================================================================================================================================================================================================================================================================================================================== CENSUS YEAR: 1900 STATE: OH COUNTY: Cuyahoga DISTRICT: Collinwood Township INCORP-PLACE: Collinwood Village MICROFILM#: T623-1260 ENUM/DISTR: 212 ENUMERATOR: E A Wisuell ==================================================================================================================================================================================================================================================================================================================================================================== BIRTH BIRTH S-M #YRS # #CHILD BIRTH FATHER MOTHER YEAR #YRS NATUR- MONTHS #MO AT CAN CAN SPEAK O-R O-F FARM #FARM PG# LN# STREET HS# DW# FM# LAST NAME FIRST NAME RELATION RACE SEX MONTH YEAR AGE W-D MAR CHILD LIVING PLACE BIRTHPL BIRTHPL IMMI US ALIZED OCCUPATION UNEMPL SCHOOL READ WRITE ENG? HOME MORT HOME SCH REMARKS (1) (2) (3) (3) (4) (5) (6) (7) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) ==================================================================================================================================================================================================================================================================================================================================================================== 90B 51 Putman 220 554 577 Colmorgen Frederick Son W M May 1894 6 S . . . Ohio Germany Pennsylvania . . . . . . . . . . . . . Enumerated 20 June 1900 90B 52 Putman 217 555 579 Sherman Charles H Head W M Sep 1866 33 M 11 . . Ohio Connecticut Ohio . . . Locomotive Engineer 0 . Yes Yes Yes O F H . . 90B 53 Putman 217 555 579 Sherman Flora B Wife W F May 1867 33 M 11 2 2 Ohio Ohio Ohio . . . . . . Yes Yes Yes . . . . . 90B 54 Putman 217 555 579 Sherman Willie H Son W M May 1891 9 S . . . Ohio Ohio Ohio . . . at School . 9 . . . . . . . . 90B 55 Putman 217 555 579 Sherman F Mildred Daughter W F Nov 1893 6 S . . . Ohio Ohio Ohio . . . at School . 9 . . . . . . . . 90B 56 St Clair 218 556 580 Aulstre Frank Head W M Oct 1853 46 M . . . Austria Austria Austria 1889 11 Al Laborer RR 0 . Yes Yes No R . H . . 90B 57 St Clair 218 556 580 Yupoutis John Boarder W M May 1831 69 M . . . Austria Austria Austria 1899 1 Al Laborer RR 0 . Yes Yes No . . . . . 90B 58 St Clair 218 556 580 Crenpa Gertrude Servant W F Apr 1853 47 M . . . Austria Austria Austria 1895 5 . Farm Laborer 6 . Yes Yes No . . . . . 90B 59 E Collamer 146 557 581 Meper George G Head W M Jan 1844 56 M 36 . . Ohio New York Vermont . . . Dealer (Furniture) 0 . Yes Yes Yes O F H . . 90B 60 E Collamer 146 557 581 Meper Henrietta M Wife W F Jan 1842 58 M 36 4 1 Ohio Massachusetts Massachusetts . . . . . . Yes Yes Yes . . . . . 90B 61 E Collamer 146 557 581 Meper Guy F Son W M Jan 1883 17 S . . . Ohio Ohio Ohio . . . . . . Yes Yes Yes . . . . . 90B 62 School 89 558 582 Thomas Kandana Head W F Dec 1820 79 Wd . 8 4 New York Canada (Fr) Canada (Fr) . . . . . . Yes Yes Yes O F H . . 90B 63 School 89 558 582 Fine Lafayete Son W M Dec 1860 39 S . . . Ohio New York New York . . . Wagon Maker 0 . Yes Yes Yes . . . . . 90B 64	http://www.us-census.org/pub/usgenweb/census/oh/cuyahoga/1900/212-090a.txt
About tweaks and snake oil \| Stereophile.com There are three kinds of tweaks: 1. Those that have a sound (excuse the pun) electrical/physical explanation of how they work. 2. Those that do not benefit from such an explanation, but are still susceptible to work because they interfere - even if in ways unknown or not disclosed - with one of the three elements of musical reproduction (electrical, mechanical and acoustical). About tweaks and snake oil There are three kinds of tweaks: 1. Those that have a sound (excuse the pun) electrical/physical explanation of how they work. 2. Those that do not benefit from such an explanation, but are still susceptible to work because they interfere - even if in ways unknown or not disclosed - with one of the three elements of musical reproduction (electrical, mechanical and acoustical). 3. Those that simply don't work, because there is no possible way they do! And this has nothing to do with debunking myths or any other flat-earth beliefs: they cannot work simply because they have no way to affect any of the three stages of sound reproduction outlined above. Please don't get yourselves into a fit - I do love music as much as you do - but just face it: music is nothing more than sound, and sound is just "a pressure disturbance that moves through a medium in the form of mechanical waves.Yes I know this might hurt your feelings, but your favorite Beethoven, Patricia Barber or Led Zeppelin recording is nothing more than "pressure waves made up of compressions and rarefactions." So no, you won't change these pressure waves by putting your photos in the freezer, washing your hands before listening (although washing your ears might help) or writing "'x 26 'xon your mirror. Why it won't work? Well, simply because it can't! But by all means, if you are sensitive to suggestions just use them - no, your system won't sound any better but you will think it does... and at the end of the day, the only thing that matters is your own satisfaction! Piled higher and deeper iosiP wrote: There are three kinds of tweaks: 1. Those that have a sound (excuse the pun) electrical/physical explanation of how they work. 2. Those that do not benefit from such an explanation, but are still susceptible to work because they interfere - even if in ways unknown or not disclosed - with one of the three elements of musical reproduction (electrical, mechanical and acoustical). 3. Those that simply don't work, because there is no possible way they do! And this has nothing to do with debunking myths or any other flat-earth beliefs: they cannot work simply because they have no way to affect any of the three stages of sound reproduction outlined above. Please don't get yourselves into a fit - I do love music as much as you do - but just face it: music is nothing more than sound, and sound is just "a pressure disturbance that moves through a medium in the form of mechanical waves.Yes I know this might hurt your feelings, but your favorite Beethoven, Patricia Barber or Led Zeppelin recording is nothing more than "pressure waves made up of compressions and rarefactions." So no, you won't change these pressure waves by putting your photos in the freezer, washing your hands before listening (although washing your ears might help) or writing "'x 26 'xon your mirror. Why it won't work? Well, simply because it can't! But by all means, if you are sensitive to suggestions just use them - no, your system won't sound any better but you will think it does... and at the end of the day, the only thing that matters is your own satisfaction! Glad you got that out of your system! I hate to judge before all the facts are in but it appears somewhat that this stuff is starting to get to you. "Education is what's left after you forgot all the things you learned in school." A. Einstein Have a nice day, Geoff KaitMachina Dynamica iosiP. Sorry sir, but you have already started by expressing a limiting form of thinking. Quite typical of many people, I accept, but nevertheless limiting. You have already said :- >>> “ 2. Those that do not benefit from such an explanation, but are still susceptible to work because they interfere - even if in ways unknown or not disclosed - with one of the three elements of musical reproduction (electrical, mechanical and acoustical).”<<< Showing that your thinking is stuck at the ear drum (the acoustical information reaching the ear drum). Is that it ? Is that the extent of your thinking ? Haven’t you REALLY heard things which have altered your sound but which could NOT be explained within those three categories you have listed ? If you HAD heard such things happen, then you would have HAD to extend your thinking. >>> “3. Those that simply don't work, because there is no possible way they do! And this has nothing to do with debunking myths or any other flat-earth beliefs: they cannot work simply because they have no way to affect any of the three stages of sound reproduction outlined above.” <<< If you HAD heard things affect your sound which in no way could have affected any of those three stages of sound reproduction, then you would not still be saying those sentences. You would, instead, be asking “What on earth is going on ?” It is because you can still use those previous sentences that I know which stage you are at. >>> “Please don’t get yourself into a fit - I do love music as much as you do - but just face it: music is nothing more than sound, and sound is just "a pressure disturbance that moves through a medium in the form of mechanical waves. Yes I know this might hurt your feelings, but your favorite Beethoven, Patricia Barber or Led Zeppelin recording is nothing more than "pressure waves made up of compressions and rarefactions." <<< Sorry sir. My favourite Beethoven or Dvorak’s New World is COMPLEX MUSICAL INFORMATION which, after that complex information has reached the ear drum STILL has a FURTHER arduous journey to make. The ‘sound’ (acoustic information) which reaches the ear drum is NOT the final sound. The REAL (final) sound is the information which eventually reaches the working memory – to be identified by the working memory which will then present a final ‘sound picture’ to the brain. THAT is the “sound”. So, there are MORE THAN the three stages you refer to. Whichever of (your) three areas within which people have heard ‘changes in their sound’, they have been met with exactly the same reaction as you are still exhibiting now. Electrical :- Over 30 years ago, when people began to describe hearing changes in the sound from changing cables/wires, they were met with “It is not possible.” , from electronic engineers. Those electronic engineers were saying “If you describe hearing changes the sound from changing cables/wires ONE MILE long, then we will accept that there could be changes in the sound – but from changing cables/wires of just half a metre – and at audio frequencies – NO WAY. You must have imagined it, what you say you heard must have been because of autosuggestion”.THAT attitude is still continuing today. You still have electronic engineers rolling around on the floor laughing at the suggestion that changing half (or even one) metre length of cable/wire can give the substantial changes in the sound which people describe.!!! And whatever you do, don’t bring into the conversation with them that you can also change the sound by changing the AC power cord, or you will be similarly ridiculed !!!! Then you have the engineers who make the actual CDs. Who encode the musical information onto the CD in 0s and 1s. Try telling them that you can improve the sound of their CDs by cryogenically freezing them, by applying a demagnetiser to them, by applying a chemical to the label side, by applying a colour to the extreme edge and they will mock you out of the door. They will say “There is no possible way you can affect the 0s and 1s we have encoded on the disc by doing the things you suggest, so there is no way you can change the sound.” Mechanical :- The mechanical engineers will not accept reports that such as the Shun Mook discs, the Harmonix Dots can give an improvement in the sound. Then we have what Michael Green’s refers to as his ‘treated’ wood. To mechanical engineers wood is wood and ‘treated’ wood should be no different to identical but untreated wood – regarding it’s effect on ‘sound’. Acoustical :- You then have the technicians, experts in room acoustics. Dealing with reflective or absorbent surfaces. Try telling them that you can gain improvements in the sound by introducing certain crystals and strategically placing them around the room. And by introducing the tiny ART devices into the room. And by introducing such as a Schuman Resonance device into the room. And, even more absurd to them, is if they have created a Room acoustic treatment panel, which gives as near a perfect acoustic measurement to satisfy them, that if the COLOUR of the actual material being used is changed, then the SOUND will change – whilst still giving exactly the same acoustic measurement !!!!!!!!!!!!! You still have audio industry Professionals stating – in print – or in public - that the changes which people hear are just those people having their head in different positions when listening. Or that audio journalists are prepared to prostitute themselves for the latest preposterous product !!! These are obviously people who have NOT heard, for themselves, changes in the sound – and substantial changes in the sound at that – which makes them reel back on their heels saying “What on earth is going on ?” You, sir, seem to be hiding behind the sentence :- >>> “but are still susceptible to work because they interfere - even if in ways unknown or not disclosed” <<< Now, let us have a look at things (people’s experiences) differently. Away from the limited ‘electronic, mechanical or acoustic’ viewpoint which is the one you are using. Let us look at people’s experiences gaining improvements in the sound by ‘treating’ such as CDs and let us consider another outlook. That there could be ‘something else going on’ not considered by those conventional (and dismissive) viewpoints. Let us bring the human being into the discussion. The human person being actively involved in the listening process – in resolving the complexity of the music. I will now bring in Michael Green’s constant theme – which is correct - that if one can carry out a specific technique and GAIN an improvement in the sound, then PRIOR to doing that technique, there must have been something adverse happening. Michael uses the terminology “unblocking” and therefore something must have been previously “blocking”. The new (hypothetical for the moment) concept to consider is that human beings are programmed, by evolution, to be reading/sensing/monitoring their environment every second, of every minute, of every hour, of every day of their lives. That (for example) in their listening environment, whilst playing a CD, there is a plastic/aluminium/plastic layered disc, spinning horrendously in an electro-magnetic field. Could this be one of those “adverse happenings” which no one is aware of UNTIL certain ‘tweaks’ are applied – which could then reduce those ‘adverse’ effects? Such techniques as cryogenically freezing the CD, such as applying a demagnetiser to the CD, such as applying a chemical to the label side of the CD, or such as colouring the extreme edge of the CD. Then gaining an improvement in “the sound” – which is WHAT people have reported, over and over again !!!!!!!!!!! To understand what I mean by something adverse happening and then that adverse effect being reduced – and an improvement being heard, let me use the concept of temperature. Say (hypothetically) that the temperature of the room, with the CD spinning, is raised to (say) 40 degrees. Too warm for comfort. Carry out a technique on the CD which could reduce the temperature to (say) 35 degrees and one would immediately register that the temperature had gone down – to something more comfortable – and one would describe the effect as “Oh, that’s better”. Better than before – not necessarily back to a comfortable normal – but better than it had been before the treatment !! In other words BETTER. It is a relative term – better than it was before. It is the difference in the two (readings/sensings) which we (human beings) are programmed to take notice of. You say :- >>> “they (certain tweaks) cannot work simply because they have no way to affect any of the three stages of sound reproduction outlined above.” <<< ut they COULD affect the better resolving of the complexities of the music in a way outside those ”three stages”. They COULD provide a reduction of tension – tension caused by what is going on in the modern environment. Which can then begin to explain the effect of such as crystals, of the effect of the Stein Music device, of the effect of tiny ART devices and of the Less Loss Black Body device. Read again part of the review in PFO of the Stein Music Device :- >>> “Dynamics, clarity, palpable presence, excitement, definition, air, decay, extension, articulation, less distortion, louder, quieter, 3D soundstage, natural, rich, texture, warm, fast, transmission, timbre, immersion, space, tactile, engagement, propulsion, ease, etc… everything is there in abundance… everything is here.” <<< Is this device working within the conventional knowledge area of your “three stages of sound reproduction” ?Or, could it be acting by reducing stress (tension) created by trying to resolve complex music within the modern environment ? Certainly the description points to a reduction of tension and therefore a better resolving of the complex musical information. Which then leads to the very question which the reviewer actually asked :- >>> “Which leads to… has Science explained everything? And is everything explainable by Science? I would say no, perhaps not… or at very least not yet. Science is an evolving discipline of knowledge… new discoveries… new ways of looking at or defining what we know and experience around us.” <<< I repeat it, yet again, because it is important. Science is an evolving discipline of knowledge…..new discoveries….new ways of looking at or defining what we know and experience around us. Quite a difference, don’t you think from your rather rigid outlook of:- >>> “ simply don't work, because there is no possible way they do!” <<< Regards,May Belt,PWB Electronics. Strawman methods won't work And BTW, could you explain how you got to the 'x 26 'xmantra? Was it a revelation or did you try all combinations (a few billion of them) to get to the result? Strawman methods won't work So please leave the engineers out of the subject!Let me explain:1. The tiny bowls resonate on frequencies situated in the treble part of the audio spectrum, so one may hear more "air" around the instruments.2. Pure crystals have a very regular internal structure, so a well-thought out mixture of them might resonate (or rather absorb, I have not studied the phenomenon yet) some well-defined frequencies.3. The Schumann generator uses frequencies within our own brain's alpha waves, so it may cause relaxation and thus a better perception of music. BTW, one reviewer stated he felt "butterflies" in his stomach while testing the generator: no wonder, the military are developing non-lethal weapons based in infrasound.4. Freezing your CDs may release inter-layer tensions and make them more legible to the laser beam, so yes, this may work.5. I did not study the other examples, but I am sure they too have reasons to work. OTH, putting your pictures in the freezer does not work, tying your cables with whitespirals does not work (at least, not any better than tying them with spirals of any other color) and putting blue papers under your houseplants does not work. As for writing the famous mantra on your mirrors and shining a flashlight at them... no comment! You are correct about the You are correct about the straw men, Costin. I might add that the discussion of physical tweaks versus meta physical/fringe ( for lack of a better word) tweaks must be separated. It is not an all or nothing proposition as some proponents would like to have it especially in light of the often used tactic of if you are not for one tweak your are against all of them. Physical tweaks have the potential to be discussed using current known science and as science evolves perhaps some meta physical tweaks can be recategorized as physical tweaks. Meta physical/fringe tweaks are more faith based and with the lack of science to discuss them become more a pseudo religious discussion with believers and non believers. We all know where that leads. May and Geoff are there any manufacturers that endorse your products as much as you endorse others?One might misconstrue this as name dropping. http://en.wikipedia.org/wiki/Name-dropping Also, I find it strange that you hardly ever directly discuss your meta physical/fringe products. We have passed the rubicon where manufacturers discuss their products so this is not holding you back. the tuning side I'm just glad I'm on the tuning side of things and the understanding of them through experience. Bringing out more of a recording is one of the greatest thrills a listener can get and being able to do this at will for me has opened up a world that has kept me from having to fall back into a hobby that seemed more like a spin cycle instead of shaping the sound to the place of origin. I don't have the need to be tangled because the lines have been made clear through being a part of, instead of looking at. michael greenMGA/RoomTune And there are other sneaky procedures 1. Blame it on the opponent: infer that he can't hear, is rigid (and therefore cannot think) or even has the smallpox. Just don't discuss his points as this may place you in an less comfortable position, i.e. one where you actually have to explain how your "thingies" work. Now contrast this with what I wrote before: But by all means, if you are sensitive to suggestions just use them - no, your system won't sound any better but you will think it does... and at the end of the day, the only thing that matters is your own satisfaction!So I'm not accusing other people of being duped, "believers" or anything else: after all, it's their money and if using those tweaks makes them happy... well who am I to tell them not to buy? 2. Re-hatching old situations when engineers were proved to be wrong, without any inquiry into what your opponent thinks about these subjects. To make things clear, I do believe that cables make a difference, including power chords. Or better yet, especially power chords, so no need to remind me about it! 3. And finally, avoiding to explain how your own "thingies" work. And by explaining I mean starting with a proved premise and working your way up to conclusions, using a logical chain of inferences.You learn in Logic 101 that false premises can lead to any conclusion (true or false) while using perfectly logical inferences, so please do't start by telling me that "white is better" and use this as a premise: you have to prove thisfirst, and only after you can go anyway further. 4. It sickens me when a snake oil peddler implies he/she got extraterrestrial technology to somehow modify matter in his/hers own garage. Of course, this precludes any analysis of the "thingies" since whatever changes were brought to them are not detectable even using advanced scientific analysis. Nevertheless, the same non-detectable changes are enough to (somehow) alter our perception of soundwaves. No kidding? Metaphysical tweaks toledo wrote: You are correct about the straw men, Costin. I might add that the discussion of physical tweaks versus meta physical/fringe ( for lack of a better word) tweaks must be separated. It is not an all or nothing proposition as some proponents would like to have it especially in light of the often used tactic of if you are not for one tweak your are against all of them. Physical tweaks have the potential to be discussed using current known science and as science evolves perhaps some meta physical tweaks can be recategorized as physical tweaks. Meta physical/fringe tweaks are more faith based and with the lack of science to discuss them become more a pseudo religious discussion with believers and non believers. We all know where that leads. May and Geoff are there any manufacturers that endorse your products as much as you endorse others?One might misconstrue this as name dropping. http://en.wikipedia.org/wiki/Name-dropping Also, I find it strange that you hardly ever directly discuss your meta physical/fringe products. We have passed the rubicon where manufacturers discuss their products so this is not holding you back. I can certainly understand your frustration with some of tweaks that you are probably hearing about for the first time. Let me ask you, though, which tweaks are you referring to? I am afraid you might be lumping all the tweaks you are suspicious of together and calling them faith based. it might be helpful to try to identify the ones that really bother you, the most suspicious ones, and divide them into groups, say the tweaks that Are actually physical but appear to be metaphysical, e.g., the water bowls,the ones that are based on nanotechnology, e.g. Dark Matter and the intelligent chip, the quantum mechanical ones like the intelligent chip, the ones that are based on mind matter interaction or Morphic Resonance like the clever little clock. You can put all the ones you're not exactly sure what they are in a separate box to figure out later. In a world of wire directionality, slow moving electrons, colors that change the sound and telephone books that change the sound, it's no wonder there 's been such an uproar by skeptics and pseudo skeptics. I'm pretty sure the Newtonian physics guys felt exactly the same way when Einstein published his papers on relativity - very upset. Intro from Zen and the Art of Debunkery (again) "Seeing with humility, curiosity and fresh eyes was once the main point of science. But today it is often a different story. As the scientific enterprise has been bent toward exploitation, institutionalization, hyperspecialization and new orthodoxy, it has increasingly preoccupied itself with disconnected facts in a psychological, social and ecological vacuum. So disconnected has official science become from the greater scheme of things, that it tends to deny or disregard entire domains of reality and to satisfy itself with reducing all of life and consciousness to a dead physics. As the millennium turns, science seems in many ways to be treading the weary path of the religions it presumed to replace. Where free, dispassionate inquiry once reigned, emotions now run high in the defense of a fundamentalized "scientific truth." As anomalies mount up beneath a sea of denial, defenders of the Faith and the Kingdom cling with increasing self-righteousness to the hull of a sinking paradigm. Faced with provocative evidence of things undreamt of in their philosophy, many otherwise mature scientists revert to a kind of skeptical infantilism characterized by blind faith in the absoluteness of the familiar. Small wonder, then, that so many promising fields of inquiry remain shrouded in superstition, ignorance, denial, disinformation, taboo . . . and debunkery." Sincerely, Geoff KaitMachina Dynamica Coordinate system 'x iosiP wrote: And BTW, could you explain how you got to the 'x 26 'xmantra? Was it a revelation or did you try all combinations (a few billion of them) to get to the result? 'X26'x represents a coordinate system for which the number 26 is the number of spacetime dimensions in bosonic string theory and (if I'm not mistaken) the number of dimensions in the universe during the initial expansion period. Geoff KaitMachina Dynamica Tweaks >>> “So please leave the engineers out of the subject” <<< IosiP, You just can’t leave the engineers out of the subject. So many of them are the most vocal and antagonistic !!!!! AND are prepared to deny or dismiss other people’s experiences and observations. So, they ARE a constant part of the audio scene and what affects ‘sound’. >>> “Let me explain:” <<< Explain what ? All you are doing is confirming that there is STILL controversy. If there WERE acceptable explanations, then engineers (and many ‘professionals in audio’) would not react as aggressively as they do !! They would just nod in agreement. >>> “1. The tiny bowls resonate on frequencies situated in the treble part of the audio spectrum, so one may hear more "air" around the instruments.” <<< If the tiny bowls are SOOOOOOO acceptable and MIGHT be doing something to treble frequencies, then why is there such a reaction – why is there such controversy surrounding any mention of them ? A few years ago the responses (controversy) to references to them covered some 39 pages in the Stereophile forum !!! And, the latest reference to them in Stereophile (I think earlier this year – 2014 !!!) created such a vitriolic reaction that John Atkinson had to delete some of the responses. >>> “2. Pure crystals have a very regular internal structure, so a well-thought out mixture of them might resonate (or rather absorb, I have not studied the phenomenon yet) some well-defined frequencies.” <<< If the ‘crystals’ are SOOOOOO acceptable and MIGHT be doing something, then why is there such a reaction – why is there such controversy surrounding the use of them ? Are you making the suggestion that if the crystals are absorbing ‘some well’defined frequencies’, that the absorbing of these frequencies is taking place with the frequencies already in the room ? In which case you will come up against the acoustic engineers. Or, what about the concept put forward by a regular poster on Audio Asylum site that certain crystals are absorbing RF frequencies and preventing these RF frequencies getting into and interfering with the actual audio signal going through the equipment ? In which case you would then come up against the electronic engineers.Just WHO is going to be left doing (working out) the – to use your expression – “a well-thought out mixture” of crystals ? The electronic engineers or the acoustic engineers ? Then, if you bring in the concept of ‘resonance’ – you bring in the mechanical engineers. No wonder there is such a hornets nest – which does not fit your simplistic “might” or “may” be doing something acceptable !! >>> “3. The Schumann generator uses frequencies within our own brain's alpha waves, so it may cause relaxation and thus a better perception of music. BTW, one reviewer stated he felt "butterflies" in his stomach while testing the generator: no wonder, the military are developing non-lethal weapons based in infrasound.” <<< Oh, it might cause relaxation ? Surely this is exactly what I am suggesting ? Surely this is the concept I have been putting forward ? Let me expand this out for you because I still don’t think you are thinking it through. You are suggesting that this ‘relaxation’ might give a better perception of the music. So, the full musical information of the orchestra playing the musical score of Dvorak’s New World MUST HAVE already reached the ear drum – past the electronic areas, past the mechanical areas and past the acoustic areas to reach the ear drum. So, BEFORE the introduction of the Schuman Resonance why had we (human beings) not been ‘hearing’ all the information that was available – in the room - but AFTER the introduction of the Schuman Resonance device into the room, we (human beings) are able to hear (perceive) more of the complex musical information. The descriptions people give of their experiences are not merely of “better sound” but are more in the area of :- “Heard a more dimensional soundstage. Improved low end that sounded tighter and richer. Improved smoothness, detail and bass definition, not to mention greater soundstage and three-dimentionality. Greater sense of air and bloom seemed to surround the instruments. More life and vibrancy. More Natural texture. The decay structure of individual notes was cleaner and clearer. Stereo focus and image uniformity were improved. The music’s dynamics, rhythm and timing were significantly improved. Improvements in the sound as an audible decrease in glare and an increase in apparent soundstage size, both width and depth. Improvements noted are better air, sparkle, transparency, openness, imaging, soundstaging, naturalness and musicality.Wow, that was amazing. The soundstage has just opened up.” As I keep saying. You cannot add more musical score to what is already encoded on the disc. You cannot add another half of an orchestra to give you yet more musical instruments to what is already encoded on the disc, so if you can hear all that further information after introducing the Schumann Resonance device into the room, then that further information must have been there, in the room, all the time !! If the Schumann Resonance device could be providing something good (beneficial), then what was being adverse, in the room, before introducing the Schumann Resonance device ? To not be allowing us to be ‘relaxed’ ? If you can accept the concept that the Schumann Resonance device could be allowing a more ‘relaxed listening environment’ so that we (human beings) can perceive the music better, then why can’t the same concept be applied to many of the other controversial devices ? I.e That they could be ‘countering’ adverse conditions – adverse conditions which we are reacting to ? And so it goes on – controversy after controversy. There is NOT a general acceptance within the audio industry that things MIGHT work – which is what you are suggesting. If there was such an acceptance, then there would be NO controversy. >>> “2. Re-hatching old situations when engineers were proved to be wrong, without any inquiry into what your opponent thinks about these subjects. To make things clear, I do believe that cables make a difference, including power chords. Or better yet, especially power chords, so no need to remind me about it!” <<<Sorry, sir. These are NOT OLD situations !! The engineers are still insisting that they are right – ESPECIALLY on power cords. They are still saying “How can changing the last few metres of AC power cable, in the room, make any difference to the sound, when the AC power has already come miles in existing standard cabling ?” Whereas you are suggesting that they have now accepted that they were wrong !!! Just because you, yourself, have heard the effect of different power cords does not alter the fact that there is STILL considerable controversy. And, if you have the definite answer as to why changing the AC power cord could improve the sound, would you please tell the researchers so that they can pack their bags and go home and have a rest !! >>> “5. I did not study the other examples, but I am sure they too have reasons to work.” ,<< So, if such as applying a demagnetiser to LPs and CDs etc “could have reasons to work”, then why is it not accepted that they “could have reasons to work” and why do we have ‘professionals in audio” actually writing to the American Consumer Electronics Association regarding such as the Furutech CD "demagnetizer" and implying fraud because the CEA had ‘determined this is an award-winning product’ ? And this same “professional in audio” had further commented (on Stereophile Forum) :- >>> “Likewise for demagnetizing CDs and LP records, the subject of this thread. Unless the heads of Furutech are idiots, which I doubt, all that's left is dishonesty. So all they can do is reject standard testing and claim there's more to it than "science" knows.” <<< Why, iosiP, IF such things “could have reasons to work”, is it not as accepted in the general and ‘professional’ world of audio as you are accepting that they MIGHT ? >>> “3. And, finally, avoiding to explain how your own "thingies" work. And by explaining I mean starting with a proved premise and working your way up to conclusions, using a logical chain of inferences.You learn in Logic 101 that false premises can lead to any conclusion (true or false) while using perfectly logical inferences, so please do't start by telling me that "white is better" and use this as a premise: you have to prove this first, and only after you can go anyway further.” <<< I will reply to both you and Toledo here. In posting on the Stereophile Forum I use the “rules for manufacturers” as set down by the Audio Asylum site – because I find those rules fair and reasonable for both manufacturers and retailers. 1) That manufacturers must not use Audio Asylum Forums to advertise their products.2) Having respect to that rule, manufacturers can still take part in general discussions. Now regarding the conclusions we have come to. These conclusions have been arrived at using a logical chain of inferences (and considerable experiences). This chain has been fully described OVER and OVER again – for the past 30 years - until I have run out of breath doing so !! But, those past 30 years working in a particular area, just followed on from a previous 30 years designing and manufacturing audio products and working completely within conventional audio and acoustic theories. So, I am ALSO fully conversant with how conventional electronic, mechanical and acoustic engineers think and work. >>> “so please do't start by telling me that "white is better" <<< I can’t PROVE ‘white is better’. The only way to prove it to yourself is to try it in SPECIFIC areas, on SPECIFIC objects in comparison to other colours and LISTEN each time. SURELY exactly as Michael Green cannot PROVE that loosening particular screws or bolts, in equipment, WILL give you an improvement in the sound. You have to try it and listen for yourself !! I can’t PROVE the colour purple/violet is a better colour for the edge of CDs than the colour green. You would have to try it and listen for yourself. I can only give you the results of our listening experiments. Just exactly as Michael Green is giving you the results of HIS listening experiments. With all the devices I have listed – and more besides – AND all the techniques which Michael has suggested people should try to gain improvements in the sound, they are all showing that there is a wealth of additional information – available – which people are just not ‘hearing’ (resolving). Regards,May Belt,PWB Electronics. Pass the calculator Miranda iosiP wrote: So please leave the engineers out of the subject!Let me explain:1. The tiny bowls resonate on frequencies situated in the treble part of the audio spectrum, so one may hear more "air" around the instruments.2. Pure crystals have a very regular internal structure, so a well-thought out mixture of them might resonate (or rather absorb, I have not studied the phenomenon yet) some well-defined frequencies.3. The Schumann generator uses frequencies within our own brain's alpha waves, so it may cause relaxation and thus a better perception of music. BTW, one reviewer stated he felt "butterflies" in his stomach while testing the generator: no wonder, the military are developing non-lethal weapons based in infrasound.4. Freezing your CDs may release inter-layer tensions and make them more legible to the laser beam, so yes, this may work.5. I did not study the other examples, but I am sure they too have reasons to work. OTH, putting your pictures in the freezer does not work, tying your cables with whitespirals does not work (at least, not any better than tying them with spirals of any other color) and putting blue papers under your houseplants does not work. As for writing the famous mantra on your mirrors and shining a flashlight at them... no comment! Better pull out the slide rule again on the tiny little bowls for both acoustic waves and electromagnetic waves. Crystals do have a symmetrical structure, that's true. How that equates to better sound isn't exactly obvious,as ten years of debate on the subject demonstrates. The Schumann frequency resonates with internal body organs so that's not surprising. Freezing CDs might relieve stress, that's true, but have you no faith in Reed Solomon Error Correction Codes? One assumes you also believe cameras steal your soul. Audiophiles can be very superstitious about some things. You wrote, "5. I did not study the other examples, but I am sure they too have reasons to work." One assumes that's just woman's intuition. Geoff KaitMachina Dynamica Quote: Quote: I can certainly understand your frustration with some of tweaks that you are probably hearing about for the first time. Let me ask you, though, which tweaks are you referring to? I am afraid you might be lumping all the tweaks you are suspicious of together and calling them faith based. it might be helpful to try to identify the ones that really bother you, the most suspicious ones, and divide them into groups, say the tweaks that Are actually physical but appear to be metaphysical, e.g., the water bowls,the ones that are based on nanotechnology, e.g. Dark Matter and the intelligent chip, the quantum mechanical ones like the intelligent chip, the ones that are based on mind matter interaction or Morphic Resonance like the clever little clock. You can put all the ones you're not exactly sure what they are in a separate box to figure out later. In a world of wire directionality, slow moving electrons, colors that change the sound and telephone books that change the sound, it's no wonder there 's been such an uproar by skeptics and pseudo skeptics. I'm pretty sure the Newtonian physics guys felt exactly the same way when Einstein published his papers on relativity - very upset. The only frustrating part is the lack of discussion of tweak products in terms other than feel good or new ageisms or the theoretical. Dark matter? A bit of a stretch there. Morphic resonance? "Memory is inherent in nature" and telepathy.http://en.wikipedia.org/wiki/Rupert_SheldrakeI agree there is much to be learned about telepathy but it's applicability to audio and listening.. I need a little more info. You have discussed some of the 'technical' aspects of your products and there is ample opportunity to go further. Let's take intelligent chips, for example. The premise of the product is to permanently enhance the transparency of the polycarbonate CD surface. This is an easily tested situation of before and after, yet no tests verify this sem to be available. I think it is up to you as the proponent to classify tweak products to ease the discussion. I see this as number 1 on Costins list of tactics of shifting the debate to the opponent. As for the rest of your post, I will leave it up readers to figure out which tactics your are employing. The name dropping has decreased somewhat, but, still employed to add authority and credibility to your statements. What do we know and when did we know it? Dark Matter is the name of one of my newer products, the one that absorbs infrared (invisible) light. See the connection? Dark Matter is actually the only audio product to address this issue. Yeah, I know what you're thinking, "I didn't even know it WAS an issue." As for intelligent chips, here's a quick rundown. 1. The original intelligent chip introduced in US in 2004, I gave one to Clark Johnsen at CES 2005, who demo'd it for a number of folks. The intelligent chip was the product of the show, or so someone said. 2. The Chinese company that introduced the intelligent chip said he discovered the effect accidentally. He worked in some sort of medical research office where he had access to quantum dots that were being studied for use in human tissue illumination (next MRI type technology). 3. The intelligent chip was the single biggest subject of discussion on Audio Asylum for the entire year 2005 and probably ever. 4. I published The Definitive Explanation of How the Intelligent Chip Works in the summer 2005. The essence of the rather long paper is that the chip works quantum mechanically, emits coherent light in presence of laser light and the end result of all the quantum stuff going on is a more transparent polycarbonate layer. Thus the treated CD sounds like a remastered CD. 5. The intelligent chip worked when it was placed on top of the cd Player, while the CD to be treated was allowed to play for 2 seconds. The intelligent chip ran out of steam after 10 treatments for reasons that I explain in my paper. 6. The Intelligent Box, also from JSMR, was released around 2007 or so, and reviewed by the two PhDs Marge and Henk at 6 Moons a couple years later. I introduced a new version of the original chip about this time that operated somewhat like the intelligent Box in that the new chip was placed directly into the inside of the player. 7. Since I kind of have a pretty good idea how quantum dots work I was able to develop a more powerful intelligent chip around three years ago, the Super Intelligent Chip, which incorporates new technology quantum dot wise. The active ingredient as it were in the Super Chip is produced in the lab of one of the pioneering companies in nanotechnology according to my specification. 8. Pretty sure WA quantum chips from Germany also utilize quantum dots. Any questions, fire at will. Geoff KaitMachina Dynamica I have a question What if you are playing a drum on your system and you want the body of the drum to come out more, you put on the next recording and want the body of the drum to be less, what would you do? michael greenMGA/RoomTune Quote: Quote: 4. I published the Definitive Explanation of How the Intelligent Chip Works in the summer 2005. The essence of the rather long paper is that the chip works quantum mechanically, emits coherent light in presence of laser light and the end result of all the quantum stuff going on is a more transparent polycarbonate layer. Thus the treated CD sounds like a remastered CD. From your white paper you state"The clear polycarbonate layer in commercial off-the-shelf CDs has a transparency of only around 92%." How was this transparency figure arrived at? If the original transparency can be calculated, what is the transparency after treatment? Can you provide the test results? This seems like a rather simple before/after test to confirm that the permanence of the quantum superposition effect is actually permanent. It is rare to find such an easily testable and verifiable scenario in quantum mechanics. Bass performance michael green wrote: What if you are playing a drum on your system and you want the body of the drum to come out more, you put on the next recording and want the body of the drum to be less, what would you do? michael greenMGA/RoomTune The Beauty of headphones is you can ignore all the room anomalies and concentrate on the electronics and especially improving dynamic range and signal to noise ratio, which are almost always compromised by any number of things like vibration, RFI/EMI, magnetic fields, among other things. With the concept in mind that improving bass performance is like an archealogical dig, you're not really sure what you've got there untill you can remove all the dirt that covers it. My primary concerns these days are reducing seismic vibration, reducing vibration of the CD transport mechanism, reducing magnetic fields inside the player and amp, and reducing RFI/EMI emissions inside the player, especially by semiconductor chips. Cheers, Geoff KaitMachina Dynamica Wait, I think I know this one michael green wrote: What if you are playing a drum on your system and you want the body of the drum to come out more, you put on the next recording and want the body of the drum to be less, what would you do? michael greenMGA/RoomTune Put two photos of drums in my freezer? Transparency toledo wrote: Quote: 4. I published the Definitive Explanation of How the Intelligent Chip Works in the summer 2005. The essence of the rather long paper is that the chip works quantum mechanically, emits coherent light in presence of laser light and the end result of all the quantum stuff going on is a more transparent polycarbonate layer. Thus the treated CD sounds like a remastered CD. From your white paper you state"The clear polycarbonate layer in commercial off-the-shelf CDs has a transparency of only around 92%." How was this transparency figure arrived at? If the original transparency can be calculated, what is the transparency after treatment? Can you provide the test results? This seems like a rather simple before/after test to confirm that the permanence of the quantum superposition effect is actually permanent. It is rare to find such an easily testable and verifiable scenario in quantum mechanics. There are a number of on line sources for polycarbonate transparency. The number I stated 92% is probably a high (conservative) number. Polycarbonate is OK but not perfect. And probably chosen because it has a very good refractive index for the purpose and because it's cheap. We do not do testing of transparency here at Chez Machina Dynamica. Are you volunteering? Think of the transparency theory as what it is, a theory. Please don't report me to AES. You might well be correct, that's it's an easy test to perform. I should also point out that testing of products and testing of theories is probably best performed by independent third parties. The link below is a chart of polycarbonate properties that actually shows a transparency to light figure of 89%. Interesting, huh? http://optochemicals.com/polycarbonate_properties.htm Cheers, Geoff Kait, Machina Dynamica Quote: Quote: There are a number of on line sources for polycarbonate transparency. The number I stated 92% is probably a high (conservative) number. Polycarbonate is OK but not perfect. And probably chosen because it has a very good refractive index for the purpose and because it's cheap. We do not do testing of transparency here at Chez Machina Dynamica. Are you volunteering? Think of the transparency theory as what it is, a theory. Please don't report me to AES. You might well be correct, that's it's an easy test to perform. I should also point out that testing of products and testing of theories is probably best performed by independent third parties. The link below is a chart of polycarbonate properties that actually shows a transparency to light figure of 89%. Interesting, huh? http://optochemicals.com/polycarbonate_properties.htm Cheers, Geoff Kait, Machina Dynamica Thanks for your candid comments. But this begs the question of why wouldn't you have the intelligent chips tested by a third party to verify its efficacy? You could unequivocally state the benefits without cloaking it in the mysteries of quantum mechanics or wouldn't that have the "cool factor"? Are we running into the Stovepiping issue that plagues the audio industry that only new and cool sells? Testing, etc. Toledo wrote, "Thanks for your candid comments. But this begs the question of why wouldn't you have the intelligent chips tested by a third party to verify its efficacy?" That would be silly. Who would believe a third party I contracted with? That would be like an Army contractor contracting with a third party? That's not INDEPENDENT. HEL-loo! The government, not the contractor, contracts the third party "You could unequivocally state the benefits without cloaking it in the mysteries of quantum mechanics or wouldn't that have the "cool factor"?" I actually like quantum mechanics and am not afraid of it. Why hide the method of operation? It is what it is. Besides, quantum mechanics is what, 90 years old. Not exactly new and cool anymore, I'd opine. "Are we running into the Stovepiping issue that plagues the audio industry that only new and cool sells?" I suggest Stovepiping plagues individuals who are blind to developments in the industry. Geoff KaitMachina Dynamica Shucks..... no wonder it did not work..... I put the drums in freezer...... this wasn't my question Hi Geoff I think you misunderstood my question. It had nothing to do with room or non-room. lets try again What if you are playing a drum on your system and you want the body of the drum to come out more, you put on the next recording and want the body of the drum to be less, what would you do? michael greenMGA/RoomTune Quote: Quote: I suggest Stovepiping plagues individuals who are blind to developments in the industry. What recent developments might those be? You mean an industry that is in a death spiral due to short sighted goals of "new and improved" and supporting industries based on untested, unverified and theoretical products. Some of us are not as blind as you might wish us to be. If the industry produces such great products why the need for aftermarket component tweaks. Let's dispense with the cd tweaks, cd treatments, etc ... I think we heard about those. michael green wrote: michael green wrote: Hi Geoff I think you misunderstood my question. It had nothing to do with room or non-room.Just kidding, Michael.Just kidding, Michael lets try again What if you are playing a drum on your system and you want the body of the drum to come out more, you put on the next recording and want the body of the drum to be less, what would you do? michael greenMGA/RoomTune Adjust the tone control, assuming you have one? Just kidding, Michael... ; } Just kidding, Michael... ; } it's true though It's funny, but it's also truly distrubing. People shouldn't have to be listening to stuck systems. It amazes me that the early designers got it, but it goes right over the head of the audiophile designer and user. The early designers knew and accepted that every recording was different. As soon as they realized this they made "tone controls". The audiophile designer comes along and says "that makes the sound untrue to it's orginal state". The most stupid move in the history of this hoppy! Instead of figuring out how to make the sound variable in a more pure approach, we'll just start to make thousands of systems stuck playing one sound, and that's exactly what happened. One sound systems when we know they will never play a wide range of differing recordings. Then we came up with the second most stupid statement. My system is so revealing it's showing the flaws in this music. BS, it can't play the music. When are guys going to get it, we made a wrong move. We went from a solution, to completely being stuck and we've been doing it so long we can't even remember why we had tone controls to begin with. We were just so proud of ourselves being purist that we didn't realize that this was going to stop us from being able to play most of the music. We went right into the 80's with this Absolute Sound idea, but no audiophile on the planet can ever get it now because we removed an important tool without replacing it. If you have a tone control lets put you in the corner but if you can't play the music now, or tune it in we'll just blame the music. I truly hope I'm not here much longer before people start to see what has happened to our hobby. The numbers of music lovers are going up and the numbers of audiophiles are dropping like flies. Do we not see it yet? Bill, you make fun and I'm with you, I'm easy to make fun of and make fun of myself often. But what you also did was say the truth loud and clear. If we have a drum sound that we wish to change, how do we change it? The audiophile right now is dead in the water with this question. He can either falsely say it's the recordings fault, or switch out a system every time he puts on a recording, or go back to using tone controlling, or keep the purity and be able to tune to the recording both. How can a person call himself and audiophile when we can't even understand that every recording is different as we all knew 50 years ago, and we still have no system that can do anything about it? People look at me on here and say "I'm not going to tune to every recording". Well ok, but even the guys who started this thing knew they were going to have to tune. so again I setup my test I took a group of guys and had them play recordings they thought were recorded terrible. They never knew what components I was using, but before I put on the "bad" recording we played something to show that the system was sounding good to them. Put on the first bad recording and the listener said see. He left the room and 5 minutes later I had him come back in. He sat down and listened and was "wow, what in the "h" did you do". I showed him. After laughing a while at the industry I tuned up the system to play the recording with it's glory. I did this with everyone and the results were the same. Their bad recording sounded much better EQed than with the bypass on. Everyone liked the real tuning the best but the interesting part to me was that these trained audiophiles took the EQed over the bypass on recordings they liked but couldn't get to sound good. Why are we fix listening? Why have we taken a step backward? and How can we ignore the facts about recordings? I am absolutely dumb found that this part of the industry has moved away from something we knew 50 years ago to be a fact. If you are in the studio you have an EQ. If you are in your car you do there as well. You have a way to make the needed changes everywhere but in your high end home listening. Are you guys telling me you would rather listen to an extremely limited few pieces of music the rest of your life over having a system that can play it all? I hope I'm shaking up things in your minds and I also hope that you take the time to think about these things. It seems pretty remarable that a hobby could have gone off track this far but you don't have to spend the rest of your lives thinking something is when it isn't. There is music to be heard, and after that even more music. If you think you are going to after all these years put together a system that is automatically going to play recordings that are all different sounding your going to be lying to yourself and others for a long time. michael greenMGA/RoomTune Tweaks and Tuning Michael, you said :- >>> “I don’t have the need to be tangled because the lines have been made clear through being part of, instead of looking at.” <<< You can’t possibly be referring to me with that remark and to my considerable experiences, as I have been involved in “being PART of” – far more than just “looking at”. >>> “There is music to be heard, and after that even more music.” <<< You could not have said a truer sentence, Michael. Similarly someone elsewhere also used a sentence which put it in a nutshell. They said “People are not hearing what they have paid for.” Regards,May Belt,PWB Electronics. A misunderstanding michael green wrote: Hi Geoff I think you misunderstood my question. It had nothing to do with room or non-room. lets try again What if you are playing a drum on your system and you want the body of the drum to come out more, you put on the next recording and want the body of the drum to be less, what would you do? michael greenMGA/RoomTune Michael, I did not misunderstand your question. However, I'm pretty sure you misunderstood my answer. One of the benefits of my approach, which I might possibly describe as holistic or eclectic, is absolutely positively the most incredible bass performance you have ever heard - deep, powerful, taut, elastic, dynamic, propulsive, above all consistent with reality. A recipe for reality - Find the problem, fix the problem, move to next problem. It's an archaeological dig so bring it back alive! Geoff KaitMachina Dynamica Recent developments toledo wrote: Quote: I suggest Stovepiping plagues individuals who are blind to developments in the industry. What recent developments might those be? You mean an industry that is in a death spiral due to short sighted goals of "new and improved" and supporting industries based on untested, unverified and theoretical products. Some of us are not as blind as you might wish us to be. If the industry produces such great products why the need for aftermarket component tweaks. Let's dispense with the cd tweaks, cd treatments, etc ... I think we heard about those. Manufacturers seem blissfully unaware of Recent developments by advanced audiophiles such as addressing scattered background laser light in the CD or Blu Ray player, addressing RFI/EMI in a comprehensive way, addressing vibration in a comprehensive way, addressing magnetic fields in the player and amplifier in a comprehensive way. Beyond that, it is the audiophiles who are blissfully unaware of these developments by other audiophiles in many cases, no? That's really what I'm referring to when I use the word Stovepiping. I won't even get into the areas that are INDEPENDENT of the audio system, independent of the electronics, the speakers, the acoustic waves, all the cables and wiring, everything. You know what I'm talking about. That's what I mean by "recent developments." You could say it has a lot to do with a better understanding of the relation between physics and sound, not to mention a better understanding of the physics involved, "It's what I choose to believe." Dr. Elizabeth Shaw in Prometheus Geoff KaitMachina Dynamica geoffkait wrote: geoffkait wrote: 'X26'x represents a coordinate system for which the number 26 is the number of spacetime dimensions in bosonic string theory and (if I'm not mistaken) the number of dimensions in the universe during the initial expansion period. Great! And how does writing it on my mirror improve my listening experience? One question after another iosiP wrote: geoffkait wrote: 'X26'x represents a coordinate system for which the number 26 is the number of spacetime dimensions in bosonic string theory and (if I'm not mistaken) the number of dimensions in the universe during the initial expansion period. Great! And how does writing it on my mirror improve my listening experience? Geez, it's just one question after another with you. You're the phD. Shouldn't YOU be explaining why it improves the listening experience to US? Oh, wait a minute, I almost forgot. Your job is explaining why something can't possibly work. How written words influence how water crystals are formed. http://youtu.be/iu9P167HLsw Geoff KaitMachina Dynamica Michael, Michael, It's funny you bring up EQ. I was a purist for years. How could you not be since someone decided that tone control are out ;) My most recent highend system was a manley stingray amp, cec tl1x transport, audionote dac and merlin tsm. My previous system was 25watt SET mono blocks using KR tubes, transformer volume control using custom C-core transformers and copper top/bottom chassis plates encased in wood and the same transport, dac and merlin vsm towers. I won't even get into my Levinson/Rowland/watt puppy days. These systems were absolute champs at certain types of music mainly small ensemble acoustic jazz, simple classical soloists and other audiophile approved recordings. But what about my other stuff I cut my teeth on as a teenager and early adult life. Not so good. So what does a purist do ... He goes out and finds an old school Soundcraftsmen EQ! I used that for awhile and it was like the old days. I could EQ each recording and finally gain some control over each recording. I could engage the EQ when needed and bypass it for the purist in me. But, it was a bandaid and one more box and more cabling and more rack space and on and on. Thats when I said I have had enough. I realized I can't build my out way out of this problem with ever more patches, etc. Where am I today system wise? A tuned simple $100 receiver and a $29 DVD player, shoe string cabling, no power conditioning and same speakers.Where am I in enjoying my music? I have all that I had with previous systems and much more. More importantly I have gained back my tone controls so to speak. Strange theories isoiP wrote, "3. And finally, avoiding to explain how your own "thingies" work. And by explaining I mean starting with a proved premise and working your way up to conclusions, using a logical chain of inferences.You learn in Logic 101 that false premises can lead to any conclusion (true or false) while using perfectly logical inferences, so please do't start by telling me that "white is better" and use this as a premise: you have to prove this first, and only after you can go anyway further." I'm afraid logic and reason only get you so far as explanations go. Folks are not really prepared to discuss all the ins and outs of quantum mechanics or even plain old electricity, magnetic fields, electromagnetic waves, for that matter, you know, subjects I suspect many audiophiles, perhaps yourself included, believe they have a reasonably good grasp of. When you exclaimed in a recent post, Are you serious?! When I mentioned that electromagnetic waves are composed of photons, it made me realize, wow, here's a PhD in information theory and a MS in signal processing, I'm hope I'm not butchering the subjects of your degrees too much, who is thrown by that statement. One has to ask oneself, if this is the case for someone with advanced degrees what chance do manufacturers of exotic tweaks have of explaining things when the going really gets rough, when we get into quantum mechanics, quantum teleportation or say mind matter interaction or Morphic Resonance? Then I guess we'll really see the fur fly. What's the word when someone has a phobia about learning new things? Geoff KaitMachina Dynamica This brings back memories When I was a kid, the first thing I did when I bought a car was put in an EQ/amp and new 6x9 Jensen Coax speakers. I've probably had a dozen car stereo systems and always had an EQ/amp. Every tape had its own need for shaping with the equalizer. Eventually, I had all the settings for each tape memorized and simply adjusted the EQ before swapping out tapes. There was absolutely nothing left on the recording that I wasn't hearing and hearing it quite loudly, as kids are want to do. And then there's live recordings with real space and real reverb and envirnmental accoustics. That's such a different situation than engineered recordings that I don't expect a single system to play both with equal truth anymore than I would expect a car to perform equally well in traffic as it does on the track. Recordings sound different because they are created by people with differing goals and opinions on what they want them to sound like. They don't start with the notion of making them sound just like they were performed, in many cases because they would sound like shit if they did. Music is an emotional experience and will interplay with the listeners state of mind at any given moment. We may agree generally on what aspects of sound are desirable, but we will never agree on what aspects of reproduction strike that emotional involvement in each one of us to the point of becoming predictable enough to tell each other what they should or shouldn't seek in any given set of variables like gear and tweaks. For some it will be a big, wide stage. For others, tonal balance or absolute spls. I suspect it certainly changes constantly with our mood and state of mind. If equalizers and tone controls do it for people, more power to them. If that huge stage makes that connection, then that's the right choice for that listener. There's what is real and what is truthful to the original and then there's personal choices. Two very different things. The High End will only remain High End so long as the ultimate goal and the advancement of the ball is based on truth to the original. Once it leaves that starting point, it ceases to be High End and becomes something else. I submit that too many manufacturers have strayed from that starting point and really are just trying to sell stuff based on marketing campaigns that don't really fill a High End objective. Hey Catch, Hey Catch, Good memories indeed. I remember right out of college finally with a little cash in my pocket, I bought a Blaupunkt car system with eq/amp and coax. Good tunes and good times to be had. Back then, you did not obsess over a system. You bought one and enjoyed it. My mid fi system days were the same, you got a decent setup and played tunes. Then I got into high-end and my enjoyment of music began a gradual descent. First you get the new system and then starts the obsession to make it better. Before you know it, you are listening to your system and not the music in pursuit of the holy grail. Factor in different recordings and limited means to deal with them on high-end systems and I am surprised many of us stayed in the hobby. But we love music and find a way, right. For some, ironically, the path leads back to well designed, tuneable and what might be considered mid-fi components. I may sound a bit over zealous, but I am finally enjoying the hobby again. I actually packed up my high-end system for a couple of years deciding whether I wanted to stay in the hobby and also to reset my focus to music versus system listening. As with anything, there's a learning curve and discovery It's easy to jump out into the weeds with tweaks and tuning, but one very constant fact about sound reproduction and achieving truly good sound starts at one place. The one place that makes ALL THE DIFFERENCE IN THE WORLD (Catch types with his GOD voice) is proper speaker placement in the room. 90% of all the magic in audio begins with this one step and many gear chasers and sound tweakers never fully appreciate its importance. There's a lot of really great stuff being made and advances in playback within the digital domain and most especially, affordable speakers that are incredible value. However, no matter how good your gear is, if you aren't starting with good speaker placement in any given room, you really are starting down a path of never being satisfied with components that aren't even given a fighting chance of showing you what they can do. I tweak and tune with my system out of enjoyment of tweaking and tuning and learning. But, you can bet your ass my speakers are placed where they disappear from the listening environment. And that's how you will know if your speakers are placed properly in the room or at least reasonably well placed. If your speakers aren't disappearing, go back to step one until they do. If you can't use the Cardas Golden Ratio method, then use one of the variants in loading your corners with the Cardas method. Tweaks are fun after your system already sounds amazing, not before. still not getting it Hi Geoff Sorry but you are still not getting it. What if you are playing a drum on your system and you want the body of the drum to come out more, you put on the next recording and want the body of the drum to be less, what would you do? you answered "Michael, I did not misunderstand your question. However, I'm pretty sure you misunderstood my answer. One of the benefits of my approach, which I might possibly describe as holistic or eclectic, is absolutely positively the most incredible bass performance you have ever heard - deep, powerful, taut, elastic, dynamic, propulsive, above all consistent with reality. A recipe for reality - Find the problem, fix the problem, move to next problem. It's an archaeological dig so bring it back alive! " mg again The listener, and the studio and myself would get no where with this answer Geoff. We've already heard the deep, powerful, taut...all the above. What we are asking is how do you, you Geoff, go from one sound to the next making a change. The drum sounds like this specifically and we want it to sound like that instead specifically. This is what we do in the music biz. How do you do this. This has nothing to do with you or anyone proclaiming they have a better anything, this has to do with a change that listeners are doing every day. An example: last week I was listening to Selling England by the Pound. I hear the drums are recessed because I had the system tuned to Abbey Road. I made the necessary adjustment to move the drums forward and make them fill in and dropped the tone a little and bring more focus to the middle and lower part of his set. What I'm asking you is how do you do this? I'm giving you a chance to show people how you are able to bring the best out of every recording and or take the recording to different places within the stage or tonally or whatever change a person may want. In tuning we have moved past who's got the best. We have found ways to get to the signal core and make whatever sound we want. We're no longer playing the game of I got you beat. We are able to bring any part of the audio recording and take it pretty much anywhere, all from what is on the recording. Where the industry is taking snap shots of a particular sound we are suggesting they can go much further than this. So lets back up and ask the question this way. If you have the drums set at the back of the stage and you wanted to move them forward and change the pitch, fill out the middle of the drum and the lower part focusing more on this than the head, how would you do this? thanksmichael greenMGA/RoomTune Michael, you said :- >>> “I don’t have the need to be tangled because the lines have been made clear through being part of, instead of looking at.” <<< You can’t possibly be referring to me with that remark and to my considerable experiences, as I have been involved in “being PART of” – far more than just “looking at”." Nope I wouldn't make this statement about you. I would make this about people who are not actively listening and injecting opinions based on theory instead of doing. And also the ones who don't follow through on their testing. A/B testing for example can be extremely wishy washy amoung audiophiles. Those of us who have learned how to do real testing get a little chuckle out of the quick fix world and how easy it is to lead the empty of thought to the water, and get them to drink. Sad but the industry has fallen a few times by not listening with enough conviction. As far as the whole snake oil thing, me having my background in the music world as much as the audiophile thing I find it funny what makes people in this hobby so afraid. I've been a little shy in talking about my music side ever since I got into the audiophile biz because of the reputation the audiophiles have made for themselves as being off the wall and very Very stuck in their thinking. Audiophiles have a way of making theories (so do audio engineers) that are only useful in debates. When put to the test (like this guy saying you have to have a room 37' long to hear 30hz) to an audiophile this can really mess up their listening hobby. But I think the doing thing if shown more is what will help others understand what they can "do" in and with their systems. I don't think saying all the adjectives and audiophile descriptive words get through to the audiophile any more though. They need to have a particular piece of sound or music described to them and then the guidence to make a real time change. And I do think this would be helpful from you. So that the listener who is listening to something specific like the sound of a guitar in a particular recording can get from point A to point B. as far as me and other tweaks or any audio components I pretty much just do my thing and when I see something that I think I haven't done bring it in and test it for myself, and either incorporate or move on. be well michael greenMGA/RoomTune To Michael >>> “as far as me and other tweaks or any audio componentsI pretty much just do my thing and when I see something that I think I haven't done bring it in and test it for myself, and either incorporate or move on.” <<< Michael. I do not dispute your experiences with changing the sound by doing the ‘tweaks’ (tuning) you describe. The reason why I refer to so many of the other ‘tweaks’ is that all of YOURS, OURS and the OTHER ‘tweaks’ are providing CLUES !!!!!!!!!! CLUES that all the (musical) information available is not being ‘heard’ !! We have been down the same path you have been along. Some 25 years ago we ‘treated’ 99 (UK pound) CD players, ‘treated’ 99 (UK pound) amplifiers, ‘treated’ 150 (UK pound) speaker systems and blown away the competition – and have had it reported so in the UK Hi Fi magazines. WE have also ‘treated’ demonstration rooms at both retailers and Hi Fi Shows – including ‘treating’ the demonstration rooms at Hi Fi Shows run by the actual Hi FI Magazines !!! So I know that the ‘techniques’ you describe CAN have an effect on the sound. I do not challenge that !! Yes, of course you can ‘tune’ a system to a specific sound of a guitar – if that is what you wish to do. But there is also something else going on. There is also the fact that there is the subject of creating a ‘better’ sound overall. That you can create a better sound by doing something specific and then if you undo what you have just done and go back to listening to the same thing again, this time you just don’t like the sound. Full stop. You don’t LIKE the sound any more and you have to go back to doing whatever it was you had done to give you that improvement. In other words – it is no longer merely a ‘tuning’ thing, it is a ‘better or worse’ situation. In other words, cut and dried – not a question of ‘tuning’ for this sound or for that sound. Let me explain from our own experiences. You describe such as untightening screws and listening and ‘tuning’ the sound by doing so. There is also a ‘better and worse’ situation. Our experience shows that if you look at all screws which are vertical to the earth’s surface – in other words screws holding the light switch to the vertical wall, screws holding the AC socket to the vertical wall, screws holding a vertical facia plate to equipment etc and you align the SLOT of those screws so that it is parallel to the earth’s surface, and then listen to some music, you will get an improvement in the sound !! After getting used to that sound, if you then change the position of the SLOT away from being parallel to the earth’s surface, then the sound will be described as worse – i.e the improvement in the sound will have gone !! More of a Black and White situation rather than a ‘tuning’ situation for specific and individual instruments. And so it goes on – and on !! I do NOT challenge what you hear when you do the things you describe. If you hear extended soundstage (such as extended height, width, depth etc) after you have unravelled wires, after you have untightened screws, after you have rested transformers on ‘treated’ wood blocks, then that is what you have heard – I do NOT challenge your listening experiences. What I have difficulty with are the words used. It may (as I think) be merely a terminology aspect. You use the words “unblocked” to describe what happened after you applied those certain (what you call tuning) techniques. I fully appreciate that that is how it appeared, that ‘something’ (information) had been ‘unblocked’ after carrying out certain techniques, and this means that prior to doing those techniques, ‘something’ must have been ‘blocking’ that information. But ‘blocking’ what ? The audio signal ? or the ‘sound’ ? If you say ‘the audio signal’, then I know where you are coming from. If you say ‘the sound’, then my question would be “How had ‘the sound’ been blocked in the first place – to then be ‘unblocked’ by carrying out the techniques you have described ?” MY description for the effect you experienced would have been a “freeing up” of the sound. Which is exactly what people have experienced and described after introducing certain ‘room’ devices into the listening environment. But these devices cannot have been “unblocking” any audio signal – the further information being ‘freed up’ must have ALREADY been there, in the room, having been presented into the room by the loudspeakers earlier !!!!!!!!!!!! Those numerous and various ‘tweaks’ (devices) I have previously described does not, in any way, affect the realisation that doing even more things, carrying out yet more techniques, many which you have described, can give one EVEN MORE ‘freeing up’ of the musical information !!!!!!!!!!! Regards,May Belt,PWB Electronics. EQ and equipment Hi Toledo I was thinking about your post. You owned some of the same equipment as me, well what didn't I own lol. I think some people may take it wrong when some start changing their systems over to the low mass tunable ones. Something goes haywire in their $$$ dollar $$$ signs mental conditioning. I really believe that. Some people can't see or hear the sound unless it has a dollar amount up grade attached to it. Looking at something beneath them type of thing. They're the same parts rearranged but they can't deal with it. I wonder who pulled the trigger on getting rid of EQ's before finding a replacement first? That had to be a real brainiac. "Hey if you get rid of your eq all your differently recorded music is going to play just fine." Really, who sold that one? Designers originally got rid of the EQ's in preamps so they could make more separates. They didn't know people were going to cut them out of the picture. The EQ, when pres were made without them, were designed so we had yet another step. It was designed to go source, pre, EQ, amp, speakers. People started passing the EQ but then this weird thing happen. Audiophiles started doing all their systems totally EQ-less. I'm guilty, I did the same. There was lots of reporting on how you couldn't play as much music but on recordings that didn't need to be EQed for that system is sounded better than running it through the extra parts. I liked this approach but I also did a lot of per recording tuning so it wasn't that big of a deal. But audiophiles jumped the gun and outlawed their use without learning another way. It was obvious you could no longer play a wide range of music, so the audiophiles said we'll just stick to classical and jazz, but that didn't fix it cause in time they started hearing problems with a lot of even that music. So lets limit it to direct to disc. Lets say direct to disc is the music sounding it's best, then classical and jazz on some labels, then....and they worked their way down never looking at the system as needing help and trying to fix this problem. Instead they ignored that there was a problem at all. I can't even conceive of the concept of less music over more. Never have I ever heard a system even remotely come close to playing a lot of recordings without it needing to be tuned somehow. I wonder why people don't just admit that and move on. Some here have and that gains them a lot of respect with me. "My system plays one sound and I shove all the recordings through that one sound." That to me is honest. I can deal with that, but I can't deal with all this other stuff and these great raves about something that has always been impossible. Is it me, am I being mean? Is wanting to hear more music being mean? Or is it that we're using something that cost so little to get there the mean part? Toledo, I bet there are thousands that if they saw your story and saw you writing about what your hearing now as opposed to then, they would have to in time take notice. Here's what I honestly think listeners should consider. Next time they hit the listening wall instead of taking yet another big jump, buy a simple system and try it. They might say they have, but no no no, try it now and take it seriously. I bet a ton of them would never go back. They may not come up here and admit it but they wouldn't go back. Times have changed michael greenMGA/RoomTune Different Drums Michael wrote, "still not getting it Hi Geoff Sorry but you are still not getting it. What if you are playing a drum on your system and you want the body of the drum to come out more, you put on the next recording and want the body of the drum to be less, what would you do? you answered "Michael, I did not misunderstand your question. However, I'm pretty sure you misunderstood my answer. One of the benefits of my approach, which I might possibly describe as holistic or eclectic, is absolutely positively the most incredible bass performance you have ever heard - deep, powerful, taut, elastic, dynamic, propulsive, above all consistent with reality. A recipe for reality - Find the problem, fix the problem, move to next problem. It's an archaeological dig so bring it back alive! "" You then wrote, "So lets back up and ask the question this way. If you have the drums set at the back of the stage and you wanted to move them forward and change the pitch, fill out the middle of the drum and the lower part focusing more on this than the head, how would you do this?" Pretty sure I answered your question the first and second time. Maybe we should just write this one off as marching to the sound of different drummers. To summarize my position: There is no short cut for getting the diamond out of the dirt. "Genius is one percent inspiration and 99 percent perspiration." Old audiophile expression "A rich man has as much chance of getting into audio Nirvana as a camel has of passing through the eye of a needle." Old audiophile expression "It's fairly straightforward to demonstrate that you can't achieve a nuclear reaction by striking an atom with a hammer." Old audiophile expression The Law of Maximization: No matter how much you have in the end you would have had even more if you had started out with more. Cheers, Geoff KaitMarching Dramatica Another topic bites the dust! Thanks Geoff and Michael for transforming any topic you touch into a tune vs. quote story! Hi May I use a lot of different ways to describe things. Honestly I don't really care what words are used. I'm not being flippant, I really don't care. I figure people talk in their own languages anyway. In the end if people are in-harmony they end up communicating beyonds words. Freeing up is cool with me. I get into depth with this on TuneLand. As far as one person disputing another, I really only ever disbute if I do something and it doesn't work the same for me as it does for someone else. And even with that I don't try to say they are wrong but more they are different, and here was my experience. Like the products you have mentioned, I have tried them. With as many clients as I have it's hard not to demo everything out there and explore every other thing. Now I may not have tried every thing you have, and don't want to sound like a know it all or that I know the deeper stuff you guys are doing so please take this as me trying these things and doing my own studies of them. I did not have the same opinion on cryogenics as you have expressed. To me, and this was the same after many listens from many sources, it was a choice but not a statement of better in all situations. Neither were the colors, each one had a sound, but I would have liked the option of it being variable and removable. The same was with the crystals, a choice but not a cure. The resonators I personally did not like at all. I like the science of it but think maybe it needs a different mechanisum or something. And the bowls again another flavor. These flavors I don't view as bad, but did see/hear them as a flavor and not taking the systems to a more pure state, like when we variably tune a tunable room. Now there's a shocker to me everytime I experience the power of this. When you tune a physical wall to match the signature of a recording it is remarkable. Then you can go to parts of the room in correspondence to the stage and make any flavor you want happen. For me that's more along my line of tweaking. Like not just a light weight speaker but one that is variable, through tuning the transfer in the side walls, same with equipment platforms and top canopies and acoustical products, and tunable circuit boxes. That stuff to me is my world because it really is one big music instrument. The fixed stuff is cool and shouldn't be marginalized but I'm more into the variable aspect. When you hear me talk about untightening screws that's just to get peoples foot in the tuning door. If you look at TuneLand we take it a lot deeper then that, it's just that people need a starting place to get them in the right frame of mind. If I came here and talked the way I do with folks really into tuning people would be scared to death I would think. So I only go as deep as the environment suggest. There's a lot of things I do I don't even share with clients. May, most audiophiles are engineers, or engineers in their thinking. Trying to make an engineer bend is like the Matrix scene with the spoon. I don't try. They will either get it or not. My job is to do it, and share what is needed to get them there. I try to not go any further than they are able to comprehend. I have learned to be careful when talking to people about things that involve the senses. Knowledge is a two way street and wisdom is learning how to use knowledge. I look at people like this, they know stuff that I don't and I know stuff that they don't, together we learn, if we come to a place of fair exchange. If not than either they or I am pushing instead of exchanging. Points never really get made by pushing. They are only words until one gives and one receives. Proving a point is only done by doing. That's my strong point, I do and because I do I don't have a problem with someone elses point of view. I see it as their point of view until I "do" an accept it into my little storage tray of knowledge. Obviously I like the vertical tuning too, but as you know there are other ways around it when you have to. Mechanical transfer is an area that I think I have played in more than most other areas. It's fascinating, but again if I'm not in the right place to talk about it I don't. I'm more of a set the scene type of person then slowly lead as I see if someone is getting it or not. Back and forth debates are not really my thing. I'll do it if I have to but I'd rather show someone or have them try something and get back to me. Or of course them show me something. I've been with some tunees that have knocks my socks off with their abilities, and I love to be in the student seat, but not so much with talking. And it's not that I doubt a person I just like to experience it. I'm sorry that my experiences with some of the things you have talked about was different from yours, and again they all made a difference and in some cases good but not all the time with all the different music. However things like the screws I'm hip on that. It's a good tweak and variable. I'm sure we have far more incommon than not, and I look forward to learning. michael greenMGA/RoomTune a little disappointed Hi Costin I'm a little disappointed you just got on me. Sorry that I made you upset! I thought I was talking about tweaks, and my tweaking is tuning so I don't think I was off topic. so again sorry but I'm not sure what you wanted michael greenMGA/RoomTune Topic: Tweaks and Snake Oil iosiP wrote: Thanks Geoff and Michael for transforming any topic you touch into a tune vs. quote story! Yeah, right. The topic being tweak bashing. Which you started, if I can be so bold, with your opus OP "Tweaks and Snake Oil." If you aspire to be a troll you'll have to learn how to deal with a certain amount of blow-back. Your original rant, which is actually nothing more than the usual, puffed up anti tweak pseudo-skeptical jibber jabber we see so often on audio forums, was, "About tweaks and snake oilThere are three kinds of tweaks: 1. Those that have a sound (excuse the pun) electrical/physical explanation of how they work. 2. Those that do not benefit from such an explanation, but are still susceptible to work because they interfere - even if in ways unknown or not disclosed - with one of the three elements of musical reproduction (electrical, mechanical and acoustical). 3. Those that simply don't work, because there is no possible way they do! And this has nothing to do with debunking myths or any other flat-earth beliefs: they cannot work simply because they have no way to affect any of the three stages of sound reproduction outlined above. Please don't get yourselves into a fit - I do love music as much as you do - but just face it: music is nothing more than sound, and sound is just "a pressure disturbance that moves through a medium in the form of mechanical waves. Yes I know this might hurt your feelings, but your favorite Beethoven, Patricia Barber or Led Zeppelin recording is nothing more than "pressure waves made up of compressions and rarefactions." So no, you won't change these pressure waves by putting your photos in the freezer, washing your hands before listening (although washing your ears might help) or writing "'x 26 'x on your mirror. Why it won't work? Well, simply because it can't! But by all means, if you are sensitive to suggestions just use them - no, your system won't sound any better but you will think it does... and at the end of the day, the only thing that matters is your own satisfaction!" Tootles, Geoff KaitMachina Dynamica Metaphysical tweaks, preposterous tweaks, what have you iosiP wrote: Thanks Geoff and Michael for transforming any topic you touch into a tune vs. quote story! Ok, I am going to reach out a little bit, here, on the subject you started, which unless I miss my guess was a rant against tweaks that make no sense, what we refer to as preposterous tweaks, unconventional tweaks, or maybe metaphysical tweaks. The problem with attacking these tweaks willy nilly is that just going by the name or the description doesn't necessarily tell you much about the tweak or how it works. So, here is an olive branch, I will list a bunch of unconventional tweaks, preposterous tweaks, what have you, then you can select the ones that really get your goat, that really set your hair on fire and we can discuss the pros and cons of them. My short list of metaphysical tweaks, the ones that I'm either familiar with, have read a lot about or have invented myself include the Teleportation Tweak, the Schumann Frequency Generator, the Red X Pen (PWB Electronics), The Intelligent Chip, Silver Rainbow Foil (also PWB), Mpingo disc from Shun Mook, Photos in the Freezer Tweak (of course, Duh!), black cable tie on drainpipe tweak, clever little clock (battery powered), small copper foil Flying Saucers for Windows (from yours truly), the colors orange, purple and green for coloring CDs, WA Quantum Chips (for fuses, capacitors, cables, etc.), SteinMusic Harmonizer (Gives air molecules an initial acceleration, so he says), Reef Knot device for all cables including ones not in use, Walker Audio Black Diamond Crystal for stereo cartridge and Tchang's tiny little bowl resonators. Cheers,Geoff KaitMachina Dynamica June 12, 2014 - 8:19am Geoff, Geoff, Can we add photos in the freezer and x 26 x tweaks and other similar tweaks to the list. These clearly delineate the physical tweaks from the metaphysical/fringe tweaks that I was attempting to differentiate. You have to admit that is some pretty fringe stuff and you may lose people right from the get go. The other physical tweaks can get lost in the mix and can suffer from guilty by association. OK Geoff, this sounds better And actually this was the purpose of my OP. Now let me clarify my thought process. In order to be effective, a tweak must meet two conditions:1. Just work, as in doing what it's supposed to do... well, just be functional, if you prefer.2. Influence our perception of the music, either by modifying the soundwaves or our perception of them. Obviously there is no point in asking the first question for simple tweaks: there is nothing susceptible to work or not work in writing a string on your mirror and using a flashlight on it, so only the second condition must be met (how doing this can modify our perception of music). However, some science-based tweaks must pass both tests: I'll take on your example of the Stein Music Harmonizer - first of all, it must be proven that it accelerates the air molecules, and thento prove such an acceleration bring any benefit to the listening experience.I will give you a list of the tweaks you mentioned and how I think these pass (or not) the "composite test". Cheers,Costin P.S. I would appreciate if you would just answer to questions, i.e. without "smart quotes" and irrelevant analogies. Just think this will avoid any frustration on both sides. 'x26'x toledo wrote: Geoff, Can we add photos in the freezer and x 26 x tweaks and other similar tweaks to the list. These clearly delineate the physical tweaks from the metaphysical/fringe tweaks that I was attempting to differentiate. You have to admit that is some pretty fringe stuff and you may lose people right from the get go. The other physical tweaks can get lost in the mix and can suffer from guilty by association. The coordinate 'x26'x is actually incorporated in the Photos in the Freezer Tweak and the Red X Pen ( a real doozie), which are both my list above. You don't think I'd leave The FITFT off the list, do you? You might be surprised to know there 'a very fine line between what you would probably consider fringe and physical tweaks. Just like line between classical physics and quantum physics. The lines are getting blurred. Better strap yourself in. Pop quiz - Would you accept a placebo if it improved the sound? Geoff Kait @ Machinadynamica.com	https://www.stereophile.com/comment/539160
Isolation of cyclo(His-Pro)-like immunoreactivity from human urine and demonstration of its immunologic, pharmacologic, and physico-chemical identity with the synthetic peptide \| Request PDF Request PDF \| Isolation of cyclo(His-Pro)-like immunoreactivity from human urine and demonstration of its immunologic, pharmacologic, and physico-chemical identity with the synthetic peptide \| Measurements of cyclo(His-Pro) levels in human urine were carried out by specific radioimmunoassay. Cyclo(His-Pro)-like immunoreactivity in Human... \| Find, read and cite all the research you need on ResearchGate Article Isolation of cyclo(His-Pro)-like immunoreactivity from human urine and demonstration of its immunologic, pharmacologic, and physico-chemical identity with the synthetic peptide February 1990 Biochemistry International21(3):425-34 Source PubMed Authors: <here is a image 2d6c71ba40faa3c8-0f9a6fc3b43c6f74> Chandan Prasad Texas Woman's University <here is a image 352ab473dcf56137-8e7293ce82c5b94d> Francis Ragan Louisiana State University Health Sciences Center New Orleans <here is a image f2f62089ad6ff61c-d19572ff1996375a> C W Hilton C W Hilton Abstract Measurements of cyclo(His-Pro) levels in human urine were carried out by specific radioimmunoassay. Cyclo(His-Pro)-like immunoreactivity in Human urine was found to be immunologically, pharmacologically, and physico-chemically identical to that of synthetic cyclo(His-Pro). The concentration of urinary cyclo(His-Pro) in 24-h collection was 1133.8 +/- 122.5 nmol/L, with a range of 606 to 1865 nmol/L. The daily excretion rate of cyclo(His-Pro) was 1812 +/- 248 nmol cyclo(His-Pro)/g creatinine, or 1814 +/- 199 nmol cyclo(His-Pro/day. Amino Acids and Nitrogen Compounds Chapter Dec 2015 <here is a image ce351800653adce6-401edde7724dcd05> Martin Kohlmeier The amino acids relevant for human nutrition comprise a group of dozens of compounds with broad variation of characteristics and functions. By definition, they are always made up of an amino group, an acid, and a side chain. The amino group is most often adjacent to the primary carboxyl group (alpha-position), but may be in beta-position instead. Some amino acids form only a few specific peptides, such as taurine as part of glutaurine, and beta-alanine as part of carnosine and anserine. Several other amino acids such as camitine. taurine, ornithine, and citrulline are not a regular part of human proteins, but serve specific important functions. Several amino acids are synthesized through the addition of an amino group to a common alpha-keto acid. Most amino acids are consumed with a wide variety of proteins and peptides in foods of animal and plant origin. These foods provide all the twenty amino acids used for making the body's own proteins, peptides, and other compounds requiring amino acids as precursors. Daily protein turnover may be as much as 300 g, which means that the same amount has to be resynthesized. 20 basic amino acids are required for the synthesis of most of the more than 30,000 different proteins that constitute the human body. Deficiency of any single one affects all body functions and is ultimately not compatible with life. Nutrient Metabolism: Structures, Functions, and Genetics Article Jan 2003 <here is a image ce351800653adce6-401edde7724dcd05> Martin Kohlmeier Nutrient Metabolism defines the molecular fate of nutrients and other dietary compounds in humans, as well as outlining the molecular basis of processes supporting nutrition, such as chemical sensing and appetite control. It focuses on the presentation of nutritional biochemistry; and the reader is given a clear and specific perspective on the events that control utilization of dietary compounds. Slightly over 100 self-contained chapters cover all essential and important nutrients as well as many other dietary compounds with relevance for human health. An essential read for healthcare professionals and researchers in all areas of health and nutrition who want to access the wealth of nutrition knowledge available today in one single source. Key Features * Highly illustrated with relevant chemical structures and metabolic pathways * Foreword by Steven Zeisel, Editor-in-chief of the Journal of Nutritional Biochemistry * First comprehensive work on the subject. Could dietary proteins serve as cyclo(His-Pro) precursors? Article Jun 1991 NEUROPEPTIDES <here is a image 2d6c71ba40faa3c8-0f9a6fc3b43c6f74> Chandan Prasad C.W. Hilton Frank Svec <here is a image 8290149539bb5415-4973b390d54ec72d> Patrick Vo Cyclic dipeptides or diketopiperazines are readily generated during in vitro hydrolysis of proteins and polypeptides. This led us to examine whether cyclo(His-Pro) (CHP), a diketopiperazine containing histidine and proline, could be formed in vivo from dietary proteins. The data presented here show that at least in rat, neither urinary nor plasma concentration of CHP is elevated by consumption of a diet rich in proteins. Several dietary supplements derived from casein and/or soy protein hydrolysates, however, contain high levels of CHP-LI. Oral intake of one such supplement led to a sharp increase in the plasma level of CHP-LI. Bioactive cyclic dipeptides Feb 1995 PEPTIDES <here is a image 2d6c71ba40faa3c8-0f9a6fc3b43c6f74> Chandan Prasad Cyclic dipeptides are among the simplest peptide derivatives commonly found in nature. Most cyclic dipeptides found to date appear to have emerged as by-products of fermentation and food processing. However, many are endogenous to members of animal and plant kingdoms; these include cyclo(Pro-Leu), cyclo(Pro-Val), cyclo(Pro-Phe), cyclo(Ala-Leu), cyclo(Pro-Tyr), cyclo(Pro-Trp), and cyclo(His-Pro). Although the five cyclic dipeptides--cyclo(His-Pro), cyclo(Leu-Gly), cyclo(Tyr-Arg), cyclo(Asp-Pro), and cyclo(Pro-Phe)--exhibit interesting physiological and/or pharmacological activities in mammals, only one of these, cyclo(His-Pro), has been conclusively shown to be endogenous to mammals. On the other hand, cyclo(Leu-Gly), cyclo(Tyr-Arg), and cyclo(Asp-Pro) are structurally related to endogenous peptides Pro-Leu-Gly-NH2 (melanocyte-stimulating hormone release inhibiting factor), Tyr-Arg (kyotorphin), and Val-Pro-Asp-Pro-Arg (enterostatin), respectively, which may serve as precursor peptides. It needs to be determined, however, whether these peptides can indeed result from the processing of their respective precursors. In conclusion, it appears that cyclic dipeptides are a relatively unexplored class of bioactive peptides that may hold great promise for the future. Enterostatin (Val-Pro-Asp-Pro-Arg)-Like immunoreactivity in rat urine: Relationship to corticosterone output Feb 1998 LIFE SCI Makoto Imamura Amit Prasad <here is a image 2d6c71ba40faa3c8-0f9a6fc3b43c6f74> Chandan Prasad Numerous studies have documented a role for enterostatins in appetitive behavior. However, due to the lack of knowledge about the distribution of enterostatins in tissues and body fluids, it has not been possible to examine the role of endogenous enterostatin in this process. To this end, using a polyclonal antibody raised against enterostatin -- Val-Pro-Asp-Pro-Arg (VPDPR), we examined the nature and distribution of enterostatin-like immunoreactivity in the rat urine by ELISA and chromatography. The results reported here show for the first time the presence of VPDPR-like immunoreactivity (VPDPR-LI) in rat urine. Further characterization of rat urine VPDPR-LI revealed that it is not due to VPDPR but to another peptide similar to VPDPR. Furthermore, as urinary excretion of corticosterone increases, the level of VPDPR-LI in urine decreases. Relationship between Plasma Cyclo (His-Pro), a Neuropeptide Common to Processed Protein-rich Food, and C-Peptide/Insulin Molar Ratio in Obese Women Feb 2001 C.W. Hilton Haruo Mizuma Frank Svec <here is a image 2d6c71ba40faa3c8-0f9a6fc3b43c6f74> Chandan Prasad Cyclo (His-Pro) (CHP) is a gut-brain peptide whose plasma levels in humans are increased after glucose ingestion and preferentially altered by oral glucose ingestion compared to intravenous administration in rats, suggesting a role in the enteroinsular response to nutrient ingestion. We were interested in examining levels of CHP in women of differing weights and comparing these levels to various parameters of insulin secretion. Plasma from 26 fasting, nondiabetic women ranging from 21 to 70 years of age and weighing 43 to 114 kg was assayed for CHP. Insulin and C-peptide levels were measured in 17 of the 26. Fasting CHP levels were elevated in obese compared to nonobese women (2075+/-144 vs. 905+/-187 pg/ml; p < 0.001) and were related by regression analysis to weight (r = 0.668, p < 0.001) and body mass index (r = 0.636, p = 0.001). The fasting C peptide/insulin molar ratio, which may be used as an estimate of hepatic insulin clearance (HIC), was inversely related to CHP levels (r = -0.568, p = 0.017). We conclude CHP levels are increased in obese women and inversely related to their C-peptide/insulin molar ratio. The elevation of CHP in those with a decrease in this estimate of HIC (obese) is interesting as the greater insulin response seen in normal persons after oral glucose compared to intravenous glucose has been postulated to be due to a decrease in HIC by some gut factor. The presence of such a factor in excess in the obese might explain part of their hyperinsulinemia.	https://www.researchgate.net/publication/20932551_Isolation_of_cycloHis-Pro-like_immunoreactivity_from_human_urine_and_demonstration_of_its_immunologic_pharmacologic_and_physico-chemical_identity_with_the_synthetic_peptide
The PACT Act: An essential first step in protecting those who protect us \| The Hill President Biden was finally able to get it done — for Beau. We don’t know definitively that Beau Biden’s cancer was caused by exposure to burn pits during his time in Iraq, but we do know that millions of veterans can now count on getting the treatments they need for chronic illness from exposure to… The PACT Act: An essential first step in protecting those who protect us President Biden was finally able to get it done — for Beau. We don’t know definitively that Beau Biden’scancer was caused by exposure to burn pits during his time in Iraq, but we do know that millions of veterans can now count on getting the treatments they need for chronic illness from exposure to burn pits. Burn pits are large areas where military waste is incinerated in the open air. Chemicals, weapons and ammunition, metals, medical and human waste, plastics and rubber are all burned, often with jet fuel as an accelerant, resulting in toxic pollution. A 2020 survey by the advocacy organization Iraq and Afghanistan Veterans of America found that 86 percent of respondents were exposed to these burn pits or other toxins during their service. The PACT Act, H.R. 3967 (117), requiring the Department of Veterans Affairs to cover care for toxic exposure related to burn pits during military service. While the importance of this legislation cannot be overstated, it begs the question: What should be done for those here at home who risk their health every day to keep us safe? As Elizabeth Beck, a former army reservist who served in Iraq described it during the signing event, “You saw the burn pits. You smelled the burn pits. You felt the burn pits in your body.” Her words are not too different than that of the aftermath of a housefire as described by Thomas Magliano, a retired firefighter who was diagnosed with lung cancer after a simple screening — thanks to a unique partnership between RUSH University Medical Center and the Chicago Firefighters Union Local 2. Firefighters, regardless of regional location, have a 60 percent increased risk of developing lung cancer. “When you’re looking for hot spots or hidden fires in the fire buildings, you can take your mask off. But that asbestos and insulation and smoke from the plastic is still lingering in the air, so you’re breathing in these toxic fumes — you’re still getting exposed to it.” As a thoracic surgeon, I am trained to diagnose and treat lung cancer. A cancer diagnosis is a life-changing event for both patients and their families. Unfortunately, by the time I meet most patients, their cancer is at a later stage, having spread beyond the lung. This alters my role from sharing the joy of cure, to breaking the devastating news that a patient’s disease is more difficult to treat and unlikely to be curable. Smoking remains the greatest risk factor for developing lung cancer. We are also learning more about how environmental factors, such as where we live and work, impact the risk of developing lung cancer and other lung diseases. The International Agency for Research on Cancer has identified at least a dozen carcinogens linked to lung cancer that are routinely encountered in various occupations. Soldiers. First responders. Selflessly dedicating one’s life to the protection of others, apparently, is a risk factor for lung cancer. Lung cancer is the leading cause of cancer-related death worldwide. It kills almost three times as many men as prostate cancer, and almost three times as many women as breast cancer. And while it’s easy to feel powerless in the face of these odds, there is hope. The number of lung cancer deaths are decreasing, and the reason is early detection. Early detection of lung cancer in high-risk patients can reduce the chance of death by up to 20 percent. For people who are at higher risk of developing lung cancer, there is an easy screening that can provide peace of mind or save your life. A low dose computed tomography (CT) scan uses X-rays and a smaller dose of radiation to take images of the lungs in an average of 10 minutes. It is often covered by insurance for this high-risk population. Currently, the screening is available for people 50 to 80 years old who are current smokers and those who quit within the previous 15 years. It is estimated that approximately 8 million Americans are at high risk for lung cancer, yet we currently are screening only about 5 percent of those individuals. That means there are more than 7 million people we could be saving. Talk to your primary care doctor, who can let you know if you are a candidate and help you schedule a screening. Passage of the PACT Act is an important step in protecting those who protect us. But it should only be the first step. It is time to not only ensure our first responders are cared for should they develop chronic illnesses while on the job — but also that we make it as easy as possible to receive life-saving screenings before things get that far. Nicole M. Geissen is Associate Program Director of the Cardiothoracic Residency Program and assistant professor at the Department of Cardiovascular and Thoracic Surgery, Rush Medical College.	https://thehill.com/opinion/congress-blog/3604645-the-pact-act-an-essential-first-step-in-protecting-those-who-protect-us/
tractor23131 \| NHTSA Mr. Mark Ireland Senior Engineer - Engineering Standards and Legislation JCB Research Rocester Saffordshire England ST 1 4 5JP Dear Mr. Ireland: Interpretation ID: tractor23131 Mr. Mark IrelandSenior Engineer - Engineering Standards and LegislationJCB ResearchRocester SaffordshireEngland ST 1 4 5JP Dear Mr. Ireland: This responds to your letter received on May 18, 2001, asking for information about the application of glazing marking requirements to a range of construction, industrial and agricultural equipment. More specifically, you ask whether you should use "uniform/zone Toughened or Laminated glazing in the windshield and other cab areas in your machines and, also, whether glazing requirements change with the design speed of the machine." The following generally discusses:1) the applicability of our laws to your machines, and 2) glazing requirements based on the facts set forth in your letter. However, without specific information on a particular machine, we cannot provide an opinion as to whether our glazing standard is applicable to a particular machine as a "motor vehicle." Motor Vehicle By way of background information, the National Highway Traffic Administration (NHTSA) issues and enforces the Federal motor vehicle safety standards (FMVSS). NHTSA's statute defines the term "motor vehicle" as follows: [A] vehicle driven or drawn by mechanical power and manufactured primarily for use on the public streets, roads and highways, but does not include a vehicle operated only on a rail line. 49 USC '30102(a)(6). Whether NHTSA considers various pieces of construction, industrial or agricultural equipment to be motor vehicles depends on their use. In the past, we have concluded that this statutory definition does not encompass mobile construction equipment, such as cranes and scrapers, which use the highway only to move between job sites and which typically spend extended periods of time at a single job site. In such cases, the on-road use of the equipment is merely incidental and is not the primary purpose for which they were manufactured. Other construction vehicles, such as dump trucks, frequently use the highway going to and from job sites, and stay at a job site for only a limited time. Such vehicles are considered motor vehicles, since the on-highway use is more than "incidental." Based on the information provided in your letter, we do not have sufficient information about the use of the equipment to determine whether they are motor vehicles. If, however, certain equipment is used frequently on the highways, they would be considered motor vehicles and would be required to comply with all applicable FMVSSs, including that pertaining to glazing as discussed below. If you write us again with more information about a particular vehicle, we would be happy to provide an interpretation as to whether it is a motor vehicle. FMVSS No. 205 FMVSS No. 205, Glazing Materials (49 CFR 571.205), establishes performance, location, certification, and marking requirements for all glazing installed in motor vehicles. The standard incorporates by reference the requirements of Standard ANS Z26, "Safety Code for Safety Glazing Materials for Glazing Motor Vehicles Operating on Land Highways," of the American National Standard Institute (Standard ANS Z26). Standard ANS Z26 specifies performance requirements for various types of glazing (called "items") and specifies the locations in vehicles in which each item of glazing may be used. Standard ANS Z26 requires that glazing for windshields must pass a specified group of test requirements. ANS Z26 specifies that glazing materials that comply with these test requirements for windshields must be marked with AS1. To date, the only glazing materials that have been marked with AS1 have been laminated safety glass. Unless the non-laminated glazing material cited in your letter can meet the requirements for AS1 glazing and are marked AS1, they do not comply with the requirements for windshields specified in Standard ANS Z26 or FMVSS No. 205. Finally, you should also be aware that FMVSS No. 205 permits glass-plastic glazing. For your further information, I am enclosing a fact sheet we prepared entitled Information for New Manufacturers of Motor Vehicles and Motor Vehicle Equipment, and Where to Obtain NHTSA's Safety Standards and Regulations. I hope this information is helpful. If you have any questions or need additional information, feel free to contact Nancy Bell of my staff at (202) 366-2992. Sincerely, John WomackActing Chief Counsel Enclosureref:205d.6/26/01	https://www.nhtsa.gov/es/interpretations/tractor23131
(PDF) Comparison of CT images with average intensity projection, free breathing, and mid-ventilation for dose calculation in lung cancer PDF \| The purpose of this study was to compare three computed tomography (CT) images under different conditions—average intensity projection (AIP), free... \| Find, read and cite all the research you need on ResearchGate Comparison of CT images with average intensity projection, free breathing, and mid-ventilation for dose calculation in lung cancer March 2017 Journal of Applied Clinical Medical Physics 18(2):26-36 DOI: 10.1002/acm2.12037 Abstract and Figures The purpose of this study was to compare three computed tomography (CT) images under different conditions—average intensity projection (AIP), free breathing (FB), mid-ventilation (MidV)—used for radiotherapy contouring and planning in lung cancer patients. Two image sets derived from four-dimensional CT (4DCT) acquisition (AIP and MidV) and three-dimensional CT with FB were generated and used to plan for 29 lung cancer patients. Organs at risk (OARs) were delineated for each image. AIP images were calculated with 3D conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT). Planning with the same target coverage was applied to the FB and MidV image sets. Plans with small and large tumors were compared regarding OAR volumes, geometrical center differences in OARs, and dosimetric indices. A gamma index analysis was also performed to compare dose distributions. There were no significant differences (P > 0.05) in OAR volumes, the geometrical center differences, maximum and mean doses of the OARs between both tumor sizes. For 3DCRT, the gamma analysis results indicated an acceptable dose distribution agreement of 95% with 2%/2 mm criteria. Although, the gamma index results show distinct contrast of dose distribution outside the planning target volume (PTV) in IMRT, but within the PTV, it was acceptable. All three images could be used for OAR delineation and dose calculation in lung cancer. AIP image sets seemed to be suitable for dose calculation while patient movement between series acquisition of FB images should be considered when defining target volumes on 4DCT images. RADIATION ONCOLOGY PHYSICS Comparison of CT images with average intensity projection, free breathing, and mid-ventilation for dose calculation in lung cancer Fax: (662) 576 6020. Abstract The purpose of this study was to compare three computed tomography (CT) images under different conditions — average intensity projection (AIP), free breathing (FB), mid-ventilation (MidV) — used for radiotherapy contouring and planning in lung cancer patients. Two image sets derived from four-dimensional CT (4DCT) acquisition (AIP and MidV) and three-dimensional CT with FB were generated and used to plan for 29 lung cancer patients. Organs at risk (OARs) were delineated for each image. AIP images were calculated with 3D conformal radiotherapy (3DCRT) and intensity- modulated radiation therapy (IMRT). Planning with the same target coverage was applied to the FB and MidV image sets. Plans with small and large tumors were com- pared regarding OAR volumes, geometrical center differences in OARs, and dosimet- ric indices. A gamma index analysis was also performed to compare dose distributions. There were no signi ﬁ cant differences ( P > 0.05) in OAR volumes, the geometrical center differences, maximum and mean doses of the OARs between both tumor sizes. For 3DCRT, the gamma analysis results indicated an acceptable dose dis- tribution agreement of 95% with 2%/2 mm criteria. Although, the gamma index results show distinct contrast of dose distribution outside the planning target volume (PTV) in IMRT, but within the PTV, it was acceptable. All three images could be used for OAR delineation and dose calculation in lung cancer. AIP image sets seemed to be suitable for dose calculation while patient movement between series acquisition of 87.53.Kn, 87.55.D-, 87.55.-x, 87.57.-s, 87.57.Q- KEY WORDS 4DCT, average intensity projection, dose calculation, lung cancer, mid-ventilation 1 \| INTRODUCTION Advances in radiation therapy, radiation doses can now be tightly conformed to target volumes while minimizing dose delivery to surrounding normal organs. 1,2 Respiratory motion is a signi ﬁ cant and challenging problem in radiation therapy due to geometrical uncertainties of both the target and normal organs in the thora- coabdominal region. 3 The motion can potentially cause underdosage to tumor and overdosage to normal organs, and sig- ni ﬁ cantly diverted the planned and the delivered doses. 4 Several approaches have been developed to manage the effects of respira- tory motion during radiation therapy. 5,6 One of them is a motion- encompassing method, which addresses the entire range of tumor motion and adds a margin to the target volumes. For dose calcula- tion in this method, Vinogradskiy et al. 7 and Guckenberger et al. 8 compared three-dimensional (3D) and four-dimensional (4D) dose calculations and revealed minimal dosimetric differences in the gross tumor volume and the internal target volume (ITV). Thus, 3D dose calculation is still required in radiation therapy. For 3D radia- tion treatment planning in lung cancer, the ITV was delineated on maximum intensity projection (MIP) images, whereas organ at risk (OAR) contouring and static 3D dose calculation were done with 3DCT images. 9 – 12 3DCT images were also used to de ﬁ ne OARs and targets for radiation therapy treatment, but the use of static images of a moving organ remains problematic. 13 A common approach is to acquire heli- cal computed tomography (CT) scans during free breathing (FB). Res- piration-induced target motion during acquisition, however, can cause motion artifacts. 14 – 16 Several groups have demonstrated that dose calculation on average intensity projection (AIP) images, with each pixel holding the average value of all equivalent pixels in the data set, can yield results comparable to those attained with 4D dose calculation. 17 – 20 Others have proposed that mid-ventilation (MidV) CT images represent the tumor in its time-averaged position over the respiratory cycle and can be used for dose calculation. This position is an appropriate representation of the mean geometry and density of the target volumes for respiration-induced anatomical variations. 21 – 24 This study was designed to compare three types of CT imaging (AIP, FB, MidV) for contouring and radiation treatment planning for lung cancer using 3D conformal radiation therapy (3DCRT) and inten- sity-modulated radiation therapy (IMRT). Their differences are com- pared in terms of the OAR volume, geometrical center of the OARs, dosimetric indices, and dose distribution with regard to tumor size. 2 \| MATERIALS AND METHODS 2.A \| Patient selection A total of 31 patients with various stages of lung cancer were enrolled in this study between January 2012 and December 2013. Our institutional review board approved the study protocol. Two patients were excluded because of their movement between the FB and 4DCT acquisitions. 2.B \| CT scanning for treatment planning The patients were po sitioned in an immob ilization devic e with a wing board on the scanner tab le, in the supine positi on with arms raised above the head (the tr eatment positi on). CT images of the thorax were acqui red as normal FB and 4DC T scans using a helical 16-slice Bri lliance Big Bore CT sc anner (Philips Medic al Systems, Clevelan d, OH, USA). The parame ters for image acqui si- tion were 120 kVp, 400 mAs, 512 9 512 matrix, 3. 0-mm slice thickness, and 0.5 s per rotation, wi th pitch values acc ording to the manufacturer ’ s recommendation fo r the particular r espiratory rate of each patien t. During CT image ac quisition, the r espiratory signal was recorded u sing either a Phili ps bellows system or a real-time position ma nagement respira tory gating system (Va rian Medical System, Pal o Alto, CA, USA) synch ronized with the CT data. For the 4DCT i mages, respirat ory signal data were rec on- structed and sorted into 10 eq uidistant time-per centage bins (0% at maximum inhala tion to 90%) throug hout a respirator y cycle, each re ﬂ ecting 10% of th e respiratory cycl e. Thus, the 0% respiratory phase cor responded to peak inhala tion and the 50% respiratory phase corresponde d to peak exhalati on. MIP and AIP images were reconstr ucted from 10-phase 4DCT da ta relating to the percentage of time. MidV ima ges (representing the tumor in its time-averaged p osition over the resp iratory cycle) wer e cho- sen from the 10 phases of the 4DCT im age data set. To ma ke them appropriate f or clinical use, t he 4DCT images durin g the exhalation phase w ere displayed. We t hen selected the d ata set image that was close st to the central position of t he tumor. All CT images (AIP, FB, Mi dV, MIP, 10-phase 4 DCT) were then transferred to a ra diation treatmen t planning system ( Eclipse, ver- sion 10.0.42; Varia n Medical System) w ith a DICOM protocol connection. 2.C \| Delineation of the target and OARs An experienced radiation oncologist generally delineated the plan- ning target volume (PTV) and OARs are created by a geometric expansion based on the setup methods and the institutional guide- lines. For each patient, the ITV was de ﬁ ned on the MIP images. The 10-phase 4DCT was used to verify that the target motion was contained within the ITV during all phases. Each patient ’ s PTV was obtained by adding 5 mm of circumferential expansion from the ITV and then copied to the AIP, FB, and MidV images. For these images, the OARs were delineated according to the guidelines pro- vided by our respective protocols. The OARs used for plan compar- isons in this study included the lung, trachea, heart, esophagus, and spinal cord, which are also shown on the images. The lung and tra- chea (including the main bronchus) were delineated with lung win- dows. Both lungs were automatically segmented using a threshold algorithm in the treatment planning system. The rest were con- toured using mediastinal windows. The spinal cord was de ﬁ ned based on the bony limits of the spinal canal. The heart was delin- eated along with the pericardial sac starting below the level at which the pulmonary trunk branched into the left and right pul- monary arteries and extending inferiorly to the heart apex. The esophagus was de ﬁ ned from the bottom of the cricoid to the gas- troesophageal junction. 14 KHAMFONGKHRUEA ET AL . \| 27 2.D \| OAR geometrical center To identify an OAR ’ s geometrical center, the OAR ’ s volume was ﬁ rst determined from a CT image. The geometrical center of the OAR was then calculated in the Eclipse treatment planning system. The centroid of the volume coordinates for each OAR was measured from the radiation beam isosenter. The coordination was displayed as x, y, and z, which refer, respectively, to displacement in the medi- olateral (ML), anteroposterior (AP), and superoinferior (SI) directions. The 3D vector was calculated for comparing the centroid of the OAR ’ s volume in each image. The difference of the geometrical center of FB and MIP image sets comparison with respect to AIP image sets was calculated and analyzed. 2.E \| Radiation treatment planning Based on AIP images obtained during the planning stage, the isocen- ter was within the tumor at the approximately geometrical center of the PTV. The treatment plan was calculated on a 2.0-mm grid using an analytical anisotropic algorithm for dose calculation. The algorithm took into account the tissue inhomogeneity of the patient ’ s body volume. The forward conventional 3D conformal and inverse IMRT T ABLE 1 Patients ’ PTV information and planned dose prescription. Patient no. Target location PTV volume (cm 3 ) Target motion amplitude (cm) Prescribed dose (Gy) Number of fractions SI ML AP 1 RLL 368.7 1.00 0.54 0.55 60 30 2 LLL 358.4 0.30 0.15 0.34 60 30 3 LLL 400.8 0.27 0.38 0.10 54 27 4 RUL 347.7 0.46 0.47 0.52 66 33 5 RUL 315.1 0.30 0.20 0.20 60 30 6 RLL 43.9 1.25 1.14 0.37 66 33 7 RUL 35.5 0.95 0.26 0.17 66 33 8 LUL 948.1 0.20 0.10 0.10 66 33 9 RUL 449.9 0.42 0.00 0.15 66 33 10 RUL 315.6 0.48 0.14 0.25 66 33 11 RUL 280.2 0.40 0.10 0.20 60 30 12 LLL 187.3 0.20 0.10 0.10 66 33 13 RLL 110.0 0.58 0.32 0.10 66 33 14 RLL 71.3 0.37 0.24 0.10 66 33 15 LLL 184.0 0.92 0.33 0.15 66 33 16 LUL 286.0 0.26 0.15 0.10 50 25 17 LUL 96.5 0.40 0.20 0.20 60 30 18 RLL 298.1 0.80 0.20 0.10 60 30 19 RLL 221.0 0.90 0.60 0.20 60 30 20 LLL 10.0 0.49 0.30 0.23 60 30 21 RUL 606.7 0.57 0.33 0.24 50 25 22 RLL 298.3 0.40 0.10 0.10 50 25 23 LUL 127.9 0.40 0.16 0.10 60 30 24 RUL 33.4 0.60 0.20 0.24 60 30 25 LUL 290.2 0.10 0.10 0.10 60 30 26 RLL 221.1 0.40 0.10 0.30 60 30 27 RUL 48.1 0.90 0.40 0.14 60 30 28 RUL 22.6 0.60 0.50 0.20 66 33 29 LUL 425.1 0.40 0.20 0.20 50 25 30 LUL 705.0 0.55 0.30 0.22 60 30 31 RLL 349.1 0.82 0.60 0.35 50 25 Average (range) 272.77 (10.30 – 948.10) 0.54 (0.1 – 1.25) 0.29 (0 – 1.14) 0.21 (0.1 – 0.55) PTV, planning target volume; SI, superoinferior; ML, mediolateral; AP, anteroposterior; RLL, right lower lobe; LLL, left lower lobe; RUL, right upper lobe; LUL, left upper lobe. 28 \| KHAMFONGKHRUEA ET AL . techniques were applied. For 3DCRT planning, four to seven copla- nar static 10-MV photon beams were created for each patient using the beam ’ s eye view technique. The beam arrangement was cus- tomized for each patient based on tumor location and nearby OARs. The multileaf collimators (MLCs) were conformed to the PTV with a 0.5-cm margin around the PTV, except in the SI direction, where a 10-mm margin was set. Beam weights and wedge angles were adjusted to provide homogeneous dose distribution and conform to the PTV. Total prescription doses were 50 – 66 Gy, with 2 Gy per fraction for the dose to be delivered to 95% of the PTV. Plans were manually optimized to meet all tumors and OAR objectives. The dose constraints to the OARs included the mean lung dose (lung minus ITV), which was < 20 Gy. The maximum dose to the spinal cord was < 50 Gy, the mean heart dose was < 35 Gy, and the maximum dose to the esophagus was < 105% of the prescribed dose. The plans based on AIP images were subsequently used for com- parisons with their respective MidV and FB image plans. The beam angle, beam modi ﬁ er, ﬁ eld size, collimation, and beam weighting used in the AIP image plan were copied to the FB and MidV images, where they were re-calculated. For IMRT planning recalculation, the plans were re-optimized with the same objective and priority from the AIP plans. Re-optimization and dose-volume calculation in IMRT were performed with a sliding window MLC mode using a dose- volume optimization algorithm and an analytical anisotropic algo- rithm, respectively. Both of these plans were normalized with the same 95% PTV dose coverage as was used for the AIP image plan. In addition to the PTV, ring structures were created around the target structures to help force the optimization to minimize doses to surrounding OARs. Three control structures were created. The ﬁ rst and second control structures were 1- and 2-cm rings around the PTV. The dose constraints of these structures were de ﬁ ned as < 90% and < 80% of the PTV prescribed dose, respectively. The third control structure was an outer ring that encompassed all tis- sues beyond the second ring. Only 50% of the PTV dose was assigned to this area. For an OAR that overlapped with the PTV, a virtual structure was created in which 5 mm of the OAR was sub- tracted from the PTV. Optimization dose constraints and priorities based on tolerance to the dose were initially applied. They were adjusted as the optimization process progressed to improve target coverage and reduce the OAR dose. When satis ﬁ ed with the plan (a1) (a2) (b1) (b2) (c1) (c2) F IG .1 . Isodose distributions in a patient as shown by three types of CT imaging of AIP images plan (a1 & a2), FB image plan (b1 & b2), and MidV image plan (c1 & c2) in 3DCRT (top row) and IMRT (bottom row). Orange = 66 Gy, red = 60 Gy, pink = 57 Gy, dark blue = 50 Gy, cyan = 40 Gy, blue = 30 Gy, green = 20 Gy. KHAMFONGKHRUEA ET AL . \| 29 derived from the AIP image, it was copied and recalculated for the FB and MidV images with the same beam direction, dose constraints, and priorities. These plans were normalized with the same 95% PTV dose coverage as was used for the AIP imaging plan. 2.F \| Plan comparison and statistical analyses The volume of each OAR and the centroid of each OAR ’ s volume were measured and recorded. The impact of target volume size was studied with separation of small and large volume using vol- ume cut-off at 150 cm 3 . For dosimetric indices comparisons, the maximum (Dmax) and mean (Dmean) doses for each OAR were determined. MapCHECK software (Sun Nuclear Corporation, Mel- bourne, FL, USA) was used to evaluate the dose distribution. Planar dose analyses were then performed in the axial, sagittal, and coro- nal planes passing through the isosenter. Each plane of the dose distribution was transferred from the Eclipse treatment planning system (30 9 30 cm ﬁ eld of view, 512 9 512 matrix) to the Map- CHECK software. The dose differences in each data set of the three image planes were then compared (AIP vs MidV, AIP vs FB, FB vs MidV). The dose distribution was analyzed to calculate the percentage of pixels passing gamma using a gamma index analysis with 2% dose difference and a 2-mm distance-to-agreement crite- rion (2%/2 mm). Although, the report of the AAPM Task Group 119 25 reported that the 3% ∕ 3 mm gamma criteria is the most commonly used by clinical IMRT but higher sensitivity was observed with 2%/2 mm than with 3%/3 mm. 26 All the data points with doses < 10% and 70% of the normalized dose were excluded from the gamma analysis for considering the difference of the low- and high-dose regions, respectively. A gamma passing rate of 100% was considered strong agreement of the plans, and 0% was regarded as total disagreement. T ABLE 2 OARs volumes by three types of CT imaging. OARs Tumor size CT images Volume (cm 3 ) Comparison P Lungs-ITV Small PTV AIP 2832.66  1043.00 AIP vs FB 0.241 FB 2906.34  1009.79 AIP vs MidV 0.075 MidV 2810.81  1030.88 Large PTV AIP 2342.69  797.50 AIP vs FB 0.184 FB 2317.95  782.67 AIP vs MidV 0.879 MidV 2318.57  790.72 Trachea Small PTV AIP 41.39  11.95 AIP vs FB 0.575 FB 41.63  12.22 AIP vs MidV 0.386 MidV 40.88  11.84 Large PTV AIP 41.21  14.35 AIP vs FB 0.619 FB 40.43  14.05 AIP vs MidV 0.984 MidV 41.56  12.85 Heart Small PTV AIP 719.22  237.89 AIP vs FB 0.799 FB 726.11  223.14 AIP vs MidV 0.959 MidV 720.24  235.15 Large PTV AIP 627.87  104.05 AIP vs FB 0.084 FB 619.87  108.70 AIP vs MidV 0.171 MidV 623.25  110.41 Esophagus Small PTV AIP 44.55  12,58 AIP vs FB 0.959 FB 44.58  12.76 AIP vs MidV 0.799 MidV 44.56  12.56 Large PTV AIP 39.23  8.19 AIP vs FB 0.064 FB 39.58  8.16 AIP vs MidV 0.117 MidV 39.59  8.16 Spinal cord Small PTV AIP 39.08  16.19 AIP vs FB 0.208 FB 39.29  16.06 AIP vs MidV 0.139 MidV 39.34  16.22 Large PTV AIP 35.96  8.82 AIP vs FB 0.494 FB 36.19  8.70 AIP vs MidV 0.324 MidV 36.15  8.88 Results are reported as the average  SD. 30 \| KHAMFONGKHRUEA ET AL . Data analysis to compare the OARs ’ volumes, the centroid of the OARs ’ volumes, and dosimetric indices of the various CT images was performed using a Wilcoxon Signed Ranks test from the Statistical Package of Social Sciences (SPSS version 18.0; SPSS Inc., Chicago, IL, USA). Statistical signi ﬁ cance was indicated at P < 0.05. 3 \| RESULTS In all, 31 lung cancer patients underwent FB and 4DCT simulations. The patients ’ PTV information regarding target location, PTV volume, and target motion amplitude in the SI, ML, and AP directions as well as the prescribed dose and number of fractions were recorded. They are shown in Table 1. According to the ﬁ ndings, tumors were found in the upper lobes in 17 patients and in the lower lobes in 14 patients. PTV volumes were in the range of 10.30 – 948.10 cm 3 . Tumor motion amplitudes were 0.10 – 1.25 cm in the SI direction, 0 – 1.14 cm in the ML direc- tion, and 0.10 – 0.55 cm in the AP direction. Two patients (Patient no. 4 and 5) were later excluded from the study because they moved during the CT simulation process. The movement resulted in unmatched FB and 4DCT images in the series (based on bony anat- omy), which could be a potential source of error. For instance, with the 3DCRT technique (not shown in the results), patient 4 had a huge deviation in the maximum dose to the esophagus. The dose was recorded as 63.11 Gy in the FB image plan; whereas it was 29.32 in the AIP plan and 29.17 in the MidV plan. For patient 5, the maximum dose to the spinal cord was 58.03 Gy in the FB image plan; whereas it was 49.16 in the AIP plan and 48.37 in the MidV plan. To evaluate the dosimetric differences between the calculated plans from the three types of CT images, the AIP image plan was copied to the FB and MidV images and recalculated using the same beam arrangement and PTV coverage. Figure 1 represents the com- parison between the three plans to illustrate the dose distributions for 3DCRT and IMRT. The volumes for OAR contouring in the remaining 29 patients are shown in Table 2. There were no signi ﬁ cant differences in the OARs ’ dose volumes for both small and large target volumes. The average volumes from the AIP, FB, and MidV images were 2832.66, 2906.34, and 2810.81 cm 3 , respectively, for small targets and 2342.69, 2317.95, and 2318.57 cm 3 for large targets, respectively. The difference of magnitudes in vector geometrical center (3D vectors) between the reference AIP image sets with respect to the test image sets (FB and MidV) are shown in Table 3. There were no signi ﬁ cant differences in both tumor sizes in the centers of the OARs ’ volumes ( P > 0.05) between AIP image and test image sets. The averages and standard deviations of the maximum doses for each OAR determined from the CT images are summarized in T ABLE 3 OARs geometric center difference between AIP and FB and MidV CT imaging. OARs Conditions 3D vector difference (mm) P Average Min. Max. Lungs-ITV Small PTV AIP vs FB  0.04  0.61 0.18 0.799 AIP vs MIP 0.03  0.07 0.18 0.445 Large PTV AIP vs FB  0.05  0.78 0.52 0.658 AIP vs MIP 0.06  0.34 0.57 0.084 Trachea Small PTV AIP vs FB 0.02  0.15 0.22 0.721 AIP vs MIP  0.01  0.13 0.20 0.799 Large PTV AIP vs FB 0.02  0.22 0.28 0.601 AIP vs MIP  0.03  0.22 0.17 0.133 Heart Small PTV AIP vs FB 0.02  0.19 0.25 0.799 AIP vs MIP 0.01  0.17 0.18 0.799 Large PTV AIP vs FB  0.06  0.27 0.23 0.078 AIP vs MIP  0.02  0.40 0.31 0.546 Esophagus Small PTV AIP vs FB 0.00  0.71 0.34 0.441 AIP vs MIP 0.01  0.28 0.21 0.735 Large PTV AIP vs FB  0.09  0.54 0.39 0.171 AIP vs MIP  0.02  0.44 0.37 0.520 Spinal cord Small PTV AIP vs FB  0.01  0.21 0.13 0.799 AIP vs MIP 0.02  0.05 0.10 0.575 Large PTV AIP vs FB  0.06  0.49 0.17 0.227 AIP vs MIP  0.01  0.28 0.24 0.809 OARs, organs at risk; AIP, average intensity projection; FB, free breathing; MidV, mid-ventilation. KHAMFONGKHRUEA ET AL . \| 31 Table 4. For 3DCRT, there were no signi ﬁ cant differences in the maximum dose of any of the OARs (lung – ITV, trachea, heart, esophagus, spinal cord) among the three plans. For IMRT, there were also no signi ﬁ cant differences in the maximum doses for the OARs among the three plans. The averaged values and standard deviations of the mean doses for the OARs are shown in Table 5. No signi ﬁ cant differences ( P > 0.05) were found for the OARs in all image data sets with both 3DCRT and IMRT. The results of the gamma index analyses in 29 patients are shown in Table 6. Two-dimensional (2D) dose distributions were cal- culated on three orthogonal planes at the isosenter. An average gamma passing rate > 98% (2%, 2 mm) was obtained for all investi- gated scenarios using 3DCRT. For IMRT, the 2D dose distribution agreement had a higher than 90% gamma passing rate. As a result of gamma passing rate with 10% and 70% cut-off levels, high gamma passing rate at 70% has a value more than 10% cut-off level. This indicated that the high-dose region appeared to be in agreement with dose distribution for both 3DCRT and IMRT. 4 \| DISCUSSION Several studies have focused on 3DCT images for radiation treat- ment planning on moving targets. In most cases, stereotactic body radiation therapy (SBRT) planning was investigated. Our study com- pared conventional radiation doses using 3DCRT and IMRT to deter- mine the usefulness of three types of CT imaging for radiation treatment planning. For 3DCRT, there is no change in the radiation beam parameters (beam ﬂ uence), unlike when using advanced T ABLE 4 Maximum doses to the OARs seen by three types of CT imaging. P Lungs-ITV Small PTV AIP 66.01  3.73 66.39  3.73 AIP vs FB 0.879 0.721 FB 61.66  4.12 66.59  3.53 AIP vs MidV 0.285 0.075 MidV 66.13  3.73 66.56  3.64 Large PTV AIP 60.70  6.03 62.81  7.18 AIP vs FB 0.212 0.260 FB 60.68  6.11 63.02  7.14 AIP vs MidV 0.794 1.00 MidV 60.68  6.04 62.82  7.21 Trachea Small PTV AIP 30.64  26.95 25.79  1.71 AIP vs FB 0.386 0.647 FB 31.37  26.93 25.83  25.72 AIP vs MidV 0.203 0.386 MidV 30.78  26.92 24.12  25.47 Large PTV AIP 46.53  22.08 45.32  23.62 AIP vs FB 0.137 0.990 FB 46.72  22.04 45.93  23.58 AIP vs MidV 0.778 0.091 MidV 46.57  22.11 45.87  23.58 Heart Small PTV AIP 42.83  24.88 28.63  27.93 AIP vs FB 0.241 0.575 FB 42.56  24.99 27.93  27.82 AIP vs MidV 0.285 0.075 MidV 42.65  24.77 28.12  27.66 Large PTV AIP 45.15  22.49 45.24  24.72 AIP vs FB 0.593 0.809 FB 43.28  22.56 45.22  24.63 AIP vs MidV 0.070 0.872 Esophagus Small PTV AIP 36.41  23.51 34.26  23.16 AIP vs FB 0.285 0.241 FB 34.81  21.61 33.97  22.95 AIP vs MidV 0.879 0.285 MidV 36.82  22.20 34.46  22.95 Large PTV AIP 48.69  16.29 51.68  15.21 AIP vs FB 0.260 0.376 FB 48.76  16.55 51.39  15.44 AIP vs MidV 0.243 0.872 MidV 48.54  16.26 51.76  15.17 Spinal cord Small PTV AIP 25.51  14.42 19.06  9.99 AIP vs FB 0.333 0.114 FB 25.99  14.62 19.24  9.90 AIP vs MidV 0.445 0.241 MidV 25.85  14.64 19.02  9.92 Large PTV AIP 41.62  10.70 36.00  6.07 AIP vs FB 0.469 0.421 FB 41.70  10.43 36.17  5.84 AIP vs MidV 0.520 0.841 MidV 41.36  10.45 36.03  5.32 Results are reported as the average  SD. 32 \| KHAMFONGKHRUEA ET AL . techniques such as IMRT or volumetric modulated arc therapy. For SBRT, however, the PTV volume is smaller than that needed for 3DCRT. In addition, the differences in OARs ’ dose volumes and dosi- metric indices are evaluated using the same plan as for PTV dose coverage. who compared AIP and FB images regarding OAR contouring and radiation treatment (SBRT) planning for 10 lung cancer patients. They found differences in the volumes of lungs – ITV but no signi ﬁ cant differences in the rest of the OAR volumes. Tian et al. 13 compared the dosimetric indices during treatment (SBRT) planning calculated using FB, MIP, and AIP images for 20 lung cancer patients. They observed no signif- icant differences in dosimetric indices for PTVs and the lung between the FB and AIP plans. We found limitations in the use of FB images for planning radiation treatment. We demonstrated patient movement between series acquisition using 4DCT and FB imaging to delineate the target dose volume. Two patients were excluded as they moved during the CT simulation process, invalidat- ing the data. When comparing the planning of AIP vs FB and FB vs MidV, the 2%/2 mm average gamma passing rates of the 2D dose distribution were less than 90% on three orthogonal planes at the isocenter. For 3DCRT, the 2D dose distribution using three types of CT imaging in three orthogonal planes at the isocenter location in 29 patients showed good dose distribution agreement between AIP and MidV plans, with a higher than 98% gamma passing rate. The gamma ning were compared. The difference may be due to the use of differ- ent types of CT imaging, which could produce density variations Comparison P 3DCRT IMRT 3DCRT IMRT Lungs-ITV Small PTV AIP 7.57  2.57 5.85  1.75 AIP vs FB 0.374 0.169 FB 7.26  2.47 5.58  1.77 AIP vs MidV 0.721 0.114 FB 8.11  8.84 6.04  6.59 AIP vs MidV 0.169 0.169 MidV 7.93  8.67 5.95  6.61 Large PTV AIP 23.61  15.54 19.82  13.72 AIP vs FB 0.904 0.809 FB 23.83  15.94 19.92  13.90 AIP vs MidV 0.766 0.171 MidV 23.12  15.46 19.49  13.84 Heart Small PTV AIP 5.52  4.98 2.33  2.72 AIP vs FB 0.386 0.285 Large PTV AIP 11.44  7.10 7.25  4.82 AIP vs FB 0.711 0.904 FB 11.62  7.12 7.25  4.83 AIP vs MidV 0.468 0.658 MidV 11.66  7.03 7.37  4.75 Esophagus Small PTV AIP 8.51  4.84 6.67  4.61 AIP vs FB 0.647 0.721 FB 8.46  4.76 6.77  4.90 AIP vs MidV 0.799 0.139 MidV 8.51  4.78 6.83  4.66 Large PTV AIP 18.98  7.85 16.94  7.15 AIP vs FB 0.809 0.398 FB 19.33  8.87 16.60  7.92 AIP vs MidV 0.260 0.277 MidV 19.46  8.11 16.74  7.21 Spinal cord Small PTV AIP 9.72  17.72 2.77  1.25 AIP vs FB 0.386 0.647 FB 9.54  16.30 2.79  1.26 AIP vs MidV 0.285 0.959 MidV 9.62  16.96 2.79  1.31 Large PTV AIP 11.77  4.24 8.90  2.71 AIP vs FB 0.398 0.617 FB 11.86  4.44 8.97  2.79 AIP vs MidV 0.184 0.629 MidV 11.53  4.44 8.98  2.72 Results are reported as the average  SD. KHAMFONGKHRUEA ET AL . 33 induced by movement effects. Furthermore, the FB images were of lower quality than the AIP and MidV images because of motion arti- facts as reported in study of Han et al. and Tian et al. The motion being imaged as distinct parts, distorted, or displaced, resulting in errors associated with the target volume, OAR delineation, and dose calculation. FB acquisition was also undertaken with an increased imaging dose. FB images are still used by some groups, because they can more clearly distinguish the target volume from contrast agent ﬁ ltration into the tumor than in 4DCT images. As acquisition of 4DCT images may require a long period, the contrast agent inside the tumor becomes less evident. The two imaging data sets from 4DCT acquisitions (AIP and MidV) were obtained for OAR delin- eation and dose calculation using only one CT acquisition. This capa- bility can reduce one source of error from the radiation treatment planning process. Overall, for each percentage of the gamma passing rate, the IMRT dose was lower than that with 3DCRT. The results also showed that most of the dose difference was outside the PTV volume. This result can be explained by considering the basic con- cept of the IMRT technique — that the intensity of the dose was modulated throughout the radiation ﬁ eld. Thus, a comparison of the doses in each plane showed that the difference diminished as one approached the target volume. For impact of target size to dosimet- ric parameters, this study found that no difference for either small and large targets in terms of OAR volumes, geometrical center dif- There was also good agreement between dose distributions in PTV from different CT images as shown by the gamma index analy- sis. There were also no signi ﬁ cant differences in the geometrical cen- ter of the OARs. Hence, it is likely that all three images could be used for radiation treatment planning for a moving target. Nonethe- less, determining the effects of patient movement on FB images is crucial. T ABLE 6 Gamma passing rate derived from a comparison of the 2D dose distribution according to three types of CT imaging on three orthogonal planes at the isocenter. CT type and image plane % Cut-off Tumor size Gamma passing rate (%) 3DCRT IMRT AIP vs FB Axial 10% Small PTV 98.9  1.6 95.8  5.3 Large PTV 99.5  0.7 94.3  9.4 70% Small PTV 99.3  1.9 97.4  5.1 Large PTV 99.9  0.3 98.4  3.7 Coronal 10% Small PTV 99.3  0.2 98.6  2.5 Large PTV 99.2  1.9 95.9  6.2 70% Small PTV 99.5  1.2 98.6  2.7 Large PTV 99.7  1.1 97.9  3.3 Sagittal 10% Small PTV 98.4  2.8 96.6  3.8 Axial 10% Small PTV 100  0.0 96.6  5.8 Sagittal 10% Small PTV 100  0.1 99.1  1.3 Further study is needed to evaluate the accuracy of dose deliv- ery to patients. As radiation treatment planning represents the actual dose distribution, it is necessary to verify dose distribution in a mov- planning. 5 \| CONCLUSION Radiation treatment planning according to the data sets derived from the three types of CT imaging (AIP, FB, MidV) using conventional 3DCRT and IMRT techniques for lung cancer patients revealed no sig- ni ﬁ cant difference in the OAR volumes and the geometric centers of the OARs. Our data also indicated good agreement of the 2D dose distributions for all the three plans, with a higher than 90% average gamma passing rate (2%, 2 mm) for 3DCRT and IMRT. Although the IMRT plan displayed dose differences outside the PTV, doses border- ing to the PTV were in closer agreement with the targeted dose distri- bution. The dosimetric indices (maximum and mean doses) for all three plans, however, showed no signi ﬁ cant differences among the OARs and the size of target volume. We also demonstrated that the AIP, FB, and MidV images could be used for OAR contouring and dose calculation. AIP image sets seemed to be suitable for contouring and dose calculation. It is essential to be aware of the variations in patient movement regarding the FB images because they affect delimitation of the target volume on 4DCT images. ACKNOWLEDGMENTS The authors would like to thank Dr. Danupon Nantajit and Ms. Sunattee Kessung for their assistance in writing the manuscript. We would also like to thank Ms. Kamonwan Soonklang for her helpful statistical analysis. REFERENCES 1. Balter JM, Ten Haken RK, Lawrence TS, Lam KL, Robertson JM. Uncertainties in CT-based radiation therapy treatment planning asso- ciated with patient breathing. Int J Radiat Oncol Biol Phys . 1996;36:167 – 174. 2. Shimizu S, Shirato H, Kagei K, et al. Impact of respiratory movement on the computed tomographic images of small lung tumors in three- dimensional (3D) radiotherapy. 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Guckenberger M, Wilbert J, Krieger T, et al. Four-dimensional treat- ment planning for stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys . 2007;69:276 – 285. 9. Under berg RW, Lagerwaard FJ, Slotman BJ, Cuijpers JP, Senan S. Use of maximum intensity projections (MIP) for target volume gener- ation in 4DCT scans for lung cancer. Int J Radiat Oncol Biol Phys . 2005;63:253 – 260. 10. Wang L, Hayes S , Paskalev K, et a l. Dosimetr ic comparis on of stereotactic body radiotherapy using 4D CT and multiphase CT images for treatment planning of lung cancer: evaluation of the impact on daily dose coverag e. Radiother Oncol . 2009;91: 314 – 324. 11. Bradley JD, Nofal AN, El Naqa IM, et al. Comparison of helical, maxi- mum intensity projection (MIP), and averaged intensity (AI) 4D CT imaging for stereotactic body radiation therapy (SBRT) planning in lung cancer. Radiother Oncol . 2006;81:264 – 268. 12. Zamora DA, Riegel AC, Sun X, et al. Thoracic target volume delin- eation using various maximum-intensity projection computed tomog- raphy image sets for radiotherapy treatment planning. Med Phys . 2010;37(11):5811 – 5820. 13. Tian Y, Wang Z, Ge H, et al. Dosimetric comparison of treatment plans based on free breathing, maximum, and average intensity projection CTs for lung cancer SBRT. Med Phys . 2012;39:2754 – 2760. 14. Han K, Basran PS, Cheung P. Comparison of helical and average computed tomography for stereotactic body radiation treatment planning and normal tissue contouring in lung cancer. Clin Oncol (R Coll Radiol) . 2010;22:862 – 867. 15. Franks KN, Purdie TG, Dawson LA, Bezjak A, Jaffray DA, Bisson- nette JP. Incorporating heterogeneity correction and 4DCT in lung stereotactic body radiation therapy (SBRT): the effect on target cov- erage, organ-at-risk doses, and dose conformity. Med Dosim . 2010;35:101 – 107. 16. Chen GT, Kung JH, Beaudette KP. Artifacts in computed tomo- graphy scanning of moving objects. Semin Radiat Oncol . 2004;14: 19 – 26. 17. Admiraal MA, Schuring D, Hurkmans CW. Dose calculations accounting for breathing motion in stereotactic lung radiotherapy based on 4D-CT and the internal target volume. Radiother Oncol . 2008;86:55 – 60. 18. Riegel AC, Ahmad M, Sun X, Pan T. Dose calculation with respira- tion-averaged CT processed from cine CT without a respiratory sur- rogate. Med Phys . 2008;35:5738 – 5747. 19. Glide-Hurst CK, Hugo GD, Liang J, Yan D. A simpli ﬁ ed method of four-dimensional dose accumulation using the mean patient density representation. Med Phys . 2008;35:5269 – 5277. 20. Huang L, Park K, Boike T, et al. A study on the dosimetric accuracy of treatment planning for stereotactic body radiation therapy of lung cancer using average and maximum intensity projection images. Radiother Oncol . 2010;96:48 – 54. 21. Wolthaus JW, Schneider C, Sonke JJ, et al. Mid-vent ilation CT scan construction from four-dimensional respiration-correlated CT scans for radiotherapy planning of lung cancer patients. Int J Radiat Oncol Biol Phys . 2006;65:1560 – 1571. 22. Guckenberger M, Wilbert J, Krieger T, Richter A, Baier K, Flentje M. Mid-ventilation concept for mobile pulmonary tumors: internal tumor trajectory versus selective reconstruction of four-dimensional com- puted tomography frames based on external breathing motion. Int J Radiat Oncol Biol Phys . 2009;74:602 – 609. 23. Mexner V, Wolthaus JW, van Herk M, Damen EM, Sonke JJ. Effects of respiration-induced density variations on dose distributions in KHAMFONGKHRUEA ET AL . 35 radiotherapy of lung cancer. Int J Radiat Oncol Biol Phys . 2009;74:1266 – 1275. 24. Wolthaus JW, Sonke JJ, van Herk M, et al. Comparison of differ- ent strategies to use four-dimensional computed tomography in treatment planning for lung cancer patients. Int J Radiat Oncol Biol Phys . 2008;70:1229 – 1238. 25. Ezzell GA, Burmeister JW, Dogan N, et al. IMRT commissioning: multiple institution planning and dosimetry comparisons, a report from AAPM Task Group 119. Med Phys . 2009;36:5359 – 5373. 26. Yan G, Liu C, Simon TA, Peng LC, Fox C, Li JG. On the sensitivity of patient-speci ﬁ c IMRT QA to MLC positioning errors. J Appl Clin Med Phys . 2009;10:120 – 128. 36 KHAMFONGKHRUEA ET AL . ... Computed tomography (CT) imaging correlated with breathing movement (4D-CT) is considered a method of choice for capturing moving targets. The accuracy of defining the target volume determines treatment success [5] . 4D-CT diminishes movement artefacts for precise target volume definition and concurrently permits patient-individual motion evaluation for safety margins [6]. ... ... Thomas et al. [10] suggest planning on a Mid-V image because the image can reduce the target volume and allow more accurate definition of the GTV. Several studies have conducted planning and dose calculations using average intensity projection (AIP) images [5, 11]. ... ... Tumour motion potentially leads to a difference between the planned dose and delivered dose due to setup errors [5] . Therefore, breathing-correlated 4D-CT must be unified into a 4D-IG workflow. ... Evaluation of target volume and dose accuracy in intrafractional cases of lung cancer based on 4D-CT and 4D-CBCT images using an in-house dynamic thorax phantom Background: This study aimed to evaluate the target volume and dose accuracy in intrafraction cases using 4-dimensional imaging modalities and an in-house dynamic thorax phantom. Intrafraction motion can create errors in the definition of target volumes, which can significantly affect the accuracy of radiation delivery. Motion management using 4-dimensional modalities is required to reduce the risk. Materials and methods: Two variations in both breathing amplitude and target size were applied in this study. From these variations, internal target volume (ITVs) contoured in 10 phases of 4D-CT (ITV10), average intensity projection (AIP), and mid-ventilation (Mid-V) images were reconstructed from all 4D-CT datasets as reference images. Free-breathing (FB), augmentation free-breathing (Aug-FB), and static images were also acquired using the 3D-CT protocol for comparisons. In dose evaluations, the 4D-CBCT modality was applied before irradiation to obtain position correction. Then, the dose was evaluated with Gafchromic film EBT3. Results: The ITV10, AIP, and Mid-V provide GTVs that match the static GTV. The AIP and Mid-V reference images allowed reductions in ITVs and PTVs without reducing the range of target movement areas compared to FB and Aug-FB images with varying percentages in the range of 29.17% to 48.70%. In the dose evaluation, the largest discrepancies between the measured and planned doses were 10.39% for the FB images and 9.21% for the Aug-FB images. Conclusion: The 4D-CT modality can enable accurate definition of the target volume and reduce the PTV. Furthermore, 4D-CBCT provides localization images during registration to facilitate position correction and accurate dose delivery. ... For partial breast irradiation, previous studies have demonstrated that 4D-CT radiotherapy improves the target definition and decreases the radiation dose of OAR (18,19). Furthermore, certain previous studies have compared different composite methods for lung cancer and liver cancer (21,(23)(24)(25) (26) (27)(28); however, to the best of our knowledge, at present, there is no study that has been published in English for breast cancer. ... ... Previous studies have established that radiotherapy based on 4D-CT simulation enhances the accuracy of dosage and determines the locations of tumour(s) and OAR in the chest and abdomen (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) (26) 33). Certain previous studies have compared the composite methods of 4D-CT radiotherapy for lung cancer and liver cancer (9,17,20,(23)(24)(25)(26)33); however, at present, to the best of our knowldege, there is no study that has been published in English, which has investigated the same for breast cancer. ... ... Previous studies have established that radiotherapy based on 4D-CT simulation enhances the accuracy of dosage and determines the locations of tumour(s) and OAR in the chest and abdomen (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)33). Certain previous studies have compared the composite methods of 4D-CT radiotherapy for lung cancer and liver cancer (9,17,20,(23)(24)(25) (26) 33); however, at present, to the best of our knowldege, there is no study that has been published in English, which has investigated the same for breast cancer. To the best of the our knowledge, the present study is the first to compare the target volume and dosimetric differences between the 3D-CT radiotherapy plan and four 4D-CT radiotherapy plans (T00, T50, MIP and AIP plans) for whole breast radiotherapy. ... Dosimetric comparison between three‑ and four‑dimensional computerised tomography radiotherapy for breast cancer At present, methods of radiotherapy simulation for breast cancer based on four-dimensional computerised tomography (4D-CT) or three-dimensional CT (3D-CT) simulation remain controversial. In the present study, 7 patients with residual breast tissue received whole breast radiotherapy based on 3D-CT and 4D-CT simulation. For the 4D-CT plan, four types of CT images were produced, including images of the end of inspiration and the end of expiration, and images acquired by the maximal intensity projection (MIP) and average intensity projection (AIP). In the 3D-CT plan, the clinical target volume (CTV) and plan target volume (PTV) were marginally higher compared with the 4D-CT plan. In addition, the minimum point dose of the target volume (Dmin), the maximum point dose of the target volume (Dmax) and the mean point dose of the target volume (Dmean) of the CTV and PTV in the MIP and AIP plans were marginally higher compared with the 3D-CT plan. For the contralateral breast (C-B), volumes of the 4D-CT plan were markedly lower compared with the 3D-CT plan. Furthermore, Dmin, Dmax and Dmean of the 3D-CT plan were higher compared with the AIP and MIP plans. For the ipsilateral lungs (I-L), volumes of the 3D-CT and AIP plans were higher compared with the MIP plan. Furthermore, when breast lesions were on the left side, for the heart, the volume receiving no less than 40% of the prescription dose (V40) and the volume receiving no less than 30% of the prescription dose (V30) of the MIP and AIP plans were slightly lower compared with those of the 3D plan. In conclusion, 4D-CT radiotherapy based on the MIP and AIP plans provides a slightly smaller radiation area and slightly higher radiotherapy dosage of the CTV and PTV compared with 3D-CT radiotherapy for breast radiotherapy. Therefore, the MIP and AIP plans prevent C-B radiation exposure and improve sparing of the heart and I-L. ... The static dose is the dose calculated from a single computed tomography (CT) data set, be it the average CT, midventilation CT, or FB CT. 33 4D accumulated dose or 4D dose (4DD) is the weighted average of the doses calculated on either selected or all (typically 10) individual phases of a 4D CT simulation scan using the planned delivery sequence. 4DD is calculated using only the treatment plan and 4DCT image set without considering the time dependence of the delivery fluence. ... Report of AAPM Task Group 290: Respiratory motion management for particle therapy Dose uncertainty induced by respiratory motion remains a major concern for treating thoracic and abdominal lesions using particle beams. This Task Group report reviews the impact of tumor motion and dosimetric considerations in particle radiotherapy, current motion‐management techniques, and limitations for different particle‐beam delivery modes (i.e., passive scattering, uniform scanning, and pencil‐beam scanning). Furthermore, the report provides guidance and risk analysis for quality assurance of the motion‐management procedures to ensure consistency and accuracy, and discusses future development and emerging motion‐management strategies. This report supplements previously published AAPM report TG76, and considers aspects of motion management that are crucial to the accurate and safe delivery of particle‐beam therapy. To that end, this report produces general recommendations for commissioning and facility‐specific dosimetric characterization, motion assessment, treatment planning, active and passive motion‐management techniques, image guidance and related decision‐making, monitoring throughout therapy, and recommendations for vendors. Key among these recommendations are that: 1) facilities should perform thorough planning studies (using retrospective data) and develop standard operating procedures that address all aspects of therapy for any treatment site involving respiratory motion; 2) a risk‐based methodology should be adopted for quality management and ongoing process improvement. This article is protected by copyright. All rights reserved ... Based on the recorded CT data and respiratory pattern, certain breathing phases can be reconstructed and equally divided in time-percentage bins of the whole respiratory cycle. If a 4DCT is reconstructed to 10 breathing phases, then the so-called 0% phase corresponds to the maximum inhale, while the 50% phase to maximum exhale of the respiratory cycle [41] . Based on the acquired 4DCT, other 3DCT images used at the contouring and planning stages could be reconstructed, e.g. an average or maximum intensity projection (MIP), as well as mid-ventilation (MidV) CT scans [42][43]. ... ... 27 The various CT reconstructions as a basis for dose calculation are to some degree shown to be equivalent in terms of dosimetric accuracy and anatomical representation. [28] [29][30] In the current study, we seek to determine whether optimizing and calculating plans based on different CT reconstructions has an impact on plan robustness, in terms of dosimetric deviations due to respiration-induced target motion during treatment. Relative dose deviations will be obtained by comparing dynamic measurements with stationary measurements, thereby isolating interplay and blurring effects from dosimetric agreement with TPS calculated dose. ...	https://www.researchgate.net/publication/315322703_Comparison_of_CT_images_with_average_intensity_projection_free_breathing_and_mid-ventilation_for_dose_calculation_in_lung_cancer
SAE MOBILUS A Practical Economic Solution to Weight Reduction and Increased Performance in Diesel Engines Technical Paper 912711 ISSN: 0148-7191 , e-ISSN: 2688-3627 DOI: https://doi.org/10.4271/912711 Published November 01, 1991 by SAE International View list of content related to the publisher(s) in United States Sector: Commercial Vehicle Content related to Commercial Vehicle Event: International Truck & Bus Meeting & Exposition Technical Paper presented at International Truck & Bus Meeting & Exposition Language: English Abstract Compacted Graphite Iron (CGI) has been recognized for years as a unique material possessing a fortunate combination of properties intermediate between gray iron and ductile iron. This material, for reasons outlined in this paper, is ideal for cylinder blocks, heads and other cast iron components for diesel engines. It makes possible casting weight savings of up to 1/3 and/or increased power output. This paper will outline reasons why this is now possible, whereas it has seldom been applied in volume production heretofore. Physical and mechanical properties of CGI, which provide the opportunity for weight reduction and increased power, are discussed. Currently, most diesel engine cylinder blocks, heads, liners and many other castings are produced from gray iron, which requires relatively heavy sections to provide the strength, stiffness and durability necessary for commercial application. Traditionally, gray iron has been selected for its properties, such as: and because gray iron has always been highly available at relatively low cost. A design disadvantage of gray iron, due to its low tensile strength, is its high weight-to-horsepower compared to alternative materials. The value of the favorable gray iron properties and its low cost, however, have prevailed. The present design structure of specific cylinder blocks or heads may limit engine output below desired performance level. However, increased output may be possible without structure changes by substituting a stronger material, such as compacted graphite iron for the gray iron. In cases where engine power output is satisfactory, a substantial reduction in weight (up to 1/3 of block, heads, liners and other gray iron component castings) is possible by redesigning to take advantage of the superior properties of compacted graphite iron. Instances of high mileage fatigue failures in blocks or heads can be eliminated by simply substituting CGI for the original gray iron. Technical Paper Effect of Geometric Structure of Cylinder Head on the Combustion Process in a Diesel Engine Technical Paper Why Not Convert to Ductile Iron? Authors T. N. Louckes Works by T. N. Louckes Topic Engine cylinders Content related to Engine cylinders Diesel / compression ignition engines Content related to Diesel / compression ignition engines Iron Content related to Iron Tensile strength Content related to Tensile strength Graphite Content related to Graphite Citation References Nechtelberger E. Puhr H. von Nesselrode J. B. Nakaysu A. “Cast Iron with Vermicular/Compacted Graphite - State of the Art. Development, Production, Properties, Applications,” 49th International Foundry Congress April 1982 Powell J. “A Review of Some Recent Work on Compacted Graphite Irons,” THE BRITISH FOUNDRYMAN November 1984 Powell W. L. Wieske J. “C.G. Iron - A case history,” IRONCASTER May 1980 Chen C. T. Ford Motor Co. 1983 Altstetter J. D. Nowicki R. M. “Compacted Graphite Iron: Its Properties and Automotive Applications,” AFS Transactions 1982 Fugiel T. F. Clark S. E. “Use of Compacted Graphite Iron in Power Steering Pumps,” SAE Technical Paper, 810814 Oathout R. R. “Compacted Graphite Iron for Diesel Engines,” METAL PROGRESS May 1978 Chongyu Tan and others “Wear Resistance of Cylinder Liner of Compacted Graphite Iron Containing Boron,” 1988 Phillips C. W. “Machinability of Compacted Graphite Iron.” AFS Transactions 1981 Papapdakis E. P. Bartosiewicz L. Altstetter J. D. Chapman G. B. II “Morphological Severity Factor For Graphite Shape In Cast Iron And Its Relation To Ultrasonic Velocity And Tensile Properties,” AFS Transactions Product Code Document Title File Type Download 912711 A Practical Economic Solution to Weight Reduction and Increased Performance in Diesel Engines Download File Type Download	https://saemobilus.sae.org/content/912711
Guidance for Researchers Developing and Conducting Clinical Trials in Practice-based Research Networks (PBRNs) \| American Board of Family Medicine Guidance for Researchers Developing and Conducting Clinical Trials in Practice-based Research Networks (PBRNs) Rowena J. Dolor , Kristine M. Schmit , Deborah G. Graham , Chester H. Fox and Laura Mae Baldwin The Journal of the American Board of Family Medicine November 2014, 27 (6) 750-758; DOI: https://doi.org/10.3122/jabfm.2014.06.140166 Rowena J. Dolor the Duke Clinical Research Institute, Duke University, Durham, NC (RJD); Department of Community and Family Medicine, Duke University Medical Center, Durham, NC (KMS); American Academy of Family Physicians National Research Network, Leawood, KS (DGG); DARTNet Institute, Wilmette, IL (DGG); Department of Family Medicine, University of Buffalo, Buffalo, NY (CHF); and the Department of Family Medicine, University of Washington, Seattle, WA (LMB). Kristine M. Schmit the Duke Clinical Research Institute, Duke University, Durham, NC (RJD); Department of Community and Family Medicine, Duke University Medical Center, Durham, NC (KMS); American Academy of Family Physicians National Research Network, Leawood, KS (DGG); DARTNet Institute, Wilmette, IL (DGG); Department of Family Medicine, University of Buffalo, Buffalo, NY (CHF); and the Department of Family Medicine, University of Washington, Seattle, WA (LMB). the Duke Clinical Research Institute, Duke University, Durham, NC (RJD); Department of Community and Family Medicine, Duke University Medical Center, Durham, NC (KMS); American Academy of Family Physicians National Research Network, Leawood, KS (DGG); DARTNet Institute, Wilmette, IL (DGG); Department of Family Medicine, University of Buffalo, Buffalo, NY (CHF); and the Department of Family Medicine, University of Washington, Seattle, WA (LMB). Laura Mae Baldwin the Duke Clinical Research Institute, Duke University, Durham, NC (RJD); Department of Community and Family Medicine, Duke University Medical Center, Durham, NC (KMS); American Academy of Family Physicians National Research Network, Leawood, KS (DGG); DARTNet Institute, Wilmette, IL (DGG); Department of Family Medicine, University of Buffalo, Buffalo, NY (CHF); and the Department of Family Medicine, University of Washington, Seattle, WA (LMB). Article Abstract Background:There is increased interest nationally in multicenter clinical trials to answer questions about clinical effectiveness, comparative effectiveness, and safety in real-world community settings. Primary care practice-based research networks (PBRNs), comprising community- and/or academically affiliated practices committed to improving medical care for a range of health problems, offer ideal settings for these trials, especially pragmatic clinical trials. However, many researchers are not familiar with working with PBRNs. Methods:Experts in practice-based research identified solutions to challenges that researchers and PBRN personnel experience when collaborating on clinical trials in PBRNs. These were organized as frequently asked questions in a draft document presented at a 2013 Agency for Health care Research and Quality PBRN conference workshop, revised based on participant feedback, then shared with additional experts from the DARTNet Institute, Clinical Translational Science Award PBRN, and North American Primary Care Research Group PBRN workgroups for further input and modification. Results:The “Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice-Based Research Networks” offers guidance in the areas of recruiting and engaging practices, budgeting, project management, and communication, as well as templates and examples of tools important in developing and conducting clinical trials. Conclusion:Ensuring the successful development and conduct of clinical trials in PBRNs requires a highly collaborative approach between academic research and PBRN teams. Clinical Trials as Topic Practice-based Research There is increased interest nationally in multicenter clinical trials, especially pragmatic clinical trials (PCTs), to answer questions about clinical effectiveness, comparative effectiveness, and safety in real-world community settings. PCTs measure the effectiveness that a community-, clinical-, or system-level intervention produces in routine clinical settings. 1Primary care practice-based research networks (PBRNs) are an ideal setting for these PCTs. PBRNs are composed of community- and/or academically affiliated practices that are committed to improving medical care for a range of health problems by conducting primary care research, engaging understudied populations, and accelerating the adoption of new knowledge and best practices. More than 100 PBRNs are registered with the Agency for Health care Research and Quality. 2A number of PBRNs have conducted PCTs in community-based primary care practices to evaluate treatment effectiveness and behavioral interventions for chronic conditions. 3 ⇓ – 5However, many investigators have not had experience working with PBRNs. Through extensive involvement with clinical trials, PBRN leaders have found that the projects are most successful when the PBRN team (Figure 1) is engaged to assist with trial design, procedures, and budgeting (during the proposal submission phase); practice recruitment, participant recruitment, and communications (during the enrollment phase); management of the trial (during the trial conduct phase); and interpretation and dissemination of trial results, manuscripts, and presentations (during the close-out and dissemination phase). We created a toolkit consisting of a set of frequently asked questions (FAQs), templates, and examples of tools to guide researchers who are interested in conducting a clinical trial in a PBRN setting. In addition, these FAQs will assist PBRN directors and their teams in communicating with researchers about the project-specific needs of their PBRN. Download figure Open in new tab Figure 1. Academic and practice-based research network (PBRN) teams and personnel. Methods Experts in practice-based research who are members of 2 workgroups—the DARTNet Institute (DI) Research Steering Committee and the Clinical Translational Science Award (CTSA) Community Engagement PBRN workgroup—identified the need to better communicate solutions to the challenges that researchers and PBRN personnel experience when collaborating while developing and conducting clinical trials in PBRNs. Five topic areas for development were originally proposed by these workgroups: (1) practice recruitment and engagement, (2) budgeting, (3) project management, (4) engaging and maintaining study teams, and (5) communication. Each section was written in an FAQ format with advice relevant to different phases of a clinical trial: trial development, conduct, close out, and dissemination. A draft of the 5 sets of FAQs was presented at the 2013 North American Primary Care Research Group PBRN conference in Bethesda, Maryland, in a workshop format with small-group breakouts to discuss and refine each section. Based on feedback from the workshop participants, 2 sections (project management and engaging and maintaining study teams) were merged into 1 section entitled project management, and the resulting 4 FAQ documents were revised based on participant feedback. A revised draft of the FAQs and an introduction to these documents were sent to the DI Research Steering Committee, the CTSA Community Engagement PBRN, and North American Primary Care Research Group Committee for the Advancement of Science in Family Medicine PBRN workgroups for further input and modification. The FAQ documents have been combined with templates and examples of tools important to clinical trial development and conduct, as well as with a glossary of terms (seeTable 1and Appendix 1) to create a web-based toolkit entitled “Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice Based Research Networks.” This toolkit is available on the DARTNet Institute website atwww.dartnet.info/clinicaltrialsPBRNtoolkit.htm. Table 1. Glossary of Terms for Practice-based Research Network (PBRN) Research Project Teams Results Summaries of the key recommendations from the FAQs are presented in the following sections. Recruiting and Engaging Practices Including a PBRN core team member (eg, PBRN director, PBRN investigator, PBRN coordinator) on the clinical trial research team is critical to facilitate practice recruitment. PBRNs have established relationships and garnered the trust of the practices and know or can determine the research capacities and suitability of the practices specific to a clinical trial. A short, 1-page information sheet that emphasizes the value of the trial to the practices and outlines the work required is ideal for recruiting purposes. There are a variety of different venues (eg, PBRN meetings, regular practice meetings) and communication tools (eg, newsletters, E-mails) that may be used to attract practices to participate in a trial. The PBRN team can help to determine the most effective venues and tools for a particular clinical trial and/or practice. Strategies to keep practices engaged include minimizing the amount of work required by the practices, working with practices to implement the intervention(s) into their existing workflow, adequately compensating practices for their participation, providing additional training as needed throughout the trial, and frequently soliciting feedback from the practices. Keeping practices engaged can also be facilitated by identifying a practice lead physician/clinician who can provide leadership for the trial at the practice. Good communication is critical to keeping practices engaged and excited about a project.Table 2summarizes the key points regarding recruiting and engaging practices. Table 2. Key Points Regarding Recruiting and Engaging Practices Budgeting As with other areas of a clinical trial, engagement of PBRN core team members as early as possible in the development of the budget is crucial. Ideally, a clearly designated scientific lead and administrative lead, including representation from the PBRN, should be involved in the budget process from the beginning. The PBRN core team will be able to advise on the overall structure of the budget as well as particular costs unique to a PBRN-based clinical trial (eg, PBRN infrastructure costs, practice honoraria, dissemination of findings to practices). Because of the multiple collaborators, following a strict timeline for completion of a grant proposal's budget, including a draft budget completed at least 6 weeks before the grant proposal due date and a final budget at least 3 weeks before the due date, is important. Discussion of any changes to the budget by all research team leaders and clear communication of these changes to participating entities is critical.Table 3summarizes the key points related to the budgeting process. Table 3. Key Points Regarding Budgeting Project Management Practice-based research is distinctive because PBRN and practice representatives (eg, PBRN investigators, practice lead physicians/clinicians) are essential members of the research project team. Their roles are critical in all stages of a clinical trial. Early engagement of these team members is essential for the appropriate design and implementation of the trial protocol. 6With their knowledge of the capacity of the participating practices, the PBRN director and PBRN coordinator are able to offer critical feedback on the effort required by the PBRN central research project team and the participating practices to implement the clinical trial. Given its established research relationships with the practices, the PBRN central research project team also plays a key role in the ongoing conduct of the clinical trial. Because responsibilities differ for each clinical trial, determining before the start of the trial which tasks will be performed by the academic research project team, the PBRN central research project team, and the PBRN on-site research project team is imperative. For most studies, a PBRN research project manager will be assigned to coordinate clinical trial implementation with the academic research project team. The PBRN research project manager and PBRN central research project team may manage the trial directly or they may work closely with an on-site practice liaison/research project coordinator who manages on-site trial implementation. Given the different personnel and organizations involved, a PBRN-based clinical trial will run more smoothly with a formal manual of protocol procedures that outlines all trial procedures and is accessible to all project personnel; the manual should include flow charts or summaries that address any workflow questions. This helps to ensure fidelity to the intervention and the collection of high-quality data. In addition the PBRN should maintain a regulatory binder, which contains the study protocol, consent form, institutional review board (IRB) approval/correspondence, regulatory documents (such as the US Food and Drug Administration Statement of Investigator 1572 form, drug accountability form, if applicable), curriculum vitae and training documents of the principal investigator and key personnel, and other site-related documents. Managing the quality of the trial also requires documenting trial progress in detail and maintaining organized trial files. Communication is key to keeping all members of the PBRN on-site research project team engaged. Finally, keeping the participating practices and patients informed by providing updates on trial results and publications through letters, E-mail, or newsletters is important.Table 4summarizes the key points regarding project management. Table 4. Key Points Regarding Project Management Communication Good communication ensures that the clinical trial runs smoothly and that patient care is enhanced and not compromised. Clinical trials conducted in collaboration with a PBRN often have a number of diverse collaborators. Given these many diverse collaborators, establishing clear lines of communication is especially important. To be effective, communication should be multidirectional, allowing all the collaborators the ability to share ideas, ask questions, or voice concerns. Good communication depends on the recognition that each collaborator brings particular skills and expertise that are important to the success of the trial. Good communication is designed to keep all collaborators updated on issues such as trial progress, issues or concerns that have arisen, and changes in the clinical trial protocol. Toward the end of the trial, ensuring that the participating practices receive trial results and have a chance to help interpret research findings is particularly important. These “observations from the field” help to explain research results and inform the discussion of the findings.Table 5summarizes the key points regarding communication. Table 5. Key Points Regarding Communication Discussion PBRNs provide an ideal setting in which to conduct clinical trials, especially PCTs. However, many academic researchers have not worked with PBRNs and may not be aware of the many elements specific to designing and implementing an effective clinical trial with PBRN partners. We have developed the “Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice Based Research Networks” to offer guidance to investigators interested in conducting clinical trials with PBRNs with the hope of facilitating collaborations between investigators and PBRN teams and promoting the success of clinical trials. To reach as broad an audience as possible, this toolkit will be hosted on the DARTNet Institute website with links to the CTSA/National Center for Advancing Translational Sciences, Community Campus Partnerships for Health, and research toolkit web sites, among others. As an example, the Translating Research into Primary Care Practice for Postpartum Depression (TRIPPD) study funded by the Agency for Health care Research and Quality assessed the effectiveness of postpartum depression screening and management in 28 practices in a single PBRN, the American Academy of Family Physicians National Research Network. During the grant submission phase, the project principal investigator, co-investigators, and PBRN director were involved in writing the proposal and developing the budget. Together they modified the research plan (eg, recruitment and study procedures) to fit a busy clinical environment and calculated the personnel time and practice reimbursement required during the course of a project. The PBRN director served as the principal investigator for the PBRN subcontract. When the grant was awarded, the PBRN central research team was instrumental in recruiting practices using established communication venues (practice meetings, teleconferencing) and materials (research summary with copies of recruitment materials and consent) that were collaboratively developed by the academic research project team and the PBRN core team. The practice personnel received study-specific training, IRB training, regulatory document support, and a manual of protocol procedures was created to ensure implementation fidelity. After IRB approval, recruitment commenced and the academic research project and PBRN core teams collaboratively monitored enrollment metrics and retention rates. Regular communication between the academic research project team, the PBRN central research and core teams, and the participating practices was established through weekly team (academic project research team and PBRN core team) conference calls, weekly project calls between PBRN central research team members and practice staff, weekly study E-newsletters called “FAQs,” and monthly calls between academic study investigators, the PBRN principal investigator, and practice lead clinicians. The academic research project team and the PBRN core team met face to face at least once a year to discuss data analysis, interim results, dissemination of results, and publications. The budget included personnel effort for the PBRN director, PBRN associate director, PBRN research assistant, and PBRN system analyst. Practice lead clinicians and practice research project coordinators were compensated for time spent on training. Participating practices were provided an annual stipend based on completing milestones. A 2-day face-to-face study kickoff meeting with 2 attendees from each practice site, as well as annual meetings for the academic research project team and PBRN central research project team during the life of the grant, were budgeted. All practice staff were invited to periodic events funded by the academic research project team, such as pizza parties, to encourage practice-wide involvement in the trial. Indirect costs for the PBRN were included. 5 , 7 A listing of documents such as those used for practice recruitment, participant recruitment, and site communication is included in Appendix 1. The full resources are available as links or downloads on the DARTNet website (www.dartnet.info/clinicaltrialsPBRNToolkit.htm). Many were developed for projects we conducted and were determined to be good examples to list as resources. Conclusion Ensuring the successful development and conduct of clinical trials in PBRNs requires a highly collaborative approach between academic research and PBRN teams—collaboration that we hope is facilitated by our “Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice Based Research Networks.” Acknowledgments The DARTNet Institute Research Steering Committee, CTSA Community Engagement PBRN workgroup members, the North American Primary Care Research Group (NAPCRG) Committee on Advancing the Science of Family Medicine PBRN workgroup, workshop participants at the NAPCRG PBRN 2013 conference, Kim Kimminau, PhD, and Wilson D. Pace, MD, FAAFP, all contributed to the development of the “Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice Based Research Networks.” Appendix 1 Toolkit Resources Notes This article was externally peer reviewed. Funding:This work was supported in part by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR000423 and UL1TR001117. Conflict of interest:none declared. Received for publication June 5, 2014. Revision received July 31, 2014. Accepted for publication August 6, 2014. References 1. ↵ Concannon TW , Guise JM , Dolor RJ , et al . A national strategy to develop pragmatic clinical trials infrastructure . Clin Transl Sci 2014 ; 7 : 164 – 71 . 2. ↵ Peterson KA , Lipman DB , Lange CJ , Cohen RA , Durako S . Supporting better science in primary care: a description of practice-based research networks (PBRNs) in 2011 . J Am Board Fam Med 2012 ; 25 : 565 – 71 . 3. ↵ Bosworth HB , Olsen MK , Grubber JM , et al . Two self-management interventions to improve hypertension control: a randomized trial . Ann Intern Med 2009 ; 151 : 687 – 95 . ↵ Svetkey LP , Pollak KI , Yancy WS , et al . Hypertension Improvement Project (HIP): randomized trial of quality improvement for physicians and lifestyle modification for patients . Hypertension 2009 ; 54 : 1226 – 33 . 5. ↵ Yawn BP , Dietrich AJ , Graham D , et al . Preventing the voltage drop: practice-based research network (PBRN) practices engaged in studies . J Am Board Fam Med 2014 ; 27 : 123 – 35 . 6. ↵ Graham DG , Spano MS , Stewart TV , Staton EW , . Strategies for planning and launching PBRN research studies: a project of the Academy of Family Physicians National Research Network (AAFP NRN) . J Am Board Fam Med 2007 ; 20 : 220 – 8 . 7. ↵ Yawn BP , Dietrich AJ , Wollan P , et al . TRIPPD: a practice-based network effectiveness study of postpartum depression screening and management . Ann Fam Med 2012 ; 10 : 320 – 9 .	https://www.jabfm.org/content/27/6/750
FirstPort blows a fuse: Why are energy subsidies absent from the £265,784 electricity bills - an increase of 154% - at St David's Square, tribunal is asked - Leasehold Knowledge Partnership The First Tier Tribunal was asked yesterday why subsidies from the Energy Bill Relief Scheme were not included in the annual energy budget set by FirstPort at the prime site St David's Square in London's Docklands. FirstPort blows a fuse: Why are energy subsidies absent from the £265,784 electricity bills – an increase of 154% – at St David’s Square, tribunal is asked Public interest request to advance the dispute to Upper Tribunal as other sites may also have similar budget omissions was declined The First Tier Tribunal was asked yesterday why subsidies from the Energy Bill Relief Scheme were not included in the annual energy budget set by FirstPort at the prime site St David’s Square in London’s Docklands. Mains gas and electricity supplies to common areas – corridors, lifts etc – in residential blocks of flats are subject to commercial electricity contracts rather than price-capped domestic arrangements. FirstPort places its contract for the supply of gas and electricity for the 5,500 sites it manages via a broker, EnergyCentric. FirstPort and EDF have refused repeated requests to disclose the commission earned by EnergyCentric on the contract. From the figures leaseholders can see, total expenditure on electricity at St David’s Square is estimated to increase from £104,830 in 2022 to £265,784 in 2023: an increase of £160,954. Yet the service charge demand does not explain how the increase has been calculated. It amounts to 154% increase overall. Some parts of the electricity budget have been increased by 210%. FirstPort has twice refused to provide leaseholders with the full budget and twice refused to explain how the figures have been calculated. The site’s total electricity bill could be near £600,000 for 2023. The issue is being disputed by Liam Spender, a City solicitor and an LKP trustee who earlier this year mounted a four-day case over the service charge demands at St David’s Square, for which a ruling is still awaited: Mr Spender goes to war over St David’s Square service charges … and landlord caves in over more than £100,000 buildings insurance commissions on eve of tribunal A case management hearing was held at the First tier Tribunal yesterday morning in front of Judge Vance. Mr Spender argued that application to the tribunal “is necessary only because the Respondent (ie FirstPort) has refused a perfectly reasonable request to re‐calculate service charge payments on account to give credit for the Energy Bill Relief Scheme subsidy received in the period 1 January to 31 March 2023”. Accounting for the Energy Bill Relief Scheme subsidy would knock off roughly 30% of the costs of electricity between January and March 2023, perhaps equivalent to between £40,000 and £60,000. Mr Spender also asked for the case to be transferred to the Upper Tribunal as an important public interest issue involving other sites, arguing that FirstPort “has made no effort to comply with its obligations as an intermediary under the Pass‐Through Regulations, including its continuing failure to perform any of its duties under Regulations 3, 4 and 5. The same has apparently occurred at all FirstPort sites, under this Respondent and other landlords. This is plainly a matter of wider public importance.” However, this request was declined, and instead a hearing in the FTT is set for 17 May. The LKP has seen reports of various sites, managed by FirstPort and other managing agents, with huge increases in gas and electricity budgets that also appear not to have taken into account the government subsidies. Mr Spender first raised the issue of the electricity budget with FirstPort managing director Kully Sahdra on 12 December 2022 after receiving a service charge demand that was 19% higher than in the same period in 2022. He wrote: “Total expenditure on electricity is estimated to increase from £104,830 to £265,784, being an increase of £160,954, or 154%. The service charge demand does not explain how the increase has been calculated. Please explain by return how the increases have been calculated.” Mr Spender also questioned why FirstPort had apparently not taken into account the Energy Bill Relief Scheme, which was included in the 25 October 2022 Energy Prices Act 2022, which came into force subsidising commercial consumers’ energy bills from 1 October 2022 to 31 March 2023. On 27 October 2022, the government made the Energy Bill Relief Scheme Pass-Through Requirement (England and Wales and Scotland) Regulations, which came into force on 1 November 2022. These made FirstPort, as a “relevant intermediary”, subject to a requirement to effect pass-through to end users. Mr Spender pointed out that FirstPort had had five weeks to consider the Pass-Through regulations before issuing its service charge budget at St David’s Square. Although not relevant to the energy issue, Mr Spender’s letter to Ms Sahdra also included reference to the 20% increase in insurance costs at St David’s Square and FirstPort’s own 7% increase in management fees. Mr Spender added in his letter: “It has become your practice to refer routine correspondence of this nature to JB Leitch [solicitors based in Liverpool]. FirstPort is paid a significant management fee to manage the site, now in the region of £175,000 a year. Having made a service charge demand with insufficient information to justify the large increase demanded, you are obliged to answer the questions set out in this letter. In the event that you choose to refer this correspondence to JB Leitch, be advised that the costs of that will not be reasonably incurred and should not be passed to leaseholders.” “At present, there is no information about whether any discount will be available after 31 March and we have been advised that a decision is not likely to be forthcoming for some time. As a prudent property manager, we do not consider it appropriate when setting budgets for 2023 to assume that the discount will continue for the full year. It is not in the interests of residents to run the risk of a deficit arising as the year progresses. “For the above reasons, we consider the budgeted increase of 154% for the year as a whole to be reasonable.” The letter did not confirm whether the subsidies had been factored into the 2023 budget or not. At today’s hearing, Judge Vance ordered the landlords – which are part of NatWest Trustee and Depositary Services – to hand over copies of electricity bills received between 1 October 2022 and the date of the service charge demand. The landlords were also ordered to say when the electricity contract was signed and to provide a copy of the full 2023 service charge budget. The site’s landlords hold the freeholds of the site on trust for ground rent investor the ARC Time Freehold Income Fund. In turn, the fund uses the Tchenguiz Family Trust owned Freehold Managers plc – part of the Consensus Business Group – to administer a portfolio of roughly 60,000 ground rents. The case illustrates the lengths leaseholders have to go through to get even basic information about service charges, even after the government has made regulations requiring this information to be provided. The landlords were represented at yesterday’s hearing by JB Leitch and barrister Miriam Seifert, of Landmark Chambers. The case continues.	https://www.leaseholdknowledge.com/firstport-blows-a-fuse-why-are-energy-subsidies-absent-from-the-265784-electricity-bills-an-increase-of-154-at-st-davids-square-tribunal-is-asked/
The Launch of the Euro - Towards European unity? \| EU \| Europe The euro's launch has been greeted with a well-orchestrated campaign of official enthusiasm, designed to silence all doubts on the question. The Euro has finally been introduced as a common currency in 12 of the EU states. This is an important development. A common currency is the first condition towards European integration. It ought to boost internal trade and thus act as a powerful stimulus to the development of the productive forces. But is this going to happen? The Launch of the Euro - Towards European unity? European Union The euro's launch has been greeted with a well-orchestrated campaign of official enthusiasm, designed to silence all doubts on the question. The Euro has finally been introduced as a common currency in 12 of the EU states. This is an important development. A common currency is the first condition towards European integration. It ought to boost internal trade and thus act as a powerful stimulus to the development of the productive forces. But is this going to happen? On January the first 2002, with great pomp and ceremony, the euro was introduced into circulation in a trading zone numbering 300 million people. What does this mean? And what are the prospects for the new European currency? The euro's launch has been greeted with a well-orchestrated campaign of official enthusiasm, designed to silence all doubts on the question. French newspapers greeted the birth of the currency with enthusiasm and lurid colour diagrams. All opposition has melted away. The conservative daily, Le Figaro, which sometimes flirts with euroscepticism, declared itself in a front-page editorial to be the "Fig-Euro". "Is a little bit of France vanishing today?" it asked. "No, the single currency of the Roman Empire never prevented its peoples from expressing themselves." The centre-left newspaper Libération filled its front page with a euro symbol made up of euro coins. It also chose a Roman metaphor to describe the day. "The European Union has crossed the Rubicon," it said. "No more U-turns are possible on the road to the unification of Europe." Le Monde, more subtly, had a front-page cartoon by Serguei, which showed a two-headed Frenchman weeping over a franc and a euro. The caption read: "Heads or tails". The enthusiasm was replicated elsewhere. Complacency must be avoided, the Irish Independent said: "So smoothly did the transition go on its first day that one could easily forget its deeper meaning. The citizens handling the new money were taking part in a momentous political occasion." For The Irish Times, Euro launch day was "a powerful symbol of closer EU integration". But the move raises concerns about a one-size-fits-all interest rate policy, it said: "Both the ECB and the member states will have much to learn in the years ahead about economic management in a single currency area." And tax harmonisation is likely to come onto the agenda, it said. "The advent of the euro is clearly a landmark in the development of the EU. It will throw other issues relating to the future of Europe into sharp focus." There were even approving noises across the Atlantic. An article in The New York Times marvelled that the same coins can now be used "to buy a cup of coffee and the morning paper in Amsterdam, Lisbon, Helsinki, Naples, Dublin and Dresden". The paper assessed the launch as "more than a breathtaking logistical challenge and financial milestone for Europe. It is also a day of great political significance. With euros in circulation, the process of European integration &endash; first championed half a century ago by a visionary French statesman named Jean Monnet &endash; acquires its most potent and tangible symbol". Can Europe avoid crisis? It is true that we underestimated the degree to which the European capitalists could arrive at a compromise and push towards greater economic and monetary unification. We did not think that the Euro would succeed to the degree that it has. We were wrong. The Euro has finally been introduced as a common currency in 12 of the EU states. This is an important development. A common currency is the first condition towards European integration. It ought to boost internal trade and thus act as a powerful stimulus to the development of the productive forces. Is this going to happen? The European capitalists display an amazing capacity for self-delusion. Only a few months ago they were boasting that they would avoid the recession. Now these boasts are shown to be hollow. Ironically, the worst affected sector is the communications industry (mobile phones), which was supposed to be the main motor of a new period of expansion for European capitalism. Vodafone, the big British mobile phone company, announced pre-tax losses of £8.4 billion ($12 billion) in the six months to the beginning of December 2001. Profits at Siemens, the German engineering giant, fell by 76 percent to the end of September, including restructuring charges and a write-down of assets in its mobile and fixed-line telephone divisions. German unemployment now stands officially at 8 percent of the workforce. The idea of the European capitalists that they will be able to insulate themselves against the cold winds of world recession through monetary union and a more thorough exploitation of the European market is a dream. The colossal development of world trade, and the huge weight of the world market, rules this out. Already, reports of a slight rally in US manufacturing have forced the euro to give up some of its gains against the dollar. And European industry is still mired in recession. Ray Attrill, research director at 4castweb.com, said the euro's exchange rate would still be led by performance of the euroland economy compared with the United States. "The exchange rate will be determined by the US business cycle and we believe the first quarter of the year will look quiet in the US while euroland is labouring, pushing the euro down to 85 cents," he said. (Independent, Jan. 3rd.) This is the real context in which the euro has been launched. Under conditions of world crisis, rising unemployment and a struggle for markets, the rigid framework of the Maastricht agreement will aggravate the crisis and increase the contradictions between the states of the EU. Question mark over the euro The Economist recently drew a negative balance of the Euro's achievements: "When the Euro was conceived a decade ago, there was much heady talk of how it would boost competition in Europe, of all the structural reforms it would promote, even of how Europe would displace America as the world's economic dynamo. Yet, as a recent report by the European Commission concluded, the gap between Europe and America in both productivity and GDP per head has widened rather than narrowed over the past decade. This year's theory that, thanks to the Euro, Europe would largely escape the effect of a global recession has also proved false, as its biggest economy, Germany, has shuddered to a halt. As if to trumpet Europe's failings, the Euro has spent most of its first three years of ethereal life testing new lows against the dollar." (The Economist, 1/12/2001) Contrary to the hopes of the European bourgeois, the Euro has been a weak currency from birth. The need to maintain its level is one of the reasons why interest rates in Europe have not been reduced as fast as in America. This will aggravate the crisis in Europe and increase unemployment in the coming months. Paradoxically, the Germans, who were the most adamant in demanding strict adherence to the Maastricht rules, are now suffering the consequences in the shape of four million unemployed. The German economy, which ought to act as the main motor-force for Europe, is hopelessly stalled. The stubborn refusal of Duisenberg and the European Bank to lower interest rates has set the stage for conflict between the Bank and the European governments. They would like to see a further fall in the Euro to boost exports - the main reason for the relative success of the countries of the Euro zone in the last period. But despite this success, the performance of the core countries, especially Germany and Italy has been miserable, and their problems will now increase. Unemployment is beginning to climb again. One effect of the introduction of a common currency will be to increase cross-border competition. The aim is to increase productivity by eliminating weak companies. But this places countries like Italy, Greece, Spain and Portugal at a disadvantage. Increased competition spells more bankruptcies, factory closures and unemployment. From this, new contradictions arise. In the past, Italy got out of difficulties by devaluing the currency. But this is now ruled out by the Maastricht agreement. Devaluations by nation states are not allowed, and neither is any other state permitted to help Italy. Therefore, the full weight of the crisis will be placed on the shoulders of the working class. The Italian employers are already putting pressure on Berlusconi to take action. The stage is thus being set for an explosion of the class struggle in one European country after another. This will lead, not to European integration, but to increased tensions and antagonisms between the national states. In the end, it is probable that the Euro experiment will break down amidst mutual recriminations. Already there are indications of conflict between the states in the Euro zone, as each government tries to protect its own capitalists against foreign competition. Contradictions between states Two years ago, at the Lisbon Summit, the EU heads of government agreed to a programme of further liberalisation with the aim of making the EU the world's most competitive economy by 2010. What has happened? France has implemented only minimal energy liberalisation and blocked the setting of any deadline for a total opening-up of the market. Full competition in the postal services has been delayed. Germany has put its boot through an EU directive on take-overs that took 12 years to work out and then introduced new rules to protect German owners. The Lamfalussy Plan to liberalise wholesale financial services has been sabotaged by procedural manoeuvering in the European parliament, even though it was unanimously endorsed in Stockholm in March. An agreement on a EU-wide patent regime has been prevented by disagreements on language policy. And so on and so forth. What this shows is that each national government, while paying lip service to the "ideal of European integration", is mainly concerned with the defence of "national interests" - that is to say, the interests of its own bourgeoisie. Thus, Germany's decision to sabotage the law on take-overs was dictated by its desire to protect its domestic companies against foreign take-overs - such as Vodafone's bid for Mannesmann. The French opposition to energy liberalisation has been designed to support its state-owned giant, Electricité de France. The French government protects its national monopoly, which is meanwhile pursuing an aggressive policy of taking over the companies of states with more open markets. Behind the "European" rhetoric stand the interests and ambitions of the most powerful European states, especially Germany and France, which seek to dominate Europe. Only the smaller countries take the rhetoric about the European ideal seriously, since they are too weak to stand on their own and foolishly imagine that they can be important players on the European scene. In addition, they have their own selfish interests to defend. Belgium benefits from being the main seat of the "European institutions" - which brings in a tidy sum to the national exchequer. They are therefore the most convinced "Europeans". The weaker economies like Greece, Portugal, Ireland and Spain are enthusiastic "Europeans" only to the extent that they have done very well out of European subsidies. But when these are sharply reduced or abolished, which is already happening, their enthusiasm will cool rapidly. And that is inevitable in the next period when the economic crisis begins to bite and Germany, which pays most of the bills, gets tired of this role. The truth is that the smaller states of Europe count for very little. This was shown recently in the aftermath of September 11. Britain (a semi-satellite of America) decided everything together with France and Germany. The others were not even invited to dinner in London. The Italians protested loudly. The others grumbled also: "We are being treated like candidates to join the EU. Decisions are made and then we are just informed." But that is just the real state of affairs. Only it is not supposed to be made public. Only Blair's characteristic crudity made it too obvious. The recent row at Laeken over the distribution of secondary EU institutions led to Berlusconi vetoing all decisions. When the Swedish Prime Minister complained that his country had got no institution, Chirac said maybe they "would like the headquarters for EU model agencies as they had such "pretty girls"! Such is the contempt shown for the smaller EU countries by the big Four. A further expansion of the EU will exacerbate the problem. Does anyone seriously believe that Germany, France and Britain will accept that they cannot have a discussion without inviting 22 other European leaders? The German capitalists are pushing for the entry of their client states in Eastern Europe: Poland and the Czech Republic. France, which is opposed to this, proposes the entry of Rumania. This is yet another example of the conflict of interests between Germany and France. In the end, it is likely that the expansion will go ahead. But in that case, the bigger EU states will find a way of dominating the show anyway. Britain's dilemma The launch of the new currency finds Britain as divided as ever on the issue of joining the euro zone. Newspapers in Britain delivered mixed verdicts on the euro. The reactionary chauvinist Sun's front page was devoted to what it called: "The dawn of a new error". The 12 European countries participating have taken "a giant leap in the dark" and "thank goodness Britain is not part of it", the newspaper said in a page one editorial. The Tory Daily Mail called the launch the "great euro gamble" and predicted it means "we'll all pay higher prices" as traders cash in on launch-time confusion to push up prices. The Daily Telegraph said it was a "leap into the unknown". And The Times said Britain would be wise to sit in its ringside seat "for some time". The ambiguous attitude of the British bourgeoisie to Europe and the Euro is explained by several factors. There is a sharp division between the manufacturing sector which trades with Europe and does not want a continuation of the high pound, and the parasitic finance sector based on the City that has grown immensely in power in recent years. The pound tumbled against the euro, as the successful launch of notes and coins raised hopes that British membership of the single currency was now more likely. The euro surged more than 2 per cent against sterling, its largest one-day gain to date, as it made gains across the board, when a feared chaotic launch of notes and coins failed to materialise. Against the dollar it hit a peak above the psychological 90 cents mark &endash; a gain of 1.85 per cent &endash; and hit a 27-month high against the Japanese yen. The sharp fall in the value of sterling against the euro raised hopes that British membership of the single currency was more likely. Most economists say, however, that the euro needs to rise significantly, to about 68p, to make entry possible - even if the five "economic tests" demanded by the British government as a condition for entry, are met. A further devaluation of the pound would suit the industrial wing of the British bourgeoisie, whose exports to Europe have been hit by the strong pound. They need the pound to fall against the euro in order to restore competitivity. Thus, shares in Corus Group, the UK's largest steelmaker, rose more than 6 per cent to a seven-month high after the news of the falling pound. The company recently said the pound needed to fall at least to ¤1.40 (or above 70p to the Euro), for it to compete with its continental rivals. Mark Miller, UK economist at Morgan Stanley, said he believed the anticipation of that announcement would push the euro towards an exchange rate of 70p, which he described as "fair", by the end of the year: "The successful transition to notes and coins and the movement against sterling suggests that as the assessment comes closer there is a real chance the pound will move closer to 70p, which does not look so distant now," he was quoted as saying in The Independent (Jan. 3rd). But other analysts warned that yesterday's movement &endash; the fourth New Year rally for the euro in four years &endash; was not necessarily the start of a long-term revival after three years of weakness. Since its launch as an electronic currency in January 1999, the euro has fallen 23 per cent against the dollar, 11 per cent against the yen and 12 per cent against the pound. They said the launch of notes and coins had little economic implication as they only made up 6 per cent of total euros in circulation. In short, the British ruling class is still split on the issue of the euro. The powerful financial sector favours a strong pound and is unconcerned at the plight of British manufacturing industry - already in recession - or the threat of rising unemployment. This wing of the bourgeoisie looks more to US imperialism than to Europe. Having lost its empire and being reduced to a second-rate power off the coast of Europe, the British ruling class is reluctant to relinquish its dreams of being a world power, and is hesitating between a role in Europe and that of a satellite of US imperialism. But the underlying weakness of the Euro and doubts about its future are undoubtedly important factors in its calculations. The future of Europe The main danger for the capitalist system is not the prospect of slump. The boom-slump cycle has been a constant feature of capitalism for the last 200 years. They know that sooner or later, they can get out of even the deepest slump. The real danger is the threat of the unravelling of free trade and the rise of protectionism as a result of the slump. This is what turned the slump of 1929-33 into a world depression which lasted until the Second World War. The expansion of world trade has played a vital role in the last half century, and particularly the last twenty years. It has enabled the capitalists, partially at least and for a temporary period, to overcome the limitations of the nation state. But the basis on which this rests is quite fragile and can easily be destroyed, especially under conditions of world slump in which they are all fighting for limited markets. Already there are tensions between Europe and America over trade which led to the breakdown of the Seattle talks. Although some issues have been resolved, new conflicts are emerging all the time. Particularly in the USA, protectionist tendencies are building up. America is the biggest economy in the world and is prepared to use its muscle to gain access to foreign makers, while protecting its own. It has benefited from lower trade barriers more than any other country, hence its public enthusiasm for free trade. But the Republicans in Congress (and the Democrats also) are ready to sacrifice the principle of free trade in order to protect American agricultural and manufacturing interests. At the moment the capitalists are driving on with "free trade" by proposing a new round of reductions in trade restrictions at the WTO meeting in Dohar). The last Uruguay Round took a decade to achieve. This one will be still born. The development of world recession will inevitably lead to an increase in protectionist tendencies which will threaten the fragile structure of world trade so carefully constructed over the past half century. This is the main fear of the strategists of capital. They have understood what the Marxists have long ago explained: namely, that the main motor-force of the world economy has been the growth of world trade ("globalisation"). Even in the period of the boom there has been a tendency for the world to fragment into rival blocs. US imperialism has created Nafta, including Canada and Mexico, which aspires to control the whole American continent, north and south of the Rio Grande. Europe has created the EU which strives to control North Africa, the Balkans and Eastern Europe. In Asia, Japan has created a weaker yen bloc. As the slump deepens, the contradictions between these rival trading blocs will increase. The tensions between Europe and America, and between America and Japan, will intensify under these conditions. America will attempt to export unemployment to Europe and Japan, provoking retaliation. The prospect opens up of trade wars and competitive devaluations which will deepen and prolong the crisis. The developing crisis will intensify the contradictions between the nation states of Europe, and particularly between Germany and France, with Britain manoeuvering between them. But it is unlikely that the EU will break up, because of the need to compete with the USA. The European capitalists must hang together, for fear of hanging separately. But the dream of a united Europe on a capitalist basis remains what Lenin said it was: a reactionary utopia. For the Socialist United States of Europe! The EU was formed after the Second World War because the weak capitalist powers of Europe were too small to maintain themselves against the might of the Soviet Union on the one side and the United States on the other. This was a tacit admission that the nation state had become a reactionary fetter on the development of the productive forces. In itself, the idea of pooling the productive resources of Europe is progressive. But on a capitalist basis it is utterly impossible to unite Europe. This is because the capitalists of Germany, France, Italy etc. put their own national interests first. They compete against each other, and occasionally wage war against each other. The only time Europe has been united on a capitalist basis was when Hitler reduced it to slavery. After the War, France and Germany arrived at a modus vivendi, with the idea of jointly dominating Europe. Initially, the French ruling class had the illusion that they could play the leading role, while tying Germany closely to France, in order to prevent a new war in Europe. However, it soon became evident that Germany, with her powerful industrial base, would be the dominant partner. Since then, the relation between the two states has been uneasy. In the future, it is inevitable that conflict will break out between them. In many ways, the national interests of France and Germany are in conflict: over the expansion to the East, agricultural policy, etc. Likewise, there are conflicts developing with all the other European states. Under conditions of slump, these antagonisms will tend to intensify. Thus, on a capitalist basis, Europe can never be united. Each national bourgeoisie jealously guards its own interests, markets, spheres of interest, army and so on. In order to achieve a genuine integration of Europe, it is first necessary to overthrow the rule of the big banks and monopolies. Only then will it be possible to introduce a genuine socialist plan of production for the whole of Europe, under the democratic control and administration of the workers and small farmers. The huge increase in the production of wealth made possible by a planned and harmonious utilisation of the productive forces would lay the basis for a general reduction of the working day - not just to 35 hours a week, but to 30 hours immediately, and steadily reducing after that. It would lay the basis for a cultural revolution which would put in the shade all the achievements of the Renaissance. Europe would be rescued from decades of ignoble decline and recover her former glory a centre of world civilization, and the pioneer of the new socialist world order.	https://www.bolshevik.info/launch-euro-european-unity030101/print.htm
$2,233 in 1900 → 2022 \| Inflation Calculator The 2.95% inflation rate means $2,233 in 1900 is equivalent to $77,797.68 in 2022. This inflation calculator uses the official US consumer price index. $2,233 in 1900 is worth $77,797.68 in 2022 Value of $2,233 from 1900 to 2022 $2,233 in 1900 is equivalent in purchasing power to about $77,797.68in 2022, an increase of $75,564.68 over 122 years. The dollar had an average inflation rate of 2.95% per yearbetween 1900 and 2022, producing a cumulative price increase of 3,384.00%. This means that prices in 2022 are 34.84 times as high as average prices since 1900, according to the Bureau of Labor Statistics consumer price index. The inflation rate in 1900 was 1.20%. The inflation rate in 2022 was 8.00%. The 2022 inflation rate is higher compared to the average inflation rate of 3.66% per year between 2022 and 2023. Contents Overview Buying Power of $2,233 Inflation by Country Inflation by Spending Category Formulas & How to Calculate Comparison to S&P 500 Index Data Source Inflation from 1900 to 2022 Cumulative price change 3,384.00% Average inflation rate 2.95% Converted amount $2,233 base $77,797.68 Price difference $2,233 base $75,564.68 CPI in 1900 8.400 CPI in 2022 292.656 Inflation in 1900 1.20% Inflation in 2022 8.00% $2,233 in 1900 $77,797.68 in 2022 USD inflation since 1900 Annual Rate, the Bureau of Labor Statistics CPI Buying power of $2,233 in 1900 This chart shows a calculation of buying power equivalence for $2,233 in 1900 (price index tracking began in 1635). For example, if you started with $2,233, you would need to end with $77,797.68 in order to "adjust" for inflation (sometimes refered to as "beating inflation"). When $2,233 is equivalent to $77,797.68 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 1900 dollars, the chart below shows how $2,233 is worth less over 122 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: 1900-2022 Year Dollar Value Inflation Rate 1900 $2,233.00 1.20% 1901 $2,259.58 1.19% 1902 $2,286.17 1.18% 1903 $2,339.33 2.33% 1904 $2,365.92 1.14% 1905 $2,339.33 -1.12% 1906 $2,392.50 2.27% 1907 $2,498.83 4.44% 1908 $2,445.67 -2.13% 1909 $2,419.08 -1.09% 1910 $2,525.42 4.40% 1911 $2,525.42 0.00% 1912 $2,578.58 2.11% 1913 $2,631.75 2.06% 1914 $2,658.33 1.01% 1915 $2,684.92 1.00% 1916 $2,897.58 7.92% 1917 $3,402.67 17.43% 1918 $4,014.08 17.97% 1919 $4,598.92 14.57% 1920 $5,316.67 15.61% 1921 $4,758.42 -10.50% 1922 $4,466.00 -6.15% 1923 $4,545.75 1.79% 1924 $4,545.75 0.00% 1925 $4,652.08 2.34% 1926 $4,705.25 1.14% 1927 $4,625.50 -1.69% 1928 $4,545.75 -1.72% 1929 $4,545.75 0.00% 1930 $4,439.42 -2.34% 1931 $4,040.67 -8.98% 1932 $3,641.92 -9.87% 1933 $3,455.83 -5.11% 1934 $3,562.17 3.08% 1935 $3,641.92 2.24% 1936 $3,695.08 1.46% 1937 $3,828.00 3.60% 1938 $3,748.25 -2.08% 1939 $3,695.08 -1.42% 1940 $3,721.67 0.72% 1941 $3,907.75 5.00% 1942 $4,333.08 10.88% 1943 $4,598.92 6.13% 1944 $4,678.67 1.73% 1945 $4,785.00 2.27% 1946 $5,183.75 8.33% 1947 $5,928.08 14.36% 1948 $6,406.58 8.07% 1949 $6,326.83 -1.24% 1950 $6,406.58 1.26% 1951 $6,911.67 7.88% 1952 $7,044.58 1.92% 1953 $7,097.75 0.75% 1954 $7,150.92 0.75% 1955 $7,124.33 -0.37% 1956 $7,230.67 1.49% 1957 $7,469.92 3.31% 1958 $7,682.58 2.85% 1959 $7,735.75 0.69% 1960 $7,868.67 1.72% 1961 $7,948.42 1.01% 1962 $8,028.17 1.00% 1963 $8,134.50 1.32% 1964 $8,240.83 1.31% 1965 $8,373.75 1.61% 1966 $8,613.00 2.86% 1967 $8,878.83 3.09% 1968 $9,251.00 4.19% 1969 $9,756.08 5.46% 1970 $10,314.33 5.72% 1971 $10,766.25 4.38% 1972 $11,111.83 3.21% 1973 $11,803.00 6.22% 1974 $13,105.58 11.04% 1975 $14,301.83 9.13% 1976 $15,125.92 5.76% 1977 $16,109.50 6.50% 1978 $17,332.33 7.59% 1979 $19,299.50 11.35% 1980 $21,904.67 13.50% 1981 $24,164.25 10.32% 1982 $25,652.92 6.16% 1983 $26,477.00 3.21% 1984 $27,620.08 4.32% 1985 $28,603.67 3.56% 1986 $29,135.33 1.86% 1987 $30,198.67 3.65% 1988 $31,448.08 4.14% 1989 $32,963.33 4.82% 1990 $34,744.42 5.40% 1991 $36,206.50 4.21% 1992 $37,296.42 3.01% 1993 $38,412.92 2.99% 1994 $39,396.50 2.56% 1995 $40,513.00 2.83% 1996 $41,709.25 2.95% 1997 $42,666.25 2.29% 1998 $43,330.83 1.56% 1999 $44,287.83 2.21% 2000 $45,776.50 3.36% 2001 $47,079.08 2.85% 2002 $47,823.42 1.58% 2003 $48,913.33 2.28% 2004 $50,215.92 2.66% 2005 $51,917.25 3.39% 2006 $53,592.00 3.23% 2007 $55,118.42 2.85% 2008 $57,234.71 3.84% 2009 $57,031.09 -0.36% 2010 $57,966.55 1.64% 2011 $59,796.28 3.16% 2012 $61,033.74 2.07% 2013 $61,927.74 1.46% 2014 $62,932.32 1.62% 2015 $63,007.02 0.12% 2016 $63,801.86 1.26% 2017 $65,161.07 2.13% 2018 $66,785.31 2.49% 2019 $67,962.29 1.76% 2020 $68,800.77 1.23% 2021 $72,032.90 4.70% 2022 $77,797.68 8.00% 2023 $80,644.00 3.66%* Download as CSV/Excel This conversion table shows various other 1900 amounts in 2022 dollars, based on the 3,384.00% change in prices: Conversion: 1900 dollars in 2022 Initial value Equivalent value $1 dollar in 1900 $34.84 dollars in 2022 $5 dollars in 1900 $174.20 dollars in 2022 $10 dollars in 1900 $348.40 dollars in 2022 $50 dollars in 1900 $1,742.00 dollars in 2022 $100 dollars in 1900 $3,484.00 dollars in 2022 $500 dollars in 1900 $17,419.99 dollars in 2022 $1,000 dollars in 1900 $34,839.98 dollars in 2022 $5,000 dollars in 1900 $174,199.90 dollars in 2022 $10,000 dollars in 1900 $348,399.80 dollars in 2022 $50,000 dollars in 1900 $1,741,999.01 dollars in 2022 $100,000 dollars in 1900 $3,483,998.02 dollars in 2022 $500,000 dollars in 1900 $17,419,990.08 dollars in 2022 $1,000,000 dollars in 1900 $34,839,980.16 dollars in 2022 Inflation by Country Inflation can also vary widely by country. For comparison, in the UK £2,233.00 in 1900 would be equivalent to £317,210.26 in 2022, an absolute change of £314,977.26 and a cumulative change of 14,105.56%. Compare these numbers to the US's overall absolute change of $75,564.68 and total percent change of 3,384.00%. 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 1900 and 2022. Compare these values to the overall average of 2.95% per year: Category Avg Inflation (%) Total Inflation (%) $2,233 in 1900 → 2022 Food and beverages 4.01 11,942.16 268,901.34 Housing 4.23 15,599.52 350,570.26 Apparel 1.99 1,001.33 24,592.70 Transportation 3.43 5,999.73 136,207.04 Medical care 4.68 26,484.00 593,620.74 Recreation 1.27 366.91 10,426.02 Education and communication 1.81 792.39 19,926.96 Other goods and services 4.98 37,272.19 834,521.09 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 1900. 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 $2,233, 1900 to 2022 Our calculations use the following inflation rate formula to calculate the change in value between 1900 and 2022: CPI in 2022 CPI in 1900 × 1900 USD value = 2022 USD value Then plug inhistorical CPI values. The U.S. CPI was 8.4 in the year 1900 and 292.65583333333 in 2022: 292.65583333333 8.4 × $2,233 = $77,797.68 $2,233 in 1900 has the same "purchasing power" or "buying power" as $77,797.68 in 2022. To get the total inflation rate for the 122 years between 1900 and 2022, we use the following formula: CPI in 2022 - CPI in 1900 CPI in 1900 × 100 = Cumulative inflation rate (122 years) Plugging in the values to this equation, we get: 292.65583333333 - 8.4 8.4 × 100 = 3,384% Comparison to S&P 500 Index The average inflation rate of 2.95% has a compounding effect between 1900 and 2022. As noted above, this yearly inflation rate compounds to produce an overall price difference of 3,384.00% over 122 years. To help put this inflation into perspective, if we had invested $2,233 in the S&P 500 index in 1900, our investment would be nominallyworth approximately $207,147,453.61in 2022. This is a return on investment of 9,276,543.69%, with an absolute return of $207,145,220.61 on top of the original $2,233. 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 97.13% of returns ($201,201,771.30) during this period. This means the inflation-adjusted realreturn of our $2,233 investment is $5,943,449.31. You may also want to account for capital gains tax, which would take your real return down to around $5,051,932 for most people. Investment in S&P 500 Index, 1900-2022 Original Amount Final Amount Change Nominal $2,233 $207,147,453.61 9,276,543.69% Real Inflation Adjusted $2,233 $5,945,682.31 266,164.32% 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 1900 to latest available data for 2022 using average monthly close price. For more details on the S&P 500 between 1900 and 2022, see thestock market returns calculator. 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. You may use the following MLA citation for this page: “$2,233 in 1900 → 2022 \| Inflation Calculator.” Official Inflation Data, Alioth Finance, 31 May. 2023, https://www.officialdata.org/us/inflation/1900?amount=2233&endYear=2022. Special thanks to QuickChart for theirchart image API, which is used for chart downloads. Ian Webster is an engineer and data expert based in San Mateo, California. He has worked for Google, NASA, and consulted for governments around the world on data pipelines and data analysis. Disappointed by the lack of clear resources on the impacts of inflation on economic indicators, Ian believes this website serves as a valuable public tool. Ian earned his degree in Computer Science from Dartmouth College.	https://www.officialdata.org/us/inflation/1900?amount=2233&endYear=2022
(PDF) Immunoglobulin-Specific Responses to Chlamydia Elementary Bodies in Individuals with and at Risk for Genital Chlamydial Infection PDF \| Renewed interest in chlamydia vaccination has revealed the need for a greater understanding of the seroprevalence of chlamydial infection in US... \| Find, read and cite all the research you need on ResearchGate Article Immunoglobulin-Specific Responses to Chlamydia Elementary Bodies in Individuals with and at Risk for Genital Chlamydial Infection October 2012 The Journal of Infectious Diseases206(12) DOI: 10.1093/infdis/jis621 Source PubMed Authors: <here is a image 1101322e41f74147-69258255c0ae782c> William Geisler University of Alabama at Birmingham <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sandra G Morrison University of Arkansas for Medical Sciences <here is a image f2f62089ad6ff61c-d19572ff1996375a> Martha L Doemland Martha L Doemland <here is a image f2f62089ad6ff61c-d19572ff1996375a> Shehzad M Iqbal Shehzad M Iqbal Abstract and Figures Renewed interest in chlamydia vaccination has revealed the need for a greater understanding of the seroprevalence of chlamydial infection in US populations. We used a Chlamydia trachomatis elementary body (EB)–based enzyme-linked immunosorbent assay to define the characteristics of the humoral immune response and to determine seroprevalence. Two groups were analyzed: one consisting of patients with current, laboratory confirmed, genital chlamydial infection (n = 98) and one group of individuals whose chlamydia infection history was unknown (n = 367). C. trachomatis seropositivity was detected in 90% of the infected group and in 31% of the chlamydia-unknown group. IgG1 and IgG3 comprised the predominant anti-Chlamydia serum antibody responses. Serum IgA1 responses were variably positive, and individuals were rarely positive for anti-chlamydia IgG2, IgG4 or IgA2. The magnitude of the IgG1 and IgG3 responses was greatest in female and African American individuals and was sustained for at least 6 months. Antibody responses were not serovar restricted or confounded by Chlamydia pneumoniae cross-reactivity. <here is a image 7b8115a82b0e8c3f-92510ba6fc51b006> . Characteristics of Study Populations … <here is a image c141b94a41435554-e9b3debf5c446d3c> Effect of race, sex, and prior Ct infection on IgG1 and IgG3 Ct EB ELISA responses. The IgG1 and IgG3 CT EB ELISA responses of the 88 seropositive patients from group 1 ( patients with current genital Ct infection) were compared to assess differences in responses between (A) African American vs white patients (IgG1: median OD, 1.61 vs 0.55 [P < .001]; IgG3: median OD, 1.96 vs 1.03 [P = .048]); (B) female vs male patients (IgG1: median OD, 1.58 vs 1.00 [P = .082]; IgG3: median OD, 1.95 vs 0.7 [P = .018]); and C, subjects with vs without prior Ct infection (as assessed by self-report or clinic record review); IgG1: median OD, 2.16 vs 1.26 [P = .013]; IgG3: median OD, 1.96 vs 1.32 [P = .029]). Data are presented as described in Figure 1 legend. … <here is a image 179303bc1d999e50-dd42e3df5167278f> Comparison of IgG1 and IgG3 Ct EB ELISA responses at the initial and 6-month follow-up visits. Data represent OD405 values of serum samples from 28 patients with current genital Ct infection who were seropositive at baseline and who had serum samples collected at a 6-month follow-up visit. Data are presented as described in Figure 1 legend. No statistically significant difference was found in the magnitude of the median IgG1 response of serum samples collected at the time of the initial visit and at 6 months after infection diagnosis and treatment (IgG1: median OD, 1.30 vs 1.20; P = .67), but the median IgG3 response decreased slightly during that period (IgG3: median OD, 1.90 vs 1.50; P = .015). … <here is a image ad267d1f3a982264-adcba202ebc67ac4> Seropositivity and immunoglobulin subclass-specific responses in patients with current genital Ct infection. Serum samples from 98 patients with current genital Ct infection (group 1) were analyzed using EB ELISA. Data for positive serum samples only are presented as box-and-whiskers graphs of OD405 values. The box extends from the 25th percentile to the 75th percentile, with the median response indicated by the horizontal line within the box. Whiskers represent the range of responses from minimum to maximum for positive serum samples. The broken line (---) indicates the cutoff OD value for a positive response. The number of patients who tested negative for a given response is indicated beneath the cutoff line. IgG1 (shaded boxes), IgG3 (open boxes), and IgA1 (lined boxes) responses are indicated on the graph. … <here is a image ef20c43b367fe857-4d3b9a83b868a218> +1 Relationship of Cp seropositivity to Ct seropositivity. Serum samples from all 367 group 2 patients (Ct infection status unknown) were tested using a Cp EB ELISA, and the results of the IgG1 responses are plotted along with the Ct IgG1 EB ELISA results. Each dot represents a single patient. Ct EB ELISA OD405 values are plotted along the x axis, and the Cp EB-ELISA values are plotted along the y axis. Cutoff values for seropositive Ct (OD405 ≥ 0.4) and Cp (OD405 ≥ 0.5) EB ELISA responses are indicated by the dashed lines (––). … MAJORARTICLE Immunoglobulin-Speci ﬁ cResponsesto Chlamydia ElementaryBodiesinIndividuals withandatRiskforGenitalChlamydial Infection WilliamM.Geisler, 1 SandraG.Morrison, 3 MarthaL.Doemland, 4,a ShehzadM.Iqbal, 5 JinSu, 5 AusraMancevski, 5 EdwardW.HookIII, 1,2 andRichardP.Morrison 3 1 DivisionofInfectiousDiseases,DepartmentofMedicine,UniversityofAlabamaatBirmingham; 2 JeffersonCountyDepartmentofHealth, Birmingham,Alabama; 3 DepartmentofMicrobiologyandImmunology,UniversityofArkansasforMedicalSciences,LittleRock; 4 Sano ﬁPasteur, Swiftwater,Pennsylvania;and 5 Sano ﬁ Pasteur,Toronto,Ontario,Canada Renewedinterestinchlamydiavaccinationhasrevealedtheneedforagreaterunderstandingoftheseropreva- lenceofchlamydialinfectioninUSpopulations.Weuseda Chlamydiatrachomatis elementarybody(EB) – basedenzyme-linkedimmunosorbentassaytode ﬁ nethecharacteristicsofthehumoralimmuneresponseand todetermineseroprevalence.Twogroupswereanalyzed:oneconsistingofpatientswithcurrent,laboratory con ﬁ rmed,genitalchlamydialinfection( n =98)andonegroupofindividualswhosechlamydiainfection historywasunknown( n =367). C.trachomatis seropositivitywasdetectedin90%oftheinfectedgroupand in31%ofthechlamydia-unknowngroup.IgG1andIgG3comprisedthepredominantanti- Chlamydiaserum antibodyresponses.SerumIgA1responseswerevariablypositive,andindividualswererarelypositivefor anti-chlamydiaIgG2,IgG4orIgA2.ThemagnitudeoftheIgG1andIgG3responseswasgreatestinfemale andAfricanAmericanindividualsandwassustainedforatleast6months.Antibodyresponseswerenot serovarrestrictedorconfoundedby Chlamydiapneumoniae cross-reactivity. Chlamydiatrachomatis (Ct)infectionisthemostcom- monlyreportedsexuallytransmittedbacterialinfection intheUnitedStates,with>1.3millioncasesreported in2010[ 1 ].However,becausemanyinfectionsgoun- detectedorunreported,theactualincidenceofCtin- fectionintheUnitedStatesisestimatedtobe2.8 millioncasesannually[ 2 ].GenitalCtinfectionis readilydiagnosedbyanucleicacidampli ﬁ cationtest (NAAT)andiseffectivelytreatedwithantibiotics. However,becausemostCtinfectionsareasymptomat- icandmanyinfectionsgoundiagnosed,screeningpro- gramshavebecomeanessentialcomponentof chlamydiapreventionstrategies.Withouteffectivean- tibiotictherapy,asymptomaticinfectionsmaypersist forlongperiodsandleadtoseriouscomplications and/orfurthertransmissiontosexpartners[ 3 ].Al- thoughchlamydiascreeningprogramshavebeen showntobeeffectiveinreducingpelvicin ﬂ ammatory diseaseincidence[ 4 ],theycurrentlyreachlessthan halfofthewomenforwhomscreeningisrecommend- ed(routinescreeningofmalesisnotcurrentlyrecom- mended),andCtinfectionremainshighlyprevalent [ 1 , 5 ].Thus,althoughchlamydiascreeningandtreat- mentstrategiesreducetheincidenceofreproductive sequelae,otherpreventionstrategies,suchasvaccina- tion,areneededtocontrolCtinfection. EvaluationofCtvaccineswillrequireamorethor- oughunderstandingofthenaturalhistoryofinfection, theimmuneresponseselicitedafterinfection,andthe Received26April2012;accepted17July2012;electronicallypublished8 October2012. Presentedinpart:5thBiennialConferenceoftheChlamydiaBasicResearch Society,RedondoBeach,CA,18 – 21March2011. a PresentAf ﬁ liation:Exponent,Washington,DC. Correspondence:RichardP.Morrison,DepartmentofMicrobiologyandImmu- nology,UniversityofArkansasforMedicalSciences,4301WMarkhamSt,Slot 511,LittleRock,AR72205-7194([email protected]). TheJournalofInfectiousDiseases2012;206:1836 –43 ©TheAuthor2012.PublishedbyOxfordUniversityPressonbehalfoftheInfectious DiseasesSocietyofAmerica.Allrightsreserved.ForPermissions,pleasee-mail: [email protected]. DOI:10.1093/infdis/jis621 seroprevalenceofthetargetpopulation.Theproportionofthe USpopulationwhohashadCtinfectionisnotknown,nor canitbeinferredfromavailablescreeningandcasereport data.CharacterizingtheCt-speci ﬁ cantibodyclass-and subclass-speci ﬁ cresponseselicitedafterinfectionwillprovide informationneededtodetermineseroprevalenceandtoesti- matebothtargetandeligiblepopulationsforinclusionin vaccinetrials.Inaddition,acentralroleforantibodyinpro- tectiveimmunityhasemergedfromstudiesusingthemurine genitalchlamydialinfectionmodel[ 6 – 8 ],whichprovidesan impetusforfurtherinvestigationstocharacterizeantibodyre- sponseselicitedafterhumanCtinfection.Inthisstudy,the speci ﬁ cityandusefulnessofanelementarybody –based enzymelinkedimmunosorbentassay(EBELISA)forcharac- terizingCt-speci ﬁ cIgclassandsubclassresponsesinindividuals withlaboratory-con ﬁ rmedgenitalCtinfectionwasdemon- strated.TheperformanceoftheEBELISAwascomparedwith acommercialCtELISAandwasusedtomeasuretheseropre- valenceamonghealthyfemalesinBirmingham,Alabama. MATERIALSANDMETHODS StudyPopulations Twogroupsofindividualsevaluatedusedinthisstudy.Group1 consistedof98patientswithlaboratory-con ﬁ rmedgenitalCt infection.Thesepatientshadbeenrecentlyscreenedforsexually transmitteddiseases(STDs)andweresubsequentlyreturningto theJeffersonCountyDepartmentofHealth(JCDH)STDclinic inBirmingham,Alabama,fortreatmentofapositivegenitalCt nucleicacidampli ﬁ cationtest(NAAT;Gen-ProbeAptima Combo2Assay;Gen-Probe).Atthetimeoftheirreturn,serum sampleswerecollectedaspartofachlamydianaturalhistory study.Forthosepatients,ahistoryofCtinfectionwassought throughself-reportandreviewoftheclinicrecordforpriorpos- itiveCttestresults.Asubgroupofgroup1,consistingof32 patients,alsohadserumsamplescollectedata6-monthfollow- upvisit,allowingforevaluationofchangesinserologicalre- sponsesoverthatperiod.Group2,theseroprevalencestudy group,consistedof367adultfemales(age,18 – 30years)from theBirmingham,Alabamacommunitywhosepriorandcurrent Ctinfectionstatuswasunknownandwhohadserumsamples collectedatthetimeofscreeningforaphaseIIIgenitalherpes vaccinetrial[ 9 ].Demographic,clinical,andbehavioraldata werecollectedfromgroup1patients,butonlydemographic datawerecollectedforgroup2individuals(Table 1 ).Approval forthisstudywasobtainedfromtheInstitutionalReview BoardsoftheUniversityofAlabamaatBirminghamandthe UniversityofArkansasforMedicalSciences. PreparationofELISAAntigen Elementarybodies(EBs)ofCtserovarsD/UW-3,F/IC- Cal-13,andJ/UW-36,representingserovarsfromeachofthe 3Ctserogroups(B,intermediate,andCserogroups,respec- tively),and Chlamydiapneumoniae (Cp)strainAR39were grownincellculture,densitygradientpuri ﬁ ed[ 10 ],andused asantigenintheEB-ELISA.Puri ﬁ edEBpreparationswere ﬁ xedovernightat4°Cin10mMphosphate-bufferedsaline (PBS)containing0.2%formalin.After ﬁ xation,EBswere washedoncewithPBSandresuspendedinPBSwith0.02% formalin.ForCtELISAantigen,equalvolumesofeachforma- lin- ﬁ xedserovar(2mg/mL)werecombinedtomakea2mg/ mLmixtureofserovarsD,F,andJ.Formalin- ﬁ xedCpEBs werepreparedsimilarly.Ninety-six – wellImmunlon2HBU- bottomsplates(ThermoScienti ﬁ c)werecoatedwith2µgEB/ well(100µLof20µgEB/mL)foruseintheELISA EB-ELISA AntibodyresponsestoCtandCpwereassessedusinganEB ELISAasdescribedpreviously[ 11 ].Anti-CtorCpimmu- noglobulin(Ig)class-andsubclass-speci ﬁ cresponseswere detectedusingthefollowingalkalinephosphatase – labeled anti-humanIgmonoclonalantibodiesandSigmaFastp-nitro- phenylphosphatesubstrate(1mg/mL;Sigma):anti-IgM (cloneSA-DA4;SouthernBiotech),anti-IgG(cloneJDC-10; SouthernBiotech),anti-IgG1(apoolofclones4E3,Southern Biotech;andHP6069;CalBiochem),anti-IgG2(clone31-7-4; SouthernBiotech),anti-IgG3(cloneHP6050;Southern Table1.CharacteristicsofStudyPopulations Group1Group2 Characteristic CurrentGenitalCt Infection a CtInfectionStatus Unknown b Groupsize(n)98367 Medianage(range)23(17 – 54)21(18 –30) Sex Female86(88%)367(100%) Male12(12%)0(0%) Race AfricanAmerican80(82%)142(39%) White18(18%)219(60%) Hispanic0(0%)1(0.3%) Asian0(0%)5(1.4%) Mediansexpartners 6months 1(1 – 15)NA c Priorchlamydia45(46%)NA Urethritis d 5(42%)NA Cervicitis e 19(22%)NA Hormonalcontraceptive usee 28(33%)NA a PatientswithcurrentgenitalCtinfectionasdiagnosedbyaCtNAAT. b TheCtinfectionstatusofpatientsinthisgroupisunknown. c NA=datanotavailable. d Dataformalesonly. e Dataforfemalesonly. HumanAntibodyResponsetoChlamydia • JID2012:206(15December) •1837 by guest on December 26, 2015 http://jid.oxfordjournals.org/ Downloaded from didnotreachstatisticalsigni ﬁ cance(medianOD,1.58vs1.00; P =.082)(Figure 2 B ).PatientswithahistoryofCtinfection (eitherbyself-reportingorbydocumentationthroughmedical recordreviewforpositivetestresults)hadhigherIgG1 (medianOD,2.16vs1.26; P =.013)andIgG3responses(1.96 vs1.32; P =.029)thandidthosereportingnohistoryofinfec- tion(Figure 2 C ),andanti-CtIgG3responsesweresigni ﬁ cantly higherinfemaleswithacervicitisdiagnosis(2.90vs1.72; P =.018).Antibodyresponsesdidnotsigni ﬁ cantlydifferby ageorhormonalcontraceptiveuse. Seroprevalencewasalsoassessedusingacommercialimmu- noassay(Medac).Seventy-two(73%)of98patientswith currentgenitalCtinfectiontestedseropositiveusingthecom- mercialimmunoassay,comparedwith90%seropositivebyour CtEBELISA.Ofthe72patientsseropositivebythecommer- cialimmunoassay,71(99%)werepositivebyCtEBELISA.A numberoffemalepatients(11[14%]of78)whowereCt NAATpositiveandCtEBELISApositivetestednegativeby thecommercialassay,andtheCtEBELISAmissed1patient (1.3%)whowaspositivebythecommercialimmunoassay. Five(46%)of11maleswithcurrentgenitalCtinfectiontested seronegativebycommercialimmunoassay,butall(11)tested seropositivebyCtEBELISA.Thus,morepatientswith currentCtinfectiontestedseropositivebyCtEBELISAthan bythecommercialimmunoassay. TenpatientswithcurrentgenitalCtinfectiontestedsero- negativebyEBELISA.Tofurtherevaluatetheirseronegativity andtodemonstratethattheseronegativeresponsesdidnot resultfromunder-representationofCtserovarsintheantigen mixture,weanalyzedserumsampleswithuseofadditional serovarmixtures.Wetestedtheserumsamplesfromgenital Ct – positivepatientsfromwhomwehadperformedCt ompA genotypingtoidentifytheinfectingserovar.Nostatistically signi ﬁ cantdifferenceswerefoundinantibodyresponseswhen serumsamplesweretestedbyEBELISAusingeitherpooled (serovarsD,F,andJ)orinfection-matchedserovarEB antigen,evenwhentheinfectingserovarwasnotincludedin thepooledEBantigenpreparation.Furthermore,the10 genitalCt – positivepatientswhowereseronegativebyCt ELISAusingpooledserovarD,F,andJEBsasantigenalso testedseronegativewithotherserovarmixtures.Collectively, seronegativeresponsesdonotappeartoresultfromfailureof CtELISAtodetectpositiveantibodyresponsesforpatients withinfectingserovarsnotrepresentedintheEBantigen mixture. CtSeropositivityata6-MonthFollow-upVisit Asubsetof32patientsfromthegroupof98patientswith currentgenitalCtinfection(group1)hadserumsamplescol- lectedduringa6-monthfollow-upvisit(medianfollow-up, 168days;range,106 – 245days),atwhichtimearepeatCt NAATwasperformed;allpatientsreceivedtreatmentattheir initial(baseline)visit,and4(13%)wereCtpositivebyNAAT atthefollow-upvisit.Testingserumsamplesfromthefollow- upvisitenabledustoevaluatechangesinCtserumantibody Figure2. Effectofrace,sex,andpriorCtinfectiononIgG1andIgG3 CtEBELISAresponses.TheIgG1andIgG3CTEBELISAresponsesof the88seropositivepatientsfromgroup1(patientswithcurrentgenital Ctinfection)werecomparedtoassessdifferencesinresponsesbetween ( A )AfricanAmericanvswhitepatients(IgG1:medianOD,1.61vs0.55 [ P <.001];IgG3:medianOD,1.96vs1.03[ P =.048]);( B )femalevsmale patients(IgG1:medianOD,1.58vs1.00[ P =.082];IgG3:medianOD, 1.95vs0.7[ P =.018]);andC,subjectswithvswithoutpriorCtinfection (asassessedbyself-reportorclinicrecordreview);IgG1:medianOD, 2.16vs1.26[ P =.013];IgG3:medianOD,1.96vs1.32[ P =.029]).Data arepresentedasdescribedinFigure 1legend. HumanAntibodyResponsetoChlamydia • JID2012:206(15December) •1839 by guest on December 26, 2015 http://jid.oxfordjournals.org/ Downloaded from responsesovertimeandtherelationshipofthoseresponsesto recurrentgenitalCtinfection.CtEBELISAIgG1,IgG3,and IgAresponseswerecomparedamongserumsamplescollected attheinitialand6-monthfollow-upvisits.Twenty-eight (88%)wereseropositiveforIgG1andIgG3attheirinitialvisit, with18ofthe28alsotestingpositiveforCtIgA.All28pa- tientswhowereIgG1andIgG3seropositiveatinitialvisitre- mainedseropositiveatfollow-up,andonly11(61%)of18 IgA-positivepatientsremainedCtIgApositiveatfollow-up. ThemedianCtEBELISAIgG1responsewasstablebetween initialandfollow-upvisits(medianOD,1.30vs1.20; P =.67), butthemagnitudeofthemedianIgG3responsediminished slightlyduringthatperiod(medianOD,1.90vs1.50; P =.015) (Figure 3 ).FourpatientswereseronegativebyCtEBELISA andMedacatbothbaselineandfollow-upvisits,despite havingapositivebaselinegenitalCtNAATresult.Although theIgG1andIgG3antibodyresponsestoCtappearstobe durable,itwasnotpossibletoknowwhethertherelativestable serologicresponseoverthe6-monthperiodwasattributable speci ﬁ callytothedurabilityoftheantibodyresponsefromthe initialinfectionorwhetherre-exposure/re-infectionduring thefollow-upperiodservedtomaintaintheantibodyre- sponse.However,weobservednoupwardtrendinthemagni- tudeoftheantibodyresponsesinthe4patientswhowereCt positiveatthe6-monthfollow-up. CtSeroprevalenceandImmunoglobulinSubclass-Speci ﬁ c ResponsesinPatientswithUnknownCtInfectionStatus Characteristicsofthe367patientswhosepriorandcurrentCt infectionstatuswasunknownareprovidedinTable 1 .One hundredthirteen(31%)of367patientstestedCtseropositive byEBELISA.Ofthe113seropositivepatients,89(79%)were IgG1positive(medianODreading,1.25;range,0.404 – 4.1),96 (85%)wereIgG3positive(medianOD,1.03;range,0.203 – 4.1),and43(38%)wereIgApositive(medianOD,0.471; range,0.30 – 1.71)(Figure 4 A ).Thus,thefrequencyofIgclass andsubclassCt-speci ﬁ cantibodyresponsesinthisgroupwas similartothatseeninpatientswithcurrentgenitalCtinfec- tion(group1).TheIgG1andIgG3EBELISAcapturedallbut Figure3. ComparisonofIgG1andIgG3CtEBELISAresponsesatthe initialand6-monthfollow-upvisits.DatarepresentOD 405 valuesof serumsamplesfrom28patientswithcurrentgenitalCtinfectionwho wereseropositiveatbaselineandwhohadserumsamplescollectedata 6-monthfollow-upvisit.DataarepresentedasdescribedinFigure 1 legend.Nostatisticallysigni ﬁ cantdifferencewasfoundinthemagnitude ofthemedianIgG1responseofserumsamplescollectedatthetimeof theinitialvisitandat6monthsafterinfectiondiagnosisandtreatment (IgG1:medianOD,1.30vs1.20; P =.67),butthemedianIgG3response decreasedslightlyduringthatperiod(IgG3:medianOD,1.90vs1.50; P =.015). Figure4. Ctseropositivityandimmunoglobulinsubclass-speci ﬁ cre- sponsesinpatientswithunknownchlamydiainfectionstatus(group2). Thestudypopulationconsistedof367adultfemaleswhosepriorand currentCtinfectionstatuswasunknown.Dataarepresentedasde- scribedinFigure 1 legend.( A )theIgG1,IgG3,andIgA1CtEBELISA responsesofseropositivepatients.Thenumberofpatientstestingsero- negativeforeachspeci ﬁ cIgsubclassisindicatedbelowthepositiveOD cutoffvalue.( B )comparisonofIgG1andIgG3responsesofseropositive group2AfricanAmericanvswhitepatients(totalof112IgG1orIgG3 seropositivepatients;IgG1:medianOD,1.43vs0.36[ P <.001];IgG3: medianOD.1.03vs0.35[ P =.011]). 1840 • JID2012:206(15December) • Geisleretal by guest on December 26, 2015 http://jid.oxfordjournals.org/ Downloaded from	https://www.researchgate.net/publication/232223771_Immunoglobulin-Specific_Responses_to_Chlamydia_Elementary_Bodies_in_Individuals_with_and_at_Risk_for_Genital_Chlamydial_Infection
Public register of Aquaculture Production Businesses in England and Wales Public register of Aquaculture Production Businesses in England and Wales Molluscs Aquaculture production business: Filter:ALL3ABCDEFGHIJKLMNOPQRSTUVWYZ Angle Bay (Woolmer) (MILFORD HAVEN) Appledore Fish Dock - Purification Centre (BIDEFORD) Aquafish Solutions - River Exe (EXMOUTH) Atlantic Edge Shellfish Purification Centre (PEMBROKE) Bangor University - Menai Bridge (MENAI BRIDGE) Barn - Purification Centre, The (TIVERTON) Belbin Purification Centre (COLCHESTER) Berghiaonline (LEEDS) Bincleaves Site A (WEYMOUTH) Blackwater Estuary - Dawson (COLCHESTER) Blackwater Estuary - Haward (COASTAL) Blakeney Harbour - Athill (BLAKENEY) Blakeney Oysters - Purification Centre (MELTON CONSTABLE) Bob Hall Sands - Frary (WELLS-NEXT-THE-SEA) Brancaster - Large (KING'S LYNN) Brancaster - Loose & Sons (KING'S LYNN) Brancaster - R E Loose (KING'S LYNN) Brancaster - Southerland (KING'S LYNN) Brancaster Harbour (KING'S LYNN) Brancaster Oysters Purification Centre (KING'S LYNN) Brancaster Staithe - Purification Centre (KING'S LYNN) Brancaster Staithe (C Southerland) - Purification Centre (KING'S LYNN) Brancaster Staithe (T Large) - Purification Tanks (KING'S LYNN) Brancaster Staithe (T Loose) - Purification Centre (KING'S LYNN) Bridlington Harbour (BRIDLINGTON) Brixham Sea Farms - Purification Centre (BRIXHAM) Butley Creek (WOODBRIDGE) Butley Orford Oysterage - Purification Plant (WOODBRIDGE) Câr-Y-Môr 'For the Love of the sea' (PEMBROKE) Congdon - Long Wood (DARTMOUTH) Conwy Mussel Company - Purification Centre (CONWY) Cornish Native Oysters - Purification Centre (FALMOUTH) Deganwy & Conwy Marina (CONWY) Dorset Oyster Ltd - Purification Centre (POOLE) Dorset Shellfish Co - Purification Centre (POOLE) Earlmaur Shellfish - Purification Centre (ALRESFORD) Early Creek (WOODBRIDGE) East Quay End Point - Purification Centre (WELLS-NEXT-THE-SEA) Fal Fishery Cooperative CIC (TRURO) Fishcoombe - Brixham Harbour (COASTAL) Fleet Oyster Farm - Purification Centre (WEYMOUTH) Fleet Oyster Farm (WEYMOUTH) Fowey Shellfish Co - Purification Centre (FOWEY) Frank Greenslade Ltd - Purification Centre (POOLE) Freiston Shore Shellfish - Purification Centre (BOSTON) Goldhanger and Lawling Creek (MALDON) Gower Coast Seafoods - Purification System (SWANSEA) Harbour Garden Cafe - Purification Centre, The (WHITSTABLE) Helford River (FALMOUTH) HMS EXCELLENT - Whale Island (PORTSMOUTH) Hollow Shore Fisheries - Purification Centre (FAVERSHAM) Inside Earl Stones () Institute of Marine Sciences (IMS) (PORTSMOUTH) Labrador Bay - Sessions (TEIGNMOUTH) Langstone Harbour - Milton Lake (CHICHESTER) Lindisfarne Oysters - Purification Centre (BELFORD) Lindisfarne Oysters (BELFORD) Lordship - Rock Oysters, The (LONDON) Lyme Bay Sites 1, 2, 3 (COASTAL) Lympstone Lake (EXMOUTH) Lynn Shellfish Ltd - Purification Centre (KING'S LYNN) Maldon (Essex) Oyster Company Ltd Purification Centre (CHELMSFORD) Menai - Krijnen (LLANFAIRPWLLGWYNGYLL) Menai Oysters - Purification Centre (LLANFAIRPWLLGWYNGYLL) Menai Strait East (Fishery Order) (BANGOR) Mumbles Road (SWANSEA) North Farm - Purification Centre (COLCHESTER) Offshore Experimental Shellfish Site (MENAI BRIDGE) Old Quarry - Purification Centre, The (PLYMOUTH) Othniel Oysters (POOLE) Oyster Perch - Redsands (MINEHEAD) Oyster Shack - Purification Centre, The (KINGSBRIDGE) Paglesham Pool (COASTAL) Poole Fishery Order (POOLE) Porlock Bay Oysters - Purification Centre (MINEHEAD) Port Hamble Marina (SOUTHAMPTON) Port of Blyth (BLYTH) Porthallow (COASTAL) Queens Dock Purification Centre - 360 (SWANSEA) Queens Dock Swansea - 360 (SWANSEA) Richard Haward (Oyster House) - Purification Centre (COLCHESTER) Richard Nicolas - Purification Centre (LLANELLI) River Avon/Aveton Gifford (KINGSBRIDGE) River Camel - Porthilly Shellfish (COASTAL) River Colne - Kerrison (COLCHESTER) River Crouch - Cliff Reach & Ray Pits & Roach 6 (BURNHAM-ON-CROUCH) River Crouch - Purification Centre (CHELMSFORD) River Dart Mollusc Farming Area (DARTMOUTH) River Exe - Exmouth Mussels (EXMOUTH) River Fal - Rawle (COASTAL) River Roach Oyster Fishery (ROCHFORD) River Teign - Sessions (TEIGNMOUTH) River Yealm Estuary (COASTAL) Roosebeck Foreshore -Seasalter -Walney (BARROW-IN-FURNESS) Rossmore Oysters Ltd - Purification Centre (CRAWLEY) S & J Wass - West Mersea (COLCHESTER) Saggiomo Luxury Foods - Purification Centre (CROYDON) Sailors Creek Shellfish - Purification Centre (FALMOUTH) Scallop Hatchery (BRIXHAM) Scarborough Harbour (SCARBOROUGH) Seasalter Foreshore (WHITSTABLE) Selsea Fish & Lobster Co Ltd - Purification Centre (CHICHESTER) Short Meals Creek (KING'S LYNN) Solent Seafood Ltd - Purification Centre (PORTSMOUTH) South Walney Island -Seasalter - Walney Ltd (BARROW-IN-FURNESS) Spurn Point (HULL) St Austell Bay - Rawle (COASTAL) St Austell Bay – Ropehaven West & South Mevagissey (ST. AUSTELL) Staithes harbour (SCARBOROUGH) Steinvora Mussels - Purification Centre (KING'S LYNN) Sunderland Marina (SUNDERLAND) Tollesbury & Mersea (Blackwater) Fishery Order, The (MALDON) Tollesbury and Salcott -William Baker (MALDON) Tollesbury, Little Ditch and Salcott (COASTAL) Tor Bay Scallop Nursery (TORQUAY) Torridge Oysters - Purification Centre (BIDEFORD) Torridge Oysters - River Torridge (COASTAL) Wash Fisheries Order, The (BOSTON) West Mersea Oysters - Purification Centre (COLCHESTER) West Whelks - Purification Centre (WHITSTABLE) Westcountry Mussels - Purification Centre (FOWEY) Whitby Harbour (WHITBY) Whitstable Bay Between Pollard and Street (WHITSTABLE) Whitstable Oyster Fishery Co - Purification Centre (WHITSTABLE) Wild Harbour Fish Company - Purification Centre (HAYLE) Wild Oyster Company - Purification Centre, The (TRURO)	https://www.cefas.co.uk/eu-register/molluscs/?id=3134442
Family and personal life - MemoryBC Family and personal life 589 archival descriptions results for Family and personal life Sonner family fonds Add to clipboard CA VHEC RA010 · Fonds · 1916-2007 Collection consists of vital records, administrative documents, original drawings, publications, educational certificates, academic papers, photographs, correspondence, letters of reference and audio-visual testimony relating to the life and work of Eric and Rose Sonner. Records detail the vital statistics, career history, education, travels and emigration efforts of the family from the late 1940s until the mid-2000s. Collection has been arranged into the following series: Terezín (1942–1945); Prague (1946–1949); Academic works (horticulture) (1947–1950); Correspondence and ephemera (1949–2000); Vital statistics records (Canada) (1949–2007); Eric Sonner testimony ([194-]–[before 2009]); and Photographs ([192-], 2016). Sonner family Bick family fonds Add to clipboard CA VHEC RA012 · Fonds · 1868-2002 Fonds consists of photograph albums, loose photographs, books, memoir, table cloth and official documents relating to the lives of members of the Bick family. Fonds has been arranged into the following series: Werner Bick memoir series (2002), Prayer books series (1868–1933), Bick family photographs series ([1891?]–[200-]), Siegfried and Johanna Bick emigration documents series (1938–1939) and Household object series ([before 1979]). Bick family Jennie Phillips fonds Add to clipboard CA VHEC RA013 · Fonds · [1912?]-1987 Fonds consists of photographs, vital records, personal notes, transcribed songs, correspondence and ephemera relating to the life of Jennie Phillips. Fonds has been arranged into the following series: JP photographs series (1912–1982), JP vital records series (1953–1979), JP personal papers series (1946–1987), Transcribed ghetto and camp songs series (1946), Stutthof Museum correspondence series (1984–1985) and JP ephemera series (1972). Phillips, Jennie Baltuch, Schmucker family fonds Add to clipboard CA VHEC RA015 · Fonds · [188-]–[before 1994] Fonds consists of photograph albums and loose photos, personal records, passports, financial records, reparation and compensation claims forms, correspondence, notebooks and notes, ephemera and published materials relating to the lives of the Baltuch and Schmucker families before, during, and after the Second World War. Fonds has been arranged into the following series: Baltuch, Schmucker family photographs series ([188-]–1964); Baltuch, Schmucker family personal records series (1906–1961); Josef and Rosa Baltuch emigration and immigration documents series (1943–1961); Household and financial records (1919–1984); Rosa Baltuch reparation and compensation documents series (1934–1966); Baltuch, Schmucker family correspondence series ([before 1941]–1980); Notebooks and notes series ([before 1994]); Baltuch, Schmucker family ephemera series ([before 1994]); Baltuch, Schmucker family artefacts series ([before 1994]); and Baltuch, Schmucker family collected books series (1930–1980). Baltuch, Schmucker family Alexander and Gina Dimant fonds Add to clipboard CA VHEC RA016 · Fonds · [1920?]–2019 Fonds is comprised of correspondence, photographs, identity and personal documents, society registration documents, minutes, clippings, memorabilia and ephemera created or collected by Alexander and Gina Dimant in Poland, the Union of Soviet Socialist Republics (USSR), Italy and Canada. Records pertain to their family history, work, school, and social and volunteer activities prior to and after the Second World War.Records have been arranged into the following series: Correspondence (1941–2019), Photographs ([1920?]–[2016], Personal records (1938–2013), Artefacts (1940–[before 1948], 1997), Clippings and ephemera ([after 1942]–2016) and Janusz Korczak Association of Canada records (2001–2008). Dimant family Dr. Leon Komar collection Add to clipboard CA VHEC RA022 · Fonds · 1938-1942 Collection consists of materials relating to Warsaw, Poland, in the Second World War era. Records include correspondence from Komar's family living in the Warsaw ghetto, documents showing a German leaflet dropped on Warsaw in 1938 and accompanying translations and commentary by the donor. Collection has been arranged into two series: German leaflet dropped from planes ([1939?], 1990) and Letters from the Warsaw ghetto (1938-1942; 1996). Komar, Leon Teitelbaum, Buckman family fonds Add to clipboard CA VHEC RA023 · Fonds · [194-]-1974 Fonds consists of records relating to the pre- and post-war experience of Rebecca (née Buckman) Teitelbaum, Herman Teitelbaum and their family. Fonds is arranged into five series: Notebooks (1944-1945), Correspondence (1944-1945), Identification and related records (1938-1974), Photographs ([1941]-1947) and Objects [1944]. Teitelbaum, Rebecca Louise Stein Sorensen fonds Add to clipboard CA VHEC RA024 · Collection · [ca. 1921]-2019 Fonds consists of textual records, graphic materials, and artefacts relating to Louise Sorensen’s life in the Netherlands, some of which was spent in hiding. Many of the items are wartime records, including photographs and negatives, correspondence, paper currency, drawings, notice of registration, official and forged identity cards, and ration cards. Additionally, the fonds contains copies of Sorensen’s great-uncle’s daughter’s, Ans’, testimonies; several English translations of items provided by Sorensen; and a 1947 second edition of Anne Frank’s Het Achterhuis, or The Diary of a Young Girl, also known as the Diary of Anne Frank. The fonds has been arranged by the archivist into the following six series: Personal records, Family records, Photographs, Correspondence, Currency and Publications and writings. Louise Stein Sorensen Family records Add to clipboard CA VHEC RA024-02 · Series · 1941-[19--?] Part of Louise Stein Sorensen fonds Series consists of records pertaining to several family members of Sorensen. Included is a photocopy of a copy of an original document announcing the death of Sorensen’s great-grandfather, Mozes van Dam; an original notice of registration from the American Consulate in Rotterdam, Netherlands; an official identity card for Marianne Stein (née van Dam); forged identity cards used by Sorensen’s mother, Marianne Stein, and great aunt, Jansje van Dam; and original ration cards used to receive textiles and to buy food staples like potatoes, butter, bread, milk and meat. Louise Stein Sorensen Photographs Add to clipboard CA VHEC RA024-03 · Series · [ca. 1921]-2006 Part of Louise Stein Sorensen fonds Series consists of graphic materials concerning Sorensen and her family members and their experiences before, during and after the Second World War. Records include original and copied photographs and negatives. Many of the original materials remain in the custody of Sorensen or her sister, Elenore. Although some of the exact dates are unknown, the known dates of items in this series range from ca. 1921 to 2006. Louise Stein Sorensen Correspondence Add to clipboard CA VHEC RA024-04 · Series · 1940-2019 Part of Louise Stein Sorensen fonds Series consists of records generated by the correspondence between Sorensen and family members, as well as emails between Sorensen and individuals from the United States Holocaust Memorial Museum and Vancouver Holocaust Education Centre. Records include handwritten and typed letters, postcards, and emails. The letters and postcards were primarily typewritten on a typewriter, with two postcards being handwritten. The series includes an envelope addressed to Loesje Stein. Louise Stein Sorensen Collection about Rudolf Vrba Add to clipboard CA VHEC RA028 · Collection · 1987-2014 Collection consists of articles, lectures, correspondence, newspaper clippings and other textual material produced and collected by John Conway relating to the life, activity and legacy of Dr. Rudolf Vrba, a Slovak Jewish Holocaust survivor escaped from Auschwitz and associate professor of pharmacology at the University of British Columbia in Vancouver, BC. Collection includes audiovisual records related to Vrba from the VHEC’s institutional holdings.Collection has been arranged into the following series: Vierteljahrshefre für Zeitgelchichte documents series (1997–2010); Vrba memorial lecture series (2006–2014); Biographical material series (1987–2010); Correspondence and research records series (2004–2007); and Articles and lectures series (1992–2013). Vilcsek family fonds Add to clipboard CA VHEC RA033 · Fonds · [after 1881]–1971 Collection consists primarily of records generated or used during the period of the Second World War by the Vilcsek family in Budapest, Hungary. These include vital statistics and personal records of the Vilcsek family, photographs, and postcards mailed to the family from Ernő Vilcsek while he was in a labour camp in Hungary. Collection also consists of artworks, several on the theme of the Holocaust, created by Eva Kero after her immigration to Vancouver, BC.Collection has been arranged into three series: Correspondence (1942), Family records ([after 1881]–1949) and Artworks (1969–1971). Vilcsek family Pollák, Deneberger, Kiss family fonds Add to clipboard CA VHEC RA034 · Fonds · 1900–[after 1990] Fonds is comprised of correspondence, family records and photographs created and/or kept by members of the Pollák, Deneberger and Kiss family, a Jewish family living in Tápiószele, Hungary during the Second World War. Records document the family's separation, internment, hiding and well as pre- and post-war activities. Pollák, Deneberger, Kiss family Dr. Serge Vanry fonds Add to clipboard CA VHEC RA035 · Fonds · 1940–1946; 2018 Fonds is comprised of photographs, certificates, identity and repatriation cards, correspondence and photocopies of administrative records. Records pertain to the experiences of the Vanry family during the Holocaust in France. Fonds also includes photographs and a speech created as a result of Serge Vanry’s participation in a ceremony honouring his rescuers, René and Marguerite Poignard of Neuvy-en-Sullias, held in France in 2018.Fonds is arranged into the following two series: Family records ([1942 or 1943]–1945, 2018) and Photographs (1940–[circa 1945]; 2018). Vanry, Serge Writing Lives Memoir Project collection Add to clipboard CA VHEC RA036 · Collection · 2016–2018 Collection is comprised of records accumulated as a result of the participation of the Vancouver Holocaust Education Centre in a project entitled Writing Lives: The Holocaust Survivor Memoir Project. Writing Lives was a partnership between Langara College’s English and History departments, the Azrieli Foundation and the VHEC. For the project, students at Langara College worked closely with Vancouver-based Holocaust survivors to produce their written memoirs over the course of two semesters. In the first semester, students learned the history of the Holocaust. In the second semester, students interviewed survivors, transcribed the interviews and together with the survivors, completed written memoirs. In this fonds are the memoirs, administrative files and digital photographs produced during the two-year run of the project. Seven survivors participated in the first year of the project, from 2016–2017; five survivors participated in the second year of the project, from 2017 to 2018.Collection is divided into three series: Memoirs (2017–2018), Administrative files (2016–2018) and Photographs (2017–2018). Survivors Today project fonds Add to clipboard CA VHEC RA055 · Fonds · [1977]–1987 Fonds consists of multimedia materials created by Brauer as a result of her Survivors Today project, which documented the lives of Holocaust and Hiroshima survivors after the war and documented attendees at the Canadian Gathering of Jewish Holocaust Survivors and their Children held in Ottawa from April 28–30, 1985. Materials in fonds include audio cassette tape recordings of one-on-one interviews with survivors and one tape of four survivors speaking at a symposium on the Holocaust. Assorted textual materials include manuscripts, correspondence, biographies, transcripts of interviews, book proposals, publications, financial records and a matted display panel. Lastly, photographic materials in the fonds consist of negatives, contact sheets and prints produced by Brauer.The Survivors Today project aimed to honour survivors’ recollections of sorrow while also expressing their hopes and triumphs in their new lives. Interviews focus on how survivors came to Canada, their adjustments and contributions to life in Canada, and their perceptions of Canadian society. Other topics covered include Judaism and faith, Israel, Europe, nuclear weapons and global peace. Brauer, Celia Michel Mielnicki fonds Add to clipboard CA VHEC RA056 · Fonds · [1939–2005] Fonds consists of records created by, accumulated by, or about Michel Mielnicki related to his experience as a survivor of the Holocaust, the publication of Bialystok to Birkenau: The Holocaust Journey of Michel Mielnicki and Mielnicki’s reunion with his brother after nearly fifty years of separation. Records include photographs, newspaper clippings, correspondence, ephemera, video and audio cassette tapes, identity documents, notes and research materials.Fonds is arranged into the following eight series: —Identity documents (1945–1966) —Photographs ([ca. 1939–1996]) —Memorabilia ([194–198-?]) —Mielnicki correspondence (1954–2005) —Clippings and publications (1947–2000) —Notes, research and speech ([198-]–[6 Oct. 1992]) —Leon Mendelewicz documents ([198-]–5 Mar. 1989) —Audio records (1995) Mielnicki, Michel Peck family fonds Add to clipboard CA VPL 13584-13619 · Fonds · 1906-1915 The fonds consists of photographs of the Peck family of Cranbrook, B.C. Peck (family) Fitzgerald McCleery fonds Add to clipboard CA VPL 17188-17348 · Fonds · [ca. 1860-1900] The fonds consists of portraits of the McCleery family and photographs of the McCleery farm on the North Arm of the Fraser River. McCleery, Fitzgerald Van Dyke Studios fonds Add to clipboard CA VPL 35877-35942 · Fonds · [ca. 1930-1955] The fonds consists of photographs depicting people, activities, and scenery in Vancouver. Fonds includes portraits taken by the studio. Van Dyke Studios Tony Archer fonds Add to clipboard CA VPL 60001-72265 · Fonds · 1960-1972 The fonds consists of studio portrait photographs for approximately 900 assignments. Archer, Tony Jardine family fonds Add to clipboard CA WMA 88.4;88.26;89.10;89.17 · Fonds · [ca. 1920-1950] The fonds consists of photographs of the Betts, Jardine and Neiland families depicting family members, other people, events and scenes in the Alta Lake/Whistler area.	https://www.memorybc.ca/family-and-personal-life?listLimit=25&listPage=2&page=14&sort=referenceCode&sortDir=asc
Difference between revisions of "REAP main" - LearnLab Difference between revisions of "REAP main" Revision as of 15:23, 21 April 2008 (view source) Juffs (talk\|contribs) ← Older edit Latest revision as of 19:19, 22 November 2010 (view source) Jbodnar (talk\|contribs) (→‎ Annotated bibliography) (10 intermediate revisions by 4 users not shown) Line 46: Line 46: === Independent variables === === Independent variables === − e.g., availabilityof dictionary definitions , presentation of definitions, highlightingof target words in readings , personalizationof readings by topicsof interest , etc. + + * Availabilityof dictionary definitions (control condition: not able to click on target words to get a definition) + + [[Image:dictionaryDefinitionSmall.jpg\|Dictionary Definition]] + + * Highlightingof target words in readings (control condition: target words not hightlighted) + + * Personalizationof interest (control condition: document retrieval algorithm does not take into account students' preferences) + + [[Image:interest.jpg\|Personalizationof interest ]] === Hypotheses === === Hypotheses === Line 64: Line 73: === Descendents === === Descendents === − REAP Summer 2005 Study − − REAP Fall 2005 Study [[REAP Study on Vocabulary Stretch (Spring 2006)]]. [[REAP Study on Vocabulary Stretch (Spring 2006)]]. Line 85: Line 91: [[REAP Study on Highlighting Target Vocabulary to Focus Learner Attention]] [[REAP Study on Highlighting Target Vocabulary to Focus Learner Attention]] + + *[[REAP_Multimodal_Learning_Fall_09 \| REAP Study on Multi-Modal Learning (Fall 2009)]]. === Annotated bibliography === === Annotated bibliography === Line 97: Line 105: Hatch, E., & Brown, C. (1995). Vocabulary, semantics, and language education. Cambridge: Cambridge University Press. Hatch, E., & Brown, C. (1995). Vocabulary, semantics, and language education. Cambridge: Cambridge University Press. + + M. Heilman, K. Collins-Thompson, M. Eskenazi, A. Juffs, L. Wilson. (2010). Personalization of Reading Passages Improves Vocabulary Acquisition. International Journal of Artificial Intelligence in Education, Vol. 2 (1).<http://iaied.org/journal/> Hulstijn, J., Hollander, M., & Greidanus, T. (1996). Incidental vocabulary learning by advanced foreign language students: the influence of marginal glosses, dictionary use, and re-occurrence of unknown words. Modern Language Journal, 80, 327-339. Hulstijn, J., Hollander, M., & Greidanus, T. (1996). Incidental vocabulary learning by advanced foreign language students: the influence of marginal glosses, dictionary use, and re-occurrence of unknown words. Modern Language Journal, 80, 327-339. Contents [ hide] 1 The REAP Project Root Node 1.1 Logistical Information 1.2 Abstract 1.3 Glossary 1.4 Research question 1.5 Dependent variables 1.6 Independent variables 1.7 Hypotheses 1.8 Explanation 1.9 Notes 1.10 Descendents 1.11 Annotated bibliography The REAP Project Root Node Logistical Information See individual studies under Descendants. Abstract The REAP project investigates the effects of implicit and explicit instruction on the learning of word meanings. The REAP tutor (http://reap.cs.cmu.edu) is in LearnLab studies at the English Language Institute at the Univ. of Pittsburgh. Glossary Implicit Learning: The learning of meaning for a word from the context in which that word occurs. Explicit Learning: The learning of meaning for a word from explicit instruction, either in the form of a dictionary definition or a practice exercise. Intentional Learning: The learning of meanings for words that are focused on in instructional materials. Targeted words might be highlighted in a reading, or practiced in vocabulary exercises. Incidental Learning: The learning of meanings for words that appear in instructional materials but are not explicitly taught. For example, a student may learn an unknown word that occurs in a practice reading but is not the focus of the reading. Research question The general question of theCoordinative Learningcluster that the REAP project is aimed at is the following: "When and how should explicit explanations be added or requested of students before, during, or after example study and problem solving practice?" In REAP's case, the verbal explication comes primarily in the form of dictionary definitions of vocabulary words. However, in contrast to other domains, explicit instruction is the first means of instruction for vocabulary rather than the secondary means of instruction. In the case of vocabulary for second language learners, explicit instruction may provide the most economical means of learning, but this learning may be shallow. The question for language learning is then, "How much and in what ways does adding or requesting coordinated implicit examples (of word usage in context) increase robust learning?" Additional questions: What are the characteristics of instruction that lead to robust knowledge of vocabulary? Do students learn better from explicit instruction (e.g., dictionary definitions), or can they learn implicitly (e.g., from context)? To what extent does incidental learning of vocabulary occur (e.g., learning of words not targeted by a practice reading, but looked up by the student as he or she read the text.)? Examples of REAP Issues in a table of Different Types of Instruction and Learning <table><tbody><tr><td></td><td> Passive</td><td> Active</td><td> Interactive</td></tr><tr><td> Explicit (general)</td><td> Dictionary definitions</td><td></td><td> Multiple-choice definition questions (for practice or assessment)</td></tr><tr><td> Implicit (instance)</td><td> Interpreting meaning in context while reading</td><td> Novel sentence production (post-test measure of transfer)</td><td> Cloze Vocabulary Practice Questions</td></tr></tbody></table> Dependent variables Normal post-testscores, on exercises similar to practice exercises. These test items are usually cloze/fill-in-the-blank questions on target vocabulary words. Long-term retentiontest scores similar to post-test but administered at least one month later. Transferof knowledge: practice vocabulary questions of other types, sentence production tasks for target words, correct use of words in writing assignments for other courses. Independent variables Availability of dictionary definitions (control condition: not able to click on target words to get a definition) <here is a image c5f0fc59401b60e0-6914003ab7a51f95> Highlighting of target words in readings (control condition: target words not hightlighted) Personalization of interest (control condition: document retrieval algorithm does not take into account students' preferences) <here is a image a0c7c31e8a641c8c-3d4188724c75cecd> Hypotheses Students require both explicit and implicit instruction to effectively acquire vocabulary. Students do not efficiently learn vocabulary implicitly (e.g., from context alone). Similarly, learning solely from explicit dictionary definitions will lead to shallow acquisition. Students who only have definitions available will have difficulty generalizing their knowledge and producing sentences using new vocabulary. Therefore, words need to be seen in context with definitions available in order for robust learning to occur. Explanation Notes The words which the REAP tutor provides practice for are from the Academic Word List (Coxhead, 2000). Beginning with the Spring 2006 study, dictionary definitions were available for all words in a reading unless noted otherwise. Definitions came from the Cambridge Advanced Learner's Dictionary (dictionary.cambridge.org) unless noted otherwise. ELI students use REAP in their reading class about 40 minutes per week as part of a 4 hour reading course. The rest of the class time is spent on the textbook and other vocabulary exercises. Descendents REAP Study on Vocabulary Stretch (Spring 2006). REAP Study on Question Types (Summer 2006). REAP Study on Personalization of Readings by Topic (Fall 2006). REAP Comparison to Classroom Instruction (Fall 2006). REAP Study on Focusing of Attention (Spring 2007). ELI Study on Activity Theory and student use of REAP (Spring 2007). REAP Study on Word Sense Disambiguation (Summer 2007). REAP Study on Hearing Words Pronounced (Summer 2007). REAP Study on Highlighting Target Vocabulary to Focus Learner Attention REAP Study on Multi-Modal Learning (Fall 2009). Annotated bibliography Craik, F. & Lockhardt, R. (1972). Levels of processing: a framework for memory research. Journal of Verbal Learning and Verbal Behavior, 11, 671-684. Cobb, T. (2006). The old vocabulary, the new vocabulary, and the Arabic learner. A TESOL symposium on Vocabulary words matter: The importance of vocabulary in English Language Teaching and Learning. Alexandria, VA: TESOL. Coxhead, Averil (2000) A New Academic Word List. TESOL Quarterly, 34(2): 213-238. Ellis, N. C., & Sinclair, S. (1996). Working memory in the acquisition of vocabulary and syntax. Quarterly journal of experimental psychology, 49, 234-250 Hatch, E., & Brown, C. (1995). Vocabulary, semantics, and language education. Cambridge: Cambridge University Press. M. Heilman, K. Collins-Thompson, M. Eskenazi, A. Juffs, L. Wilson. (2010). Personalization of Reading Passages Improves Vocabulary Acquisition. International Journal of Artificial Intelligence in Education, Vol. 2 (1).<http://iaied.org/journal/ > Hulstijn, J., Hollander, M., & Greidanus, T. (1996). Incidental vocabulary learning by advanced foreign language students: the influence of marginal glosses, dictionary use, and re-occurrence of unknown words. Modern Language Journal, 80, 327-339. Krashen, S. (1989). We acquire vocabulary and spelling by reading: additional evidence for the input hypothesis. Modern Language Journal, 73, 440-464. McCarthy, M. (1994). A new look at vocabulary in EFL. Applied Linguistics, 5, 12-22. Meara, P. (1984). The study of lexis in interlanguage. In A. Davies, C. Criper & A. Howatt (Eds.), Interlanguage (pp. 225-235). Nation, I. S. P. (2001). Learning vocabulary in another language. Cambridge: Cambridge University Press. Prince, P. (1996). Second language vocabulary learning: the role of context versus translations as a function of proficiency. Modern Language Journal, 80, 478-493. Richards, J. (1976). The role of vocabulary teaching. TESOL Quarterly, 10, 77-89. Stanowicz, K. E. (1986). Matthew effects in reading: some consequences of individual differences in the aquisition of literacy. Reading Research Quarterly, 21, 360-407. REAP Web Page Heilman, M., Collins-Thompson, K., Callan, J. & Eskanazi, M. (2006). Classroom success of an Intelligent Tutoring System for lexical practice and reading comprehension. Proceedings of the Ninth International Conference on Spoken Language Processing.[PDF ] Heilman, M. & Eskenazi, M. (2006). Language Learning: Challenges for Intelligent Tutoring Systems. Proceedings of the Workshop of Intelligent Tutoring Systems for Ill-Defined Domains. 8th International Conference on Intelligent Tutoring Systems. [Heilman, M. & Eskenazi, M. (2006). Language Learning: Challenges for Intelligent Tutoring Systems. Proceedings of the Workshop of Intelligent Tutoring Systems for Ill-Defined Domains. 8th International Conference on Intelligent Tutoring Systems.[PDF ] J. Brown, G. Frishkoff, and M. Eskenazi. (2005). "Automatic question generation for vocabulary assessment." In Proceedings of HLT/EMNLP 2005. Vancouver, B.C.[PDF ] J. Brown and M. Eskenazi. (2005). "Student, text and curriculum modeling for reader-specific document retrieval." In Proceedings of the IASTED International Conference on Human-Computer Interaction 2005. Phoenix, AZ.[PDF ] J. Brown and M. Eskenazi. (2004.) "Retrieval of authentic documents for reader-specific lexical practice." In Proceedings of InSTIL/ICALL Symposium 2004. Venice, Italy.PDF ] A. Juffs, L. Wilson, M. Eskenazi, J. Callan, J. Brown, K. Collins-Thompson, M. Heilman, T. Pelletreau, and J. Sanders. (2006.) "Robust learning of vocabulary: investigating the relationship between learner behaviour and the acquisition of vocabulary" (poster). At The 40th Annual TESOL Convention and Exhibit (TESOL 2006).[PDF ] K. Collins-Thompson and J. Callan. (2004.) "A language modeling approach to predicting reading difficulty." In Proceedings of the HLT/NAACL 2004 Conference. Boston.[PDF ] Pelletreau, T. (2006). Computer assisted vocabulary acquisition in the ESL classroom. Unpublished Master of Arts, University of Pittsburgh, Pittsburgh.[1] The following is a literature review of CALL and vocabulary instruction. It was written by Ben Friedline after discussion with Alan Juffs about what kinds of improvements we would like to see in REAP as it develops for full classroom use. CALL and Vocabulary Acquisition: Implications for the Design of CALL for the ESL Classroom Benjamin E. Friedline University of Pittsburgh Department of Linguistics Dr. Alan Juffs April 9, 2008 CALL and Vocabulary Acquisition: Implications for the Design of CALL for the ESL Classroom Abstract The purpose of this paper is to provide suggestions on how to design materials for English as a Second Language (ESL) CALL-based vocabulary instruction based on current research findings. To this end, the current paper examines: 1) how CALL can be used to promote long-term vocabulary retention, 2) the issue of word selection in CALL design, 3) how output related computer-mediated tasks can influence vocabulary retention, and 4) the idea of individual differences in students’ approaches to CALL. The purpose of this paper is to review the findings from the literature on CALL and vocabulary acquisition not to propose new research, but to provide a principled foundation for the design of ESL CALL-based vocabulary instruction that promotes learning and long-term retention of vocabulary words. Introduction Current vocabulary acquisition research highlights an L2 learner’s need to acquire a large working vocabulary in order to comprehend and communicate effectively in an L2 (Folse, 2006; Nation, 2002). Research has also revealed that the frequency of occurrence of vocabulary words in English drops considerably after the first 3,000 most frequent words (Nation, 2002). Three overarching research agendas have resulted from these findings. Firstly, researchers are concerned with determining which words and the quantity of words students need to learn in order to ‘succeed’ in an academic program in English (Coxhead, 2001; Hunt & Beglar, 2002; Nation, 2002). Secondly, many research studies have been concerned with the question of how to teach vocabulary to ESL students in the most effective way. Some research studies have shown that extensive reading leads to enhanced vocabulary learning and long-term retention (Grabe, 2002; Horst, 2005; Renandya & Jacobs, 2002) and how different exercise types can influence vocabulary retention (Folse, 2006). Additionally, other research has highlighted the importance of interaction (output) in getting learners to retain the word knowledge that they have gained through intensive reading (Hunt & Beglar, 2002; Nation, 2002). Lastly, an important trend in past research (not-necessarily vocabulary research) has been to determine how individual differences contribute to what learners are capable of learning from completing a particular task (Dörnyei & Skehan, 2000). The previously cited research has all been conducted within face-to-face contexts. Interestingly enough, many of the same issues that are present in research in face-to-face conversations and vocabulary research are also issues within the literature that looks at CALL and vocabulary acquisition. The purpose of this paper is to review the findings from the literature on CALL and vocabulary acquisition not to propose new research, but to provide a principled foundation for the design of ESL CALL-based vocabulary instruction that promotes learning and long-term retention of vocabulary words. Additionally, this paper assumes that users of the CALL applications will be academically oriented and needing to learn vocabulary in order to engage in there respective academic programs. This paper is important for developers of ESL curriculums and materials. For the materials developer, this paper provides a theoretical rationale for designing CALL applications that promote vocabulary acquisition. On the other hand, this paper provides a ‘checklist’ for curriculum developers who are looking to implement CALL programs into their language learning curriculum. That is, if certain applications do not meet the criteria that are proposed in this paper, then one should be cautious in bringing such a program into his/her instructional context. Word Presentation in CALL Learners and language instructors will find that CALL offers a variety of methods for presenting new vocabulary words. In spite of the plethora of options that CALL programs can offer in terms of activity design, research reveals that the selection of words and the way that they are presented will directly impact vocabulary learning. Firstly, I will examine the issue of which words to teach through CALL. Based on past research on word selection for vocabulary instruction within face-to-face conversation (Coxhead, 2001; Nation, 2002), it makes sense to conclude that CALL applications should also present words that are not frequent in the input and words that will be needed to engage in academic disciplines. Indeed, the literature suggests that some CALL applications (Juffs, Friedline, Wilson, Eskenazi, & Heilman, submitted) are being designed to teach words from word lists such as the AWL (Coxhead, 2001). Unfortunately, these programs are the exception to the general trend in the design of CALL programs that promote vocabulary acquisition. The words in these programs are generally selected based on native speaker judgments (Groot, 2000), high-frequency (Tozcu & Coady, 2006), or from an in-class textbook (Allum, 2004). The problem with the vocabulary used in these programs pertains to the question: Do learners need these words? In other words, there is no theoretical basis for the selection of the words that are being taught by these CALL applications. This argument can also be applied to words that are excluded from CALL applications. For example, Nesselhauf and Tschichold (2002) reviewed seven different CALL vocabulary-building programs and found that collocations were largely neglected in these programs. This result is surprising if we consider the frequency and importance of multi-word units in everyday speech and writing (Nesselhauf & Tschichold, 2002), and the difficulty that second-language learners have in learning them (Chan & Liou, 2005; Sun & Wang, 2003). A recent approach that has been forwarded to address the need to teach collocations is the use of online concordancers. Benefits of the use of concordancers may include contextual word learning (Cobb, 1999), extensive exposure to naturally occurring input (Chan & Liou, 2005; Sun & Wang, 2003), and consciousness raising of the existence of multi-word units among L2 learners (Chan & Liou, 2005). Cobb (1999) found that learners who used a concordancer learned definitional knowledge of words and were able to transfer the knowledge of words to the comprehension of novel texts, both long-term and short-term. On the other hand, students in Cobb’s (1999) study who used a list and dictionary method (instead of a concordancer) to learn new words were able to learn definitional meanings, but these meanings were not retained in the long-term, nor were the learners able to transfer their knowledge to novel texts. Chan and Liou (2005) explored the learning of collocations through a web-based bilingual concordancer by using a one-group pretest/posttest experiment. The results of their study revealed that the use of a bilingual concordancer could aid learners in acquiring immediate collocational knowledge; however, this knowledge was not retained over time. The previously cited research highlights some of the problems with the words that have been selected for instructional purposes by current CALL vocabulary-building software. These problems include the lack of a theoretical basis for word selection and the exclusion of multi-word units such as collocations. In light of these problems, a synthesis of current research may provide insights for improving CALL vocabulary-building software. Firstly, the words that students learn should be selected based upon their frequency (e.g., AWL) and their utility for functioning within an academic discipline. Additionally, CALL vocabulary-building software should focus on teaching multi-word units because of the difficulties that such words present for second language learners. Current research (e.g., Cobb, 1999) suggests that concordancers may help learners to acquire collocational knowledge by presenting them with large amounts of contextual evidence. CALL and Vocabulary Retention Recent CALL research suggests that CALL vocabulary tutors can promote long-term vocabulary retention. Grace (1998) did a study in which she used a pretest/posttest/delayed posttest design to test to see if L1 translations of target words helped learners to learn and retain vocabulary words. There were 181 beginning-level French students involved in this study; 89 were placed in the experimental condition (L1 Translations) and 92 were placed in the control condition (no L1 Translations). Grace found that both groups exhibited gains in short-term and long-term vocabulary retention, but the experimental condition demonstrated more significant gains in vocabulary retention. Grace attributes the increased retention for the experimental condition to the fact that having an L1 translation allows a learner to process a word more deeply by connecting an L2 word with and L1 word than learners who have to guess the meaning of a word from context. Additionally, Grace mentions that having learners guess word meaning from context can be detrimental to vocabulary learning because learners will often make a wrong guess and store an incorrect word meaning to memory (Grace, 1998, p. 540). Groot (2000) conducted a study in which he compared the performance of two groups of students on two different vocabulary learning tasks. In this study, one of the groups learned words from a bilingual list, while the other group learned words from a CALL program that modeled the vocabulary acquisition process (e.g., noticing, storage, and consolidation of storage). On the immediate posttest and delayed posttest, the control group (bilingual list) outperformed the experimental group (CALL) in terms of vocabulary knowledge. However, in one of the two repeated experiments, the researchers observed less retention loss for the experimental condition on the delayed posttest. The researcher attributes the enhanced retention to the CALL application’s ability to promote deep-processing of the lexical items and proposes that the best method is an approach that combines bilingual lists and CALL. These findings are supported by other studies that have specifically examined the benefits that L1 translations (Grace, 1998) and language-specific feedback that promotes depth of processing (Zapata & Sagarra, 2007) have on vocabulary retention. Also related to depth of processing, a study by Zapata and Sagarra (2007) compared the performance of two groups of students using different vocabulary exercises for 24 weeks; 245 students worked with an online workbook, and 304 students used a paper workbook. The two different types of workbooks contained exactly the same content. During the first 2-4 months, there was no significant difference between the two groups. However, the students using the online workbook performed better than the control group on tests of lexical knowledge 6-8 months after the treatment. The researchers suggest that this difference was due to the differences in feedback between the two types of activities. That is, CALL was able to provide learners with immediate feedback, whereas students had to wait on their teachers to receive feedback on the written workbook. The final study that will be included in this section on CALL and vocabulary acquisition is a study by Nakata (2008) in which the researcher compared the effectiveness of vocabulary instruction through computers, cards, and lists in terms of vocabulary retention. The computer was designed to accommodate optimal spaced learning, which takes place when the item to be learned is rehearsed over a long period of time in a sequence that promotes deep processing. (Nakata, 2008, p. 5-6). In this study, 226 first and second year high-school EFL learners were placed into one of three groups: 1) a list group, 2) a card group, and 3) a computer group. The results on the immediate posttest revealed that there was no significant difference between the three groups in terms of vocabulary knowledge. However, a significant difference was found between the scores on the delayed posttest, which was administered 4 days after the treatment. According to these results, the PC group scored significantly higher than the list group, but there was no significant difference between the card group and the computer group. These results suggest that learning vocabulary from cards and CALL are more effective for long-term vocabulary retention, especially when one considers the idea of optimal spaced learning that comes from cognitive psychology. In this case, cards and computer work better than lists because they are not subject to rehearsal in a static order. In sum, CALL tutors should be designed to promote long-term retention of vocabulary items. As the previously cited research indicates, there are several different interrelated factors that can contribute to long-term retention. That is, CALL has the ability to promote deep-processing of lexical items through immediate feedback, optimally spaced rehearsal, and by presenting L2 learners with the option of consulting an L1 translation of a vocabulary item. Negotiated Interaction and Vocabulary Retention Research suggests that vocabulary retention is enhanced if learners perform an output related task in connection with a vocabulary learning task (Hunt & Beglar, 2002; Nation, 2002). This same principle holds true for vocabulary tasks that take place through CALL. Smith (2004) conducted a study of NNS-NNS interactions over Internet-Relay Chat (IRC) in order to determine if NNS-NNS interactions through Computer-Mediated Communication (CMC) could facilitate learners’ abilities to recognize and produce new lexical items, and if the effects would hold up over time. His study included 45 intermediate-level ESL students, who interacted over IRC to negotiate the meanings of several target words over 5 sessions. According to Smith’s (2004) study, negotiated items were learned much better than non-negotiated items, and the vocabulary gains were shown to hold up over time. Thus, this study provides support for Long’s interaction hypothesis (as cited in Mitchell & Myles, 2004) as it relates to CALL and vocabulary acquisition. A study by De la Fuente (2003) also provides support for the utility of computer mediated interaction in lexical development. In her study, De la Fuente (2003) researched if computer mediated interactions could help students to advance their lexical L2 interlanguage. The participants in this study included 24 students from 3 different classes of second-semester elementary Spanish. The researcher divided students into pairs and placed them in either the face-to-face interaction group or the computer mediated group and had them negotiate the meaning of 43 Spanish nouns through an information gap activity over 2 days. In terms of receptive and productive oral acquisition, both groups showed gains in vocabulary knowledge; however, the face-to-face group outperformed the computer group on both measures. In terms of receptive and productive written acquisition, both groups showed gains, but this time neither group’s performance was significantly different on either of these measures. Once again, this study provides support for the fact that computer mediated interaction can lead to lexical development. The superior performance on oral tasks by the face-to-face group would be expected since they received oral input and quite possibly textual input from their interlocutors, whereas the computer group was limited to text-based input only. In sum, the previously cited research provides evidence that interactive CMC tasks enhance vocabulary learning. Thus, CALL designers may want to consider including interactive tasks (e.g., online chat or voice chat) that involve learner-to-learner interactions as opposed to interactions that involve a learner ‘interacting’ with a computer interface. Individual Differences and CALL The final portion of this literature review will discuss how the idea of individual differences might affect the design of CALL vocabulary tutors. In a study of a CALL vocabulary tutor in an Intensive English Program (IEP), Juffs et al. (submitted) found that the goals of the students and researchers were not aligned. That is, the researchers expected students to engage in extensive reading and to have some interest in the articles; however, some learners spent too much time reading a single article and looking up every word, while others sped through the articles as fast as they could just to get done with the articles. This study is important because it shows that CALL design involves ‘getting into the heads of the learners’ and being able to anticipate how they will use the program. Certainly, this is no easy task. Current research includes some ideas for designing CALL to accommodate many individual differences. I say ‘many’ here because I know that it is never possible to please every learner. Firstly, research highlights the importance of having a user-friendly and contemporary-looking interface (Nesselhauf & Tschichold, 2002). Although factors such as a programs’ looks may not appear to be all that important, learners believe otherwise, and will often choose a program based on how it looks as opposed to the program’s true merit. Secondly, Tozcu and Coady (2004) mention that learners in their study can individualize their own word lists while using the New Lexis software. This was not the main goal of the article, but the idea of allowing users to manipulate and individualize some aspects of their vocabulary-learning experience seems to be a good feature to add to any CALL program to accommodate individual differences. Lastly, a CALL vocabulary tutor (especially one that promotes vocabulary acquisition through extensive reading) should allow learners to select texts based on interest (Juffs et al., submitted; Renandya & Jacobs, 2002). Accommodating student interest is important for any extensive reading program because interesting readings can provide students with the necessary intrinsic motivation to read large amounts of texts. Past research on the use of CALL vocabulary tutors has revealed the importance of considering individual differences when designing CALL applications. To some extent, it is impossible to predict exactly how students will use a CALL application, but it is important to pilot test new tutors and to interview students who use the program to understand students’ attitudes towards the program and predict problems that students might have. This research also indicates that a tutor’s looks, ease of use, and ability to be appropriated for a learner’s individual use are important factors to consider for designing CALL vocabulary tutors. Furthermore, CALL should allow learners to choose texts that are of interest to individual learners. Conclusions: Best Practices for Designing CALL Vocabulary Tutors In light of the previously cited research, some general conclusions can be drawn in regards to ‘best practices’ for the design of vocabulary tutors. Firstly, CALL vocabulary tutors should teach words that students need to learn in order to enter into academic programs and make them noticeable for language learners. Words that come from the AWL or another well-known word list should be taught, as well as frequent multi-word units such as phrasal verbs and collocations. Current research has shown that concordancers or bilingual concordancers may be useful in promoting knowledge and recognition of multi-word units. Secondly, CALL tutors should: 1) provide immediate feedback to learners, 2) allow optimally spaced rehearsal, and 3) provide learners with L1 translations so that learners can verify the meanings of words in their L1 before committing them to memory. It is argued that all of these factors lead to deep-processing, which is linked to long-term retention. Thirdly, CALL vocabulary tutors should include features which allow learners to interact with other learners while or immediately after using CALL. Lastly, CALL designers must consider the role of individual differences in vocabulary learning from CALL. In order to accommodate individual differences, CALL programs should be easy to use, modern-looking, and customizable, while at the same time providing learners with interesting materials to learn from. References Allum, P. (2004). Evaluation of CALL: Initial vocabulary learning. ReCALL, 16(2), 488-501. Chan, T., & Liou, H. (2005). Effects of web-based concordancing instruction on EFL students' learning of verb-noun collocations. Computer Assisted Language Learning, 18(3), 231-250. Cobb, T. (1999). Breadth and depth of lexical acquisition with hands-on concordancing. Computer Assisted Language Learning, 12(4), 345-360. Coxhead, A. (2001) A new academic word list. TESOL Quarterly 34: 213-238. De la Fuente, M. (2003). Is SLA interactionist theory relevant to CALL? A study on the effects of computer-mediated interaction in L2 vocabulary acquisition. Computer Assisted Language Learning, 16(1), 47-81. Dörnyei, Z., & Skehan, P. (2005). Individual differences in second language learning. In C. Doughty & M. Long (Eds.), The handbook of second language acquisition. Massachusetts: Blackwell. Folse, K. (2006). The effect of type of written exercise on L2 vocabulary retention. TESOL Quarterly, 40(2), 273-293. Grabe, W. (2002). Dilemmas for the development of second language reading abilities. In J. C. Richards & W. A. Renandya (Eds.), Methodology in language teaching. New York: Cambridge University Press. Grace, C. A. (1998). Retention of word meanings inferred from context and sentence-level translations: Implications for the design of beginning-level CALL software. The Modern Language Journal, 82(iv), 533-544. Groot, P. (2000). Computer assisted second language vocabulary acquisition. Language Learning and Technology, 4, 60-81. Horst, M. (2005). Learning L2 vocabulary through extensive reading: A measurement study. The Canadian Modern Language Review, 61(3), 355-382. Hunt, A., & Beglar, D. (2002). Current research and practice in teaching vocabulary. In J. C. Richards & W. A. Renandya (Eds.), Methodology in language teaching. New York: Cambridge University Press. Juffs, A., Friedline, B., Wilson, L., Eskenazi, M., & Heilman, M. (submitted). Activity theory and computer-assisted learning of English vocabulary. Applied Linguistics. Mitchell, R., & Myles, F. (2004). Second language learning theories (2nd ed.). New York: Hodder Arnold. Nakata, T. (2008). English vocabulary learning with word lists, word cards and computers: Implications from cognitive psychology research for optimal spaced learning. ReCALL, 20(1), 3-20. Nation, P. (2002). Best practice in vocabulary teaching and learning. In J. C. Richards & W. A. Renandya (Eds.), Methodology in language teaching. New York: Cambridge University Press. Nesselhauf, N., & Tschichold, C. (2002). Collocations in CALL: An investigation of vocabulary-building software for EFL. Computer Assisted Language Learning, 15(3), 251-279. Renandya, W., & Jacobs, G. (2002). Extensive reading: Why aren't we all doing it? In J. C. Richards & W. A. Renandya (Eds.), Methodology in language teaching. New York: Cambridge University Press. Smith, B. (2004). Computer-mediated negotiated interaction and lexical acquisition. SSLA, 26, 365-398. Sun, Y., & Wang, L. (2003). Concordancers in the EFL classroom: Cognitive approaches and collocation difficulty. Computer Assisted Language Learning, 16(1), 83-94. Tozcu, A., & Coady, J. (2004). Successful learning of frequent vocabulary through CALL also benefits reading comprehension speed. Computer Assisted Language Learning, 17(5), 473-495. Zapata, G., & Sagarra, N. (2007). CALL on hold: The delayed benefits of an online workbook on L2 vocabulary learning. Computer Assisted Language Learning, 20(2), 153-171.	https://learnlab.org/wiki/index.php?diff=cur&oldid=7873&title=REAP_main
Police and Criminal Evidence Act 1984 An Act to make further provision in relation to the powers and duties of the police, persons in police detention, criminal evidence, police discipline and complaints against the police; to provide for arrangements for obtaining the views of the community on policing and for a rank of deputy chief constable; to amend the law relating to the Police Federations and Police Forces and Police Cadets in Scotland; and for connected purposes. Police and Criminal Evidence Act 1984 What Version Legislation is available in different versions: Latest Available (revised):The latest available updated version of the legislation incorporating changes made by subsequent legislation and applied by our editorial team. Changes we have not yet applied to the text, can be found in the ‘Changes to Legislation’ area. Original (As Enacted or Made):The original version of the legislation as it stood when it was enacted or made. No changes have been applied to the text. 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Changes to legislation: Police and Criminal Evidence Act 1984, Cross Heading: Entry and search without search warrant is up to date with all changes known to be in force on or before 29 May 2023. There are changes that may be brought into force at a future date. Changes that have been made appear in the content and are referenced with annotations. Changes to Legislation Changes and effects yet to be applied by the editorial team are only applicable when viewing the latest version or prospective version of legislation. They are therefore not accessible when viewing legislation as at a specific point in time. To view the ‘Changes to Legislation’ information for this provision return to the latest version view using the options provided in the ‘What Version’ box above. Entry and search without search warrant E+W 17 Entry for purpose of arrest etc. E+W (1) Subject to the following provisions of this section, and without prejudice to any other enactment, a constable may enter and search any premises for the purpose— (a) of executing— (i) a warrant of arrest issued in connection with or arising out of criminal proceedings; or (ii) a warrant of commitment issued under section 76 of the M1 Magistrates’ Courts Act 1980; (b) of arresting a person for an arrestable offence; (c) of arresting a person for an offence under— (i) section 1 (prohibition of uniforms in connection with political objects), . . . F1 of the M2 Public Order Act 1936; (ii) any enactment contained in sections 6 to 8 or 10 of the M3 Criminal Law Act 1977 (offences relating to entering and remaining on property); [ F2 (iii) section 4 of the Public Order Act 1986 (fear or provocation of violence); ] [ F3 (iv) section 76 of the Criminal Justice and Public Order Act 1994 (failure to comply with interim possession order); ] [ F4 (ca) of arresting, in pursuance of section 32(1A) of the Children and Young Persons Act 1969, any child or young person who has been remanded or committed to local authority accommodation under section 23(1) of that Act; (cb) of recapturing any person who is, or is deemed for any purpose to be, unlawfully at large while liable to be detained— (i) in a prison, remand centre, young offender institution or secure training centre, or (ii) in pursuance of [ F5 section 92 of the Powers of Criminal Courts (Sentencing ) Act 2000 ] (dealing with children and young persons guilty of grave crimes), in any other place; ] (d) of recapturing [ F6 any person whatever ] who is unlawfully at large and whom he is pursuing; or (e) of saving life or limb or preventing serious damage to property. (2) Except for the purpose specified in paragraph (e) of subsection (1) above, the powers of entry and search conferred by this section— (a) are only exercisable if the constable has reasonable grounds for believing that the person whom he is seeking is on the premises; and (b) are limited, in relation to premises consisting of two or more separate dwellings, to powers to enter and search— (i) any parts of the premises which the occupiers of any dwelling comprised in the premises use in common with the occupiers of any other such dwelling; and (ii) any such dwelling in which the constable has reasonable grounds for believing that the person whom he is seeking may be. (3) The powers of entry and search conferred by this section are only exercisable for the purposes specified in subsection (1)(c)(ii) [ F7 or (iv) ] above by a constable in uniform. (4) The power of search conferred by this section is only a power to search to the extent that is reasonably required for the purpose for which the power of entry is exercised. (5) Subject to subsection 6 below, all the rules of common law under which a constable has power to enter premises without a warrant are hereby abolished. (6) Nothing in subsection (5) above affects any power of entry to deal with or prevent a breach of the peace. Textual Amendments F1 Words repealed by Public Order Act 1986 (c. 64, SIF 39:2) , s. 40(2)(3) , Sch. 2 para. 7 , Sch. 3 F2 S.17(1)( c )(iii) inserted by Public Order Act 1986 (c. 64, SIF 39:2) , s. 40(2) , Sch. 2 para. 7 F3 S. 17(1)(c)(iv) inserted (24.8.1995) by 1994 c. 33 , s. 168(2) , Sch. 10 para. 53(a) ; S.I. 1995/1957 , art. 3 F4 S. 17(1)(ca)(cb) inserted (5.9.1995) by 1995 c. 16 , s. 2(1) ; S.I. 1995/2021 , art. 2 F5 Words in s. 17(1)(cb) substituted (25.8.2000) by 2000 c. 6 , ss. 165 , 168(1) , Sch. 9 para. 95 F6 Words in s. 17(1)(d) substituted (5.9.1995) by 1995 c. 16 , s. 2(1) ; S.I. 1995/2021 , art. 2 F7 Words in s. 17(3) inserted (24.8.1995) by 1994 c. 33 , s. 168(2) , Sch. 10 para. 53(b) ; S.I. 1995/1957 , art. 3 Modifications etc. (not altering text) C1 Ss. 8, 9, 15, 16, 17(1)( b (2) (4), 18–20, 21, 22(1)–(4), 28, 29, 30(1)–(4)( a )(5)–(11), 31, 32(1)–(9), 34(1)–(5), 35, 36, 37, 39, 40–44, 50, 51( d ), 52, 54, 55, 64(1)–(4)(5)(6), Sch. 1 applied with modifications by S.I. 1985/1800 , arts. 3–11 , Schs. 1 , 2 Marginal Citations M1 1980 c. 43 . M2 1936 c. 6 . M3 1977 c. 45 . 18 Entry and search after arrest. E+W (1) Subject to the following provisions of this section, a constable may enter and search any premises occupied or controlled by a person who is under arrest for an arrestable offence, if he has reasonable grounds for suspecting that there is on the premises evidence, other than items subject to legal privilege, that relates— (a) to that offence; or (b) to some other arrestable offence which is connected with or similar to that offence. (2) A constable may seize and retain anything for which he may search under subsection (1) above. (3) The power to search conferred by subsection (1) above is only a power to search to the extent that is reasonably required for the purpose of discovering such evidence. (4) Subject to subsection (5) below, the powers conferred by this section may not be exercised unless an officer of the rank of inspector or above has authorised them in writing. (5) A constable may conduct a search under subsection (1) above— (a) before taking the person to a police station; and (b) without obtaining an authorisation under subsection (4) above, if the presence of that person at a place other than a police station is necessary for the effective investigation of the offence. (6) If a constable conducts a search by virtue of subsection (5) above, he shall inform an officer of the rank of inspector or above that he has made the search as soon as practicable after he has made it. (7) An officer who— (a) authorises a search; or (b) is informed of a search under subsection (6) above, shall make a record in writing— (i) of the grounds for the search; and (ii) of the nature of the evidence that was sought. (8) If the person who was in occupation or control of the premises at the time of the search is in police detention at the time the record is to be made, the officer shall make the record as part of his custody record. Modifications etc. (not altering text) C2 Ss. 8, 9, 15, 16, 17(1)( b (2) (4), 18–20, 21, 22(1)–(4), 28, 29, 30(1)–(4)( a )(5)–(11), 31, 32(1)–(9), 34(1)–(5), 35, 36, 37, 39, 40–44, 50, 51( d ), 52, 54, 55, 64(1)–(4)(5)(6), Sch. 1 applied with modifications by S.I. 1985/1800 , arts. 3–11 , Schs. 1 , 2 Next: Crossheading Back to top	https://www.legislation.gov.uk/ukpga/1984/60/part/II/crossheading/entry-and-search-without-search-warrant/2000-08-25
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DynaStudy, Inc. v. Hous. Indep. Sch. Dist., CIVIL ACTION NO. H-16-1442 - Federal Cases - Case Law - VLEX 892461839 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]. 5: [object Object] Federal Cases DynaStudy, Inc. v. Hous. Indep. Sch. Dist., CIVIL ACTION NO. H-16-1442 Court United States District Courts. 5th Circuit. United States District Courts. 5th Circuit. Southern District of Texas Writing for the Court EWING WERLEIN, JR., UNITED STATES DISTRICT JUDGE Citation 325 F.Supp.3d 767 Parties DYNASTUDY, INC., Plaintiff, v. HOUSTON INDEPENDENT SCHOOL DISTRICT, Defendant. Docket Number CIVIL ACTION NO. H-16-1442 Decision Date 06 April 2017 325 F.Supp.3d 767 DYNASTUDY, INC., Plaintiff, v. HOUSTON INDEPENDENT SCHOOL DISTRICT, Defendant. CIVIL ACTION NO.H-16-1442 United States District Court, S.D. Texas, Houston Division. Signed April 6, 2017 325 F.Supp.3d 770 Gary R. Sorden, Mandi M. Phillips, Timothy J. H. Craddock, Darin Michael Klemchuk, Klemchuk LLP, Dallas, TX, for Plaintiff. Cheyenne Jayne Pate, Bracewell LLP, Dallas, TX, Jonathan R. Spivey, LaTasha Mabry Snipes, Stacianne Morgan Wilson, Bracewell LLP, Houston, TX, for Defendant. MEMORANDUM AND ORDER EWING WERLEIN, JR., UNITED STATES DISTRICT JUDGE Pending is Defendant Houston Independent School District's Renewed Motion to Dismiss Pursuant to Rule 12(b)(6) and Motion to Strike Pursuant to Rule 12(f) (Document No. 28). 1 After carefully considering the motion, response, reply, and applicable law, the Court concludes as follows. I. Background Plaintiff DynaStudy, Inc. ("Plaintiff") is a Texas-based educational publishing company that produces student study aids for a variety of subjects and grade levels based on Texas's state standards. 2 Plaintiff sells its study aids to school districts, either in print form or through digital licensing, but prohibits reproduction and distribution of its copyrighted materials. 3 Plaintiff has registered numerous copyrights with the United States Copyright Office, including copyrights in its End-of-Course Review Guides ("EOC") for Biology, Chemistry, Physics, and English I. 4 Plaintiff also owns the federally-registered trademark "DynaNotes." 5 Plaintiff alleges that Defendant Houston Independent School District ("Defendant"), one of its customers, "has participated in an ongoing pattern and practice of infringing [these] intellectual property rights, ... despite the fact that [Plaintiff] has repeatedly placed Defendant on notice of such ongoing and repeated infringement." 6 Plaintiff alleges upon information and belief that "Defendant's schools, teachers, and administrators have and continue to unlawfully reproduce, distribute, adapt, and publicly display [Plaintiff's] Copyrighted Works." 7 Plaintiff alleges the following specific instances of infringement by Defendant's employees: 325 F.Supp.3d 771 • Teacher Dennis Huffman at Lanier Middle School "posted a nearly identical copy of [Plaintiff's] Grade 8 Science for STAAR guide online for anyone to download," and when Plaintiff contacted Defendant, Defendant represented that Huffman had received the copyrighted material "from someone by email." 8 • Teacher Nicole Diluglio at the High School for the Performing and Visual Arts "posted the DynaNotes Biology EOC online for anyone to download." 9 The High School for the Performing and Visual Arts had never purchased any copy of the EOC and had no right of access to it, and upon inquiry Defendant represented that Diluglio received the copyrighted material "from a colleague." 10 • Teacher Thomas Dohoney at Westside High School "plagiarized a significant portion of DynaStudy's Physics EOC and Chemistry EOC student course notes and then posted these unauthorized derivative works online at Defendant's website for anyone to download," after removing Plaintiff's copyright notices. 11 Plaintiff's website was included at the bottom of each page that Dohoney distributed. 12 • Teacher Marla Maharaj at DeBakey High School "posted a full version of DynaStudy's Biology EOC student course notes online at Defendant's website." 13 • Teacher Amanda Schultz-Weaver at Reagan High School "posted a copy of DynaStudy's Biology EOC student course notes online," from which copy Plaintiff's copyrights and trademarks had been removed. 14 Numerous other school districts and organizations infringed on Plaintiff's copyright by posting and reposting this document. 15 The document appears to have been created by teacher Michael Partridge at Reagan High School, which never purchased Plaintiff's Biology EOC Student Course. 16 • When Plaintiff's sales representative met with administrator Jacqueline Thompson at Yates High School to showcase Plaintiff's course notes, Thompson asked her to leave some examples for teachers to review, assuring her that the materials would not be copied. 17 When the representative returned to collect the notes, they had tape over the language at the bottom stating, "COPYING THIS MATERIAL IS STRICTLY PROHIBITED," and Thompson did not deny that the works had been copied, although she professed to not know who had copied them. 18 Plaintiff alleges that despite knowing of Plaintiff's intellectual property rights in its works and receiving repeated notices of ongoing infringement from 2012 to 2016, "Defendant's teachers and administrators 325 F.Supp.3d 772 continued to unlawfully distribute [Plaintiff's] materials amongst themselves" and to make unauthorized paper copies, and "Defendant has failed to take adequate steps to halt all infringement of [Plaintiff's] intellectual property rights." 19 In this suit Plaintiff seeks injunctive relief and damages for Defendant's violation of its intellectual property rights. 20 Plaintiff's First Amended Complaint alleges claims for: (1) copyright infringement; (2) contributory copyright infringement; (3) vicarious copyright infringement; (4) violation of § 1202(B) of the Digital Millennium Copyright Act ("DMCA"); and (5) trademark infringement. 21 Defendant moves to dismiss Counts 2-5 for failure to state a claim, to dismiss as time-barred the allegations related to Huffman, to dismiss with prejudice the claims alleged in Plaintiff's original Complaint but not realleged in its First Amended Complaint, and to strike certain allegations as immaterial, impertinent, and unduly prejudicial to Defendant. 22 II. Motion to Strike Not as a separate focused motion, but rather as an add-on to several of its Rule 12(b)(6) arguments, Defendant moves under Rule 12(f) to strike Plaintiff's allegations in paragraphs 1, 25-27, 40-45, and the figures on pages 12-15 of Plaintiff's First Amended Complaint. 23 Rule 12(f) provides that " [t]he court may strike from a pleading an insufficient defense or any redundant, immaterial, impertinent, or scandalous matter." FED. R. CIV. P. 12(f). Striking a pleading "is a drastic remedy to be resorted to only when required for the purposes of justice" and a motion to strike "should be granted only when the pleading to be stricken has no possible relation to the controversy." Augustus v. Bd. of Pub. Instruction , 306 F.2d 862 , 868 (5th Cir. 1962) (quoting Brown & Williamson Tobacco Corp. v. United States , 201 F.2d 819 , 822 (6th Cir. 1953) ); see also Encore Bank, N.A. v. Bank of Am., N.A. , 918 F.Supp.2d 633 , 642 (S.D. Tex. 2013) ( "Motions to strike are usually viewed with disfavor and rarely granted since they seek a drastic remedy and are frequently sought merely to delay." ). After carefully reading Plaintiff's above-referenced allegations, it is evident that Defendant's conclusory arguments that they should be stricken as "immaterial, impertinent and unduly prejudicial" are wholly without merit under the standard of Rule 12(f). The allegations have at least some "possible relation to the controversy," Augustus , 306 F.2d at 868, and are not the kind of impertinent or scandalous pleadings that Rule 12(f) proscribes. " [T]he purposes of justice" therefore do not require striking any of Plaintiff's pleadings, id. , and Defendant's motion to strike is denied. III. Motion to Dismiss A. Legal Standard Rule 12(b)(6) provides for dismissal of an action for "failure to state a claim upon which relief can be granted."FED. R. CIV. P. 12(b)(6). When a district court reviews the sufficiency of a complaint before it receives any evidence either by affidavit or admission, its task is inevitably a limited one. See Scheuer v. Rhodes , 416 U.S. 232 , 94 S.Ct. 1683 , 1686, 40 L.Ed.2d 90 (1974), abrogated on other grounds by 325 F.Supp.3d 773 Harlow v. Fitzgerald , 457 U.S. 800 , 102 S.Ct. 2727 , 73 L.Ed.2d 396 (1982). The issue is not whether the plaintiff ultimately will prevail, but whether the plaintiff is entitled to offer evidence to support the claims. Id. In considering a motion to dismiss under Rule 12(b)(6), the district court must construe the allegations in the complaint favorably to the pleader and must accept as true all well-pleaded facts in the complaint. See Lowrey v. Tex. A&M Univ. Sys. , 117 F.3d 242 , 247 (5th Cir. 1997). To survive dismissal, a complaint must plead "enough facts to state a claim to relief that is plausible on its face." Bell Atl. Corp. v. Twombly , 550 U.S. 544 , 127 S.Ct. 1955 , 1974, 167 L.Ed.2d 929 (2007). "A claim has facial plausibility when the plaintiff pleads factual content that allows the court to draw the reasonable inference that the defendant is liable for the misconduct alleged." Ashcroft v. Iqbal , 556 U.S. 662 , 129 S.Ct. 1937 , 1949, 173 L.Ed.2d 868 (2009). While a complaint "does not need detailed factual allegations ... [the] allegations must be enough to raise a right to relief above the speculative level, on the assumption that all the allegations in the complaint are true (even if doubtful in fact)." Twombly , 127 S.Ct. at 1964-65 (citations and internal footnote omitted). B. Discussion 1. Plaintiff's Prior Claims ...	https://case-law.vlex.com/vid/dynastudy-inc-v-hous-892461839
Publications - Global Disability Innovation Hub The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good. Type Report Themes Assistive & Accessible Technology Assistive Technology Changes Lives: an assessment of AT need and capacity in England Vicki Austin,Dilisha Patel,Jamie Danemayer,Kate Mattick,Anna Landre,Marketa Smitova,Maryam Bandukda, Aoife Healy, Nachiappan Chockalingam,Diane Bell,Cathy Holloway This report was prepared by Global Disability Innovation (GDI) Hub for the Disability Unit in the Cabinet Office His Majesty’s Government (HMG). The report presents findings from a Country Capacity Assessment (CCA) of AT access in England. Findings illustrate a complex state of AT in England. While delivery systems tend to provide quality products that have a strong, positive impact on people’s lives, processes are often slow and stressful for users and providers alike. Startlingly, there is also an AT access gap of 31% of disabled people not having the assistive products they need to flourish, thrive, or even participate in daily life. The Cabinet Office; 2023 Abstract Assistive Technology Changes Lives: an assessment of AT need and capacity in England The aim of this research was to undertake a Country Capacity Assessment (CCA) to inform a more integrated approach to Assistive Technology (AT) provision in England. The results aim to support policymakers in identifying actions to strengthen service delivery to better meet disabled people’s needs, improving outcomes for AT users and reducing inefficiencies in the current approach. The research was undertaken from November 2022 to March 2023 and led by the Global Disability Innovation (GDI) Hub, which is the World Health Organization (WHO) Global Collaborating Centre on AT access, using WHO tools in the Assistive Technology Assessment (ATA) suite. Cite Assistive Technology Changes Lives: an assessment of AT need and capacity in England Suggested Citation: Austin, V, Patel, D, Danemayer, J, Mattick, K, Landre, A, Smitova, M, Bandukda, M, Healy, A, Chockalingam, N, Bell D, and Holloway, C; Assistive Technology Changes Lives: an assessment of AT need and capacity in England; Cabinet Office, HMG; 2023 Assistive Technology Changes Lives: an assessment of AT need and capacity in England Type Conference Paper Themes Assistive & Accessible Technology Culture and Participation The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Giulia Barbareschi,Catherine Holloway, Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, Joyce Olenja We present the findings of a case study of mobile technology use by People with Visual Impairment (VIPs) in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted. CHI '20: Proceedings of the 2020 CHI Conference; 2020 Abstract The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Living in an informal settlement with a visual impairment can be very challenging resulting in social exclusion. Mobile phones have been shown to be hugely beneficial to people with sight loss in formal and high-income settings. However, little is known about whether these results hold true for people with visual impairment (VIPs) in informal settlements. We present the findings of a case study of mobile technology use by VIPs in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted. Cite The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Giulia Barbareschi, Catherine Holloway, Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, and Joyce Olenja. 2020. The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya. In Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems (CHI '20). Association for Computing Machinery, New York, NY, USA, 1–15.https://doi.org/10.1145/331383... The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Type Editorial Themes Culture and Participation COVID-19 as social disability: the opportunity of social empathy for empowerment Ikenna D Ebueny, Emma M Smith,Catherine Holloway, Rune Jensen, Lucía D'Arino, Malcolm MacLachlan Social empathy is ‘the ability to more deeply understand people by perceiving or experiencing their life situations and as a result gain insight into structural inequalities and disparities’. Social empathy comprises three elements: individual empathy, contextual understanding and social responsibility. COVID-19 has created a population-wide experience of exclusion that is only usually experienced by subgroups of the general population. Notably, persons with disability, in their everyday lives, commonly experience many of the phenomena that have only recently been experienced by members of the general population. COVID-19 has conferred new experiential knowledge on all of us. We have a rare opportunity to understand and better the lives of persons with disabilities for whom some aspects of the COVID- 19 experience are enduring. This allows us greater understanding of the importance of implementing in full a social and human rights model of disability, as outlined in the UNCRPD. BMJ Global Health; 2020 Abstract COVID-19 as social disability: the opportunity of social empathy for empowerment COVID-19 has conferred new experiential knowledge on society and a rare opportunity to better understand the social model of disability and to improve the lives of persons with disabilities. The COVID-19 experience may offer contextual knowledge of the prepandemic lives of persons with disabilities and foster greater social awareness, responsibility and opportunities for change towards a more inclusive society. Information, family and social relationships, health protection and healthcare, education, transport and employment should be accessible for all groups of the population. The means must be developed and deployed to ensure equity – the deployment of resources so that people with different types of needs have the same opportunities for living good lives in inclusive communities. We have learnt from COVID-19 that inclusive healthcare and universal access should be the new normal, that its provision as a social good is both unifying and empowering for society as a whole. Cite COVID-19 as social disability: the opportunity of social empathy for empowerment Ebuenyi ID, Smith EM, Holloway C , et alCOVID-19 as social disability: the opportunity of social empathy for empowerment BMJ Global Health2020;5:e003039. COVID-19 as social disability: the opportunity of social empathy for empowerment Type Editorial Themes Assistive & Accessible Technology Research Group Social Justice Developing inclusive and resilient systems: COVID-19 and assistive technology Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi,Catherine Holloway&Victoria Austin While the inadequacies of our existing assistive technology systems, policies, and services have been highlighted by the acute and rapidly changing nature of the COVID-19 pandemic, these failures are also present and important during non-crisis times. Each of these actions, taken together, will not only address needs for more robust and resilient systems for future crises, but also the day-to-day needs of all assistive technology users. We have a responsibility as a global community, and within our respective countries, to address these inadequacies now to ensure an inclusive future. Disability & Society; 2020 Abstract Developing inclusive and resilient systems: COVID-19 and assistive technology Assistive technology is a critical component of maintaining health, wellbeing, and the realization of rights for persons with disabilities. Assistive technologies, and their associated services, are also paramount to ensuring individuals with functional limitations have access to important health and social service information, particularly during a pandemic where they may be at higher risk than the general population. Social isolation and physical distancing have further marginalized many within this population. We have an opportunity to learn from the COVID-19response to develop more inclusive and resilient systems that will serve people with disabilities more effectively in the future. In this Current Issues piece, we present a starting point for discussion, based on our experiences working to promote access to assistive technologies through inclusive and sustainable systems and policies. Developing inclusive and resilient systems: COVID-19 and assistive technology Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi, Catherine Holloway & Victoria Austin (2021) Developing inclusive and resilient systems: COVID-19 and assistive technology, Disability & Society, 36:1, 151-154, DOI:10.1080/09687599.2020.1829558 Developing inclusive and resilient systems: COVID-19 and assistive technology Type Conference Paper Disability design and innovation in computing research in low resource settings Dafne Zuleima Morgado-Ramirez,Giulia Barbareschi, Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney,Catherine Holloway 80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes. ASSETS '20: Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility; 2020 Abstract Disability design and innovation in computing research in low resource settings 80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes. In short, researchers rarely examine what was challenging in the process of collaboration. We present reflections from the field across four studies. Our contributions are: (1) an overview of past work in computing with a focus on disability in low resource settings and (2) learnings and recommendations from four collaborative projects in Uganda, Jordan and Kenya over the last two years, that are relevant for future HCI studies in low resource settings with communities with disabilities. We do this through a lens of Disability Interaction and ICT4D. Cite Disability design and innovation in computing research in low resource settings Dafne Zuleima Morgado-Ramirez, Giulia Barbareschi, Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney, and Catherine Holloway. 2020. Disability design and innovation in computing research in low resource settings. In Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS '20). Association for Computing Machinery, New York, NY, USA, Article 11, 1–7.https://doi.org/10.1145/337362... Disability design and innovation in computing research in low resource settings Type Editorial Research Group Social Justice Assistive Technology (AT), for What? Vicki Austin, Catherine Holloway This year (2022) has seen the publication of the World’s first Global Report on Assistive Technology (GReAT) [1]. This completes almost a decade of work to ensure assistive technology (AT) access is a core development issue. The lack of access to assistive products (APs), such as wheelchairs, hearing aids, and eyeglasses, as well as less well-referenced products such as incontinence pads, mobile phone applications, or walking sticks, affects as many as 2.5 billion people globally. Furthermore, the provision of APs would reap a 1:9 return on investment [2]. This could result in a family in need netting (or living without) over GBP 100,000 in their lifetime [2] or more, if we count dynamic overspills in the economy such as employment of assistive technology services and manufacturing of devices [3]. Societies; 2021 Abstract Assistive Technology (AT), for What? Amartya Sen’s seminal Tanner lecture: Equality of What?began a contestation on social justice and human wellbeing that saw a new human development paradigm emerge—the capability approach (CA)—which has been influential ever since. Following interviews with leading global assistive technology (AT) stakeholders, and users, this paper takes inspiration from Sen’s core question and posits, AT for what?arguing that AT should be understood as a mechanism to achieve the things that AT users’ value. Significantly, our research found no commonly agreed operational global framework for (disability) justice within which leading AT stakeholders were operating. Instead, actors were loosely aligned through funding priorities and the CRPD. We suggest that this raises the possibility for (welcome and needed) incoming actors to diverge from efficiently designed collective action, due to perverse incentives enabled by unanchored interventions. The Global Report on Assistive Technology (GReAT) helps, greatly! However, we find there are still vital gaps in coordination; as technology advances, and AT proliferates, no longer can the device-plus-service approach suffice. Rather, those of us interested in human flourishing might explore locating AT access within an operational global framework for disability justice, which recognizes AT as a mechanism to achieve broader aims, linked to people’s capabilities to choose what they can do and be. Assistive Technology (AT), for What? Austin, V.; Holloway, C. Assistive Technology (AT), for What? Societies2022, 12, 169.https://doi.org/10.3390/soc120... Assistive Technology (AT), for What? Type Workshop Themes Assistive & Accessible Technology Research Group Disability Interactions Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Sahan Bulathwela, María Pérez-Ortiz,Catherine Holloway, John Shawe-Taylor This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Workshop on Machine Learning for the Developing World (ML4D) at the Conference on Neural Information Processing Systems 2021; 2021 Abstract Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Artificial Intelligence (AI) in Education has been said to have the potential for building more personalised curricula, as well as democratising education worldwide and creating a Renaissance of new ways of teaching and learning. Millions of students are already starting to benefit from the use of these technologies, but millions more around the world are not. If this trend continues, the first delivery of AI in Education could be greater educational inequality, along with a global misallocation of educational resources motivated by the current technological determinism narrative. In this paper, we focus on speculating and posing questions around the future of AI in Education, with the aim of starting the pressing conversation that would set the right foundations for the new generation of education that is permeated by technology. This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Finally, we ask what would it take for this educational revolution to provide egalitarian and empowering access to education, beyond any political, cultural, language, geographical and learning ability barriers. Share Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Type Workshop Themes Assistive & Accessible Technology Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Tabish Ahmed, Sahan Bulathwela The informational needs of people are highly contextual and can depend on many different factors such as their current knowledge state, interests and goals [1, 2, 3]. However, an effective information retrieval companion should minimise the human effort required in i) expressing a human information need and ii) navigating a lengthy result set. Using topical representations of the user history (e.g. [4]) can immensely help formulating zero shot queries and refining short user queries that enable proactive information retrieval (IR). While the world has digital textual information in abundance, it can often be noisy (e.g. extracted through Automatic Speech Recognition (ASR), PDF text extraction etc.), leading to state-of-the-art neural models being highly sensitive to the noise producing sub-optimal results [5]. This demands denoising steps to refine both query and document representation. In this paper, we argue that Wikipedia, an openly available encyclopedia, can be a humanly intuitive knowledge base [6] that has the potential to provide the world view many noisy information Retrieval systems need. Published at the First Workshop on Proactive and Agent-Supported Information Retrieval at CIKM 2022; 2022 Abstract Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Extracting useful information from the user history to clearly understand informational needs is a crucial feature of a proactive information retrieval system. Regarding understanding information and relevance, Wikipedia can provide the background knowledge that an intelligent system needs. This work explores how exploiting the context of a query using Wikipedia concepts can improve proactive information retrieval on noisy text. We formulate two models that use entity linking to associate Wikipedia topics with the relevance model. Our experiments around a podcast segment retrieval task demonstrate that there is a clear signal of relevance in Wikipedia concepts while a ranking model can improve precision by incorporating them. We also find Wikifying the background context of a query can help disambiguate the meaning of the query, further helping proactive information retrieval. Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Type Editorial Themes Assistive & Accessible Technology Research Group Disability Interactions The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative Chapal Khasnabis,Catherine Holloway, Malcolm MacLachlan We are now in an era of assistive care and assistive living—whereby many people, of all ages, in good health, and those who are more frail, or with cognitive or functional impairments, are using a broad range of technologies to assist and enhance their daily living. Assistive living 1is becoming an important part of population health and rehabilitation, which can help to maximise an individual's abilities, regardless of age or functional capacity. This encouraging shift in ethos has been strengthened by the response to the COVID-19 pandemic, in which a plethora of digital and remote technologies have been used. The Lancet; 2020 The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative Type Editorial Themes Assistive & Accessible Technology Culture and Participation Research Group Social Justice Critical Junctures in Assistive Technology and Disability Inclusion Dr Maria Kett,Catherine Holloway,Vicki Austin,Dr Maria Kett It is clear from the events of the last 18 months that while technology has a huge potential for transforming the way we live and work, the entire ecosystem—from manufacturing to the supply chain—is vulnerable to the vagaries of that ecosystem, as well as having the potential to exacerbate new and existing inequalities [1]. Nowhere has this been more apparent than in the lives of people with disabilities, who make up around 15% of the world’s population and already face barriers to accessing education, employment, healthcare and other services [2]. Some of these barriers are a result of unequal access and opportunities. However, there is a growing movement to better understand how assistive technology systems and services can be designed to enable more robust and equitable access for all. As part of this growing movement, the Paralympic Games in Tokyo this autumn saw the launch of a new global campaign to transform the lives of the world’s 1.2 bn persons with disabilities: the ‘WeThe15’ campaign reached more than 4.5 billion people through its marketing and stands ready to be the biggest of its kind in history. Next year, the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF), AT scale and GDI Hub will publish the first World Report on Access to Assistive Technology, which will include research from the £20 million, UK Aid funded, GDI Hub-led, programme, AT2030. Ahead of that, in this Special Issue, we focus on how some events and situations—as diverse as the coronavirus pandemic and the Paralympics—can act as ‘critical junctures’ that can enable a rethink of the status quo to facilitate and promote change. Sustainability; 2021 Cite Critical Junctures in Assistive Technology and Disability Inclusion Kett, M.; Holloway, C.; Austin, V. Critical Junctures in Assistive Technology and Disability Inclusion. Sustainability2021, 13, 12744.https://doi.org/10.3390/su1322... Share Critical Junctures in Assistive Technology and Disability Inclusion Type Book Research Group Disability Interactions Disability Interactions Creating Inclusive Innovations Catherine Holloway,Giulia Barbareschi ; 2021 Abstract Disability Interactions Creating Inclusive Innovations Disability interactions (DIX) is a new approach to combining cross-disciplinary methods and theories from Human Computer Interaction (HCI), disability studies, assistive technology, and social development to co-create new technologies, experiences, and ways of working with disabled people. DIX focuses on the interactions people have with their technologies and the interactions which result because of technology use. A central theme of the approach is to tackle complex issues where disability problems are part of a system that does not have a simple solution. Therefore, DIX pushes researchers and practitioners to take a challenge-based approach, which enables both applied and basic research to happen alongside one another. DIX complements other frameworks and approaches that have been developed within HCI research and beyond. Traditional accessibility approaches are likely to focus on specific aspects of technology design and use without considering how features of large-scale assistive technology systems might influence the experiences of people with disabilities. DIX aims to embrace complexity from the start, to better translate the work of accessibility and assistive technology research into the real world. DIX also has a stronger focus on user-centered and participatory approaches across the whole value chain of technology, ensuring we design with the full system of technology in mind (from conceptualization and development to large-scale distribution and access). DIX also helps to acknowledge that solutions and approaches are often non-binary and that technologies and interactions that deliver value to disabled people in one situation can become a hindrance in a different context. Therefore, it offers a more nuanced guide to designing within the disability space, which expands the more traditional problem-solving approaches to designing for accessibility. This book explores why such a novel approach is needed and gives case studies of applications highlighting how different areas of focus—from education to health to work to global development—can benefit from applying a DIX perspective. We conclude with some lessons learned and a look ahead to the next 60 years of DIX. Share Disability Interactions Creating Inclusive Innovations Type Editorial Themes Assistive & Accessible Technology Research Group Disability Interactions Introduction to the companion papers to the global report on assistive technology Johan Borg, Wei Zhang, Emma M. Smith,Cathy Holloway GReAT, but do we care? If accessible, assistive technology would be life changing for a billion people across the world today – and two billion people in 2050 (WHO,2018). It would make the difference between independence and dependence, inclusion and exclusion, life and death. It holds the potential to improve and transform health, education, livelihood and social participation; fundamental human rights everyone is entitled to. And if we are lucky to grow old, the chances are that we all would use assistive technology by then. But do we care? Assistive Technology, The Official Journal of RESNA; 2021 Cite Introduction to the companion papers to the global report on assistive technology Johan Borg, Wei Zhang, Emma M. Smith & Cathy Holloway (2021) Introduction to the companion papers to the global report on assistive technology, Assistive Technology, 33:sup1, 1-2, DOI:10.1080/10400435.2021.2003658 Share Introduction to the companion papers to the global report on assistive technology Type Conference Paper Themes Assistive & Accessible Technology Value beyond function: analyzing the perception of wheelchair innovations in Kenya Barbareschi, G; Daymond, S; Honeywill, J; Singh, A; Noble, D; Mbugua, N; Harris, I;Austin, V;Holloway, C The World Health Organization (WHO) defines Assistive Technology (AT) as “an umbrella term covering the systems and services related to the delivery of assistive products and services” [6]. This definition highlights how AT encompasses not only the physical and digital products used by millions of persons with disabilities (PWDs) worldwide, but also the systems and services that accompany the provision of these devices [78]. ASSETS '20: The 22nd International ACM SIGACCESS Conference on Computers and Accessibility.; 2020 Abstract Value beyond function: analyzing the perception of wheelchair innovations in Kenya Innovations in the field of assistive technology are usually evaluated based on practical considerations related to their ability to perform certain functions. However, social and emotional aspects play a huge role in how people with disabilities interact with assistive products and services. Over a five months period, we tested an innovative wheelchair service provision model that leverages 3D printing and Computer Aided Design to provide bespoke wheelchairs in Kenya. The study involved eight expert wheelchair users and five healthcare professionals who routinely provide wheelchair services in their community. Results from the study show that both users and providers attributed great value to both the novel service delivery model and the wheelchairs produced as part of the study. The reasons for their appreciation went far beyond the practical considerations and were rooted in the fact that the service delivery model and the wheelchairs promoted core values of agency, empowerment and self-expression. Share Value beyond function: analyzing the perception of wheelchair innovations in Kenya Type Conference Paper Themes Assistive & Accessible Technology Culture and Participation Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Nusrat Jahan,Giulia Barbareschi, Clara Aranda Jan, Charles Musungu Mutuku, Naemur Rahman,Victoria Austin,Catherine Holloway Worldwide it is estimated that there are over a billion people who live with some form of disability[1]. Approximately 80% of people with disabilities live in low-and-middle income countries (LMICs). The combination of an inaccessible environment compounded by socio-economic factors such as poverty and stigma, makes it more likely for people with disabilities to be marginalised and excluded from society[1]. Assistive Technologies (ATs) are known to bridge the accessibility gaps and allow for greater social inclusion. However, there is a lack of adequate access to ATs in LMICs, combined with often poorly designed services, which only magnifies these challenges, thus limiting the opportunities for persons with disabilities to live an independent life[2]. Despite the importance of AT, access to AT globally is inadequate with only 10 percent of those in need having access to the ATs that they need[2]. 2020 IEEE Global Humanitarian Technology Conference Abstract Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Globally, mobile technology plays a significant role connecting and supporting people with disabilities. However, there has been limited research focused on understanding the impact of mobile technology in the lives of persons with disabilities in low or middle- income countries. This paper presents the findings of a participatory photovoice study looking at the role that mobile phones play in the daily lives of 16 persons with disabilities in Kenya and Bangladesh. Participants used a combination of pictures and voice recordings to capture their own stories and illustrate the impact that mobile phone use has on their lives. Through thematic analysis, we categorized the benefits of mobile phones captured by participants as 1) Improved social connection; 2) Increased independence and 3) Access to opportunities. While mobile phones are ubiquitously used for communication, for persons with disabilities they become essential assistive technologies that bridge barriers to opportunities which are not accessible otherwise. Our paper adds evidence to the need for mobile phones for persons with disabilities to enable communication and connectivity in support of development. Cite Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh N. Jahan et al., "Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh," 2020 IEEE Global Humanitarian Technology Conference (GHTC), Seattle, WA, USA, 2020, pp. 1-8, doi: 10.1109/GHTC46280.2020.9342934. Share Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Type Conference Paper Themes Assistive & Accessible Technology Research Group Local Productions A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries Tigmanshu Bhatnagar, George Torrens, Ben Oldfrey, Priya Morjaria Felipe Ramos Barajas, Katherine PerryandCatherine Holloway Access to information on digital platforms not only facilitates education, employment, entertainment, social interaction but also facilitates critical governmental services, ecommerce, healthcare services and entrepreneurship [1]. Article 9 of United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) enforces its signatories to commit to provide full accessibility to every citizen of the nation [2]. This has helped to spearhead accessibility directives such as the European Accessibility Act [3] that aims to improve the functioning of markets for accessible products and services. Such directives contribute to ensure that mainstream digital technologies (smartphones, computers etc.) are accessible for everyone and without being socially remarkable, they are able to assist in daily living. Additionally, there is evidence that improving access in mainstream technologies improves product experience and usability for everyone [4]. However, mainstream access has not been fully realized, leading to inferior opportunities for people with disabilities, a disparity which is more prominent in lower and middle-income countries [5]. RESNA Annual Conference; 2021 A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries Type Workshop Themes Assistive & Accessible Technology Culture and Participation Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions Maryam Bandukda, Aneesha Singh,Catherine Holloway,Nadia Berthouze, Emeline Brulé, Ana Tajadura-Jiménez, Oussama Metatla, Ana Javornik, and Anja Thieme The emerging possibilities of multisensory interactions provide an exciting space for disability and open up opportunities to explore new experiences for perceiving one's own body, it's interactions with the environment and also to explore the environment itself. In addition, dynamic aspects of living with disability, life transitions, including ageing, psychological distress, long-term conditions such as chronic pain and new conditions such as long-COVID further affect people's abilities. Interactions with this diversity of embodiments can be enriched, empowered and augmented through using multisensory and cross-sensory modalities to create more inclusive technologies and experiences. To explore this, in this workshop we will explore three related sub-domains: immersive multi-sensory experiences, embodied experiences, and disability interactions and design. CHI EA '21: Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems Abstract Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions The emerging possibilities of multisensory interactions provide an exciting space for disability and open up opportunities to explore new experiences for perceiving one's own body, it's interactions with the environment and also to explore the environment itself. In addition, dynamic aspects of living with disability, life transitions, including ageing, psychological distress, long-term conditions such as chronic pain and new conditions such as long-COVID further affect people's abilities. Interactions with this diversity of embodiments can be enriched, empowered and augmented through using multisensory and cross-sensory modalities to create more inclusive technologies and experiences. To explore this, in this workshop we will explore three related sub-domains: immersive multi-sensory experiences, embodied experiences, and disability interactions and design. The aim is to better understand how we can re-think the senses in technology design for disability interactions and the dynamic self, constructed through continuously changing sensing capabilities either because of changing ability or because of the empowering technology. This workshop will: (i) bring together HCI researchers from different areas, (ii) discuss tools, frameworks and methods, and (iii) form a multidisciplinary community to build synergies for further collaboration. Cite Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions Maryam Bandukda, Aneesha Singh, Catherine Holloway, Nadia Berthouze, Emeline Brulé, Ana Tajadura-Jiménez, Oussama Metatla, Ana Javornik, and Anja Thieme. 2021. Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions. Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA, Article 118, 1–5. DOI:https://doi.org/10.1145/341176... Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions Type Conference Paper Themes Assistive & Accessible Technology Opportunities for Supporting Self-efficacy through Orientation and Mobility Training Technologies for Blind and Partially Sighted People Maryam Bandukda,Catherine Holloway, Aneesha Singh,Giulia Barbareschi, Nadia Berthouze We conducted semi-structured interviews with 20 BPS people and 8 Mobility and Orientation Trainers (MOT). The interviews were thematically analysed and organised into four overarching themes discussing factors influencing the self-efficacy belief of BPS people: Tools and Strategies for O&M training, Technology Use in O&M Training, Changing Personal and Social Circumstances, and Social Influences. We further highlight opportunities for combinations of multimodal technologies to increase access to and effectiveness of O&M training. ASSETS '21: Proceedings of the 23rd International ACM SIGACCESS Conference on Computers and Accessibility Abstract Opportunities for Supporting Self-efficacy through Orientation and Mobility Training Technologies for Blind and Partially Sighted People Orientation and mobility (O&M) training provides essential skills and techniques for safe and independent mobility for blind and partially sighted (BPS) people. The demand for O&M training is increasing as the number of people living with vision impairment increases. Despite the growing portfolio of HCI research on assistive technologies (AT), few studies have examined the experiences of BPS people during O&M training, including the use of technology to aid O&M training. To address this gap, we conducted semi-structured interviews with 20 BPS people and 8 Mobility and Orientation Trainers (MOT). The interviews were thematically analysed and organised into four overarching themes discussing factors influencing the self-efficacy belief of BPS people: Tools and Strategies for O&M training, Technology Use in O&M Training, Changing Personal and Social Circumstances, and Social Influences. We further highlight opportunities for combinations of multimodal technologies to increase access to and effectiveness of O&M training. Share Opportunities for Supporting Self-efficacy through Orientation and Mobility Training Technologies for Blind and Partially Sighted People Type Conference Paper Themes Assistive & Accessible Technology What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT Giulia Barbareschi, Norah Shitawa Kopi,Ben Oldfrey,Catherine Holloway In this paper, we examine how young Kenyans without disabilities view people with disabilities and AT users. Findings show that while the portrayal of disability is often shaped by negative emotion, participants felt that many of the barriers affecting people with disabilities were created by society. Perceptions of AT differed –devices were not only seen as a mark of disability but also as a sign of access to resources. Therefore, what we see is an emergent picture where social barriers can be reinforced by poverty, and where poverty reinforces social barriers faced by people with disabilities. We conclude that access to appropriate technology alongside societal interventions tackling incorrect beliefs about disability can help to overcome the stigma faced by people with disabilities. ASSETS '21: Proceedings of the 23rd International ACM SIGACCESS Conference on Computers and Accessibility Abstract What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT Most research which investigates stigma towards with people with disabilities and the use of Assistive Technology (AT) are based in the Global North and focus on the experiences of people with disabilities and the consequences that stigma has on choices surrounding AT. However, stigma is a societal construct rooted in the attitude and beliefs that people without disabilities hold on disability and AT. Furthermore, the portrayal of people with disabilities and AT is dependent on the social context. In this paper, we examine how young Kenyans without disabilities view people with disabilities and AT users. Findings show that while the portrayal of disability is often shaped by negative emotion, participants felt that many of the barriers affecting people with disabilities were created by society. Perceptions of AT differed –devices were not only seen as a mark of disability but also as a sign of access to resources. Therefore, what we see is an emergent picture where social barriers can be reinforced by poverty, and where poverty reinforces social barriers faced by people with disabilities. We conclude that access to appropriate technology alongside societal interventions tackling incorrect beliefs about disability can help to overcome the stigma faced by people with disabilities. Cite What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT Giulia Barbareschi, Norah Shitawa Kopi, Ben Oldfrey, and Catherine Holloway. 2021. What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT. In The 23rd International ACM SIGACCESS Conference on Computers and Accessibility( ASSETS '21). Association for Computing Machinery, New York, NY, USA, Article 18, 1–13. DOI:https://doi.org/10.1145/3441852.3471226 Share What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT Type Editorial Themes Assistive & Accessible Technology A right to the frivolous? Renegotiating a wellbeing agenda for AT research Giulia Barbareschi& Tom Shakespeare Assistive products (APs) are broadly defined as “ any product (including devices, equipment, instruments, and software), either specially designed and produced or generally available, whose primary purpose is to maintain or improve an individual’s functioning and independence and thereby promote their wellbeing” (Khasnabis et al.,2015). Although the concept of wellbeing is extremely slippery and researchers have yet to agree on a single definition for it, as individuals we instinctively develop mental models about what does, and does not, promote our happiness and wellbeing. Considerations about values, wellbeing and happiness are extremely personal and are shaped by a variety of factors ranging from our age and socio-cultural background to our life experiences (Schwartz & Bardi,2001). RESNA Abstract A right to the frivolous? Renegotiating a wellbeing agenda for AT research Assistive products (APs) are broadly defined as “ any product (including devices, equipment, instruments, and software), either specially designed and produced or generally available, whose primary purpose is to maintain or improve an individual’s functioning and independence and thereby promote their wellbeing” (Khasnabis et al.,2015). Although the concept of wellbeing is extremely slippery and researchers have yet to agree on a single definition for it, as individuals we instinctively develop mental models about what does, and does not, promote our happiness and wellbeing. Considerations about values, wellbeing and happiness are extremely personal and are shaped by a variety of factors ranging from our age and socio-cultural background to our life experiences (Schwartz & Bardi,2001). However, when it comes to assistive technology (AT) research, our focus seems to be primarily geared toward values and activities in the domains of education, employment, transport or health, often framed according to an outcome driven perspective that is heavily influenced by what is seen as useful (often what is measurable), vs what is frivolous (less tangible social or emotional aspects). This disparity parallels the priorities of the disability rights movement and disability studies research that have helped to shape the research agenda around disability and AT. Often influenced by labor movement politics, or feminism, there appears to have been more concern with public and practical aspects of social life as opposed to the more private and sensitive ones (Shakespeare,2014). The focus on the public utilitarian function of AT becomes even more evident when we consider AT research carried out in the Global South. In this context the success of an intervention is usually assessed using measures of outcome and impact which can be somehow linked to economic improvement (Alkire,2016). In this editorial, we are not suggesting that enabling people with disabilities to gain a good education, obtain a fulfilling job or be able to vote are not important goals for the APs we develop and research. But are those the only worthwhile goals? Should we not also enquire whether existing and future APs could help people with disabilities to develop meaningful friendships, enjoy fulfilling sex lives with their partners of choice, cook sociable dinners, or engage in their favorite hobbies? Although sporadic publications focus on the role of APs in the context of personal relationships, sexuality, or fun and play for people with disabilities do exist, these are rare, and often framed around utilitarian goals. For example, research around AT and play is largely focused on children and often examined in connection to learning outcomes. Similarly, sex and sexuality are often explored solely in connection to dysfunction, abuse or sexual health (Shakespeare & Richardson,2018). These unbalanced narratives show how the AT research agenda is dictated by a set of universal priorities that are largely focused on global measurable goals that do not necessarily match the everyday values of people with disabilities. We invite researchers and practitioners to consider ways to find a better balance between public and private aspects of life, and between utilitarian and emotional values. Both approaches have a significant impact on the lives of people with disabilities. Ultimately, as AT researchers we need to actively engage with people with disabilities to uncover their priorities, understand what different people with disabilities most value in life, and identify how current and future APs might help to make a positive impact on wellbeing. Aspects of life such as friendship, socialization, sexuality, love and play might indeed be more frivolous than practical ones such as education, health, employment and civil rights, but they are inherent to our shared humanity and fundamental to our happiness. Cite A right to the frivolous? Renegotiating a wellbeing agenda for AT research Giulia Barbareschi & Tom Shakespeare (2021) A right to the frivolous? Renegotiating a wellbeing agenda for AT research, Assistive Technology, 33:5, 237, DOI:10.1080/10400435.2021.1984112 Share A right to the frivolous? Renegotiating a wellbeing agenda for AT research Type Workshop Themes Assistive & Accessible Technology Research Group Disability Interactions Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI. Giulia Barbareschi,Dafne Zuleima Morgado-Ramirez,Catherine Holloway, Swami Manohar Swaminathan, Aditya Vashistha, and Edward Cutrell. Approximately 15% of the world's population has a disability and 80% live in low resource-settings, often in situations of severe social isolation. Technology is often inaccessible or inappropriately designed, hence unable to fully respond to the needs of people with disabilities living in low resource settings. Also lack of awareness of technology contributes to limited access. This workshop will be a call to arms for researchers in HCI to engage with people with disabilities in low resourced settings to understand their needs and design technology that is both accessible and culturally appropriate. Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Abstract Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI. Approximately 15% of the world's population has a disability and 80% live in low resource-settings, often in situations of severe social isolation. Technology is often inaccessible or inappropriately designed, hence unable to fully respond to the needs of people with disabilities living in low resource settings. Also lack of awareness of technology contributes to limited access. This workshop will be a call to arms for researchers in HCI to engage with people with disabilities in low resourced settings to understand their needs and design technology that is both accessible and culturally appropriate. We will achieve this through sharing of research experiences, and exploration of challenges encountered when planning HCI4D studies featuring participants with disabilities. Thanks to the contributions of all attendees, we will build a roadmap to support researchers aiming to leverage post-colonial and participatory approaches for the development of accessible and empowering technology with truly global ambitions. Cite Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI. Giulia Barbareschi, Dafne Zuleima Morgado-Ramirez, Catherine Holloway, Swami Manohar Swaminathan, Aditya Vashistha, and Edward Cutrell. 2021. Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI. Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA, Article 124, 1–5. DOI:https://doi.org/10.1145/3411763.3441340 Share Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI. Type Conference Paper Themes Assistive & Accessible Technology Inclusive Educational Technology Transforming a Monolithic Sheet of Nitinol into a Passive Reconfigurable Tactile Pixel Array Display at Braille Resolution Tigmanshu Bhatnagar, Nicolai Marquardt, Mark Miodownik,Catherine Holloway Shape changing materials create a unique opportunity to design reconfigurable tactile display actuators. In this paper, we present a method that transforms a single thin monolithic sheet of Nitinol into a passive reconfigurable tactile pixel array at Braille resolution. We have designed a 27x27 tactile pixel array in which each pixel can be selectively actuated with an external source of heat. The pixels rise 0.4mm vertically with a peak blocked force of 0.28kg and have an average blocked force of 0.23kg at room temperature. After cooling, the pixels can be mechanically reconfigured back to their flat state for repeatable actuation. We demonstrate this actuator’s interactive capabilities through a novel erasable tactile drawing interface. IEEE World Haptics Conference; 2021 Abstract Transforming a Monolithic Sheet of Nitinol into a Passive Reconfigurable Tactile Pixel Array Display at Braille Resolution Shape changing materials create a unique opportunity to design reconfigurable tactile display actuators. In this paper, we present a method that transforms a single thin monolithic sheet of Nitinol into a passive reconfigurable tactile pixel array at Braille resolution. We have designed a 27x27 tactile pixel array in which each pixel can be selectively actuated with an external source of heat. The pixels rise 0.4mm vertically with a peak blocked force of 0.28kg and have an average blocked force of 0.23kg at room temperature. After cooling, the pixels can be mechanically reconfigured back to their flat state for repeatable actuation. We demonstrate this actuator’s interactive capabilities through a novel erasable tactile drawing interface. Cite Transforming a Monolithic Sheet of Nitinol into a Passive Reconfigurable Tactile Pixel Array Display at Braille Resolution T. Bhatnagar, N. Marquardt, M. Miodownik and C. Holloway, "Transforming a Monolithic Sheet of Nitinol into a Passive Reconfigurable Tactile Pixel Array Display at Braille Resolution," 2021 IEEE World Haptics Conference (WHC), 2021, pp. 409-414, doi: 10.1109/WHC49131.2021.9517239. Share Transforming a Monolithic Sheet of Nitinol into a Passive Reconfigurable Tactile Pixel Array Display at Braille Resolution	https://www.disabilityinnovation.com/publications?page=7&type=editorial+workshop+conference-paper+report+book
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. 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. 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. 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 Congratulations to David who was baptised on Saturday! #oxfordoratory 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 View on Instagram 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 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. God save the King! Photo from our Coronation watch party today. #oxfordoratory 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 Praying with words There is an idea among some people that our prayer is meant to evolve with time. They think that while we all start with vocal prayer (made with words either aloud or silently), we are meant, as we grow up, to use fewer words, to move on to mental prayer or meditation, and eventually move beyond that and learn pure contemplative prayer, where we are silent both without and within. Some authors speak as if the silence of contemplation were the only true prayer. And yet one of the Church’s greatest mystics, St Theresa of Avila, spent her day, in between periods of contemplation, reciting the words of the psalms of the Divine Office with her fellow sisters. Mental and contemplative prayer are certainly forms of prayer we only learn about when we are older, but vocal prayer cannot be something that we are meant to grow out of. When the Apostles asked Our Lord to teach them to pray, he told them: ‘Pray like this: Our Father, who art in heaven…’ (Matthew 6:9) He taught them, in the first place, the wordsof a prayer. Catholic interest in the Mass (which is certainly a good thing) also seems to have eclipsed our interest in other prayers, so that the only prayer book most people might own is a missal. And many other books of prayers have little space for other devotions, because so much space is given to the text of the Mass. There haven’t been so many books of prayersprinted in recent decades. When we look back a hundred years, we find a combination of factors led to a golden age of prayer books for ordinary people. I remember inheriting my grandfather’s prayer book from 1959, and feeling that I had discovered a hidden treasure. While freedom in choosing how to pray is essential, sometimes we do need someone to teach us, like Our Lord: ‘Pray like this. Say these prayers.’ And that’s what I found in that prayer book of my grandfather. Many of the prayers inour new prayer book(pretty much the entire collection of night prayers) come straight from that old prayer book. And many other collections have been plundered for their treasures too, together with a handful of newly adapted or translated texts. But that is only meant to be a starting point. It is a wonderful thing to build up — committing to memory or even to paper — our own collection of favourite prayers: from the scriptures, from the writings of the saints, from the prayers of the Church. Metropolitan Anthony of Sourozh writes in School for Prayer: Mark these passages that go deep into your heart, that move you deeply, that makes sense, that express something which is already within your experience, either of sin, or of bliss in God, or of struggle. Learn those passages, because one day when you are so completely low, so profoundly desperate that you cannot call out of your soul any spontaneous expression, any spontaneous wording, you will discover that these words come up and offer themselves to you as a gift of God, as a gift of the Church, as a gift of holiness, helping our simple lack of strength. And then you really need the prayers you have learnt and made a part of yourself. We don’t always find time to think about the words of our prayers as much as we might like. Ideally, we would spend some time thinking about not just what our prayer says to God, but also what it says to us about him and about ourselves in relation to him. St Philip used to teach people to take the Our Father slowly, word by word, phrase by phrase, and draw out all the ideas it contains. We don’t have time to do that every time we say it though. And so when we do rush through it in a few seconds, we mean implicitly whatever it was Christ meant when he gave it to his disciples and asked them to hand it down to us. And we intend to say to God all the ideas that would come to mind, if we did have a bit more time to think about it. Similarly, when our prayer has been composed by a saint, we can be confident that the thoughts those words express — even if we don’t always have time to explore them — led the author to an even closer union with God. We might think that we can compose better prayers in our own words than some of these old prayers, and that might even be true. Some part of our time of prayer can and should involve speaking to God in our own words. But there is something special about joining in a prayer that has been in use even from before we were born, that has been sanctified by centuries of use. When we use a prayer that is shared with the rest of the Church, we are reminded that we don’t just pray by ourselves. We imply not only all those ideas we might find in it, but we attach to it also all those intentions that our brothers and sisters in the Church, throughout the world, throughout time, have meant and do mean and ever will mean in their use of the same prayer. And it is a comforting thought to imagine all the saints — past, present and future — praying with us and for us in those same words. We’re delighted to launch the Oratory Prayer Book, which we’ve been working on for some time now. It’s a pocket-sized book packed with the best prayers we could find. It’s available to buy in person from our bookshop or online through our website. https://tinyurl.com/oratoryprayerbook #oxfordoratory The Oratory Prayer Book Our latest publication — now available from our Bookshop and online The Oratory Prayer Book is designed for anyone to use: children and adults, new converts and cradle Catholics. It has prayers for all sorts of occasions and for all sorts of people, but is small enough to carry around all the time in a pocket. The riches of Catholic devotion are included, with beautiful prayers from Scripture and the Saints, and texts inspired by the sacred liturgy. There are the essential prayers all Catholics should know, as well as less familiar but useful ones for everyday situations and for times of need. The antiphons to Our Lady are given in Latin with music and traditional English translations. There is an order of morning and evening prayer. It also includes straightforward guides to prayer in general, reading scripture, the examination of conscience, confession, and the rosary. (How to praywas published in our weekly reflections last summer.) Some prayers (like the special order of ‘Compline’ or Night Prayer) are laid out so that they can be used either in private devotion or shared with family and friends. Carefully typeset and beautifully printed on heavy cream paper, these small hardback books have been designed to last. They have a ribbon for marking the pages you use the most, but they are also the perfect size to house a collection of prayer cards and holy images. The Oratory was founded by St Philip Neri to help teach everyone to pray. This book is a small contribution from the Oratory in Oxford to that mission. Dimensions: 134mm x 95mm, 120 pages The Oratory Prayer Book is available now from the Oratory Bookshop in Oxford priced £8.95. Delivery is £2.05 by Royal Mail 2nd class, UK only. Today marks 30 years since our Oratory here in Oxford was established as an independent house by the Holy See. The image is a photo of the decree from Rome. We mark the anniversary each year by celebrating the feast of the Patronage of St Philip. After Mass tonight, there will be a Musical Oratory to ask St Philip’s continued intercession. We will also sing the Te Deum to thank God for all the blessings bestowed on the Fathers and Brothers and all those they serve in this city. “The time to do good is not finished yet.” — St Philip #oxfordoratory Found by God St Luke’s description of the scene of the two disciples on the road to Emmaus, and the supper which they shared with our Lord is, I think, one of the most beautiful and powerful in his Gospel. It shows what a true artist the Evangelist was — and his words have served as an inspiration to some of the world’s most gifted artists, such as Valasquez, Caravaggio and Rubens, each painter lending his talents to give us his own interpretation of the moment the two disciples ‘recognised him in the breaking of bread.’ I recently discovered the portrayal of this scene by another artist, Jean-Marie Pirot (1926–2018) who worked under the name Arcabas. His representation in the church of St Hugues-de-Chartreuse, France, was used by Bishop Erik Varden on the cover of his excellent book The Shattering of Loneliness, which I strongly recommend to those looking for their next spiritual book. The Cistercian bishop writes of the picture: ‘The mood is of friendship. It draws the spectator in, hospitably. The pilgrims talk among themselves. Christ is pensively silent, unimposing. But it is he who lends the picture warmth. He knows that his companions need to talk before they can listen. They are caught up in what they have been through.’ And he is quite right. The two figures seem hardly to notice their guest, as they are obviously rehearsing, yet again, the fiasco of the past few days in Jerusalem, when their friend whom they called Master was taken and summarily executed by the Roman authorities at the behest of the Chief Priests and the Pharisees. The rest of the group had fled, leaving the whole movement in disarray. That was why they were putting as much distance between themselves and the Holy City. It was too dangerous, frightening and, besides, their hopes of the new Messianic kingdom now lay in tatters. It was over. What was there to stay for? The picture shows the two disciples, Cleopas and his anonymous companion, deep in conversation, each holding a large glass of wine. Beside them sits Jesus, just about to change everything once again. He is holding in his hands a hunk of bread and is clearly about to break it for them, the action that will enable them to recognise his presence with them and to see what they had already been told by some of the women who had visited the empty tomb in the morning, but whose testimony they had clearly either rejected or misunderstood. ‘God,’ says Varden, ‘remembers us before we remember God. Christ seeks the wanderers out when they, for their part, have despaired of finding him. He hears their anguish as a silent call. In a moment, he will hold the bread of mourning up as a Eucharistic host.’ He goes on to make a further observation: ‘Behind the pilgrim on the right sits a fourth person, whose profile is concealed. I take that to be me — or you. We are invited to sit down and share our story, assured that we have never been out of God’s mind. The old has passed. The new has come. There is a golden shimmer of glory to things.’ I like that idea of our entering into the story too. And since it isn’t about one of the Apostles — it’s not about Peter or Thomas, but two unknown disciples, Cleopas and A.N. Other — it makes it a little easier for us to read ourselves into the story, whether as pilgrims or escapees, in a muddle, confused, disillusioned, disappointed, hopeless, angry…whatever we are feeling. Imagine we are on the way to Emmaus, running away, and then astonished, delighted even, to be found by God, who has gone in search of us. Luke uses this same effect in the parable of the Lost Son and elsewhere. It is something to hang on to when we, like Cleopas and his companion, feel disconsolate and discouraged by the difficulties and twists of life, and when we are feeling most turned in ourselves or just feeling sorry for ourselves, that we can sense the attentive and compassionate presence of Christ, who has fallen in beside us and is walking with us, quietly on the road. Now we see as in a mirror, dimly The liturgies of Holy Week and Easter are incredibly rich and moving, helping us to enter more deeply into the mysteries of the Lord’s Passion and Death and to be filled, once again, with the joy of his Resurrection. But we will all have experienced that what goes on in church doesn’t always correspond to how we are feeling or what we are thinking at our particular point in life’s journey. There are times when we are required to say the De profundispsalm when we are actually feeling rather happy. And then there are times when the circumstances of our own lives can make it very difficult for us to sing the Easter Alleluia, overcome with Paschal joy. We might identify with the disciples locking themselves in the upper room out of fear, and not so much with “This is the day that the Lord has made, let us rejoice and be glad!” We can find ourselves being plagued by all sorts of trials in the Easter season as much as in any other season. Even though we are an Easter people, we never stop being a Good Friday people also, at least this side of eternity. We can find it hard to believe in the ultimate triumph of life over death, of joy over sadness, of glory over suffering, especially during those times in our lives when we feel sad and lifeless, when we are anxious or hopeless or are grieving. St Thomas the Apostle is therefore a very consoling example for us. When the other Apostles give him the good news of Easter, “We have seen the Lord”, that message did not resonate with him in any way. The darkness of Good Friday was still too real for him and prevented him from being moved by their news. His own experience did not allow him to believe that life had triumphed over death, that the crucified Jesus was now the risen Lord. Thomas stood in the light of Easter, yet that light did not dispel his darkness. In his doubting, Thomas is like so many Christians today. Many of us are surely distressed by the doubts we have, troubled by our sense that the light of Easter does not seem to have penetrated our lives very much, that Easter Sunday really hasn’t changed anything at all. The Lord understands a doubting, questioning, troubled faith. When Jesus appeared to Thomas, he did not tell him off. His first words were, “Peace be with you”. He invited Thomas to touch his wounds as he had demanded, and then called on him to “doubt no longer but believe”. The gospel does not tell us that Thomas actually put his finger into the wounds in Christ’s hands and side. Seeing the Lord was enough: "My Lord and my God”. Thomas, like the other disciples, saw and believed. However, Jesus knew that only a small group of disciples will see and believe, and so he blessed those many future disciples who believe without seeing. That blessing is on all of us who calls ourselves Christians and try to follow the Lord. As St Peter puts it, “You did not see him, yet you love him”. The Church is the community of those who believe in and love the Lord, without having seen him in the way Thomas and the other eyewitnesses did — those Apostles and disciples who are the foundations of our faith. We look forward to that day when we will see the Lord face-to-face in his kingdom. And because we do not yet see him face-to-face, our faith is always a faith that hopes. Because we only live in hope of meeting the Lord like Thomas, there will always be some element of doubt in our own faith. As St Paul tells the Corinthians, “now we see as in a mirror, dimly”. Questions and doubts are an inevitable part of seeing dimly. Such questions and doubts are not an enemy of faith. They can lead, rather, to a deepening of our faith. If we face our doubts and our questions honestly, like St Thomas, and bring them to each other and to the Lord, we too can reach a point where we can make Thomas’ confession our own, “My Lord and my God”. We must all learn to seek the Lord with humility, sincerity and honesty, just as Doubting Thomas did, but to seek in hope, knowing that if we remain true to that search, true to the path, the Lord has his own ways to meet each one of us and to invite us, as he invited St Thomas, “Doubt no longer but believe”. Our doubts and our fears — even our sins and our failings — so often seem to us to lock the Lord out. But Jesus will always pass through the walls and doors we put up to meet us — in those doubts and worries — and to give us the peace of his presence. A post shared by The Oxford Oratory (@oxford.oratory) Congratulations to Jack, received into Full Communion with the Catholic Church today! #oxfordoratory © 2023 Oxford Oratory. All rights reserved. The Oxford Oratory of St Philip Neri is a Registered Charity number 1018455	https://www.oxfordoratory.org.uk/publications/blog/post/9850-9850/blog/post/9864-now-we-see-as-in-a-mirror-dimly/friends.php
Quantitation of Cancer Treatment Response by 18F-FDG PET/CT: Multicenter Assessment of Measurement Variability \| Journal of Nuclear Medicine Research Article Oncology Quantitation of Cancer Treatment Response by 18F-FDG PET/CT: Multicenter Assessment of Measurement Variability Joo Hyun O, Heather Jacene, Brandon Luber, Hao Wang, Minh-Huy Huynh, Jeffrey P. Leal and Richard L. Wahl Journal of Nuclear Medicine September 2017, 58 (9) 1429-1434; DOI: https://doi.org/10.2967/jnumed.117.189605 1Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 2Department of Radiology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Article Abstract The aim of this study was to assess the interobserver variability of quantitative 18F-FDG PET/CT parameters used in assessments of treatment response across multiple sites and readers. Methods: Paired pre- and posttreatment 18F-FDG PET/CT images of 30 oncologic patients were distributed to 22 readers across 15 U.S. and international sites. One reader was aware of the full medical history (read reference) of the patients, whereas the 21 other readers were unaware. The readers selected the single hottest tumor from each study, and made SUV measurements from this target lesion and the liver. Descriptive statistics, percentage changes in the measurements, and their agreements were obtained. Results: The intraclass correlation coefficient for the percentage change in SUV max (%ΔSUV max) of the hottest tumor was 0.894 (95% confidence interval [CI], 0.813–0.941), and the individual equivalence coefficient was 1.931 (95% CI, 0.568–6.449) when all reads were included ( n = 638). When only the measurements that selected the same target tumor as the read reference ( n = 486) were included, the intraclass correlation coefficient for the %ΔSUV max was 0.944 (95% CI, 0.841–0.989), and the individual equivalence coefficient was −0.688 (95% CI, −1.810 to −0.092). The absolute change in SUV mean of liver corrected for lean body mass showed upper and lower limits of agreement (average bias ± 2 SDs) of 0.13 and −0.13 g/mL. Conclusion: The quantitative tumor SUV changes measured across multiple sites and readers show a high correlation. Selection of the same tumor target among readers further increased the degree of correlation. FDG PET/CT response assessment quantification PET/CT with 18F-FDG is widely used for assessing response to therapy in clinical trials and clinical practice for patients with cancer. However, data are limited on the concordance of readers using varying software systems in quantitatively determining the treatment response using 18F-FDG PET/CT. The ability of multiple readers to assign the same treatment response is to some extent dependent on the repeatability of the quantitative data obtained from the images. Despite the numerous factors known to result in variability of SUV measured from 18F-FDG PET/CT, the interobserver reproducibility of SUV and percentage change in SUV were higher than for measurements of CT size in a single-institution study (1). Our aim was to study the consistency of the major quantitative PET parameters collected across sites and readers, to determine what component of variability there is in target lesion selection and reading software elements. When all readers have identical sets of representative human 18F-FDG PET/CT digital data available, low to no variability would be expected in the SUV measurements, except for reader selection of targets and software configurations (2,3). Low variability among sites would support quantitative 18F-FDG PET/CT studies being deployed in a more general manner for treatment response assessment whereas any variability suggests further opportunities for process improvement to minimize variance. MATERIALS AND METHODS Determining Number of Cases and Readers Preliminary data from a single-institution/workstation study estimated an intraclass correlation coefficient (ICC) of 0.94 among 4 readers for determination of percentage change in SUV max (%ΔSUV max) (1). We expected to observe an ICC of 0.90 resulting from greater variation across sites, given multiple readers and workstations. Assuming 2 readers at each site evaluating 30 cases, 15 sites lead to a 95% confidence interval (95% CI) of 0.852–0.948. This estimate will ensure the ICC is in excess of 0.85, indicating strong reproducibility across sites. Thus, a protocol of 15 sites with 2 readers per site each evaluating 30 cases was planned on the basis of desired precision of ICC estimate. Case and Site Selection Images of 31 patients who underwent 18F-FDG PET/CT obtained before and either during or after chemotherapy or combination chemobiologic therapy from a central site were selected from a group of tumor types having representative patterns of 18F-FDG avidity. All PET/CT images were acquired using a 3-dimensional PET scanner (Discovery RX; GE Healthcare) with lutetium-yttrium-oxyorthosilicate crystals and iterative 3-dimensional image acquisition/processing. Cases were chosen by consensus of 2 nuclear medicine physicians to purposely include a mix of single and multiple tumors on the pretreatment scan (1 tumor, n = 6; >1 but <10 tumors, n = 19; ≥10 tumors, n = 6) and a mix of the 4 major response categories using PERCIST 1.0 (complete metabolic response, n = 4; partial metabolic response, n = 11; stable metabolic disease, n = 4; and progressive metabolic disease, n = 12). An initial survey was sent to readers at 31 prospective sites, both National Cancer Institute Quantitative Imaging Network–affiliated and not affiliated, by e-mail. The survey requested information about the reader’s experience with PET and technical workstation status to ensure feasibility of quantitative assessment. Twenty-three sites that responded all had adequate analysis software and were invited to participate. Ideally, 2 experienced nuclear medicine physicians or nuclear radiologists at each site were asked to independently assess the cases. Patient Population and Image Distribution As a test case, the central study site provided the same digital data from 1 patient to all participating sites. Liver measurements were requested to verify the integrity of image transfer and to ensure that the values were within the expected 20% range of the reference site; all of the 17 sites that responded satisfied these 2 criteria. The mean liver SUV corrected for lean body mass was 1.12 ± 0.12 before treatment and 1.37 ± 0.17 after treatment. The remaining 30 anonymized cases of pre- and posttreatment 18F-FDG PET/CT studies (total 60 studies) were distributed with directions for measurement methods and formatted reading forms. Approval from the institutional review board was obtained, and patient consent was waived for this study of anonymized image data. Measurement Individual measurements from coupled pre- and posttreatment 18F-FDG PET/CT images from 1 patient were counted as a read. The coupled pre- and posttreatment measurements for all 30 cases from a single reader were counted as a set of reads. One reader from the central site (reader 1) had full knowledge of the primary tumors, treatment histories, and subsequent follow-up results, but all other readers had no knowledge of the patients’ medical histories because the reader is frequently masked in the setting of multicenter trials. For statistical purpose, the measurements by reader 1 were considered as the read reference (the reference standard for comparison). Each reader determined which tumor to measure. First, readers were asked to measure the SUV max of the hottest tumor in the pretreatment image and follow the same lesion in the posttreatment image, which is a common clinical practice (baseline lesion followed). Second, readers were asked to measure the SUV max of the hottest tumor in each of the pre- and posttreatment images, in which the selected lesion in the posttreatment image may or may not be the same as the lesion selected in the pretreatment image (hottest lesion to hottest lesion). The rationale was that the hottest lesion on follow-up may be the most resistant to therapy, and thus more representative of the actual response in the patient (4). Third, readers were asked to measure the SUV peak corrected for lean body mass (SUL peak) from the hottest tumor in each of the pre- and posttreatment images (hottest lesion to hottest lesion). The SUL peak was predefined as the highest SUV mean corrected for lean body mass computed from a 1-cm 3 spheric volume of interest (VOI). Finally, readers were asked to measure the mean value in the liver from a 3-cm-diameter spheric VOI centered in the right side of the liver (liver SUL mean). The tumor SUL peak and liver SUL mean were requested to test the variables suggested by PERCIST 1.0 (4). SUL max was not requested because the percentage change computation would cancel out the lean body mass correction factor and the resulting percentage change of SUL peak would essentially be the same as with %ΔSUV max, assuming there was no drastic change in body weight. When a complete metabolic response was achieved and no tumor lesion was visually perceptible, measurement was requested from the site of the original tumor. For each measurement, the readers recorded the anatomic site and screen-saved the PET/CT image from their workstation. There was no separate training session for the participating readers. Various workstations and software were used: GE Healthcare AW; Hermes Hybrid Viewer; MedImage MedView; MiMVista Maestro; Mirada Medical XD; and Siemens E-Soft, True-D, and Syngo; and in-house developed software. The read reference used Mirada Medical XD. Statistical Analysis The primary metric was the %ΔSUV max from before to after treatment. Percentage change was defined as [(posttreatment measurement – pretreatment measurement)/(pretreatment measurement)] × 100. Restricted maximum likelihood estimation of variance components in a random-effects model was used to estimate the intra- and intersubject variance components for each measure, including case and reader as random effects. The variance component estimates were used to compute the ICC, defined as the intersubject variance divided by the total variance (intersubject variance + intrasubject variance + error variance). The CI was constructed using the bias-corrected and accelerated bootstrap with 1,000 replicates, where the sampling unit was a read to adjust for both bias and skewness in the bootstrap distribution. As another approach to assess agreement, assessment of interchangeability was performed (5). The interreader variability from the reference site was assessed using the individual equivalence coefficient (IEC), setting the level of measurement error within a site. Then the effect arising when readers from different sites are involved, instead of 2 readers from the same site, was quantified. To claim satisfactory agreement, the Food and Drug Administration recommended boundary below 2.4948 for good individual agreement (6). The CI for IEC was constructed using the bootstrap percentile interval with 1,000 replicates, where the sampling unit was a case. RESULTS Twenty-two sets of reads were received from 16 sites from August to February 2014. Of the 22 sets of reads, a single nuclear medicine physician/radiologist measured all cases in 15 sets. For 2 sets, 2 readers divided the cases, and each reader measured 15 cases. For 5 sets, 2 readers worked together to reach consensus. For statistical analysis, when 2 people were involved to produce a single set of reads, they were considered as a single reader. One case was subsequently excluded from analysis due to error with the distribution server. All Reads Twenty-nine cases with 22 separate sets of reads yielded a total of 638 reads. The Bland–Altman plots of the percentage change (%Δ) in the tumor measurements are shown in Figure 1. The plots for the other PET parameters are shown in Supplemental Figure 1–3 (supplemental materials are available at http://jnm.snmjournals.org). The overall ICC for the %ΔSUV max (hottest lesion to hottest lesion) was 0.894 (95% CI, 0.813–0.941), and the IEC was 1.931 (95% CI, 0.568–6.449). The ICC and IEC for other measurements are shown in Table 1. When control for the number of readers—single reader versus 2 readers—was performed, no statistical difference was noted (ICC, 0.894; 95% CI, 0.796–0.937). <here is a image 93c6a228f0eb7bb7-2281ce0c974a49b7> FIGURE 1. Bland–Altman plots of percentage change of tumor 18F-FDG uptake from before to after treatment. The plots are for percentage changes of SUV max (hottest lesion to hottest lesion) (A), SUV max (baseline lesion followed) (B), and SULpeak (hottest lesion to hottest lesion) (C). Each dot represents a case (total, 29 cases). x-axis represents average mean percentage change measurement by all readers. y-axis represents average difference between 21 readers, the read reference. Solid line represents average bias, and the dashed lines represent corresponding bias ± 2 SDs. TABLE 1 Overall ICC and IEC for Tumor Measurements Reads with Same Target Tumor Among the 638 reads, the readers selected a different site as the target from the read reference in either the pre- or posttreatment images in 152 reads . Of a total of 29 cases, a different target was chosen from the read reference for an average of 2.9 ± 1.62 cases (range, 0–6) for the pretreatment images and 5.1 ± 1.53 cases (range, 2–10) for the posttreatment images. Only 1 reader chose the same hottest tumor in all cases as the read reference in the pretreatment images. The cases that resulted most often in discordant target selections had extensive metastases involving multiple bones or nodal stations (results per case and reader in Supplemental Figs. 4 and 5). The readers, being unaware of the medical history, sometimes selected benign condition as the hottest tumor (Fig. 2). <here is a image c9a84523b8010bc6-a525d9482f10eb16> FIGURE 2. Physiologic 18F-FDG uptake in bowel was a source of confusion for readers who were completely unaware of primary tumor and clinical history. PET maximum-intensity projection (A) and axial fused PET/CT image (B) of example case. 18F-FDG uptake in bowel (arrows) was chosen by some readers as hottest tumor. (C) Maximum-intensity-projection image of same patient is rotated to better demonstrate sarcoma mass (arrowhead). (D) Axial fused PET/CT image at more inferior level shows mass involving right iliac bone and gluteus muscle (arrowhead). This sarcoma lesion was true target lesion when considering patient’s medical history. For only the reads agreeing on target selection with the read reference, the distribution of the %Δ data is shown in Figure 3 and the Bland–Altman plots in Figure 4. For the reads agreeing on target selection with the read reference, the ICC for %ΔSUV max (hottest lesion to hottest lesion) was 0.944 (95% CI, 0.841–0.989), and the IEC was −0.688 (95% CI, −1.810 to −0.092). The ICC and IEC of other PET parameters are in Table 1. The plots for the other PET measurements are in Supplemental Figures 6–9. <here is a image 76d6b773ad731094-ffbcc5b9dc6cf74c> FIGURE 3. Data are plotted for only cases with same target lesion selected as read reference ( n = 486). Percentage change in tumor 18F-FDG uptake from before to after treatment was measured by SUV max (hottest lesion to hottest lesion). Plots for SUV max (baseline lesion followed) and SUL peak (hottest lesion to hottest lesion) are in supplemental materials. <here is a image 24d9f0ae1bd7eac1-dcc67c61873d4b83> FIGURE 4. Bland–Altman plots of percentage change of tumor 18F-FDG uptake with only cases that selected same target lesion as read reference included. Plots are for SUV max (hottest lesion to hottest lesion) (A), SUV max (baseline lesion followed) (B), and SUL peak (hottest lesion to hottest lesion) (C). x-axis represents average mean percentage change measurement by all readers. y-axis represents average difference between 21 readers and reference read. Solid line represents average bias, and dashed lines represent corresponding bias ± 2 SDs. The correlation coefficient ( r 2) for agreement between the read reference and the other 21 readers was high—the r 2 was 0.997 for %ΔSUV max (hottest lesion to hottest lesion). The r 2 values for other PET parameters are in Table 2 and graphical displays in Supplemental Figures 10 and 11. TABLE 2 Correlation Coefficient Between read reference and Other Readers Liver The ICC for the percentage change in the liver SUL mean was 0.751 (95% CI, 0.656–0.810), and the IEC was 7.799 (95% CI, 3.417–18.493). The Bland–Altman limits of agreement for absolute and percentage differences in liver SUL mean measurements were small, as seen in Figure 5. Even the outlier absolute SUL mean differences are within 0.25 SUL units from the average bias and the outlier percentage SUL mean differences within 10% from the average bias. Agreement between the read reference and the other 21 readers showed an r 2 of 0.95. <here is a image 618c968d517f809d-689a846171819c54> FIGURE 5. Bland–Altman plots for liver SUL mean measurements from pretreatment image (A), posttreatment image (B), their absolute change (C), and percentage change (D). x-axis represents average mean measurement by all readers. y-axis represents average difference between 21 readers and reference read. Solid line represents average bias, and dashed lines represent corresponding bias ± 2 SDs. DISCUSSION Quantitation of treatment response is of growing importance, especially as we look to detect early treatment–induced alterations in adaptive treatment designs. A high degree of test–retest reproducibility was demonstrated for 18F-FDG PET/CT in various studies (7–9). However, these previous studies did not examine the performance of quantitative representation of response to treatment in the clinical setting for various tumor types, across multiple sites. In the present study, we observed that multiple readers from multiple sites gave similar, but not uncommonly, somewhat different measurements for an identical set of 18F-FDG PET/CT images due to selection of different targets and differing workstation software configurations. Although generally reliable, reader selection of target lesion appeared to contribute to the variability of quantitative change. The ICC was higher and the IEC lower for all of the PET parameters when only the reads agreeing on target selection with the read reference were analyzed. The selection of the hottest tumor was sometimes problematic, especially because the patient’s diagnosis and medical history were withheld from the readers. Determining which tumor to measure may depend on subjective judgment when there are multiple lesions or prominent and discrete 18F-FDG uptake from a benign cause. Target selection was shown to be a cause of variability in anatomic response assessments with RECIST, and baseline selection of the lesion was pointed out as one of the pitfalls (10,11). Individual determination of target lesion would be required by the physician even when artificial intelligence enters the reading rooms of the PET/CT clinics and automatic measurement tools such as Auto-PERCIST become widely available (12,13). The issue arising from discrepancies of target selection needs to be addressed through comprehensive training. Being able to interpret the multitude of physiologic conditions that can be glucose-avid and being meticulous in the presence of multiple lesions are important steps to achieve the desired level of interreader agreement. In the presence of multiple lesions, sometimes the discrepancies in target selection could have been avoided simply with additional measurements. For example, in case 25, there were 2 axillary lymph nodes with intense 18F-FDG uptake, and some readers chose the node with a lower 18F-FDG uptake. In the cases with numerous tumors displaying a similar degree of 18F-FDG uptake, brief visual inspection would be insufficient for accurate selection of the target lesion. How to quantitate a complete metabolic response is difficult to answer. Even when the same target was chosen, the readers selected subtly different foci in the posttreatment images and thus recorded slightly different values. Consensus on how to best determine the site of the original tumor and what to measure for tumors showing complete resolution would further enhance the repeatability of the quantitative 18F-FDG PET/CT response. The site corresponding to the hottest uptake from baseline could be identified by automatic image coregistration across different time points, a feature of many reading software, and careful visual consideration of the anatomic structures in the CT portion. Inclusion of target lesions below the limit of measurability at baseline as suggested in PERCIST could have contributed to lowering the overall ICC. The absolute upper and lower limits of agreement for SUV max (hottest lesion to hottest lesion) were, in fact, very tight in the Bland–Altman plots: 0.279 and −0.102 for pretreatment and 0.697 and −0.377 for posttreatment measurements. However, in the equation for computing the %Δ, the measurement from the pretreatment image becomes the denominator, and the cases with relatively low 18F-FDG uptake would be susceptible to greater fluctuations in the computed %Δ. Among the 29 cases, 7 cases had target tumor SUV max below 5.0 in the pretreatment images (range, 2.65–4.60). These lesions with relatively low SUV produced wide ranges of %Δ, especially when the lesion progressed. A responding tumor can yield at most a near 100% drop in SUV, whereas progressing tumors can produce increases by several hundred or even thousand percent. Human error in drawing the VOI around the target is suspected as a cause of variation—either too big a VOI that included sites such as the kidneys and heart, or too small a VOI that excluded the pixels with the highest 18F-FDG uptake. Recording the measurements on the reading forms is another conceivable step for error. One site demonstrated SUV max consistently lower than the read reference (difference mean, 0.93; 95% CI, 0.61–1.25), possibly from incorrect configuration inherent in the software, such as conversion of the imaging time or injected dose. The difference in the liver SUL mean measurements can be assumed to be partly from the characteristic heterogeneity of hepatic 18F-FDG uptake and from the variations in the setting of the workstation software, such as the method of drawing a spheric VOI (14,15). Both the absolute difference and the percentage difference in liver measurements demonstrated narrow limits of agreement in the Bland–Altman plots. SUL peak is reported to produce lower bias in assessment of PET/CT data (16,17). However, the variations in pixel segmentation and computation methods used by the different software resulted in lower interreader agreement than for the 2 SUV max measurements in this study. As recently reviewed, consensus on the SUL peak computation method should be made before multicenter studies to use this PET parameter as an alternative to SUV max, particularly in noisy studies (18). The fact that the cases were not chosen at random from a clinical trial with uniform imaging conditions may limit the broader applicability of the results. The 30 cases evaluated in this study were specifically selected with the intention of mimicking the clinical reading room conditions, and varying types of tumors, therapeutic regimens, and imaging conditions are represented. Furthermore, the reproducibility of the percentage change in the SUV is only the initial step, and studies examining the reproducibility of the response classification among cases with uniform therapeutic and imaging protocols should follow. CONCLUSION Our study indicates that tumor selection by the reader is a major contributor to variability in quantitative 18F-FDG PET/CT assessment of treatment response. A thorough knowledge of the patient’s medical history and being meticulous during the reading process are required to reduce the inconsistency in target selection, though understanding the patient’s full medical history may not be an option in many clinical trials in which the readers are deliberately masked to the history to prevent bias. Despite the use of multiple types of workstation software, and the lack of clinical data to guide lesion selection, results from the readers from multiple U.S. and international sites showed strong reproducibility, supporting 18F-FDG PET/CT as a robust global tool for quantitative analysis of treatment response. DISCLOSURE This study was supported by funding from the Radiological Society of North America, the Quantitative Imaging Biomarkers Alliance, NIBIB contract HHSN268201000050C, the National Cancer Institute (5P30CA006973-52, 5U01CA140204-05), and the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea. No other potential conflict of interest relevant to this article was reported. Acknowledgments We thank Nancy Obuchowski, PhD, for her valuable statistical advice. The collected efforts of all the QIBA PET/CT readers made this analysis possible, and we thank Eric S. Perlman, MD, American College of Radiology Image Metrix; Hye Ok Kim, MD, Sun Young Chae, MD, and Jin-Sook Ryu, MD, PhD, Asan Medical Center; Andrew M. Scott, MD, and Sam Berlangieri, MD, The Ludwig Institute for Cancer Research; Sung Hoon Kim, MD, PhD, Sae Jung Na, MD, Narae Lee, MD, and Sonya Park, MD, Catholic University of Korea; Christopher Sakellis, MD, Dana Farber Cancer Institute; Edward A. Eikman, MD, and Jaime L. Montilla-Soler, MD, H. Lee Moffit Cancer Center and Research Institute; Huo Lee, MD, Peking Union Medical College Hospital; Sally F. Barrington, MD, and Gary Cook, MD, PET Imaging Centre at St Thomas' King’s College; Meena Kumar, MD, and Andrew Quon, MD, Stanford University; Nathan Hall, MD, PhD, Michael Knopp, MD, PhD, and Jun Zhang, PhD, The Ohio State University; Michael M. Graham, MD, PhD, and Yusuf Menda, MD, University of Iowa; James M. Mountz, MD, PhD, University of Pittsburgh; Mike Sathekge, MBChB, MMed, PhD, MASSAf, and Mariza Vorster, MBCHB, University of Pretoria & Steve Biko Academic Hospital; Andrew Shields, MD, Fatemeh Behnia, MD, and Paul Kinahan, PhD, University of Washington; and Ronald Boellaard, PhD, and Otto Hoekstra, MD, Vrije Universiteit University Medical Center. Footnotes Published online Mar. 30, 2017. © 2017 by the Society of Nuclear Medicine and Molecular Imaging. REFERENCES 1. ↵ Jacene HA, Leboulleux S, Baba S, et al . Assessment of interobserver reproducibility in quantitative 18F-FDG PET and CT measurements of tumor response to therapy. J Nucl Med. 2009; 50: 1760– 1769. 2. ↵ Paidpally V, Mercier G, Shah BA, Senthamizhchelvan S, Subramaniam RM . Interreader agreement and variability of FDG PET volumetric parameters in human solid tumors. AJR. 2014; 202: 406– 412. 3. ↵ Viner M, Mercier G, Hao F, Malladi A, Subramaniam RM . Liver SULmean at FDG PET/CT: interreader agreement and impact of placement of volume of interest. Radiology. 2013; 267: 596– 601. 4. ↵ Wahl RL, Jacene H, Kasamon Y, Lodge MA . From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009; 50( suppl 1): 122S– 150S. 5. ↵ Barnhart HX, Kosinski AS, Haber MJ . Assessing individual agreement. J Biopharm Stat. 2007; 17: 697– 719. 6. ↵ US Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER). Statistical approaches to establishing bioequivalence. U.S. Food and Drug Administration website. https://www.fda.gov/downloads/drugs/guidances/ucm070244.pdf. Published January 2001. Accessed July 19, 2017. 7. ↵ Weber WA, Gatsonis CA, Mozley PD, et al . Repeatability of 18F-FDG PET/CT in advanced non-small cell lung cancer: prospective assessment in 2 multicenter trials. J Nucl Med. 2015; 56: 1137– 1143. 8. Rockall AG, Avril N, Lam R, et al . Repeatability of quantitative FDG-PET/CT and contrast-enhanced CT in recurrent ovarian carcinoma: test-retest measurements for tumor FDG uptake, diameter, and volume. Clin Cancer Res. 2014; 20: 2751– 2760. 9. ↵ Kumar V, Nath K, Berman CG, et al . Variance of SUVs for FDG-PET/CT is greater in clinical practice than under ideal study settings. Clin Nucl Med. 2013; 38: 175– 182. 10. ↵ Keil S, Barabasch A, Dirrichs T, et al . Target lesion selection: an important factor causing variability of response classification in the Response Evaluation Criteria for Solid Tumors 1.1. Invest Radiol. 2014; 49: 509– 517. 11. ↵ Abramson RG, McGhee CR, Lakomkin N, Arteaga CL . Pitfalls in RECIST data extraction for clinical trials: beyond the basics. Acad Radiol. 2015; 22: 779– 786. 12. ↵ Jeffrey Leal RW. Auto-PERCIST™: semi-automated quantitative assessment of FDG-PET based on the PERCIST criteria. Paper presented at: the Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; December 1–6, 2013; Chicago IL. 13. ↵ Shiraishi J, Li Q, Appelbaum D, Doi K . Computer-aided diagnosis and artificial intelligence in clinical imaging. Semin Nucl Med. 2011; 41: 449– 462. 14. ↵ Tahari AK, Paidpally V, Chirindel A, Wahl RL, Subramaniam RM . Two-time-point FDG PET/CT: liver SULmean repeatability. AJR. 2015; 204: 402– 407. 15. ↵ Vanderhoek M, Perlman SB, Jeraj R Lodge MA, Chaudhry MA, Wahl RL Sugawara Y, Zasadny KR, Neuhoff AW, Wahl RL O JH, Lodge MA, Wahl RL Received for publication January 5, 2017. Accepted for publication March 10, 2017. Joo Hyun O, Heather Jacene, Brandon Luber, Hao Wang, Minh-Huy Huynh, Jeffrey P. Leal, Richard L. Wahl Journal of Nuclear Medicine Sep 2017, 58 (9) 1429-1434; DOI: 10.2967/jnumed.117.189605 FDG PET/CT	https://jnm.snmjournals.org/content/58/9/1429?rss=1
Children \| Free Full-Text \| Specialized Rehabilitation Programs for Children and Adolescents with Severe Disabling Chronic Pain: Indications, Treatment and Outcomes Children and adolescents with highly disabling chronic pain of high intensity and frequency are admitted to specialized pain rehabilitation programs. Some barriers to obtaining this specialized care include a lack of availability of treatment centers, a perceived social stigma and individual barriers such as socioeconomic status. Specialized rehabilitation programs for severe disabling chronic pain worldwide have similarities regarding admission criteria, structure and therapeutic orientation. They differ, however, regarding their exclusion criteria and program descriptions. The short- and long-term effectiveness of some rehabilitation programs is well documented. All countries should promote the establishment of future pediatric pain centers to improve the health care of children and adolescents suffering from severe chronic pain. Standardized reporting guidelines should be developed to describe treatments and outcomes to enable comparability across treatment centers. by Lorin Stahlschmidt 1,2 , Boris Zernikow 1,2 and Julia Wager 1,2,* 1 German Paediatric Pain Centre, Children’s and Adolescents’ Hospital, 45711 Datteln, Germany 2 Department of Children’s Pain Therapy and Paediatric Palliative Care, Faculty of Health, School of Medicine, Witten/Herdecke University, 58448 Witten, Germany * Author to whom correspondence should be addressed. Children 2016 , 3 (4), 33; https://doi.org/10.3390/children3040033 Received: 25 October 2016 / Revised: 26 October 2016 / Accepted: 10 November 2016 / Published: 21 November 2016 (This article belongs to the Special Issue Chronic and Recurrent Pain ) Abstract Children and adolescents with highly disabling chronic pain of high intensity and frequency are admitted to specialized pain rehabilitation programs. Some barriers to obtaining this specialized care include a lack of availability of treatment centers, a perceived social stigma and individual barriers such as socioeconomic status. Specialized rehabilitation programs for severe disabling chronic pain worldwide have similarities regarding admission criteria, structure and therapeutic orientation. They differ, however, regarding their exclusion criteria and program descriptions. The short- and long-term effectiveness of some rehabilitation programs is well documented. All countries should promote the establishment of future pediatric pain centers to improve the health care of children and adolescents suffering from severe chronic pain. Standardized reporting guidelines should be developed to describe treatments and outcomes to enable comparability across treatment centers. Keywords: chronic pain ; rehabilitation programs ; specialized pain treatment ; pediatric ; effectiveness 1. Introduction Approximately 3% to 5% of children and adolescents experience strong negative consequences of chronic pain [ 1 ]. They miss a significant amount of school and experience a decline in their grades, a considerable reduction in their quality of life and psychological distress [ 1 , 2 , 3 , 4 , 5 ]. The long-term prognosis of these children and adolescents is poor. Without effective treatment, their chronic pain is likely to continue into adulthood [ 6 , 7 , 8 ]. This process of chronification can potentially be interrupted with specialized pain treatments. However, not all children and adolescents seek treatment when they suffer recurrent pain [ 9 , 10 ]. One important and very robust predictor of health care utilization is high pain-related disability [ 1 , 10 , 11 , 12 ]. Additional factors associated with health care utilization include pain characteristics, such as high pain frequency or high pain intensity [ 1 , 10 , 11 , 12 ]. In many health care systems, the first point of contact is typically primary care, with subsequent referrals to secondary or tertiary care [ 13 , 14 ]. However, some health care systems, e.g., those in the USA, do not follow this structured approach; in these types of settings, patients may self-refer and enter the system at any level [ 13 ]. Some of the children and adolescents who visit a primary care physician for recurrent or constant functional pain are referred to specialized pain treatment centers, while many patients are (mistakenly) referred to other specialists such as rheumatologists, neurologists, gastroenterologists or orthopedic surgeons [ 11 , 15 , 16 , 17 ]. Before presenting to specialized pediatric pain treatment centers, patients undergo a substantial number of medical visits and pain-related hospital stays [ 2 , 11 , 17 , 18 ]. Furthermore, other barriers to accessing specialized pain care exist, such as availability of care [ 19 , 20 , 21 ] and socioeconomic status [ 19 , 20 ]. A lack of understanding in society and among friends, family or even primary care physicians due to the invisible nature of pain may also present a barrier to specialized care [ 22 ]. In addition, the perceived stigma associated with psychological therapy can prevent patients from seeking specialized care with a psychological focus [ 22 , 23 ], especially if the patients believe that their problem is a physical one [ 23 ]. Pain location can represent a barrier to accessing specialized care as well, as not all pediatric pain programs treat all types of pain. Specialized pain care provides treatment options with different levels of intensity. For patients with a moderate level of functional and emotional impairment, outpatient chronic pain treatment with limited intensity may be sufficient [ 24 , 25 , 26 , 27 ]. For severely disabled children and adolescents with chronic pain, an intensive specialized rehabilitation program is indicated. Figure 1 displays the usual course of health care utilization due to chronic pain. Figure 1. Usual course of health care utilization due to chronic pain. § e.g., rheumatologists, neurologists, gastroenterologists, orthopedic surgeon. a e.g., [ 1 , 10 , 11 , 12 ]; b e.g., [ 11 , 15 , 16 , 17 ]; c e.g., [ 19 , 20 , 21 ]; d e.g., [ 19 , 20 ]; e e.g., [ 26 ]; f e.g., [ 25 , 26 , 27 ]; g e.g., [ 28 ]. Currently, there are specialized pediatric pain centers in many countries around the world. According to the International Association for the Study of Pain [ 29 ], specialized pain clinics are characterized by the concurrent efforts of an interdisciplinary clinical team that is able to treat any type of pain disorder. The patient-centered treatment provided in these clinics is based on the best available evidence, and these clinics implement quality improvement efforts, for example, by routinely monitoring patient characteristics and outcomes (see [ 30 ] for an example of a successful implementation of such methods). Specialized pain centers also engage in research and academic teaching. According to the bio-psycho-social model of chronic pain, chronic pain treatment should always include medical, psychological and social treatment methods. There are pain clinics that specialize in only one pain disorder but fulfill all of the other criteria defined by the IASP. The American Pain Society additionally defined parent inclusion and school reintegration as particular requirements of specialized pediatric pain treatment [ 31 ]. The overall goal of pediatric chronic pain treatment is to assume an active self-management approach in coping with pain [ 32 , 33 ] and to enable age-appropriate daily activities despite pain [ 33 , 34 , 35 ]. In this review, we focus on specialized pain rehabilitation programs in particular and do not address specialized outpatient treatment. A recent systematic review showed strong positive results regarding the short-term effectiveness of specialized pain rehabilitation programs [ 36 ]. Here, we aim to provide a comprehensive overview of existing pain rehabilitation programs, their structure and their short- and long-term effectiveness. First, we present the criteria that suggest that intensive pain treatment is indicated. Second, we take an international perspective on the structure and the components of different pain rehabilitation programs worldwide to note their differences and similarities. Third, we provide a summary of the results regarding short- and long-term outcomes of pain rehabilitation programs. With the results presented in this review, we aim to promote the development of further specialized pain programs, to place single programs within a larger context and to advance global networking. 2. Method We conducted a literature search based on a recent systematic review of intensive interdisciplinary pain treatment [ 36 ] initiated by our research group. This published systematic review integrated results from ten studies and had a strong focus on the outcomes of chronic pain treatment. In this review, we concentrated more on providing a comprehensive description of existing specialized rehabilitation programs and therefore further included referenced studies that were excluded from the systematic review, for example due to overlapping samples [ 25 , 37 , 38 , 39 , 40 , 41 , 42 ]. Additionally, we identified five more recent studies on this topic through a nonsystematic search in Medical Literature Analysis and Retrieval System Online (MEDLINE) and by conducting a manual search [ 16 , 28 , 34 , 43 , 44 , 45 ]. Overall, information about nine different rehabilitation programs from the USA, the UK, Australia and Germany was available. We extracted information from the included studies concerning the admission criteria of the rehabilitation programs and their structure, therapeutic orientation and treatment components. We further extracted information regarding outcomes according to the core outcome domains listed in the Pediatric Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (PedIMMPACT) recommendations [ 46 ]. 3. Results 3.1. Indications for Specialized Rehabilitation Programs The criteria for admission to specialized rehabilitation centers vary slightly between the rehabilitation programs worldwide. The inclusion criteria showed considerable similarities. Most programs agree that the most important criteria is for the pain to be persistent with a high intensity for at least three months [ 33 , 35 , 47 ] and for children and adolescents to be severely impaired by the pain in daily activities such as school attendance, sports or leisure activities [ 32 , 33 , 35 , 47 , 48 , 49 ]. As family environment may be an important factor in the development or maintenance of pain, patients’ and their parents’ motivation for and compliance with treatments are important requirements [ 35 , 47 , 48 , 49 ]. In addition, failure of prior outpatient treatment is often mentioned as a necessary admission criterion [ 32 , 47 , 49 ]. This factor is important for avoiding overtreatment. The exclusion criteria vary widely between the rehabilitation programs. Patients with specific psychiatric needs requiring further treatment are often excluded [ 32 , 35 , 49 ], as are patients requiring further medical assessments [ 33 , 35 ] and patients with a medical pathology/underlying disease [ 32 , 48 ] or a malignant disease [ 47 , 48 ]. If other effective medical options are available, this can also be an exclusion criteria [ 48 ]. Table 1 provides an overview of the criteria for the different rehabilitation programs introduced in the literature. Table 1. Admission criteria for specialized rehabilitation programs. 3.2. Treatment Components of Specialized Rehabilitation Programs Specialized rehabilitation includes inpatient chronic pain treatment and intensive day-hospital approaches [ 36 ]. Most of these programs treat all types of pain disorders, although some specialize only in musculoskeletal pain [ 28 , 32 ]. Similar to the admission criteria described above, the rehabilitation programs vary slightly around the world; however, they agree on a number of core contents and structures. These programs mainly include operant and cognitive behavioral techniques, as well as some acceptance and commitment therapy-based approaches, and they consist of a number of different medical, psychological and social modules delivered by interdisciplinary teams [ 28 , 32 , 33 , 34 , 35 , 41 , 48 , 49 , 50 ]. The psychotherapy contents are mainly delivered in one-on-one sessions, but they are also delivered in group or family sessions [ 28 , 32 , 33 , 34 , 41 ]. Treatment typically lasts three weeks, with approximately eight hours of treatment per day, whether in inpatient or day-hospital treatment settings [ 32 , 33 , 34 , 41 , 48 ]. One important rehabilitation module is chronic pain education [ 16 , 35 , 41 , 49 ], i.e., informing patients about the bio-psycho-social model of chronic pain, the possible etiological causes and factors associated with the maintenance of pain, the consequences of inactivity and the benefit of activity despite pain. Regarding pain management, various strategies are taught, such as relaxation techniques [ 32 , 33 , 34 , 41 , 49 , 50 ], attention defocusing techniques [ 33 , 41 , 49 ], imagery [ 32 , 41 , 43 , 49 ], active daily structures [ 28 , 32 , 33 , 34 , 35 , 41 , 48 , 49 , 50 ], stress management [ 32 , 33 , 45 , 49 ] and problem-solving activities [ 32 , 43 , 49 ]. Physical therapy [ 28 , 32 , 33 , 34 , 35 , 41 , 48 , 49 , 50 ], biofeedback [ 32 , 33 , 45 , 49 ] and therapy for psychological comorbidities [ 33 , 41 ] such as depression or anxiety are also included in rehabilitation. In family sessions, parents actively participate in the treatment [ 28 , 32 , 33 , 34 , 35 , 41 , 48 , 49 ]; they are informed about how to support their children or adolescents in active pain management and how to avoid reinforcing inappropriate pain behavior. In addition, familial stress factors can be identified and worked on with the parents. Some programs also incorporate parent-only sessions [ 28 , 33 , 35 , 48 ]. Medical interventions include providing medical examinations [ 32 , 34 , 41 , 49 ] and tapering off or changing medications [ 28 , 33 , 41 , 49 , 50 ] if necessary and appropriate. Further treatment components incorporated by some of the programs address occupational therapy [ 28 , 32 , 33 , 34 , 35 , 41 , 49 ], recreational therapy [ 16 , 33 , 49 ], acupuncture/acupressure [ 34 , 49 , 50 ], diet [ 33 , 34 ], sleep hygiene [ 33 , 44 , 49 ], music therapy [ 28 , 41 , 43 ] and art therapy [ 16 , 28 , 41 ]. In some programs, the patients also attend some type of hospital school program [ 32 , 34 , 47 ]. To consolidate treatment strategies, the treatment plans incorporate therapeutic homework and practice [ 32 , 35 , 47 ]. Relapse prevention is an important part of therapy [ 32 , 34 , 41 , 49 ]. This stage is composed of stress tests, reintegration into the patient’s home and school routine, and arrangement of outpatient psychotherapy. Some of the rehabilitation programs offer follow-up care, in which the patient’s status and goal attainment are evaluated and treatment is resumed if necessary [ 24 , 49 , 51 ]. Table 2 provides an overview of the different rehabilitation programs and their specific components. Only components reported by two or more programs in the literature are included. Table 2. Structural and therapeutic components of the specialized rehabilitation programs. 3.3. Outcomes of Specialized Rehabilitation Programs A recent systematic review of rehabilitation programs integrated the results of ten studies regarding the short-term effectiveness two to six months after treatment [ 36 ]. We complement these results with more recent studies and with long-term outcomes. The results are presented according to the core outcome domains from the PedIMMPACT recommendations [ 46 ]. Pain intensity. The systematic review showed large short-term reductions in pain intensity [ 36 ]. More recent studies confirm these short-term reductions in pain intensity [ 28 , 34 , 43 ]. Several studies also provide evidence for long-term reductions (12 to 24–42 months after treatment) of pain intensity [ 16 , 28 , 34 , 47 , 52 , 53 ]. Satisfaction with treatment, symptoms and adverse events. None of the studies investigated satisfaction with treatment or treatment-emergent symptoms and adverse events as outcome measures. Physical functioning. There was a large effect for the reduction of pain-related disability described in the systematic review [ 36 ]. Significant short-term effects were also found in more recent studies [ 28 , 43 ]. Studies also reported positive long-term effects (12 months after treatment) of rehabilitation programs on pain-related disability [ 28 , 47 , 52 , 53 ]. Emotional functioning. The systematic review revealed a moderate effect for reduction in general anxiety, a large effect for reduction in pain-specific fear and a small to moderate effect for the reduction in depressive symptoms [ 36 ]. Benore et al. [ 43 ] replicated the short-term effects of specialized rehabilitation programs on general anxiety and on pain-specific anxiety. Sherry et al. [ 28 ] found positive short-term effects on emotional functioning that remained stable up to one year after treatment. Two more studies reported significant long-term reductions (12 months after treatment) in anxiety and depression [ 52 , 53 ]. Role functioning. According to the systematic review, school attendance as the recommended measure of role functioning [ 46 ] was significantly improved by intensive treatment with moderate to large effect sizes [ 36 ]. Recent studies replicated these short-term effects [ 28 , 34 , 43 ]. Several studies further supported the long-term effectiveness (12 to 24–42 months after treatment) of intensive pain treatment on reducing school absence [ 28 , 34 , 47 , 52 , 53 ]. Sleep. Only three studies used sleep as an outcome measure. All reported improvements in sleep disturbances [ 44 , 49 , 50 ]. One study further found stable short-term improvements in sleep onset delay, sleep duration, night waking and daytime sleepiness and an overall reduction in the use of sleep medication [ 44 ]. However, these results were based on self-report and not on validated objective measures such as actigraphy or sleep recording [ 46 ]. Economic factors. A small number of studies investigated the economic effects of intensive pain treatment in terms of health care utilization and indirect costs. Significant reductions were found for health care utilization, in both the short and long term (12 to 24–42 month after treatment) [ 16 , 34 , 48 , 52 ]. Indirect costs, such as lost work days [ 16 , 34 , 52 ] and parental subjective financial burden [ 52 ], also showed significant reductions. Evans et al. [ 16 ] concluded that chronic pain rehabilitation is a cost-effective treatment for pediatric chronic pain. Regarding moderators of treatment outcome , the results indicated that sex [ 38 , 47 ], fear of pain [ 51 ], pretreatment functional impairment [ 53 ], psychological comorbidities [ 43 , 53 ], sleep habits [ 44 ] and patients’ readiness to self-manage pain [ 37 ] were associated with treatment outcomes. Poorer treatment outcomes were associated with female sex [ 38 , 47 ], high levels of fear of pain [ 51 ], low levels of school absence before treatment [ 53 ] and high levels of anxiety and depression [ 53 ]. Furthermore, decreases in anxiety [ 43 ], increases in readiness to self-manage pain [ 37 ] and improvements in sleep habits, such as sleep duration, night-waking or sleep onset, showed associations with better treatment outcomes [ 44 ]. 4. Discussion In this review, we aimed to provide a summary of the published specialized rehabilitation programs around the world regarding their admission criteria, treatment components and outcomes. Specialized rehabilitation programs for chronic pain in children and adolescents seem to have certain similarities around the world and have proven to be effective in treating disabling chronic pain disorders. There are many similarities regarding the admission criteria for specialized rehabilitation programs, of which pain-related disability and patient and parent motivation seem to be the most important. The different programs around the world also showed substantial similarities in structure, therapeutic orientation and individual components. All programs consist of an interdisciplinary team and include operant and cognitive-behavioral therapy, physical therapy and an active daily structure. Most of the programs address medications, use relaxation techniques and occupation therapy and have family sessions as an integral component of the treatment. The results for most of the outcome domains are comparable across all studies and indicate high short- and long-term effectiveness of specialized rehabilitation programs in pain intensity and physical, school and emotional functioning. There are, however, outcome domains, such as sleep and economic factors, for which the conclusions are rather preliminary. None of the studies investigated satisfaction with treatment or symptoms and adverse events. 4.1. Indications for Specialized Rehabilitation Programs Three rehabilitation programs did not provide admission criteria. The other rehabilitation programs differed mainly in their exclusion criteria. There are large differences regarding medical issues, for example, whether patients with an underlying or active malignant disease are excluded. Furthermore, some programs include children and adolescents with psychiatric comorbidities, while others do not. This difference accounts for certain differences in treatment components. Programs that include children and adolescents with comorbidities need to be more intensive, especially concerning psychological interventions and the need to treat these comorbidities. These different exclusion criteria may further impede the comparability of the rehabilitation program outcomes, since psychological comorbidities are a risk factor for treatment failure [ 53 ]. Programs that exclude patients with comorbidities may achieve larger effects in pain-related outcome domains. Therefore, it is important that all specialized rehabilitation programs report their admission criteria to ensure that the outcomes can be interpreted accordingly. 4.2. Treatment Components of Specialized Rehabilitation Programs Despite the considerable similarities between the program components, it is difficult to compare the rehabilitation programs due to the way they are described in the literature. Some programs are described in abundant detail, while others lack basic information. The descriptions of many programs are not comprehensive. Therefore, the overview of structural and therapeutic components in this review may not be considered absolute, and more similarities or even further components could arise from a more detailed and standardized description of the programs. The medical components, for example, may be considered obvious by most authors, which may be one reason why not all programs reported ongoing medical examinations. In addition, physicians are responsible for a large part of the education process to reduce the somatic fixation of the patients, and although this was not reported, it is likely an important module of most rehabilitation programs. A standardized method of reporting treatments and treatment components is desirable for investigating the similarities and differences between programs. We recommend including a detailed description in at least one publication per rehabilitation program of the characteristics outlined in Table 2 , i.e., the structure, psychotherapy approach and the medical, psychological, social and other interventions. For the medical, psychological, social and other interventions, components that are essential and usually implemented should be reported. In addition to the differences in the components, differences between the programs could arise from the interdisciplinary team (e.g., composition, professional qualifications) or from the standardization of therapy. This information is essential and needs to be reported because a description of the components alone may not capture the core aspects of treatment. Although the rehabilitation programs can be disassembled into separate components, these components are not meant to be simply checked off to create an effective treatment. The effectiveness may instead arise from non-linear effects resulting from the strong interactions within the interdisciplinary team and from interactions between the team, the parents and the patients. These mechanisms need to be studied to precisely understand the drivers of program effectiveness to improve and strengthen existing pain centers and establish new ones. 4.3. Outcomes of Specialized Rehabilitation Programs Though the short-term effectiveness of specialized rehabilitation programs has largely been demonstrated, reliable evidence regarding the long-term effectiveness over several years is lacking. One problem that arises in longitudinal clinical studies of complex interventions involves the inclusion of an appropriate control group. It is not ethically acceptable to deny severely disabled pediatric patients an effective treatment for such a long time or to provide a treatment that is clearly less effective. Randomized controlled trials (RCTs) have been conducted on psychological interventions, i.e., a subset of components of the rehabilitation programs [ 54 , 55 ], and one RCT has even been conducted on an entire program using a waiting-list control design [ 52 ]. However, this design only allows for short-term conclusions regarding efficacy. These RCTs have certainly contributed to good progress in the field, but there remains a need for more and stronger evidence, especially concerning long-term outcomes. One Dutch study conducted a ten-year follow-up of young adults who had received inpatient rehabilitation for chronic pain or fatigue at one of five rehabilitation centers and found that the majority of these former pediatric patients had a paid job and a moderate to good health-related quality of life [ 56 ]. However, their quality of life was somewhat lower than that of the normal population. Further long-term studies similar to the Dutch analysis are needed. Additionally, reliable evidence regarding the moderators of treatment is also needed. The existing results should be interpreted with caution due to the comparatively small sample sizes. Hirschfeld et al. [ 12 ] showed, that in regression analyses, reliable results can only be achieved with samples of several hundred patients. Such large samples require an extremely long recruitment period or a multicenter data collection process. Collaborative multicenter data collection for complex data analyses and the comparability of effectiveness of different rehabilitation programs are important areas for future research. Multicenter studies also require that comparable treatments be used at each center. Currently, this cannot be assumed, despite a certain overlap across treatment sites. Regarding the comparability of effectiveness, an important issue concerns the outcome measures used to indicate effectiveness. In 2008, McGrath et al. defined the PedIMMPACT recommendations for the core outcome domains and measures for pediatric acute and chronic/recurrent pain clinical trials [ 46 ]. The aim of these recommendations was to standardize the outcome domains and measures assessed in studies to facilitate their comparability and interpretation. However, not all studies adhere to these recommendations. There are, for example, huge differences in assessing pain intensity in the studies mentioned above. Although it is one of the core outcome domains, some studies do not report pain intensity [ 25 , 49 ]. Furthermore, some studies report pain intensity in the present moment [ 28 , 32 , 33 ], while others report pain intensity in the last 24 h [ 34 ], the last seven days [ 35 , 47 , 48 ], or the last four weeks [ 24 ]. Thus, the time period varies greatly between studies. For chronic pain, short time periods are not appropriate because chronic pain is not necessarily persistent or present each day. Thus, the time period should be long enough to also account for pediatric migraine patients, who sometimes experience attacks only once a month. Using a measure of pain intensity of less than one month may lead to distorted results. In addition, the different time periods impede the comparability of study outcomes and thereby of the effectiveness of different rehabilitation programs. The different studies also vary greatly in terms of how many outcome domains they cover. Furthermore, there are outcome domains that have not yet been investigated, despite being recommended as core outcome domains [ 46 ], such as satisfaction with treatment and symptoms and adverse events. However, to date, no validated measures exist for these domains. Another important issue in effectiveness studies of chronic pain patients concerns the definition of what is considered effective. Is a treatment effective if the patients show statistically significant or clinically relevant changes or if the patients return to a normal functional level after treatment? In other words, what is more important: the degree of change or the status of the patient after treatment? Most studies to date have focused on the change from pre- to post-treatment or to follow-up, but what use is a significant or clinically relevant change when the patient is still severely impaired and far from normal? We may need to rethink and redefine the criteria that have to be fulfilled for the treatment to be considered effective or a success. 4.4. Recommendations for Future Research and Patient Care Several areas of research need to be emphasized according to the results of this review. First, we need to devote more effort into standardizing the reporting of rehabilitation programs and outcomes to enable global comparisons of programs and their effectiveness. This review provides a set of important criteria for reporting. Furthermore, efforts should be made to report outcomes according to the PedIMMPACT recommendations in order to increase comparability. This also requires the development of valid outcome measures for different languages. Reporting a wide range of outcomes over a long follow-up gives proper consideration to the complexity of chronic pain, e.g., in some patients, certain pain symptoms may remain while pain-related disability may be substantially reduced in the long term. Additionally, we need further progress regarding long-term effectiveness, moderators of treatment outcome and mechanisms of change. Therefore, collaborative multicenter data collection may play an important role in advancing research in this field and in improving worldwide networking. Improved collaborations between pain centers and the establishment of new centers are similarly important to overcome barriers to health care utilization. The limited availability of pediatric pain clinics and centers bears the risk of additional barriers to health care. Thus, nationwide availability of appropriate health care for children and adolescents with different chronic pain conditions is one, if not the most important, goal for all countries to address pediatric chronic pain. Recently developed internet-delivered or phone-based treatment approaches may be an alternative for patients with long travel distances [ 57 , 58 ]. However, these programs only consist of a few of the components of specialized rehabilitation programs such as cognitive-behavioral techniques and do not replace the complexity of intensive rehabilitation programs. Thus, the establishment of new pain centers remains essential. However, training primary care providers or nurses in psychoeducation or coping skills to initiate some form of treatment before referral to specialized rehabilitation may be a good possibility to bridge the long waiting times for treatment. Comparable evaluation research is needed for quality assurance and for further development of treatment options. 4.5. Limitations The results of this review should be interpreted in light of the following limitations. This review was restricted to descriptions of the structure and outcomes of specialized pain treatment programs that have been published, i.e., the programs of specialized pain centers. However, a considerable number of specialized pain clinics do not necessarily engage in research and thus do not conduct or publish studies on their programs. There may be differences in the structure or outcomes between published and unpublished specialized treatment programs. In addition, we did not conduct a systematic literature search. 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Criteria Specialized Rehabilitation Programs Inclusion AUS UK UK GER USA USA USA USA USA 1 2 3 4 5 6 7 8 9 Pain for more than 3 months x x x High pain-related disability x x x x x x Patient and parent motivation x x x x Failure of outpatient treatment x x x Exclusion 1 2 3 4 5 6 7 8 9 Psychiatric needs x x x Further assessment required x x Medical pathology/underlying disease x x Active malignant disease x x Effective medical options x Only criteria explicitly reported in the literature are included for each rehabilitation program, i.e., a missing “x” does not mean that this criterion does not apply to this rehabilitation program, but that it is not reported in the literature; 1: Melbourne, AUS [ 50 ]; 2: Bath, UK [ 35 ]; 3: Bath, UK [ 48 ]; 4: Datteln, GER [ 41 , 45 , 47 ]; 5: Boston, MA, USA [ 32 , 51 ]; 6: Baltimore, MD, USA [ 49 ]; 7: Rochester, MN, USA [ 33 ]; 8: Cleveland, OH, USA [ 34 , 43 ]; 9: Philadelphia, PA, USA [ 28 ]. Table 2. Structural and therapeutic components of the specialized rehabilitation programs. Components Specialized Rehabilitation Programs AUS UK UK GER USA USA USA USA USA Structure 1 2 3 4 5 6 7 8 9 Inpatient x x x x x Day-hospital x x x x x x Interdisciplinary team x x x x x x x x x Psychotherapy Approach 1 2 3 4 5 6 7 8 9 Operant and cognitive behavioral therapy x x x x x x x x x Acceptance and commitment therapy x x x Medical Interventions 1 2 3 4 5 6 7 8 9 Medication x x x x x Medical examination x x x x Physical therapy x x x x x x x x x Biofeedback x x x x Psychological Interventions 1 2 3 4 5 6 7 8 9 Education x x x x Relaxation techniques x x x x x x Attention defocusing x x x Imagery x x x x Active daily structure x x x x x x x x x Stress management x x x x Problem-solving x x x Addressing psychological comorbidities x x Social Interventions 1 2 3 4 5 6 7 8 9 Family sessions x x x x x x x x Parent-only sessions x x x x x School reintegration x x x x x Patient group sessions x x x x x Other 1 2 3 4 5 6 7 8 9 Occupational therapy x x x x x x x Recreational therapy x x x Hospital school program x x x Acupressure/acupuncture x x x Diet x x Sleep hygiene x x x Music therapy x x x Art therapy x x x Therapeutic homework and practicing x x x Relapse prevention x x x x Follow-up care x x x	https://www.mdpi.com/2227-9067/3/4/33
Appearance of Aminorex as a Designer Analog of 4-Methylaminorex - [www.rhodium.ws] Appearance of Aminorexas a Designer Analog of 4-Methylaminorex M. E. Brewster & F. T. DavisJ. Forensic Sci. 36(2), 587-592 (1991) HTML by Rhodium Abstract A case in which aminorex (cis (±)-4,5-dihydro-5-phenyl-2-oxazolamine) was prepared as a "designer" analog of a controlled substance, methylaminorex (cis-(±)-4,5-dihydro-4-methyl-5-phenyl-2-oxazolamine) is described. The confiscated drug sample was analyzed by high-field (300-MHz) proton nuclear magnetic resonance (NMR) and carbon-13 NMR spectroscopy, as well as electron impact mass spectrometry (70 eV). These examinations proved conclusively that the material in question was aminorex. <here is a image d484de221d22c0d7-758c41f80f11aeb5> An illicit compound which has recently been identified in several solid samples seized in Florida and California is cis -(±)-4,5-dihydro-4-methyl-5-phenyl-2-oxazolamine, also known as methylaminorex, ice, or euphoria (U4Euh) 1 . This oxazoline exerts potent central nervous system sympathomimetic effects not unlike those of methamphetamine 2-4 . Methylaminorex was first prepared in 1962 as a potential anorexic agent 5 . There appears to be widespread use of this designer drug, and illicit use of this compound has resulted in at least one fatality 1 . Through the efforts of various law enforcement agencies, this substance has recently been controlled (Schedule I) under emergency scheduling provisions of the controlled substances act 6,7 . With this scrutiny, alternatives to the methylaminorex structure have been sought to avoid potential prosecution. For this reason, the desmethyl derivative, that is, aminorex, was synthesized (see Fig. 1 ). It is an interesting circumstance that aminorex was reported in the same literature as was methylaminorex. Aminorex, under the trademark Menocil®, proceeded to the point that it was introduced into the European market (West Germany, Austria, and Switzerland) as an anorexic agent in February of 1966. During its use, an unacceptably high incidence of pulmonary hypertension was reported, which led to the deaths of several individuals 8-10 . These side effects caused this drug to be withdrawn from the market in November 1968. A new drug application (NDA) which was pending in the United States was also discontinued at that time. The illicit use of this formerly marketed drug as an alternative to its methylated analog was recently observed and is described here. Materials and Methods Chemicals The compound cis(±)-4,5-dihydro-4-methyl-5-phenyl-2-oxazolamine, which was used for comparative purposes, was prepared according to the method of Poos et al. 11 . All the solvents used were of reagent or spectroscopic quality and were obtained from Aldrich Chemical Co. Analytical Procedures The melting points were determined on a Thomas-Hoover capillary melting-point apparatus and were uncorrected. Proton ( 1 H) and carbon-13 ( 13 C) nuclear magnetic resonance (NMR) spectra were obtained using a Vanan XL 300 spectrometer. The samples were dissolved in an appropriate deuterated solvent, usually deuterated chloroform (CDCl 3 ), and chemical shifts 8 were reported relative to an internal standard [tetramethylsilane (TMS)]. The mass spectra were recorded on a Kratos MS8ORFA Spectrometer. Thin-layer chromatography utilized EM reagent DC-aluminum foil plates, coated to a thickness of 0.2 mm with silica gel 60. Results and Discussion A sample of a white powder was recently confiscated from a white male in Florida. The suspect indicated that the seized material was not a controlled substance. The solid was analyzed by various analytical methods, including high- field (300-MHz) proton ( 1 H) and 13 C NMR spectroscopy and electron impact (EI) mass spectrometry (70 eV). ln addition, the purity of the solid was determined chromatographically. The melting point of the sample was found to be 124 to 127°C, which was lower than the reported melting point for either methylaminorex (150 to 152°C) or aminorex (136 to 138°C) 11 . Thin-layer chromatographic analysis revealed an R f value for the material in question of 0.43 when eluted on silica plates using a mobile phase containing 85:10:5 ethyl acetate/methanol/concentrated ammonium hydroxide. Several impurities were detected at R f values both greater and less than that of the compound of interest. Another indication of the impurity of the samples examined was their microcombustion profiles, which indicated deviation from the accepted carbon values of between 2 and 15%. Fig 2.[Enlarge]Aminorex 1H NMR Spectrum with Interpretation. <here is a image b824e02eb96ae4f9-f5eb001d8f9130e2> The proton NMR spectrum for aminorex and its structural assignments are provided in Fig. 2 . Unlike the spectrum of methylaminorex, no upfield (<3δ) absorbances characteristic of a methyl group occur in the 1 H NMR spectrum of the confiscated sample. Fig 3.[Enlarge]Aminorex 13C NMR Spectrum with Interpretation. <here is a image 29ab2cbd9ddd8c3c-bfe5acd449064ae5> The obtained spectrum is indicative of the assigned structure of aminorex, with the phenyl group appearing at 7.35 δ, a benzylic methine triplet at 5.46 δ, the exchangeable amino group at 5.2 δ, and the nonequivalent hydrogens of the methylene group β to the phenyl ring at 4.13 and 3.65δ. The 13 C NMR spectrum is equally supportive of the 4,5-dihydro-5-phenyl-2-oxazolamine structure, with no upfield methyl signal and with the remaining carbon absorbances occurring at their expected 8 values ( Fig. 3 ). Decoupling analysis of this spectrum indicates quaternary and secondary carbons at 160.89 δ, 140.62 δ, and 60.63 δ, corresponding to the imine carbon (C-2), the phenyl carbon attached to C-5, and the methylene carbons (C-4). The remaining methine carbons manifested signals at 128.62 δ, 128.14 δ, 125.66 δ, corresponding to the phenyl carbons, and at 81.43 δ, which was assigned as the C-5 absorbance. Fig 4.[Enlarge]Aminorex EI/MS Spectrum. <here is a image c9357fa5ee720f8e-ebd89b98ae843027> Mass spectrometric analysis was performed on the sample in question by probe distillation introduction. This technique indicated the presence of impurities which vaporized at higher temperatures than did the object compound. An EI spectrum of the material is given in Fig. 4 . The fragmentation pattern and the molecular ion are indicative of the aminorex structure and compare well with those of standard spectra 12 . The M + peak is 162 m/z . Loss of the carboxamide group CONH 2 produces the fragment at 118 m/z , while generation of protonated benzyl alcohol results in the m/z = 107 fragment. Other important fragments include the tropylium ion (91 m/z ) and the phenyl cation at 77 m/z . The base peak of the spectra (56 m/z ) appears to be due to the imine structure, NH 2 -C=N-CH 2 + . The mass spectrum reported for methylaminorex is characterized by an M + of 176 m/z and a base peak of 70 m/z , each differing by 14 mass units from the corresponding aminorex fragments. The collected analytical information leaves little doubt that the compound in question was the desmethyl derivative, aminorex, of the controlled substance methylaminorex. Conclusions A case was identified in which a drug formerly marketed as an anorexic agent, aminorex, was found to be used in an apparently illicit manner as a substitute for methylaminorex. Analysis of a recently impounded sample conclusively proved that the material was aminorex, an identification based on 1 H and 13 C spectroscopy and mass spectrometry. References Davis, F. T. and Brewster, M. 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C., " Schedules of Controlled Substances; Temporary Placement of 3,4-Methylenedioxy-N-Ethylamphetamine, N-Hydroxy-3,4-Methylenedioxyamphetamine and 4-Methylaminorex into Schedule I," Federal Register, Vol. 52, 38225-38226 (1987) Lawn, J. C., " Schedule of Controlled Substances; Temporary Placement of 2-Amino-4-Methyl-5-Phenyl-3-Oxazoline (4-Methylaminorex) into Schedule I," Federal Register, Vol. 52, 30174-30175 (1987) Gurtner, H., " Aminorex and Pulmonary Hypertension," Cor et Vasa, Vol. 27, 160 (1985) Gurtner, H., " Pulmonary Hypertension, 'Plexogenic Pulmonary Arteriopathy,' and the Appetite Depressant Drug Aminorex: Post or Propter?" Bulletin de Physio-pathologie Respiratoire, Vol. 15, 897 (1979) Seiler, K., " Aminorex and Pulmonary Circulation," Arzneimittel-forschung, Vol. 25, 837 (1975) Poos, G. I., Carson, J., Rosenau, J., Roszkowski, A., Kelly, N., and McGowir, J., " 2-Amino-5-Aryl-2-Oxazolines: New Anorectic Agents," Journal of Medicinal Chemistry 6, 266-272 (1963) Smith, F. P. and Kidwell, D. A., " Final Report: Designer Amphetamines - Their Synthetic and Detection," Naval Research Laboratory, US Department of the Navy, Washington, DC, August 1989, p. 11.	https://chemistry.mdma.ch/hiveboard/rhodium/aminorex.html
Lomez: Uses, Price, Dosage, Side Effects, Substitute, Buy Online Find out about Lomez benefits, side effects, price, dose, how to use Lomez, interactions and contraindications Lomez ☆ ☆ ☆ ☆ ☆ 5.0/5.0 ( 1 Ratings & 0 Reviews ) 15 Capsule in 1 Strip ₹ 11 Lomez 20 Capsule 15 CAPSULE 1 Strip ₹ 11 Out of Stock Manufactured by: Meyer Organics Pvt Ltd Contains / Salt: Omeprazole (20 mg) Lomez Information Lomez, a prescription drug, is manufactured in various forms such as Capsule. Acidity, Peptic Ulcer, GERD are some of its major therapeutic uses. Lomez also has some secondary and off-label uses. These are listed below. The optimal dosage of Lomez is largely dependent on the individual's body weight, medical history, gender and age. The condition it has been prescribed for, and the route of administration also determine the right dosage. Refer to the dosage section for a detailed discussion. Some other side effects of Lomez have been listed ahead. Normally, these side effects of Lomez are not long lasting and go away when the treatment is finished. If, however, they worsen or do not go away, please speak with your physician. In addition, Lomez's effect is Mild during pregnancy and Moderate for lactating mothers. Warnings related to Lomez's effects on the liver, heart and kidney, if any, have been listed below. The section on Lomez contraindications lists all such conditions. Drug interactions for Lomez have been reported in the medical literature. See below for a complete list. Along with the above-mentioned precautions, remember that taking Lomez is considered not safe while driving, and is not addictive. Lomez Benefits & Uses Lomez Dosage & How to Take Lomez Side Effects Lomez Related Warnings Severe Interaction of Lomez with Other Drugs Lomez Contraindications Frequently asked Questions about Lomez Lomez Interactions with Food and Alcohol Lomez Benefits & Uses Lomez is used to treat the following - Main Benefits Acidity (Read More - Home remedies for acidity ) Peptic Ulcer GERD Other Benefits Gastrointestinal Bleeding Zollinger Ellison syndrome Stomach Gas Hernia Stomach Pain (Read More - Home remedies for stomach pain ) Laryngitis Food Poisoning Abdominal pain during pregnancy Acidity during pregnancy Sour Burp Digestive Disorders Throat Ulcer Lomez Dosage & How to Take This is the usual dosage recommended in most common treatment cases. Please remember that every patient and their case is different, so the dosage can be different based on the disease, route of administration, patient's age and medical history. Age Group Dosage Adult Disease: Acidity Before or After Meal: Before meal Single Maximum Dose: 20 mg Dosage Form: Capsule Dosage Route: Oral Frequency: 1 daily Course Duration: 2 weeks Special Instructions: As prescribed by the doctor Geriatric Disease: Acidity Before or After Meal: Before meal Single Maximum Dose: 20 mg Dosage Form: Capsule Dosage Route: Oral Frequency: 1 daily Course Duration: 2 weeks Special Instructions: As prescribed by the doctor 13 - 18 years (Adolescent) Disease: Acidity Before or After Meal: Before meal Single Maximum Dose: 20 mg Dosage Form: Tablet Dosage Route: Oral Frequency: 1 daily Course Duration: 2 weeks Special Instructions: As prescribed by the doctor 2 - 12 years (Child) Disease: Zollinger Ellison syndrome Before or After Meal: Before meal Single Maximum Dose: 10 mg Dosage Form: Tablet Dosage Route: Oral Frequency: 1 daily Course Duration: As directed by the doctor Special Instructions: As prescribed by the doctor Lomez Related Warnings Is the use of Lomez safe for pregnant women? Pregnant women may get mild side effects from Lomez. Mild Is the use of Lomez safe during breastfeeding? Lomez may lead to some side effects in breastfeeding women. If you witness any unusal symptoms after taking Lomez, discontinue its use and call your doctor right away. Follow your doctor's advice regarding the use of Lomez. Moderate What is the effect of Lomez on the Kidneys? Mild What is the effect of Lomez on the Liver? Side effects of Lomez rarely affect the liver. Mild What is the effect of Lomez on the Heart? Side effects of Lomez rarely affect the heart. Mild Lomez should not be taken with following medicines due to severe side effects it may cause to patients - Lomez Contraindications If you are suffering from any of the following diseases, you should not take Lomez unless your doctor advises you to do so - Kidney Disease Liver Disease Heart Disease Bartter's Syndrome Cushing's Syndrome Gastric Cancer Magnesium Deficiency Frequently asked Questions about Lomez Is this Lomez habit forming or addictive? Lomez does not cause addiction. No Is it safe to drive or operate heavy machinery when consuming? After taking Lomez, you should not drive or work on any heavy machine, as Lomez can make you drowsy. Dangerous Is it safe? Lomez should be used only after doctor's advice. Safe, but take only on Doctor's advise Is it able to treat mental disorders? No Lomez Interactions with Food and Alcohol Interaction between Food and Lomez You can take Lomez with food. Safe Interaction between Alcohol and Lomez Consumption of alcohol and Lomez together may have severe effects on your health. Severe Frequently asked Questions about Lomez How long can I safely take Lomez? Dr. Rahul Poddar MBBS, DNB, MBBS, DNB , General Surgery Take Lomez as long as your doctor has recommended you to take it. Do not exceed the prescribed dose. Consult your doctor if there is no symptomatic relief. Can I discontinue Lomez on my own without doctors advice? Dr. Amit Singh MBBS , General Physician Discontinuation of Lomez on your own can cause harmful effects on your body. It is recommended that you always consult your doctor before discontinuing medicine on your own. Question almost 4 years ago Is Lomez good for gastritis? Dr. Ajay Kumar MBBS, MD , General Physician Yes, Lomez is used in the treatment of gastritis. It helps by preventing the excess acid secretion in the stomach and additionally relieving the symptoms of gastritis such as stomach pain, stomach inflammation, and acid reflux. How to use Lomez? Dr. Vedprakash Verma MBBS, MD , Cardiology Lomez should be taken 30 - 60 minute before meal. Preferably it should be taken once a day in the morning before breakfast. However, some people may require to take it twice in a day, in this case, 1 tablet should be taken in the morning and 1 tablet in the evening before meal. Please consult your doctor regarding the exact dosage regime of medicine and follow his/her instruction. Can I take Lomez with antibiotic? Yes, Lomez can be taken with an antibiotic. Taking Lomez with a certain antibiotic can treat H.Pylori associated stomach infection. However, it is best to consult your doctor before taking these two medicines together. See all substitutes for Lomez Ocid Capsule - ₹59 Omee Capsule - ₹55 Omecip Capsule - ₹40 Omecool 20 Mg Capsule - ₹37 Omesec 20 Capsule - ₹25 Omez 20 Capsule - ₹59 Omez 10 Capsule - ₹32 Omerid Capsule - ₹28 Omore 20 Capsule - ₹24 Omekaa Capsule - ₹12 Opel Capsule - ₹9 Lokit 20 Capsule - ₹40 Nogacid Capsule - ₹40 Lomez 20 Capsule - ₹11 Olzole 20 Mg Capsule - ₹41 Biocid 20 Capsule - ₹24 Omeron 20 Mg Capsule - ₹8 Corcid Capsule - ₹38 Omepraz 20 Capsule - ₹56 Ocidon Capsule (15) - ₹9 This medicine data has been created by - Vikas Chauhan B.Pharma, Pharmacy5 Years of Experience References US Food and Drug Administration (FDA) [Internet]. Maryland. USA;Package leaflet information for the user; Prilosec (omeprazole) KD Tripathi. [link]. Seventh Edition. New Delhi, India: Jaypee Brothers Medical Publishers; 2013: Page No 651-653 April Hazard Vallerand, Cynthia A. Sanoski. [link]. Sixteenth Edition. Philadelphia, China: F. A. Davis Company; 2019: Page No 945-947	https://www.myupchar.com/en/medicine/lomez-p37092253?ref=raisan-21
Regulation (EU) No 1303/2013 of the European Parliament and of the Council of 17 December 2013 laying down common provisions on the European Regional Development Fund, the European Social Fund, the Cohesion Fund, the European Agricultural Fund for Rural Development and the European Maritime and Fisheries Fund and laying down general provisions on the European Regional Development Fund, the European Social Fund, the Cohesion Fund and the European Maritime and Fisheries Fund and repealing Council Regulation (EC) No 1083/2006 Regulation (EU) No 1303/2013 of the European Parliament and of the Council of 17 December 2013 laying down common provisions on the European Regional Development Fund, the European Social Fund, the Cohesion Fund, the European Agricultural Fund for Rural Development and the European Maritime and Fisheries Fund and laying down general provisions on the European Regional Development Fund, the European Social Fund, the Cohesion Fund and the European Maritime and Fisheries Fund and repealing Council Regulation (EC) No 1083/2006 Regulation (EU) No 1303/2013 of the European Parliament and of the Council Show full title Regulation (EU) No 1303/2013 of the European Parliament and of the Council of 17 December 2013 laying down common provisions on the European Regional Development Fund, the European Social Fund, the Cohesion Fund, the European Agricultural Fund for Rural Development and the European Maritime and Fisheries Fund and laying down general provisions on the European Regional Development Fund, the European Social Fund, the Cohesion Fund and the European Maritime and Fisheries Fund and repealing Council Regulation (EC) No 1083/2006 What Version Legislation is available in different versions: Latest Available (revised):The latest available updated version of the legislation incorporating changes made by subsequent legislation and applied by our editorial team. Changes we have not yet applied to the text, can be found in the ‘Changes to Legislation’ area. Original (As adopted by EU):The original version of the legislation as it stood when it was first adopted in the EU. No changes have been applied to the text. Latest available (Revised) Original (As adopted by EU) Advanced Features See additional information alongside the content Geographical Extent:Indicates the geographical area that this provision applies to. For further information see ‘Frequently Asked Questions’. Show Timeline of Changes:See how this legislation has or could change over time. Turning this feature on will show extra navigation options to go to these specific points in time. Return to the latest available version by using the controls above in the What Version box. Show Geographical Extent (e.g. E ngland, W ales, S cotland and N orthern I reland) Show Timeline of Changes Opening Options Expand opening options Different options to open legislation in order to view more content on screen at once This is a legislation item that originated from the EU After exit day there will be three versions of this legislation to consult for different purposes. The legislation.gov.uk version is the version that applies in the UK. The EU Version currently on EUR-lex is the version that currently applies in the EU i.e you may need this if you operate a business in the EU. The web archive version is the official version of this legislation item as it stood on exit day before being published to legislation.gov.uk and any subsequent UK changes and effects applied. The web archive also captured associated case law and other language formats from EUR-Lex. Changes over time for: Division 5. Alternative versions: 17/12/2013 - Amendment Exit day: start of implementation period 31/01/2020 11pm - Amendment End of implementation period 31/12/2020 - Amendment Changes to legislation: Changes to Legislation Revised legislation carried on this site may not be fully up to date. Changes and effects are recorded by our editorial team in lists which can be found in the ‘Changes to Legislation’ area. Where those effects have yet to be applied to the text of the legislation by the editorial team they are also listed alongside the legislation in the affected provisions. Use the ‘more’ link to open the changes and effects relevant to the provision you are viewing. Changes and effects yet to be applied to Annex I Division 5: Changes and effects yet to be applied to the whole legislation item and associated provisions Title 9 Ch. 1 omitted by S.I. 2021/400 reg. 6(30) 5. HORIZONTAL PRINCIPLES REFERRED TO IN ARTICLES 5, 7 AND 8 AND CROSS-CUTTING POLICY OBJECTIVES U.K. 5.1 Partnership and multi-level governance U.K. 1. In accordance with Article 5, the principle of partnership and multi-level governance shall be respected by Member States in order to facilitate achieving social, economic and territorial cohesion and delivery of the Union's priorities of smart, sustainable and inclusive growth. In order to respect those principles coordinated action is required, in particular between the different levels of governance, carried out in accordance with the principles of subsidiarity and proportionality, including by means of operational and institutional cooperation, with regard to the preparation and implementation of the Partnership Agreement and programmes. U.K. 2 Member States shall examine the need for strengthening the institutional capacity of partners in order to develop their potential in contributing to the effectiveness of the partnership. U.K. 5.2 Sustainable development U.K. 1. Member States and managing authorities shall, in all phases of implementation, ensure the full mainstreaming of sustainable development into the ESI Funds, respecting the principle of sustainable development as laid down in Article 3(3) TEU, as well as complying with the obligation to integrate environmental protection requirements pursuant to Article 11 TFEU and the polluter pays principle as set out in Article 191(2) TFEU. U.K. Managing authorities shall undertake actions throughout the programme lifecycle, to avoid or reduce environmentally harmful effects of interventions and ensure results in net social, environmental and climate benefits. Actions to be undertaken may include the following: (a) directing investments towards the most resource-efficient and sustainable options; (b) avoiding investments that may have a significant negative environmental or climate impact, and supporting actions to mitigate any remaining impacts; (c) (d) increasing the use of green public procurement. 2. Member States shall take into consideration the climate change mitigation and adaptation potential of investments made with the support of the ESI Funds, in accordance with Article 8, and ensure that they are resilient to the impact of climate change and natural disasters such as increased risks of flooding, droughts, heat waves, forest fires and extreme weather events. U.K. 3. Investments shall be consistent with the water management hierarchy, in line with Directive 2000/60/EC of the European Parliament and of the Council( 1 ), with a focus on demand management options. Alternative supply options shall only be considered when the potential for water savings and efficiency has been exhausted. Public intervention in the waste management sector shall complement efforts by the private sector, in particular in relation to producer responsibility. Investments shall encourage innovative approaches that promote high levels of recycling. Investments shall be consistent with the waste hierarchy established under Directive 2008/98/EC of the European Parliament and of the Council( 2 ). Expenditure related to biodiversity and the protection of natural resources shall be consistent with Council Directive 92/43/EEC( 3 ). U.K. 5.3 Promotion of equality between men and women and non-discrimination U.K. 1. In accordance with Article 7, Member States and the Commission shall pursue the objective of equality between men and women and shall take appropriate steps to prevent any discrimination during the preparation, implementation, monitoring and evaluation of operations in the programmes co-financed by the ESI Funds. When pursuing the objectives of Article 7, Member States shall describe actions to be taken, in particular with regard to selection of operations, setting of objectives for interventions, and arrangements for monitoring and reporting. Member States shall also carry out gender analyses where appropriate. In particular, specific targeted actions shall be supported through the ESF. U.K. 2. Member States shall ensure, in accordance with Articles 5 and 7, the participation of the relevant bodies responsible for promoting gender equality and non-discrimination in the partnership, and ensure adequate structures in accordance with national practices to advise on gender equality, non-discrimination and accessibility in order to provide the necessary expertise in the preparation, monitoring and evaluation of the ESI Funds. U.K. 3. Managing authorities shall undertake evaluations or self-assessment exercises, in coordination with the monitoring committees, focusing on the application of the gender mainstreaming principle. U.K. 4. Member States shall address, in an appropriate manner, the needs of disadvantaged groups in order to allow them to better integrate into the labour market, and thereby facilitate their full participation in society. U.K. 5.4 Accessibility U.K. 1. Member States and the Commission shall, in accordance with Article 7, take appropriate steps to prevent any discrimination based on disability. Managing authorities shall ensure by means of action throughout programme lifecycles that all products, goods, services and infrastructures that are open or provided to the public and are co-financed by the ESI Funds are accessible to all citizens including those with disabilities in accordance with applicable law, thereby contributing to a barrier-free environment for persons with disabilities and the elderly. In particular, accessibility to the physical environment, transport, ICT in order to promote inclusion of disadvantaged groups, including persons with disabilities, shall be ensured. Actions to be undertaken may include directing investments towards accessibility in existing buildings and established services. U.K. 5.5 Addressing demographic change U.K. 1. The challenges resulting from demographic change, including in particular those related to a shrinking working population, an increasing proportion of retired people in the overall population and to depopulation, shall be taken into account at all levels. Member States shall make use of the ESI Funds, in line with relevant national or regional strategies, where such strategies are in place, to tackle demographic problems and to create growth linked to an ageing society. U.K. 2. Member States shall use the ESI Funds, in line with relevant national or regional strategies to facilitate inclusion of all age groups, including through improved access to education and social support structures with a view to enhancing job opportunities for the elderly and young people and with a focus on regions with high rates of youth unemployment in comparison to the Union average rate. Investments in health infrastructures shall be aimed at ensuring a long and healthy working life for all of the Union's citizens. U.K. 3. To address challenges in the regions most affected by demographic change, Member States shall in particular identify measures to: U.K. (a) support demographic renewal through better conditions for families and an improved balance between working and family life; (b) boost employment, raise productivity and economic performance through investing in education, ICT and research and innovation; (c) focus on the adequacy and quality of education, training and social support structures as well as where appropriate, on the efficiency of social protection systems; (d) 5.6 Climate change mitigation and adaptation U.K. In accordance with Article 8, climate change mitigation and adaptation, and risk prevention shall be integrated in the preparation and implementation of Partnership Agreements and programmes. ( 1 ) Directive 2000/60/EC of the European Parliament and of the Council of 23 October 2000 establishing a framework for Community action in the field of water policy (OJ L 327, 22.12.2000, p. 1). ( 2 ) Directive 2008/98/EC of the European Parliament and of the Council of 19 November 2008 on waste and repealing certain Directives (OJ L 312, 22.11.2008, p. 3). ( 3 ) Council Directive 92/43/EEC of 21 May 1992 on the conservation of natural habitats and of wild fauna and flora (OJ L 206, 22.7.1992, p. 7).	https://www.legislation.gov.uk/eur/2013/1303/annex/I/division/5
Barriers to solidarity in Lebanon’s 2019 uprising, by Anne Kirstine Rønn " Barriers to solidarity in Lebanon’s 2019 uprising, by Anne Kirstine Rønn" published on 30 May 2023 by Brill. Barriers to solidarity in Lebanon’s 2019 uprising: How should we understand them, and what can be learned from them? Anne Kirstine Rønn Carlsberg Postdoctoral Fellow in the Middle East Centre at the London School of Economics and Political Science While conducting field research for my PhD dissertation on Lebanon's 2019 October Uprising, I frequently asked my interlocutors what they considered to be the uprising's most important characteristic. One of the common answers I received was "diversity." According to many of the protesters I spoke to, the uprising was remarkable because it united individuals from different walks of life. Street vendors and lawyers suddenly stood side by side and chanted slogans against Lebanon's corrupt sectarian elites that have governed the country since the civil war.The celebration of diversity, inclusivity and solidarity across societal fault lines was also evident in the news coverage of the uprising, and asstudies and survey dataconfirm, protesters did indeed come from all corners of Lebanon. They were old and young, women and men, and they broke boundaries between regions, sects, and classes. However, the October Uprising was not solely a display of unity; it also reflected underlying divisions and exclusionary practices that constitute barriers to solidarity between protesters. Like in any other popular protest movement, there were disagreements regarding tactics and political goals. Prejudices and fears also persisted, resulting in negative attitudes and suspicions toward certain segments of the population in the streets and squares of the uprising. Specifically, individuals belonging to marginalized groups in society faced such biases.I delve into the barriers to solidarity within the Lebanese uprising in my recentarticlein Middle East Law and Governance, entitled “Promoting Inclusivity in Anti-Sectarian Protests: Understanding the Dilemmas of Organizers in Lebanon's 2019 October Uprising”. The article draws on interviews with twenty-two individuals who represented a diverse range of key organizers in the protests that took place in Beirut. Its objective is to understand the dilemmas faced by these organizers when attempting to address the persistence of negative discourses concerning a particular segment of the lower classes in Lebanon, namely young men from the areas of Dahiyeh and Khandak el Ghamiq.Dahiyeh and Khandak el Ghamiq are known to be stronghold areas of Hezbollah and Amal Movement, Lebanon's two major Shiite political actors. Dahiyeh, located south of Beirut, has a population of approximately 500,000 people and comprises various impoverished and more affluent neighborhoods predominantly controlled by Hezbollah. Khandak el Ghamiq is a smaller working-class neighborhood in downtown Beirut associated with the Amal Movement.A general stereotype exists regarding people from these two areas: a man dressed in black, adorned with tattoos, and exhibiting a hypermasculine attitude. He rides a cheap motorbike and is assumed to be a supporter of Hezbollah or Amal. Allegedly brainwashed by the propaganda of these political parties, he is believed to be willing to defend them with violence. Whenever such individuals are present at demonstrations against the Lebanese regime, they are assumed to have ulterior motives, aiming to infiltrate and intimidate the crowds rather than expressing genuine discontent with the political elites.Early in the uprising, protesters encountered several attacks by people who matched this stereotype and were often identified as individuals from Khandak or Dahiyeh. Although such claims were frequently difficult to substantiate, they led to a general fear and suspicion towards men who appeared to be "infiltrators" from the two areas. Moreover, they perpetuated a negative and reductionist image of Khandak el Ghamiq and Dahiyeh, which had existed for years – an image that disregarded the political agency of people from these areas and ignored the fact that they were among the first to join the demonstrations at the beginningThe organizers interviewed in the study, some of whom lived in or had relatives in Khandak el Ghamiq and Dahiyeh, generally found the stereotype problematic. They wanted to promote an alternative and more holistic image of the areas and wished to advocate for solidarity with the communities, including those who held skeptical attitudes toward the uprising or were deterred from participating.During my interviews with the organizers, several potential discursive strategies were discussed that could have demonstrated such understanding. However, all of these strategies shared a common problem: they could be interpreted as favoritism toward a particular sectarian group. Implementing them would therefore jeopardize the integrity of the October Uprising as a movement against sectarianism, as argued by the vast majority of organizers in my study.The article not only sheds light on a sensitive issue within the October Uprising but also highlights broader challenges related to solidarity, and inclusion in popular protests. Firstly, it reminds us that these challenges should be understood through an intersectional lens, which pays attention to the intersections of class, gender, sect, ethnicity, and geography.This might seem self-evident. However, assessments of inclusivity of popular protests often tend to focus on singular identities. Especially in popular, mediatized narratives, descriptions such as cross-class and cross-sectarian are frequently used. If we examine the October Uprising through such one-dimensional lenses, we might overlook or fail to understand the complex challenges to solidarity.As the article shows, we can only fully grasp why it was difficult for the uprising to promote discourses of solidarity with the people of Khandak el Ghamiq and Dahiyeh with reference to their combined position as lower-class Shiites (and males) from geographical areas that carry specific historical, cultural, and political connotations.When a protest movement is described as cross-class, we must therefore remember to ask whether it truly includes all segments of the lower classes. When it is said to have women at the forefront, which specific women are being referred to?The article also provides lessons about the structural obstacles to protest solidarity in the context of Lebanon. More specifically, it illustrates how theomnipresence of sectarianismlimited the discursive and tactical opportunities of organizers in the October Uprising. It is, of course, possible that organizers in potential future Lebanese uprisings may learn from past experiences and find ways to enhance solidarity with the communities of Khandak el Ghamiq and Dahiyeh. However, as I discuss, mass protests in Lebanon, as well as in any other society, are unlikely to promote inclusivity of all groups.Because of this, I argue we need to pay attention to the smaller-scale and more localized forms of grassroots mobilization. How can such types of mobilization complement and compensate for the limitations of mass uprisings? In the Lebanese case, a main task for future research is to explore whether environmental campaigns, alternative labor unions, and student movements can cultivate solidarity ties that the October Uprising struggled to establish. By engaging with this question, we might reach a better understanding of the prospects for citizens to challenge the country's ingrained political and economic regime.	https://blog.brill.com/display/post/guest-post/barriers-to-solidarity-in-lebanon-s-2019-uprising--how-should-we-understand-them--and-what-can-be-learned-from-them-.xml?result=1&rskey=sZMd0l
Phase I/IIa Study of 68GaNOTA-Anti-MMR-VHH2 for PET/CT - Full Text View - ClinicalTrials.gov Phase I/IIa Study of 68GaNOTA-Anti-MMR-VHH2 for PET/CT The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. ClinicalTrials.gov Identifier: NCT04168528 Recruitment Status : Recruiting First Posted : November 19, 2019 Last Update Posted : August 4, 2022 See Contacts and Locations Sponsor: Universitair Ziekenhuis Brussel Kom Op Tegen Kanker Information provided by (Responsible Party): Universitair Ziekenhuis Brussel Study Details Study Description Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Brief Summary: Phase I/IIa study to evaluate the uptake of 68NOTA-anti-MMR-VHH2, a new tracer for positron emission tomographic imaging (PET/CT scan) of breast cancer, head and neck cancer or melanoma Condition or disease Intervention/treatment Phase Malignant Solid Tumor Breast Cancer Head and Neck Cancer Melanoma (Skin) Drug: 68GaNOTA-Anti-MMR-VHH2 Phase 1 Phase 2 Study Design Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Layout table for study information Study Type : Interventional (Clinical Trial) Estimated Enrollment : 37 participants Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Diagnostic Official Title: Phase I/IIa Study to Evaluate the Safety, Biodistribution, Radiation Dosimetry and Tumor Imaging Potential of 68GaNOTA-Anti-MMR-VHH2, a Radiopharmaceutical for in Vivo Imaging of Tumour-Associated Macrophages by Means of PET: UZBRU_VHH2_1 Actual Study Start Date : November 5, 2019 Estimated Primary Completion Date : October 2022 Estimated Study Completion Date : April 2023 MedlinePlus Genetics related topics: Breast cancer Melanoma U.S. FDA Resources Arms and Interventions Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Arm Intervention/treatment Experimental: Part I: safety, tolerability, biodistribution and dosimetry Phase I Drug: 68GaNOTA-Anti-MMR-VHH2 Injection of the radiopharmaceutical and PET/CT imaging Experimental: Part II: tumor targeting potential and correlation to ICH Phase II Drug: 68GaNOTA-Anti-MMR-VHH2 Injection of the radiopharmaceutical and PET/CT imaging Outcome Measures Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Primary Outcome Measures : Tolerability and safety of 68GaNOTA-Anti-MMR-VHH2: reported as type, frequency and severity (graded according to the CTCAEv5) (Part I). [ Time Frame: Before injection up until 6 hrs after injection ] Assessed using physical examination and blood sampling for hematology and clinical chemistry. Human biodistribution using blood sampling and PET/CT imaging: reported as relative uptake values per organ at 10, 90 and 150 minutes per individual subject and as a mean over all subjects (Part I). [ Time Frame: Immediately after injection up to 3 hrs after injection ] Measured in standard uptake values in PET/CT imaging and expressed in relation to the injected activity. Human dosimetry using PET/CT imaging data: radiation dose to individual organs and the equivalent dose for the whole body of each subject and as a mean over all subjects (Part I). [ Time Frame: 10 min up to 3 hrs after injection ] Dosimetry will be calculated using the OLINDA software. Tumor targeting potential using PET/CT and correlation to immunohistological MMR staining after resection: assessed using correlation coefficient (Part II). [ Time Frame: Resection of lesion up to 14 days after PET/CT ] PET/CT and immunohistochemistry will be assessed using a semi-quantative scale. Eligibility Criteria Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. Layout table for eligibility information Ages Eligible for Study: 18 Years and older (Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No Criteria PART I: Inclusion Criteria: Patients will only be included in the study if they meet all of the following criteria: Patients who have given informed consent Patients at least 18 years old Patients with local, locally advanced or metastatic disease of a malignant solid tumor. In order to minimize partial volume effect the diameter of at least 1 tumor lesion should be ≥ 10 mm in short axis for invaded adenopathies and ≥ 10 mm in long axis for all other types of lesions. Exclusion Criteria: Patients will not be included in the study if one of the following criteria applies: Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher Pregnant patients Breast feeding patients Patients with abnormal liver (Bilirubin ≥1.5 x ULN, ALT (SGPT) ≥3 x ULN) or kidney function (Serum creatinine clearance ≤50 ml/min as calculated with Cockcroft-Gault formula) Patients with recent (< 1 week) gastrointestinal disorders (CTCAE v4.0 grade 3 or 4) with diarrhea as major symptom Patients with any serious active infection Patients who have any other life-threatening illness or organ system dysfunction, which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test radiopharmaceutical Patients who cannot communicate reliably with the investigator Patients who are unlikely to cooperate with the requirements of the study Patients who are unwilling and/or unable to give informed consent Patients at increased risk of death from a pre-existing concurrent illness Patients who participated already in this study PART II: Inclusion Criteria: Patients will only be included in the study if they meet all of the following criteria: Patients who have given informed consent Patients at least 18 years old Patients with local, locally advanced or metastatic disease of breast cancer, head-and-neck cancer or melanoma, who is planned for resection or surgical biopsy of at least one lesion. In order to minimize partial volume effect the diameter of the tumor to be resected or biopsied should be ≥ 10 mm in short axis for invaded adenopathies and ≥ 10 mm in long axis for all other types of lesions. Exclusion Criteria: Patients will not be included in the study if one of the following criteria applies: Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher Pregnant patients Breast feeding patients Patients with recent (< 1 week) gastrointestinal disorders (CTCAE v4.0 grade 3 or 4) with diarrhea as major symptom Patients with any serious active infection Patients who have any other life-threatening illness or organ system dysfunction, which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test radiopharmaceutical Patients who cannot communicate reliably with the investigator Patients who are unlikely to cooperate with the requirements of the study Patients who are unwilling and/or unable to give informed consent Patients at increased risk of death from a pre-existing concurrent illness Patients who participated already in this study Contacts and Locations Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04168528 Contacts Layout table for location contacts Contact: UZ Brussel +3224776013 [email protected] Locations Layout table for location information Belgium Uz Brussel Recruiting Brussels, Belgium, 1090 Contact: UZ Brussel +3224776013 [email protected] Contact: MD Principal Investigator: Marleen KEYAERTS, MD Sponsors and Collaborators Universitair Ziekenhuis Brussel Kom Op Tegen Kanker Investigators Layout table for investigator information Principal Investigator: Marleen KEYAERTS, MD Universitair Ziekenhuis Brussel Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Layout table for additonal information Responsible Party: Universitair Ziekenhuis Brussel ClinicalTrials.gov Identifier: NCT04168528 History of Changes Other Study ID Numbers: UZBRU_VHH2_1 2017-001471-23 ( EudraCT Number ) First Posted: November 19, 2019 Key Record Dates Last Update Posted: August 4, 2022 Last Verified: July 2022 Individual Participant Data (IPD) Sharing Statement: Plan to Share IPD: No Layout table for additional information Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No Keywords provided by Universitair Ziekenhuis Brussel: U.S. Department of Health and Human Services	https://clinicaltrials.gov/ct2/show/study/NCT04168528
Publications - Global Disability Innovation Hub The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good. Type Journal Paper Themes Assistive & Accessible Technology Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems Jamie Danemayer,Cathy Holloway,Youngjun Cho, Nadia Berthouze, Aneesha Singh, William Bhot, Ollie Dixon, Marko Grobelnik, John Shawe-Taylor Paper highlights: Assistive technology (AT) information networks are insular among stakeholder groups, causing unequal access to information. Participants often cited fragmented international marketplaces as a barrier and valued info-sharing across industries. Current searches produce biased results in marketplaces influenced by commercial interests and high-income contexts. Smart features could facilitate searching, update centralised data sources, and disseminate information more inclusively. International Journal of Human-Computer Studies; 2023 Abstract Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems Ninety percent of the 1.2 billion people who need assistive technology (AT) do not have access. Information seeking practices directly impact the ability of AT producers, procurers, and providers (AT professionals) to match a user's needs with appropriate AT, yet the AT marketplace is interdisciplinary and fragmented, complicating information seeking. We explored common limitations experienced by AT professionals when searching information to develop solutions for a diversity of users with multi-faceted needs. Through Template Analysis of 22 expert interviews, we find current search engines do not yield the necessary information, or appropriately tailor search results, impacting individuals’ awareness of products and subsequently their availability and the overall effectiveness of AT provision. We present value-based design implications to improve functionality of future AT-information seeking platforms, through incorporating smarter systems to support decision-making and need-matching whilst ensuring ethical standards for disability fairness remain. Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems Type Journal Paper Themes Assistive & Accessible Technology Evaluating the use of a thermoplastic socket in Kenya: A pilot study Giulia Barbareschi, Wesley Teerlink, Josepg Gakunga Njuguna, Purity Musungu, Mary Dama Kirino, andCatherine Holloway According to estimates from the World Health Organization, in 2010, there were more than 30 million people in need of prosthetic and orthotic devices across Africa, Asia, and Latin America. 1This number is likely to have grown significantly in the past decade, in line with trends recorded for the general need of assistive technology. 2For many people who undergo a lower limb amputation, access to an appropriate prosthesis is essential to restore functional mobility and ensure good quality of life. 3Ultimately, an appropriate lower-limb prosthesis (LLP) can enable people with amputation to fulfill their desired role in their family, work, and community life. 4 Prosthetic and Orthotics International; 2022 Abstract Evaluating the use of a thermoplastic socket in Kenya: A pilot study Background: Many people with amputations who live in low-resourced settings struggle to access the workshops where qualified prosthetists provide appropriate care. Novel technologies such as the thermoplastic Confidence Socket are emerging, which could help facilitate easier access to prosthetic services. Objectives: The objective of this study was to evaluate the satisfaction and the performance of transtibial prosthesis featuring the Confidence Socket. Study design: This is a longitudinal repeated-measures design study. Methods: A convenience sample of 26 participants who underwent transtibial amputation were fitted with the Confidence Socket. The performance of the socket was evaluated after a follow-up period between 1 month and 6 months using the L test of functional mobility and the amputee mobility predictor. Satisfaction with the prosthesis was measured using the Trinity Amputation and Prosthetic Experience Scales and purposefully designed 7-point Likert scales. Results: Ten of the 26 participants returned for follow-up. Perceived activity restriction and L test times improved significantly at follow-up, but the self-reported satisfaction with the Confidence Socket was lower at follow-up compared with that after fitting. Conclusions: The Amparo Confidence Socket represents a potentially viable alternative to improve access to appropriate prosthesis in Kenya, but some aspects of users’ self-reported satisfaction should be further investigated. Cite Evaluating the use of a thermoplastic socket in Kenya: A pilot study Barbareschi G, Teerlink W, Njuguna JG, Musungu P, Kirino MD, Holloway C. Evaluating the use of a thermoplastic socket in Kenya: A pilot study. Prosthet Orthot Int. 2022 Oct 1;46(5):532-537. doi: 10.1097/PXR.0000000000000130. Epub 2022 Mar 25. PMID: 35333813; PMCID: PMC9554758. Evaluating the use of a thermoplastic socket in Kenya: A pilot study Type Journal Paper Themes Assistive & Accessible Technology Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges Jamie Danemayer, Andrew Young, Siobhan Green, Lydia Ezenwa, Michael Klein This study synthesizes learnings from three distinct datasets: innovator applications to the COVIDaction data challenges, surveys from organizers from similarly-aimed data challenges, and a focus group discussion with professionals who work with COVID-19 data. Thematic and topic analyses were used to analyze these datasets with the aim to identify gaps and barriers to effective data use in responding to the pandemic. Data & Policy; 2023 Abstract Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges Innovative, responsible data use is a critical need in the global response to the coronavirus disease-2019 (COVID-19) pandemic. Yet potentially impactful data are often unavailable to those who could utilize it, particularly in data-poor settings, posing a serious barrier to effective pandemic mitigation. Data challenges, a public call-to-action for innovative data use projects, can identify and address these specific barriers. To understand gaps and progress relevant to effective data use in this context, this study thematically analyses three sets of qualitative data focused on/based in low/middle-income countries: (a) a survey of innovators responding to a data challenge, (b) a survey of organizers of data challenges, and (c) a focus group discussion with professionals using COVID-19 data for evidence-based decision-making. Data quality and accessibility and human resources/institutional capacity were frequently reported limitations to effective data use among innovators. New fit-for-purpose tools and the expansion of partnerships were the most frequently noted areas of progress. Discussion participants identified building capacity for external/national actors to understand the needs of local communities can address a lack of partnerships while de-siloing information. A synthesis of themes demonstrated that gaps, progress, and needs commonly identified by these groups are relevant beyond COVID-19, highlighting the importance of a healthy data ecosystem to address emerging threats. This is supported by data holders prioritizing the availability and accessibility of their data without causing harm; funders and policymakers committed to integrating innovations with existing physical, data, and policy infrastructure; and innovators designing sustainable, multi-use solutions based on principles of good data governance. Cite Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges Danemayer, J., Young, A., Green, S., Ezenwa, L., & Klein, M. (2023). Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges. Data & Policy, 5, E11. doi:10.1017/dap.2023.6 Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges Type Conference Paper Themes Assistive & Accessible Technology Culture and Participation The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Giulia Barbareschi,Catherine Holloway, Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, Joyce Olenja We present the findings of a case study of mobile technology use by People with Visual Impairment (VIPs) in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted. CHI '20: Proceedings of the 2020 CHI Conference; 2020 Abstract The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Living in an informal settlement with a visual impairment can be very challenging resulting in social exclusion. Mobile phones have been shown to be hugely beneficial to people with sight loss in formal and high-income settings. However, little is known about whether these results hold true for people with visual impairment (VIPs) in informal settlements. We present the findings of a case study of mobile technology use by VIPs in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted. The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Giulia Barbareschi, Catherine Holloway, Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, and Joyce Olenja. 2020. The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya. In Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems (CHI '20). Association for Computing Machinery, New York, NY, USA, 1–15.https://doi.org/10.1145/331383... The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Type Conference Paper Disability design and innovation in computing research in low resource settings Dafne Zuleima Morgado-Ramirez,Giulia Barbareschi, Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney,Catherine Holloway 80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes. ASSETS '20: Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility; 2020 Abstract Disability design and innovation in computing research in low resource settings 80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes. In short, researchers rarely examine what was challenging in the process of collaboration. We present reflections from the field across four studies. Our contributions are: (1) an overview of past work in computing with a focus on disability in low resource settings and (2) learnings and recommendations from four collaborative projects in Uganda, Jordan and Kenya over the last two years, that are relevant for future HCI studies in low resource settings with communities with disabilities. We do this through a lens of Disability Interaction and ICT4D. Cite Disability design and innovation in computing research in low resource settings Dafne Zuleima Morgado-Ramirez, Giulia Barbareschi, Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney, and Catherine Holloway. 2020. Disability design and innovation in computing research in low resource settings. In Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS '20). Association for Computing Machinery, New York, NY, USA, Article 11, 1–7.https://doi.org/10.1145/337362... Share Disability design and innovation in computing research in low resource settings Type Journal Paper Themes Assistive & Accessible Technology Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey Emma M Smith, Maria Luisa Toro Hernandez, Ikenna D Ebuenyi, Elena V Syurina,Giulia Barbareschi, Krista L Best,Jamie Danemayer,Ben Oldfrey, Nuha Ibrahim,Catherine Holloway, Malcolm MacLachlan The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19.Objective:The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis. International Journal of Health Policy and Management; 2020 Abstract Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey Abstract Background:The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19.Objective:The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis. Methods:This study was a rapid, international online qualitative survey in the 6 United Nations (UN) languages (English, French, Spanish, Russian, Arabic, Mandarin Chinese) facilitated by extant World Health Organization (WHO) and International Disability Alliance networks. Themes and subthemes of the qualitative responses were identified using Braun and Clarke's 6-phase analysis. Results:Four primary themes were identified in in the data: Disruption of Services, Insufficient Emergency Preparedness, Limitations in Existing Technology, and Inadequate Policies and Systems. Subthemes were identified within each theme, including subthemes related to developing resilience in AT systems, based on learning from the pandemic. Conclusion:COVID-19 has disrupted the delivery of AT services, primarily due to infection control measures resulting in lack of provider availability and diminished one-to-one services. This study identified a need for stronger user-centred development of funding policies and infrastructures that are more sustainable and resilient, best practices for remote service delivery, robust and accessible tools and systems, and increased capacity of clients, caregivers, and clinicians to respond to pandemic and other crisis situations. Cite Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey Smith EM, Toro Hernandez ML, Ebuenyi ID, Syurina EV, Barbareschi G, Best KL, Danemayer J, Oldfrey B, Ibrahim N, Holloway C, MacLachlan M. Assistive Technology Use and Provision During COVID-19: Results From a Rapid Global Survey. Int J Health Policy Manag. 2022 Jun 1;11(6):747-756. doi: 10.34172/ijhpm.2020.210. PMID: 33201656; Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey Type Journal Paper Themes Assistive & Accessible Technology Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries Margaret Savage, Sarah Albala, Frederic Seghers, Rainer Katte, Cynthia Liao, Mathilde Chaudron, Novia Afdhila Development outcomes are inextricably linked to the health of the marketplace that delivers products and services to people in low- and middle- income countries (LMIC). Shortcomings in the market for assistive technology (AT) contribute to low access in LMIC. Market shaping is aimed at improving a market’s specific outcomes, such as access to high quality, affordable AT, by targeting the root causes of these shortcomings. The paper summarizes the findings of a market and sector analysis that was conducted under the UK aid funded AT2030 programme and aims to discuss how market shaping can help more people gain access to the AT that they need and what are the best mechanisms to unlock markets and commercial opportunity in LMICs. Assistive Technology The Official Journal of RESNA; 2021 Abstract Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries Development outcomes are inextricably linked to the health of the marketplace that delivers products and services to people in low- and middle-income countries (LMIC). Shortcomings in the market for assistive technology (AT) contribute to low access in LMIC. Market shaping is aimed at improving a market’s specific outcomes, such as access to high quality, affordable AT, by targeting the root causes of these shortcomings. The paper summarizes the findings of market analyses conducted under the UK aid funded AT2030 programme in support of ATscale and aims to discuss how market shaping can help more people gain access to the AT that they need and what are the best mechanisms to unlock markets and commercial opportunity in LMICs. The paper also explores how market shaping for AT markets could be part of a mission-oriented approach AT policy. A mission-oriented approach can help accelerate progress toward a common objective among stakeholders, at country or global level. While market-shaping activities direct the outcomes of the market toward a specific end goal, such as access to quality, affordable products and services, missions are more comprehensive and include other policy interventions and stakeholder collaborations in order to create a robust and sustainable structure. Cite Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries Margaret Savage, Sarah Albala, Frederic Seghers, Rainer Kattel, Cynthia Liao, Mathilde Chaudron & Novia Afdhila (2021) Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries, Assistive Technology, 33:sup1, 124-135, DOI: 10.1080/10400435.2021.1991050 Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries Type Journal Paper Themes Assistive & Accessible Technology Assistive technology access in longitudinal datasets: a global review Jamie Danemayer, Sophie Mitra,Cathy Holloway, Shereen Hussein A person’s access to assistive products such as hearing aids, wheelchairs, and glasses, is an essential part of their ability to age in a healthy way. But, according to the World Health Organization, a staggering 90% of people who need assistive products worldwide, do not have access to them. In many instances access is limited or simply non-existent. This is often due to assistive products being too expensive, demand outweighing supply, not always being suitable to use in different environments, or even the lack of availability of trained providers. In such circumstances, people are more likely to age ‘unhealthily’ if they do not have access to assistive products that are designed to support their day to day functioning and independence. International Journal of Population Data Science; 2023 Abstract Assistive technology access in longitudinal datasets: a global review Functional limitations become more prevalent as populations age, emphasising an increasingly urgent need for assistive technology (AT). Critical to meeting this need trajectory is understanding AT access in older ages. Yet few publications examine this from a longitudinal perspective. This review aims to identify and collate what data exist globally, seeking all population-based cohorts and repeated cross-sectional surveys through the Maelstrom Research Catalogue (searched May 10, 2022) and the Disability Data Report (published 2022), respectively. Datasets incorporating functional limitations modules and question(s) dedicated to AT, with a wave of data collection since 2009, were included. Of 81 cohorts and 202 surveys identified, 47 and 62 meet inclusion criteria, respectively. Over 40% of cohorts were drawn from high-income countries which have already experienced significant population ageing. Cohorts often exclude participants based on pre-existing support needs. For surveys, Africa is the most represented region (40%). Globally, 73% of waves were conducted since 2016. 'Use' is the most collected AT access indicator (69% of cohorts and 85% of surveys). Glasses (78%) and hearing aids (77%) are the most represented AT. While gaps in data coverage and representation are significant, collating existing datasets highlights current opportunities for analyses and methods for improving data collection across the sector. Assistive technology access in longitudinal datasets: a global review Danemayer, J., Mitra, S., Holloway, C. and Hussein, S. (2023) “Assistive technology access in longitudinal datasets: a global review”, International Journal of Population Data Science, 8(1). doi: 10.23889/ijpds.v8i1.1901. Assistive technology access in longitudinal datasets: a global review Type Journal Paper Themes Assistive & Accessible Technology Estimating need and coverage for five priority assistive products: A systematic review of global population based research Jamie Danemayer, Dorothy Boggs, Vinicius Delgado Ramos, Emma M. Smith, Ariana Kular, William Bhot, Felipe Ramos Barajas, Sarah Polack,Catherine Holloway Assistive technology (AT) includes assistive products (APs) and related services that can improve health and well-being, enable increased independence and foster participation for people with functional difficulties, including older adults and people with impairments or chronic health conditions. 1This paper uses the umbrella term ‘functional difficulty’ (FD) to refer to all of these groups. This systematic review was undertaken to identify studies presenting population-based estimates of need and coverage for five APs (hearing aids, limb prostheses, wheelchairs, glasses and personal digital assistants) grouped by four functional domains (hearing, mobility, vision and cognition). BMJ Global Health; 2021 Abstract Estimating need and coverage for five priority assistive products: A systematic review of global population based research Introduction:To improve access to assistive products (APs) globally, data must be available to inform evidence based decision-making, policy development and evaluation, and market-shaping interventions. Methods:This systematic review was undertaken to identify studies presenting population-based estimates of need and coverage for five APs (hearing aids, limb prostheses, wheelchairs, glasses and personal digital assistants) grouped by four functional domains (hearing, mobility, vision and cognition). Results:Data including 656 AP access indicators were extracted from 207 studies, most of which (n=199, 96%) were cross-sectional, either collecting primary (n=167) or using secondary (n=32) data. There was considerable heterogeneity in assessment approaches used and how AP indicators were reported; over half (n=110) used a combination of clinical and self-reported assessment data. Of 35 studies reporting AP use out of all people with functional difficulty in the corresponding functional domains, the proportions ranged from 4.5% to 47.0% for hearing aids, from 0.9% to 17.6% for mobility devices, and from 0.1% to 86.6% for near and distance glasses. Studies reporting AP need indicators demonstrated >60% unmet need for each of the five APs in most settings. Conclusion:Variation in definitions of indicators of AP access have likely led to overestimates/underestimates of need and coverage, particularly, where the relationship between functioning difficulty and the need for an AP is complex. This review demonstrates high unmet need for APs globally, due in part to disparate data across this sector, and emphasises the need to standardise AP data collection and reporting strategies to provide a comparable evidence base to improve access to APs. Cite Estimating need and coverage for five priority assistive products: A systematic review of global population based research Danemayer J, Boggs D, Delgado Ramos V, et al. Estimating need and coverage for five priority assistive products: a systematic review of global population-based research. BMJ Global Health 2022;7:e007662. doi:10.1136/bmjgh-2021-007662 Estimating need and coverage for five priority assistive products: A systematic review of global population based research Type Workshop Themes Assistive & Accessible Technology Research Group Disability Interactions Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Sahan Bulathwela, María Pérez-Ortiz,Catherine Holloway, John Shawe-Taylor This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Workshop on Machine Learning for the Developing World (ML4D) at the Conference on Neural Information Processing Systems 2021; 2021 Abstract Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Artificial Intelligence (AI) in Education has been said to have the potential for building more personalised curricula, as well as democratising education worldwide and creating a Renaissance of new ways of teaching and learning. Millions of students are already starting to benefit from the use of these technologies, but millions more around the world are not. If this trend continues, the first delivery of AI in Education could be greater educational inequality, along with a global misallocation of educational resources motivated by the current technological determinism narrative. In this paper, we focus on speculating and posing questions around the future of AI in Education, with the aim of starting the pressing conversation that would set the right foundations for the new generation of education that is permeated by technology. This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Finally, we ask what would it take for this educational revolution to provide egalitarian and empowering access to education, beyond any political, cultural, language, geographical and learning ability barriers. Share Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Type Workshop Themes Assistive & Accessible Technology Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Tabish Ahmed, Sahan Bulathwela The informational needs of people are highly contextual and can depend on many different factors such as their current knowledge state, interests and goals [1, 2, 3]. However, an effective information retrieval companion should minimise the human effort required in i) expressing a human information need and ii) navigating a lengthy result set. Using topical representations of the user history (e.g. [4]) can immensely help formulating zero shot queries and refining short user queries that enable proactive information retrieval (IR). While the world has digital textual information in abundance, it can often be noisy (e.g. extracted through Automatic Speech Recognition (ASR), PDF text extraction etc.), leading to state-of-the-art neural models being highly sensitive to the noise producing sub-optimal results [5]. This demands denoising steps to refine both query and document representation. In this paper, we argue that Wikipedia, an openly available encyclopedia, can be a humanly intuitive knowledge base [6] that has the potential to provide the world view many noisy information Retrieval systems need. Published at the First Workshop on Proactive and Agent-Supported Information Retrieval at CIKM 2022; 2022 Abstract Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Extracting useful information from the user history to clearly understand informational needs is a crucial feature of a proactive information retrieval system. Regarding understanding information and relevance, Wikipedia can provide the background knowledge that an intelligent system needs. This work explores how exploiting the context of a query using Wikipedia concepts can improve proactive information retrieval on noisy text. We formulate two models that use entity linking to associate Wikipedia topics with the relevance model. Our experiments around a podcast segment retrieval task demonstrate that there is a clear signal of relevance in Wikipedia concepts while a ranking model can improve precision by incorporating them. We also find Wikifying the background context of a query can help disambiguate the meaning of the query, further helping proactive information retrieval. Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Type Journal Paper Themes Assistive & Accessible Technology Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes Kate Mattick,Ben Oldfrey, Maggie Donovan-Hall, Grace Magomere, Joseph Gakunga,Catherine Holloway An estimated 1.5 million people undergo limb amputation each year [1]. Low- and middle-income countries (LMICs) are projected to have a rapid increase in people living with an amputation in the coming years due to prevalence of non-communicable dis-ease, trauma and conflict [1–3]. This paper explores the personal and system factors that motivate and enhance outcomes for patients accessing a prosthetic service and using a lower-limb prosthesis within a low resource setting. Disability and Rehabilitation; 2022 Abstract Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes PurposeTo explore the personal and system factors that motivate and enhance outcomes for patients accessing a prosthetic service and using a lower-limb prosthesis within a low resource setting. Materials and methodsThis study employed a qualitative approach to explore the motivations and satisfaction of individuals with lower limb loss engaging with a prosthetic service in Mombasa, Kenya. In-depth interviews were conducted over Microsoft Teams with 10 lower limb prosthesis users and thematic analysis was applied. ResultsFive key themes emerged: acceptance, self-determination, hope, clinician relationship and perception. These findings demonstrate the importance of hopeful thinking and a supportive community in overcoming physical and stigmatising challenges. The findings further highlight the value of the service provider relationship beyond just prescribing an assistive device. ConclusionThese results have relevance in developing patient-centred services, assistive devices and personnel training that are responsive, motivating, and cognisant of the service user. This is of particular interest as assistive technology services are newly developed in low resource settings. Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes Kate Mattick, Ben Oldfrey, Maggie Donovan-Hall, Grace Magomere, Joseph Gakunga & Catherine Holloway (2022) Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes, Disability and Rehabilitation, DOI:10.1080/09638288.2022.2152875 Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes Type Journal Paper Themes Culture and Participation Research Group Social Justice “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone Victoria Austin,Catherine Holloway, Ignacia Ossul Vermehren, Abs Dumbuya,Giulia Barbareschiand Julian Walker The World Health Organisation (WHO) estimates that there are currently one billion people in the world who need access to assistive technology (AT). Yet over 90% currently do not have access to assistive products (AP)—such as wheelchairs, hearing aids, walking sticks and eyeglasses—they need, nor and the systems and services necessary to support their appropriate provision [1]. This shocking deficit is set to double by 2050, with about two billion of us likely to require AT but no anticipated reduction in lack of access. The World Health Organisation defines AT as the “the umbrella term covering the systems and services related to the delivery of assistive products and services”, which are products that “maintain or improve an individual’s functioning and independence, thereby promoting their well-being” [2], and the importance of AT provision is strongly highlighted in the Convention on the Rights of Persons with Disabilities (CRPD) [3]. AT has also been shown to be essential to achieving many of the United Nation’s Sustainable Development Goals (SDG) [4]. Without access to AT, many persons with disabilities are unable to go to school, be active in their communities, earn an income, or play a full role in their families [5]. As a recent study found, “AT can make the impossible possible for people living with a wide range of impairments, but a lack of access to basic AT …excludes individuals and reduces their ability to live full, enjoyable, and independent lives” [6]. International Journal of Environmental Research and Public Health; 2021 Abstract “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone The importance of assistive technology (AT) is gaining recognition, with the World Health Organisation (WHO) set to publish a Global Report in 2022. Yet little is understood about access for the poorest, or the potential of AT to enable this group to participate in the activities of citizenship; both formal and informal. The aim of this qualitative study was to explore AT as mediator of participation in citizenship for persons with disabilities who live in two informal settlements in Freetown, Sierra Leone (SL). The paper presents evidence from 16 participant and 5 stakeholder interviews; 5 focus groups and 4 events; combining this with the findings of a house-to-house AT survey; and two national studies—a country capacity assessment and an informal markets deep-dive. Despite citizenship activities being valued, a lack of AT was consistently reported and hindered participation. Stigma was also found to be a major barrier. AT access for the poorest must be addressed if citizenship participation for persons with disabilities is a genuine global intention and disability justice is to become a reality. “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone Austin, V.; Holloway, C.; Ossul Vermehren, I.; Dumbuya, A.; Barbareschi, G.; Walker, J. “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone. Int. J. Environ. Res. Public Health2021, 18, 5547.https://doi.org/10.3390/ijerph... “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone Type Journal Paper Themes Assistive & Accessible Technology Research Group Local Productions Additive manufacturing techniques for smart prosthetic liners B Oldfrey, A Tchorzewska, R Jackson, M Croysdale, R Loureiro,C Holloway, M Miodownik Elastomeric liners are commonly worn between socket and limb by prosthetic wearers. This is due to their superior skin adhesion, load distribution and their ability to form a seal. Laboratory tests suggest that elastomeric liners allow reduced shear stress on the skin and give a higher cushioning effect on bony prominences, since they are soft in compression, and similar to biological tissues [1]. However, they also increase perspiration reducing hygiene and increasing skin irritations. Prosthetic users in general face a myriad of dermatological problems associated with lower limb prosthesis such as ulcers, cysts, and contact dermatitis, which are exacerbated by the closed environment of a fitted socket where perspiration is trapped and bacteria can proliferate [2]. Medical Engineering & Physics; 2021 Abstract Additive manufacturing techniques for smart prosthetic liners Elastomeric liners are commonly worn between the prosthetic socket and the limb. A number of improvements to the state of the art of liner technology are required to address outstanding problems. A liner that conforms to the residuum more accurately, may improve the skin health at the stump-socket interface. Previous work has shown that for effective thermal management of the socket environment, an active heat removal system is required, yet this is not available. Volume tracking of the stump could be used as a diagnostic tool for looking at the changes that occur across the day for all users, which depend on activity level, position, and the interaction forces of the prosthetic socket with the limb. We believe that it would be advantageous to embed these devices into a smart liner, which could be replaced and repaired more easily than the highly costly and labour-intensive custom-made socket. This paper presents the work to develop these capabilities in soft material technology, with: the development of a printable nanocomposite stretch sensor system; a low-cost digital method for casting bespoke prosthetic liners; a liner with an embedded stretch sensor for growth / volume tracking; a model liner with an embedded active cooling system. Cite Additive manufacturing techniques for smart prosthetic liners , Additive manufacturing techniques for smart prosthetic liners, Medical Engineering & Physics, Volume 87, 2021, Pages 45-55, ISSN 1350-4533,https://doi.org/10.1016/j.mede.... Share Additive manufacturing techniques for smart prosthetic liners Type Journal Paper Themes Assistive & Accessible Technology Culture and Participation Research Group Disability Interactions “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya Giulia Barbareschi, Mark T. Carew, Elizabeth Aderonke Johnson, Norah Kopi,Catherine Holloway Stigmatizing attitudes and beliefs towards disability represent one of the most pervasive and complex barriers that limits access to health care, education, employment, civic rights and opportunities for socialization for people with disabilities [1,2,3]. The damaging impact of disability stigma is widely acknowledged and, according to article 8 of the UN Convention on the Rights of Persons with disabilities, developing strategies, campaigns, policies and other initiatives to combat disability stigma and ensure that all people with disabilities are treated with dignity and respect is also a duty of the 182 countries who ratified the treaty [4]. Although the majority of literature focused on understanding disability stigma has been carried out in high-income settings [5,6,7], in the last decade, an increasing number of scholars have conducted studies looking at the negative stereotypes, prejudices and inaccurate beliefs that shape disability stigma in the Global South [3,8,9,10]. Most of these studies have described how these stigmatizing beliefs are often driven by a combination of personal and societal factors, ranging from misconceptions concerning the causes of different impairments (e.g., disability to be seen as a form of curse or punishment); assumptions about the lack of capabilities of people with disabilities; or discriminatory practices that actively endorse separation between people with and without disabilities [3,9,11,12]. Yet, there is a dearth of comparative studies that examine the perspectives of both people with and without disabilities of disability stigma and discrimination, including how the use of assistive technology may shape stigmatizing interactions. International Journal of Environmental Research and Public Health; 2021 Abstract “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya Disability stigma in many low- and middle-income countries represents one of the most pervasive barriers preventing people with disabilities from accessing equal rights and opportunities, including the uptake of available assistive technology (AT). Previous studies have rarely examined how disability stigma may be shaped through factors endemic to social interactions, including how the use of assistive technology itself may precipitate or alleviate disability stigma. Through two strands of work, we address this gap. Via a series of focus groups with Kenyans without disabilities (Study 1) and secondary data analysis of consultations with Kenyans with disabilities and their allies (Study 2), we identify shared and divergent understandings of what shapes disability stigma and discrimination. Specifically, Kenyans with and without disabilities were cognizant of how religious/spiritual interpretations of disability, conceptions of impairments as “different” from the norm, and social stereotypes about (dis)ability shaped the experience of stigma and discrimination. Moreover, both groups highlighted assistive technology as an influential factor that served to identify or “mark” someone as having a disability. However, whereas participants without disabilities saw assistive technology purely as an enabler to overcome stigma, participants with disabilities also noted that, in some cases, use of assistive technologies would attract stigma from others. Cite “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya Barbareschi G, Carew MT, Johnson EA, Kopi N, Holloway C. “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya. International Journal of Environmental Research and Public Health. 2021; 18(8):4272.https://doi.org/10.3390/ijerph... “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya Type Journal Paper Themes Inclusive Design Culture and Participation Research Group Disability Interactions Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement Giulia Barbareschi,Ben Oldfrey, Long Xin, Grace N. Magomere, Wyclife A. Wetende, Carol Wanjira, Joyce Olenja,Victoria Austin, andCatherine Holloway The World Health Organisation estimate that there are approximately a billion people with disabilities who require access to appropriate assistive technology and this number is set to double by 2050 [82]. Assistive technologies (ATs) play a crucial role in the lives of people with disabilities and are necessary to be able to access essential services and participate in family and community life according to one’s aspirations [40, 62, 68, 81]. Although this is not often specifcally mentioned, the large majority of people with disabilities will routinely use more than one assistive device in their everyday lives [25, 26]. For example a person with a visual impairment is likely to use a white cane to navigate from their house to the office where they work and have a screen-reader, or an equivalent accessibility software, on their computer to be able to do their work once in the office [17]. ASSETS '20: Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility; 2020 Abstract Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement Living in informality is challenging. It is even harder when you have a mobility impairment. Traditional assistive products such as wheelchairs are essential to enable people to travel. Wheelchairs are considered a Human Right. However, they are difficult to access. On the other hand, mobile phones are becoming ubiquitous and are increasingly seen as an assistive technology. Should therefore a mobile phone be considered a Human Right? To help understand the role of the mobile phone in contrast of a more traditional assistive technology – the wheelchair, we conducted contextual interviews with eight mobility impaired people who live in Kibera, a large informal settlement in Nairobi. Our findings show mobile phones act as an accessibility bridge when physical accessibility becomes too challenging. We explore our findings from two perspective – human infrastructure and interdependence, contributing an understanding of the role supported interactions play in enabling both the wheelchair and the mobile phone to be used. This further demonstrates the critical nature of designing for context and understanding the social fabric that characterizes informal settlements. It is this social fabric which enables the technology to be useable. Cite Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement Giulia Barbareschi, Ben Oldfrey, Long Xin, Grace Nyachomba Magomere, Wycliffe Ambeyi Wetende, Carol Wanjira, Joyce Olenja, Victoria Austin, and Catherine Holloway. 2020. Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal settlement. In Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS '20). Association for Computing Machinery, New York, NY, USA, Article 50, 1–13.https://doi.org/10.1145/337362... Share Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement Type Journal Paper Themes Assistive & Accessible Technology Climate & Crisis Resilience Research Group Disability Interactions Measuring assistive technology supply and demand: A scoping review Jamie Danemayer,Dorothy Boggs, Emma M. Smith, Vinicius Delgado Ramos, Linamara Rizzo Battistella,Cathy Holloway,and Sarah Polack An assistive product (AP) is defined as a product used exter-nally to the human body, whose primary purpose is to main-tain or improve an individual’s functioning and independence and thereby promote his or her well-being (WHO, 2016). Global population aging forecasts a rise in the need for solu-tions that support participation and independence, including APs. In this paper, we review current population-level AP supply and demand estimation methods for five priority APs and provide recommendations for improving national and global AP market evaluation. Assistive Technology The Official Journal of RESNA; 2021 Abstract Measuring assistive technology supply and demand: A scoping review The supply of and market demand for assistive products (APs) are complex and influenced by diverse stakeholders. The methods used to collect AP population-level market data are similarly varied. In this paper, we review current population-level AP supply and demand estimation methods for five priority APs and provide recommendations for improving national and global AP market evaluation. Abstracts resulting from a systematic search were double-screened. Extracted data include WHO world region, publication year, age-groups, AP domain(s), study method, and individual assessment approach.497 records were identified. Vision-related APs comprised 65% (n = 321 studies) of the body of literature; hearing (n = 59), mobility (n = 24), cognitive (n = 2), and studies measuring multiple domains (n = 92) were proportionately underrepresented. To assess individual AP need, 4 unique approaches were identified among 392 abstracts; 45% (n = 177) used self-report and 84% (n = 334) used clinical evaluation. Study methods were categorized among 431 abstracts; Cross-sectional studies (n = 312, 72%) and secondary analyses of cross-sectional data (n = 61, 14%) were most common. Case studies illustrating all methods are provided. Employing approaches and methods in the contexts where they are most well-suited to generate standardized AP indicators will be critical to further develop comparable population-level research informing supply and demand, ultimately expanding sustainable access to APs. Cite Measuring assistive technology supply and demand: A scoping review Jamie Danemayer, Dorothy Boggs, Emma M. Smith, Vinicius Delgado Ramos, Linamara Rizzo Battistella, Cathy Holloway & Sarah Polack (2021) Measuring assistive technology supply and demand: A scoping review, Assistive Technology, 33:sup1, S35-S49, DOI: 10.1080/10400435.2021.1957039 Share Measuring assistive technology supply and demand: A scoping review Type Journal Paper Themes Assistive & Accessible Technology Research Group Humanitarian & Disasters Meeting AT needs in humanitarian crises: The current state of provision Golnaz Whittaker, Gavin Adam Wood, Giulia Oggero,Maria Kett, Kirstin Lange This paper discusses the evidence available in the literature for the scale and quality of AT provision interventions in crises, and what is known about the challenges and facilitators of provision. We conducted a search of the academic literature and retained literature that reported on any form of AT provision following crisis, where international humanitarian response was in place, published in English between January 2010 and June 2020. Assistive Technology The Official Journal of RESNA; 2021 Abstract Meeting AT needs in humanitarian crises: The current state of provision Humanitarian coordination systems increasingly recognize and aim to respond to the needs of people with disabilities within populations affected by crises, spurred on by the UN Convention on the Rights of Persons with Disabilities (CRPD) which was adopted in 2006. Many agencies state their aim to meet the requirements of the CRPD using a “twin track” approach: ensuring the inclusion of people with disabilities in mainstream provision, alongside targeted support for their needs, which may include the need for Assistive Technology (AT). However, there is very little evidence of AT provision in humanitarian settings, which is a specific and urgent need for many people including the elderly and people with disabilities, and an implicit requirement of Article 11 of the CRPD and World Health Assembly resolution on improving access to assistive technology. There is also little evidence of effective mechanisms for AT provision in humanitarian settings. This is despite high and growing levels of unmet AT need in crises, and despite the legally binding requirement in the CRPD to provide AT for those who need it. AT provision faces unique challenges in humanitarian settings. This paper discusses the evidence available in the literature for the scale and quality of AT provision interventions in crises, and what is known about the challenges and facilitators of provision. We conducted a search of the academic literature and retained literature that reported on any form of AT provision following crisis, where international humanitarian response was in place, published in English between January 2010 and June 2020. We found very few examples in that academic literature of systematic and coordinated AT provision at the acute stage of crisis, and even less in the preparedness and post-acute stages. However, it is difficult to assess whether this is the result of insufficient academic attention or reflects a lack of provision. The small body of academic literature that describes AT provision in humanitarian settings paints a picture of small-scale provision, specialized to single types of impairments, and delivered by predominantly by NGOs. We also conducted a search of the gray literature, using the same inclusion criteria, in two countries: Afghanistan and South Sudan (case studies forthcoming). This gray literature provided supplementary evidence of the types of AT providers and AT provision available in those protracted crises. There are very few examples of how AT services can be scaled up (from a very low baseline) and maintained sustainably within a strengthened health system. The literature also describes more examples of provision of assistive products for mobility over assistive products for other impairments. If the paucity of literature on AT provision in humanitarian settings is a reflection of the scale of provision, this implies a deficiency in humanitarian response when it comes to providing people with AT needs with the essential products and services to which they have a right, and which will enable their access to basic, life-saving assistance. We conclude by providing recommendations for urgent actions that the AT and humanitarian community must take to fill this critical gap in the provision of essential products and services for a potentially marginalized and excluded group. Cite Meeting AT needs in humanitarian crises: The current state of provision Golnaz Whittaker, Gavin Adam Wood, Giulia Oggero, Maria Kett & Kirstin Lange (2021) Meeting AT needs in humanitarian crises: The current state of provision, Assistive Technology, 33:sup1, S3-S16, DOI: 10.1080/10400435.2021.1934612 Share Meeting AT needs in humanitarian crises: The current state of provision Type Conference Paper Themes Assistive & Accessible Technology Value beyond function: analyzing the perception of wheelchair innovations in Kenya Barbareschi, G; Daymond, S; Honeywill, J; Singh, A; Noble, D; Mbugua, N; Harris, I;Austin, V;Holloway, C The World Health Organization (WHO) defines Assistive Technology (AT) as “an umbrella term covering the systems and services related to the delivery of assistive products and services” [6]. This definition highlights how AT encompasses not only the physical and digital products used by millions of persons with disabilities (PWDs) worldwide, but also the systems and services that accompany the provision of these devices [78]. ASSETS '20: The 22nd International ACM SIGACCESS Conference on Computers and Accessibility.; 2020 Abstract Value beyond function: analyzing the perception of wheelchair innovations in Kenya Innovations in the field of assistive technology are usually evaluated based on practical considerations related to their ability to perform certain functions. However, social and emotional aspects play a huge role in how people with disabilities interact with assistive products and services. Over a five months period, we tested an innovative wheelchair service provision model that leverages 3D printing and Computer Aided Design to provide bespoke wheelchairs in Kenya. The study involved eight expert wheelchair users and five healthcare professionals who routinely provide wheelchair services in their community. Results from the study show that both users and providers attributed great value to both the novel service delivery model and the wheelchairs produced as part of the study. The reasons for their appreciation went far beyond the practical considerations and were rooted in the fact that the service delivery model and the wheelchairs promoted core values of agency, empowerment and self-expression. Share Value beyond function: analyzing the perception of wheelchair innovations in Kenya Type Conference Paper Themes Assistive & Accessible Technology Culture and Participation Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Nusrat Jahan,Giulia Barbareschi, Clara Aranda Jan, Charles Musungu Mutuku, Naemur Rahman,Victoria Austin,Catherine Holloway Worldwide it is estimated that there are over a billion people who live with some form of disability[1]. Approximately 80% of people with disabilities live in low-and-middle income countries (LMICs). The combination of an inaccessible environment compounded by socio-economic factors such as poverty and stigma, makes it more likely for people with disabilities to be marginalised and excluded from society[1]. Assistive Technologies (ATs) are known to bridge the accessibility gaps and allow for greater social inclusion. However, there is a lack of adequate access to ATs in LMICs, combined with often poorly designed services, which only magnifies these challenges, thus limiting the opportunities for persons with disabilities to live an independent life[2]. Despite the importance of AT, access to AT globally is inadequate with only 10 percent of those in need having access to the ATs that they need[2]. 2020 IEEE Global Humanitarian Technology Conference Abstract Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Globally, mobile technology plays a significant role connecting and supporting people with disabilities. However, there has been limited research focused on understanding the impact of mobile technology in the lives of persons with disabilities in low or middle- income countries. This paper presents the findings of a participatory photovoice study looking at the role that mobile phones play in the daily lives of 16 persons with disabilities in Kenya and Bangladesh. Participants used a combination of pictures and voice recordings to capture their own stories and illustrate the impact that mobile phone use has on their lives. Through thematic analysis, we categorized the benefits of mobile phones captured by participants as 1) Improved social connection; 2) Increased independence and 3) Access to opportunities. While mobile phones are ubiquitously used for communication, for persons with disabilities they become essential assistive technologies that bridge barriers to opportunities which are not accessible otherwise. Our paper adds evidence to the need for mobile phones for persons with disabilities to enable communication and connectivity in support of development. Cite Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh N. Jahan et al., "Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh," 2020 IEEE Global Humanitarian Technology Conference (GHTC), Seattle, WA, USA, 2020, pp. 1-8, doi: 10.1109/GHTC46280.2020.9342934. Share Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Type Conference Paper Themes Assistive & Accessible Technology Research Group Local Productions A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries Tigmanshu Bhatnagar, George Torrens, Ben Oldfrey, Priya MorjariaFelipe Ramos Barajas, Katherine PerryandCatherine Holloway Access to information on digital platforms not only facilitates education, employment, entertainment, social interaction but also facilitates critical governmental services, ecommerce, healthcare services and entrepreneurship [1]. Article 9 of United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) enforces its signatories to commit to provide full accessibility to every citizen of the nation [2]. This has helped to spearhead accessibility directives such as the European Accessibility Act [3] that aims to improve the functioning of markets for accessible products and services. Such directives contribute to ensure that mainstream digital technologies (smartphones, computers etc.) are accessible for everyone and without being socially remarkable, they are able to assist in daily living. Additionally, there is evidence that improving access in mainstream technologies improves product experience and usability for everyone [4]. However, mainstream access has not been fully realized, leading to inferior opportunities for people with disabilities, a disparity which is more prominent in lower and middle-income countries [5]. RESNA Annual Conference; 2021 A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries Type Journal Paper Themes Assistive & Accessible Technology Research Group Local Productions Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? Ben Oldfrey,Giulia Barbareschi, Priya Morjaria, Tamara Giltsoff, Jessica Massie, Mark Miodownik andCatherine Holloway From multiple studies conducted through the FCDO AT2030 Programme, as well as key literature, we examine whether Assistive Technology (AT) provision models could look towards more sustainable approaches, and by doing this benefit not only the environment, but also address the problems that the current provision systems have. Sustainability Abstract Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? From multiple studies conducted through the FCDO AT2030 Programme, as well as key literature, we examine whether Assistive Technology (AT) provision models could look towards more sustainable approaches, and by doing this benefit not only the environment, but also address the problems that the current provision systems have. We show the intrinsic links between disability inclusion and the climate crisis, and the particular vulnerability people with disabilities face in its wake. In particular, we discuss how localised circular models of production could be beneficial, facilitating context driven solutions and much needed service elements such as repair and maintenance. Key discussion areas include systems approaches, digital fabrication, repair and reuse, and material recovery. Finally, we look at what needs be done in order to enable these approaches to be implemented. In conclusion, we find that there are distinct parallels between what AT provision models require to improve equitable reliable access, and strategies that could reduce environmental impact and bring economic benefit to local communities. This could allow future AT ecosystems to be key demonstrators of circular models, however further exploration of these ideas is required to make sense of the correct next steps. What is key in all respects, moving forward, is aligning AT provision with sustainability interventions. Cite Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? Oldfrey, B.; Barbareschi, G.; Morjaria, P.; Giltsoff, T.; Massie, J.; Miodownik, M.; Holloway, C. Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? Sustainability2021, 13, 10867.https://doi.org/10.3390/su1319... Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? Type Journal Paper Themes Assistive & Accessible Technology Research Group Local Productions A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems Catherine Holloway, Dafne Zuleima Morgado Ramirez,Tigmanshu Bhatnagar,Ben Oldfrey, Priya Morjaria, Soikat Ghosh Moulic, Ikenna D. Ebuenyi,Giulia Barbareschi,Fiona Meeks, Jessica Massie, Felipe Ramos-Barajas, Joanne McVeigh, Kyle Keane, George Torrens, P. V.M. Rao, Malcolm MacLachlan,Victoria Austin, Rainer Kattel, Cheryl D Metcalf & Srinivasan Sujatha It is essential to understand the strategies and processes which are deployed currently across the Assistive Technology (AT) space toward measuring innovation. The main aim of this paper is to identify functional innovation strategies and processes which are being or can be deployed in the AT space to increase access to AT globally. Assistive Technology The Official Journal of RESNA Abstract A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems It is essential to understand the strategies and processes which are deployed currently across the Assistive Technology (AT) space toward measuring innovation. The main aim of this paper is to identify functional innovation strategies and processes which are being or can be deployed in the AT space to increase access to AT globally. We conducted a scoping review of innovation strategies and processes in peer-reviewed literature databases and complemented this by identifying case studies demonstrating innovation strategies. The review includes WHO world region, publication year, AT type and a sector analysis against the Systems-Market for Assistive and Related Technologies Framework. We analyzed the case studies and interviews using thematic analysis. We included 91 papers out of 3,127 after review along with 72 case studies. Our results showed that product innovations were more prevalent than provision or supply innovations across papers and case studies. Case studies yielded two themes: open innovation (OI); radical and disruptive innovation. Financial instruments which encourage OI are needed and we recommend pursuing OI for AT innovation. Embedding AT within larger societal missions will be key to success governments and investors need to understand what AT is and their translational socioeconomic value. Cite A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems Catherine Holloway, Dafne Zuleima Morgado Ramirez, Tigmanshu Bhatnagar, Ben Oldfrey, Priya Morjaria, Soikat Ghosh Moulic, Ikenna D. Ebuenyi, Giulia Barbareschi, Fiona Meeks, Jessica Massie, Felipe Ramos-Barajas, Joanne McVeigh, Kyle Keane, George Torrens, P. V.M. Rao, Malcolm MacLachlan, Victoria Austin, Rainer Kattel, Cheryl D Metcalf & Srinivasan Sujatha (2021) A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems, Assistive Technology, 33:sup1, 68-86, DOI:10.1080/10400435.2021.1970653 A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems Type Journal Paper Themes Inclusive Design Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities Mikaela Patrick,Iain McKinnon Public spaces, including recreational and social spaces, are often not prioritised. Inclusive public spaces are fundamental to participation and inclusive in society. Including persons with disabilities in the design and planning of the built environment supports equal rights and helps identify people’s aspirations for inclusive environments. Four city case studies will be discussed in this paper: Ulaanbaatar, Mongolia; Varanasi, India; Surakarta, Indonesia; and Nairobi, Kenya. The Journal of Public Space Abstract Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities This paper presents some of the findings from a global research study on inclusive infrastructure and city design and will focus on inclusive public spaces. Persons with disabilities can experience multi-dimensional exclusion from urban life, including but not limited to physical, attitudinal and social barriers. Public spaces, including recreational and social spaces, are often not prioritised. Inclusive public spaces are fundamental to participation and inclusive in society. Including persons with disabilities in the design and planning of the built environment supports equal rights and helps identify people’s aspirations for inclusive environments.Four city case studies will be discussed in this paper: Ulaanbaatar, Mongolia; Varanasi, India; Surakarta, Indonesia; and Nairobi, Kenya. Research participants and objectives are organised by three stakeholder groups: People - first-hand experiences of persons with disabilities living in the city and their aspirations for a more inclusive city Policy - the awareness and understanding of inclusive design among policy-makers Practice - the awareness and understanding of inclusive design among practitioners including barriers to implementation, opportunities and the relationship with assistive technology Methods include document reviews, interviews, photo diaries and co-design workshops with participatory and inclusive engagement of persons with disabilities throughout. Findings on public spaces are discussed in three ways: The types of public spaces valued by participants in each of the four cities. The barriers and challenges experienced by persons with disabilities in the public realm. Aspirations for more inclusive public spaces and opportunities for inclusive design The paper concludes by discussing how the targeted stakeholder groups of people, policy and practice also help represent three essential dimensions of inclusive city design and forming a framework for successful implementation and delivery and supporting targets set out through the UNCRPD and Sustainable Development Goals (SDGs). Cite Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities Patrick, M. and McKinnon, I. (2022) “Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities”, The Journal of Public Space, 7(2), pp. 93–116. doi: 10.32891/jps.v7i2.1500. Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities Type Journal Paper Themes Culture and Participation Research Group Social Justice Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change Jessica Noske-Turner, Emma Pullen, Mufunanji Magalasi, Damian Haslett, Jo Tacchi Communication & Sport Abstract Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change The purpose of this commentary is to discuss how Paralympic coverage in sub-Saharan Africa can be effectively mobilised to stimulate discursive and structural change around disability. Paralympic coverage has demonstrated its pedagogical power to engage public(s) and challenge stigma toward disability. Yet, the Global picture of Paralympic broadcasting is deeply uneven, with audiences in parts of the Global South afforded limited opportunities to watch the Games. Considering this, the International Paralympic Committee has begun to broadcast Paralympic coverage across sub-Saharan Africa with an explicit aim to challenge stigma toward disability. In this article, we draw on examples from research to argue that ideas from the field of Communication for Social Change (CfSC) can add value towards this aim. We begin by providing a brief overview of CfSC before critically examining one of the field’s key concepts – Communicative (E)ecologies. Following this, we critically reflect on the potential of Paralympic broadcasting as a vehicle for social change and disability rights agendas in sub-Saharan Africa. We argue that thinking with CfSC concepts show the importance of a ‘decentred’ media approach that engages with disability community advocacy groups, localised communication activities and practices, and culturally specific disability narratives. Cite Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change Noske-Turner, J., Pullen, E., Magalasi, M., Haslett, D., & Tacchi, J. (2022). Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change. Communication & Sport, 10(5), 1001–1015.https://doi.org/10.1177/216747... Share Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Troy Bodkin Doctoral Thesis. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. Loughborough University Abstract Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design For many years, the biggest issue that causes discomfort and hygiene issues for patients with lower limb amputations have been the interface between body and prosthetic, the socket. Often made of an inflexible, solid polymer that does not allow the residual limb to breathe or perspire and with no consideration for the changes in size and shape of the human body caused by changes in temperature or environment, inflammation, irritation and discomfort often cause reduced usage or outright rejection of the prosthetic by the patient in their day to day lives. To address these issues and move towards a future of improved quality of life for patients who suffer amputations, Loughborough University formed the Next Generation Prosthetics research cluster. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. The research presented in this thesis is based on three primary studies. The first study involved the conception of a CAD criteria, deciding what features are needed to represent the various properties the future socket outlined by the research cluster needs. These criteria were then used for testing three CAD systems, one each from the Parametric, Non Uniform Rational Basis Spline (NURBS) and Polygon archetypes respectively. The result of these tests led to the creation of a hybrid control workflow, used as the basis for finding improvements. The second study explored emerging CAD solutions, various new systems or plug-ins that had opportunities to improve the control model. These solutions were tested individually in areas where they could improve the workflow, and the successful solutions were added to the hybrid workflow to improve and reduce the workflow further. The final study involved taking the knowledge gained from the literature and the first two studies in order to theorise how an ideal CAD system for producing future prosthetic sockets would work, with considerations for user interface issues as well as background CAD applications. The third study was then used to inform the final deliverable of this research, a software design specification that defines how the system would work. This specification was written as a challenge to the CAD community, hoping to inform and aid future advancements in CAD software. As a final stage of research validation, a number of members of the CAD community were contacted and interviewed about their feelings of the work produced and their feedback was taken in order to inform future research in this area. Cite Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Bodkin, Troy L. (2017): Specifying a hybrid, multiple material CAD system for next-generation prosthetic design. Loughborough University. Thesis.https://hdl.handle.net/2134/25...; Share Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Giulia Barbareschi Doctoral Thesis. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. UCL (University College London) Abstract YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Transferring independently to and from their wheelchair is an essential routine task for many wheelchair users but it can be physically demanding and can lead to falls and upper limb injuries that reduce the person’s independence. New assistive technologies (ATs) that facilitate the performance of wheelchair transfers have the potential to allow wheelchair users to gain further independence. To ensure that users’ needs are addressed by ATs, the active involvement of wheelchair users in the process of design and development is critical. However, participation can be burdensome for many wheelchair users as design processes where users are directly involved often require prolonged engagement. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. A related outcome based on these contributions is a framing document to share knowledge between wheelchair users and designers to provide focus and promote an equal collaboration among participants. Cite YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Barbareschi, Giulia. “YouTransfer, YouDesign : a Participatory Approach to Design Assistive Technology for Wheelchair Transfers / Giulia Barbareschi.” Thesis (Ph.D.)--University College London, 2018., 2018. Print. Share YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Understanding wrist splint user needs and personalisation through codesign Charlotte Pyatt A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy at Loughborough University. Loughborough University Abstract Understanding wrist splint user needs and personalisation through codesign Wrist splints are a common treatment for rheumatoid arthritis, however their effectiveness is compromised by patients not wearing splints as often as prescribed. Previous research has identified a number of reasons for non-compliance, but typically lacks insights that could lead to improved splint design. This thesis investigates the motivators for patients to wear and not wear their wrist splints and, the impact of personalisation of splint appearance on patient wear. The work is based on the premise that digital design and manufacturing processes, such as Computer-Aided Design (CAD) and 3D Printing, can produce bespoke splints on demand. The research begins with a literature review across the core areas of: splinting, additive manufacture, product appearance and personalisation. This literature review identifies gaps in knowledge from which research questions are established for the work. The research employs a qualitative, generative design research approach and, follows a codesign framework employing telling, making and enacting tools. The thesis is made up of three studies. The first study is a sensitisation study and uses design probes to prepare the participants for the research and begin exploring the problem space. The second is a comprehensive study into participants splint wear behaviour and uses context mapping and scenario picture card tools to investigate the motivators for participants to wear and not wear wrist splints, along with positive and negative outcomes or wearing/not wearing splints. The final study uses a personalisation toolkit to elicit patient needs for a future wrist splint design and investigate self-reported expectations regarding compliance of patients who used the toolkit. The research finds that patient compliance is affected by practical and aesthetic limitations of current splints. It identifies 4 motivating factors to wear a splint and 10 motivating factors to not wear a splint. Additionally, it identifies 6 positive outcomes of wearing splints, 6 negative outcomes of wearing splints, 3 positive outcomes of not wearing splints and 3 negative outcomes of not wearing splints. Requirements for an improved splint design are established and form the basis of the design for a prototype personalisation toolkit. Testing of this toolkit reveals that patients are keen to own more than one splint and personalise splints to match the scenario in which it is to be worn. Patients reported that they expected to be more compliant with a personalised splint when compared to their current splint. Cite Understanding wrist splint user needs and personalisation through codesign Pyatt, Charlotte (2018): Understanding wrist splint user needs and personalisation through codesign. Loughborough University. Thesis.https://doi.org/10.26174/thesi...; Share Understanding wrist splint user needs and personalisation through codesign Type PhD Themes Assistive & Accessible Technology Shared Control for Wheelchair Interfaces Dr Chinemelu Ejiamatu Muoma Ezeh Doctoral Thesis. Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch. UCL (University College London) Abstract Shared Control for Wheelchair Interfaces Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch. Control is shared between a powered wheelchair user, using an alternative interface and a pow- ered wheelchair fitted with sensors. This shared control then produces a resulting motion that is close to what the user desires to do but a motion that is also safe. A path planning algorithm on the wheelchair is implemented using techniques in mo- bile robotics. Afterwards, the output of the path planning algorithm and the user’s com- mand are both modelled as random variables. These random variables are then blended in a joint probability distribution where the final velocity to the wheelchair is the one that maximises the joint probability distribution. The performance of the probabilistic approach to blending the user’s inputs with the output of a path planner, is benchmarked against the most common form of shared control called linear blending. The benchmarking consists of several experiments with end users both in a simulated world and in the real-world. The thesis concludes that probabilistic shared control provides safer motion compared with the traditional shared control for difficult tasks and hard-to-use interfaces. Cite Shared Control for Wheelchair Interfaces Ezeh, Chinemelu Ejiamatu Muoma. Shared Control for Wheelchair Interfaces. UCL (University College London), 2018. Print. Share Shared Control for Wheelchair Interfaces Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Materials For Facial Prostheses In Resource Limited Countries Sophia Esther Liiba Tetteh A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University Loughborough University Abstract Materials For Facial Prostheses In Resource Limited Countries Facial prostheses are artificial devices that replace a missing body part in the facial and neck regions of the body. Defects or deformities in these regions can lead to functional deficiencies; social and psychological effects in addition to cosmetic defects. Restoration or rehabilitation in resource limited countries is usually provided by charities and organisations volunteering assistance overseas, with some training of local staff in the fabrication of these prostheses. Furthermore, these countries typically lack technical knowhow and trained personnel. In industrialised nations maxillofacial prosthetics has developed into a sophisticated medical speciality requiring highly skilled staff and expensive facilities. In resource limited countries surgical procedures may be an option for rehabilitation of these deformities/defects however, they tend to be unavailable or unaffordable and donated prostheses are not suitable. Hence, this research explores, from first principles, the appropriate and affordable local provision of maxillofacial prostheses in resource constrained regions. The investigation provides knowledge on identifying requirements for resource limited areas, resulting in the creation of a guideline constituting priorities, requirements and specifications. It further explores the viability of potentially cheaper, locally available candidate materials via weathering and antimicrobial methods in ascertaining material longevity. Cite Materials For Facial Prostheses In Resource Limited Countries Tetteh, Sophia (2019): Materials for facial prostheses in resource-limited countries. Loughborough University. Thesis.https://doi.org/10.26174/thesi...; Share Materials For Facial Prostheses In Resource Limited Countries Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Rhys James Williams Thesis: Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past. UCL, ProQuest Dissertations Publishing Abstract Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Amongst lower-limb prosthesis wearers, thermal discomfort is a common problem with an estimated prevalence of more than 50%. Overheating does not just create discomfort to the user, but it has been linked to excessive sweating, skin damage caused by a moist environment and friction. Due to impermeable prosthetic components and a warm moist environment, minor skin damage can result in skin infections that can lead to prosthesis cessation, increased social anxiety, isolation and depression. Despite the seriousness of thermal discomfort, few studies explore the issue, with research predominantly constrained to controlled laboratory scenarios, with only one out of laboratory study. In this thesis, studies investigate how thermal discomfort arises and what are the consequences of thermal discomfort for lower-limb prosthesis wearers. Research studies are designed around the principles of presenting lived experiences of the phenomenon and conducting research in the context of participants' real-life activities. A design exploration chapter investigates modifying liner materials and design to create a passive solution to thermal discomfort. However, this approach was found to be ineffective and unfeasible. Study 1 presents a qualitative study which investigates the user experience of a prosthesis, thermal discomfort and related consequences. Study 2 explores limb temperature of male amputees inside and outside the laboratory, with the latter also collecting perceived thermal comfort (PTC) data. Finally, Study 3 investigates thermal discomfort in the real-world and tracks limb temperature, ambient conditions, activities, and experience sampling of PTC. While there were no apparent relationships presented in sensor data, qualitative data revealed that in situations where prosthesis wearers perceived a lack of control, thermal discomfort seemed to be worse. When combined, the studies create two knowledge contributions. Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past. Cite Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Williams, Rhys James. “Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers.” ProQuest Dissertations Publishing, 2020. Print. Share Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Design rules for additively-manufactured wrist splints Sarah Kelly A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University. Loughborough University Abstract Design rules for additively-manufactured wrist splints Additive Manufacturing (AM) often known by the term three-dimensional printing (3DP) has been acknowledged as a potential manufacturing revolution. AM has many advantages over conventional manufacturing techniques; AM techniques manufacture through the addition of material - rather than traditional machining or moulding methods. AM negates the need for tooling, enabling cost-effective low-volume production in high-wage economies and the design & production of geometries that cannot be made by other means. In addition, the removal of tooling and the potential to grow components and products layer-by-layer means that we can produce more from less in terms of more efficient use of raw materials and energy or by making multifunctional components and products. The proposed Centre for Doctoral Training (CDT) in Additive Manufacturing and 3D Printing has the vision of training the next generation of leaders, scientists and engineers in this diverse and multi-disciplinary field. As AM is so new current training programmes are not aligned with the potential for manufacturing and generally concentrate on the teaching of Rapid Prototyping principles, and whilst this can be useful background knowledge, the skills and requirements of using this concept for manufacturing are very different. This CDT will be training cohorts of students in all of the basic aspects of AM, from design and materials through to processes and the implementation of these systems for manufacturing high value goods and services. The CDT will also offer specialist training on aspects at the forefront of AM research, for example metallic, medical and multi-functional AM considerations. This means that the cohorts graduating from the CDT will have the background knowledge to proliferate throughout industry and the specialist knowledge to become leaders in their fields, broadening out the reach and appeal of AM as a manufacturing technology and embedding this disruptive technology in company thinking. In order to give the cohorts the best view of AM, these students will be taken on study tours in Europe and the USA, the two main research powerhouses of AM, to learn from their international colleagues and see businesses that use AM on a daily basis. One of the aims of the CDT in AM is to educate and attract students from complementary basic science, whether this be chemistry, physics or biology. This is because AM is a fast moving area. The benefits of having a CDT in AM and coupling with students who have a more fundamental science base are essential to ensure innovation & timeliness to maintain the UK's leading position. AM is a disruptive technology to a number of industrial sectors, yet the CDTs industrial supporters, who represent a breadth of industrial end-users, welcome this disruption as the potential business benefits are significant. Growing on this industry foresight, the CDT will work in key markets with our supporters to ensure that AM is positioned to provide a real and lasting contribution & impact to UK manufacturing and provide economic stability and growth. This contribution will provide societal benefits to UK citizens through the generation of wealth and employment from high value manufacturing activities in the UK. Cite Design rules for additively-manufactured wrist splints Kelly, Sarah (2020): Design rules for additively-manufactured wrist splints. Loughborough University. Thesis.https://doi.org/10.26174/thesi...; Share Design rules for additively-manufactured wrist splints Type PhD Themes Assistive & Accessible Technology Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece Anna Vlachaki The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies. Loughborough University Abstract Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis, the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies. Study I was an online questionnaire to explore users’ preferences towards prostheses, with respect to their culture. Study II consisted of semi-structured interviews and informational probes to comprehend the role of prostheses on users’ lives, with respect to prosthetic appearance. In Study III, the aim was to investigate prosthetists’ attitudes towards the needs of prosthetic users by conducting semi-structured interviews. Finally, Study IV was an online questionnaire to explore non-users’ attitudes towards the design of prostheses. The research showed that the use of prostheses for the completion of users’ body was not an adequate factor to improve their well-being, and a shift on users’ desires towards emotionally-driven prostheses has occurred. From the variables that were tested, sex, age, cause and area of limb-loss may affect people’s attitudes towards the design of prostheses. Furthermore, the results showed that prostheses with high emotionally-driven design evoked emotions, in both users and non-users, with higher levels of pleasantness and arousal than the emotions that were elicited by the prostheses of lower emotionally-driven designs and thus, they may trigger a greater behavioural reaction. This suggested that emotionally-driven prostheses may eliminate users’ stigmatisation by increasing their self-confidence and altering society’s attitudes. However, attention needs to be paid in collectivistic countries, as emotionally-driven prostheses may enhance users’ stigmatisation. Cite Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece Vlachaki, Anna (2020): Emotionally-driven prostheses: exploring the effects on users’ lives and societies’ attitudes in the UK and Greece. Loughborough University. Thesis.https://doi.org/10.26174/thesi...; Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece Type Working Paper Themes Culture and Participation Research Group Disability Interactions Barriers to Access and Retain Formal Employment for Persons with Disabilities in Bangladesh and Kenya Nusrat Jahan andCatherine Holloway This working paper was developed to support the development of challenge statements for a GDI Hub innovation challenge fund call related to improving access to and retention of employment for persons with disabilities in Kenya and Bangladesh and is written by GDI Hub's Nusrat Jahan andProfessor Catherine Holloway. The issue of disability and employment has taken centre stage on the global arena in part because it is recognised across several areas of the United Nations Sustainable Development Goals, in which confrontation of extreme poverty in its many manifestations is the number one goal [2]. The World Health Organization (2011) reports about 15 percent of the world’s population has a disability [1]. In developing countries, 80 to 90 percent of people with disabilities of working age are unemployed. Abstract Barriers to Access and Retain Formal Employment for Persons with Disabilities in Bangladesh and Kenya Globally persons with disabilities have lower employment rates compared to the general population due to systemic barriers particularly in the formal sector. In developing countries, 80 percent to 90 percent of people with disabilities of working age are unemployed. There has been limited research in low-income and middle-income countries focused on the barriers to access and retain formal employment for persons with disabilities. The aim of this paper, based on desk research, is to analyse the barriers to access and retain formal employment of persons with disabilities which are framed in three categories according to where the barriers primarily manifest: 1. In the workplace among employers and co-workers without disabilities, 2. Among persons with disabilities seeking or engaged in formal employment and 3. In the wider social, physical and policy environment. Although the study mainly focuses on Kenya and Bangladesh other countries’ literature on access to and retention of employment of persons with disabilities were reviewed where relevant. In the current context where the global pandemic is breaking barriers to remote working one part of the solution will be to empower persons with disabilities with appropriate access to Information and Communication Technology, assistive devices and services, digital skills, creating more accessible and inclusive digital platforms for persons with disabilities which also hold the potential to improve working conditions and productivity for the whole workforce as well as enhancing resilience to potential future shocks. Cite	https://www.disabilityinnovation.com/publications?page=6&type=phd+working-paper+workshop+conference-paper+journal-paper
Clinical trial: Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant Clinical trial: Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant Information source: Fred Hutchinson Cancer Research Center Link to the current ClinicalTrials.gov record. Condition(s) targeted:Bronchiolitis Obliterans Intervention: fluticasone propionate (Drug); montelukast sodium (Drug); pulmonary function testing (Procedure); questionnaire administration (Other); quality-of-life assessment (Procedure); laboratory biomarker analysis (Other); protein analysis (Genetic); azithromycin (Drug) Phase:Phase 2 Status:Active, not recruiting Sponsored by:Fred Hutchinson Cancer Research Center Official(s) and/or principal investigator(s): Stephanie Lee, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Kirsten Williams, Study Chair, Affiliation: National Cancer Institute (NCI) Summary This phase II trial studies how well giving fluticasone propionate, azithromycin, and montelukast sodium (FAM) together works in treating patients with bronchiolitis obliterans who previously underwent stem cell transplant. FAM may be an effective treatment for bronchiolitis obliterans Clinical Details Official title:Targeted Therapy of Bronchiolitis Obliterans Syndrome Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment Primary outcome:Treatment failure Secondary outcome: Incidence and types of National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v4.0) Changes in FEF 25-75, RV, DLCO, FEV1/FVC ratio and FEV1/SVC ratio Changes in blood molecular markers: IL8 (azithromycin), cysteinyl and LTB4 (monteleukast), and IL1B, TNF, and IL6, as well as neutrophil count (fluticasone) Using the National Institute of Health (NIH) consensus criteria, the proportion of subjects with improvements in other chronic GVHD characteristics Changes in HRQOL, exercise capacity, and symptoms compared to baseline Total systemic steroid exposure Detailed description: PRIMARY OBJECTIVES: I. To determine if the combination treatment of FAM administered in post hematopoietic cell transplantation (HCT) recipients after the diagnosis of new onset bronchiolitis obliterans syndrome (BOS) can decrease the rate of treatment failure relative to an estimated historical rate of 40% using current therapies. SECONDARY OBJECTIVES: I. To confirm the safety profile of FAM. II. To describe the effect on other standard pulmonary function test parameters: forced expiratory flow at 25%-75% of forced vital capacity (FVC) (FEF25-75), residual volume (RV), diffusion capacity of carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1)/FVC ratio and FEV1/slow vital capacity (SVC) ratio with FAM treatment. III. To determine the change in molecular markers of inflammation and fibrosis in the blood with FAM treatment. IV. To assess the impact of FAM on other chronic graft-versus-host disease (GVHD) manifestations. V. To assess the impact of FAM on functional status, and health-related quality of life (HRQOL). VI. To describe changes in steroid dosing. OUTLINE: Patients receive fluticasone propionate inhaled orally (PO) twice daily (BID), azithromycin PO 3 days a week, and montelukast sodium PO once daily (QD). Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 6 months. Eligibility Minimum age: 6 Years. Maximum age: N/A. Gender(s): Both. Criteria: Inclusion Criteria: - Diagnosis of BOS after HCT within the 6 months before study enrollment; for this study, BOS is defined as: - Forced expiratory volume in 1 second (FEV1) < 75% of the predicted normal and FEV1 to slow or inspiratory vital capacity ratio (FEV1/SVC or FEV1/IVC) =< 0. 7, both measured before and after administration of bronchodilator OR - Pathologic diagnosis of BOS demonstrated by lung biopsy - The baseline absolute FEV1 must be >= 10% lower than the pre-transplant absolute FEV1 as defined by the pre-transplant FEV1 minus the baseline FEV1, both measured before administration of a bronchodilator - Participant (or parent/guardian) has the ability to understand and willingness to sign a written consent document Exclusion Criteria: - Recurrent or progressive malignancy requiring anticancer treatment - Known history of allergy to or intolerance of montelukast, zafirlukast, azithromycin, erythromycin, or clarithromycin - Pregnancy or nursing; all females of childbearing potential must have a negative serum or urine pregnancy test < 7 days before study drug administration - Transaminases > 5 X upper limit of normal (ULN) - Total bilirubin > 3 X ULN - Chronic treatment with any inhaled steroid for > 1 month in the past three months - Treatment with montelukast or zafirlukast for > 1 month during the past three months - Treatment with prednisone at > 1. 2 mg/kg/day (or equivalent steroid) - Treatment with rifampin or phenobarbital, aspirin at doses > 325 mg/day, or ibuprofen at doses > 1200 mg/day - Treatment with any Food and Drug Administration (FDA) non approved study medication within the past 4 weeks; off-label treatment with an FDA-approved medication is allowed - Chronic oxygen therapy - Evidence of any viral, bacterial or fungal infection involving the lung and not responding to appropriate treatment - Clinical asthma (variable and recurring symptoms of airflow obstruction and bronchial hyper-responsiveness) - Any condition that, in the opinion of the enrolling investigator, would interfere with the subject's ability to comply with the study requirements - Uncontrolled substance abuse or psychiatric disorder - Inability to perform pulmonary function tests (PFT) reliably, as determined by the enrolling investigator or PFT lab - Life expectancy < 6 months at the time of enrollment as judged by the enrolling investigator - Baseline post-bronchodilator FEV1 < 20% of predicted normal before or after albuterol Locations and Contacts Mayo Clinic - Scottsdale, Scottsdale, Arizona 85054, United States Stanford University, Stanford, California 94305, United States H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, United States National Cancer Institute Experimental Transplantation & Immunology Branch, Bethesda, Maryland 20892, United States Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States Siteman Cancer Center at Washington University, Saint Louis, Missouri 63110, United States Roswell Park Cancer Institute, Buffalo, New York 14263, United States Weill Cornell Medical College, New York, New York 10065, United States University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States Vanderbilt University, Nashville, Tennessee 37232, United States Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States Additional Information	http://www.druglib.com/trial/62/NCT01307462.html
Antiulcer action of Sophora flavescens root and an active constituent. I Download Citation \| Antiulcer action of Sophora flavescens root and an active constituent. I \| The effect of a methanol extract of Sophora flavescens root was examined on gastric ulcers induced in rats by HCl/ethanol in order to substantiate... \| Find, read and cite all the research you need on ResearchGate Article Antiulcer action of Sophora flavescens root and an active constituent. I June 1990 Journal of Ethnopharmacology29(2):173-7 DOI: 10.1016/0378-8741(90)90053-V Source PubMed Authors: <here is a image f2f62089ad6ff61c-d19572ff1996375a> Johji Yamahara Johji Yamahara Michihiko Mochizuki Michihiko Mochizuki <here is a image f2f62089ad6ff61c-d19572ff1996375a> Hajime Fujimura Hajime Fujimura <here is a image f2f62089ad6ff61c-d19572ff1996375a> Yoshihisa Takaishi Yoshihisa Takaishi Abstract The effect of a methanol extract of Sophora flavescens root was examined on gastric ulcers induced in rats by HCl/ethanol in order to substantiate its reputed protective properties. Oral doses of 1 g/kg completely suppressed ulceration. Results suggest that oral administration of 50 mg/kg of vexibinol, a flavanol found in the extract, inhibited ulceration more effectively than spizofurone at 100 mg/kg. <here is a image 175d1bd4b7439d95-754927124da715c1> ... Novel dosage forms in terms of tablets, capsules, and injections were developed, recently [1]. Currently, S. flavescens is widely used to treat dysentery [1], fever [2], skin and mucosal ulcers [3] , diarrhea [4], and reduce edema by inducing diuresis [5]. Besides, S. flavescens is known to exhibit varied pharmacological properties including antitumor [6,7], anti-inflammatory [8], and antibacterial [9,10] activities. ... ... Nevertheless, it is noteworthy that S. flavescens extracts could induce CYP1A, CYP2B1/2, CYP2C11, and CYP3A in rats and mice [22]. e complexity of S. flavescens extracts may be the reason for varying experimental results, and while the alkaloids matrine and oxymatrine participated in inducting CYP isoforms [3] . Hence, clinicians should be aware of the in vivo concentration alterations of CYP1A2-metabolized substrates when their patients are administered S. flavescens with a high content of kurarinone. ... An In Vitro Study for Evaluating Permeability and Metabolism of Kurarinone Article Full-text available Sep 2020 EVID-BASED COMPL ALT Youfa Qin Yongkun Zhu Xiaoyan Xue Jian Wang Kurarinone is a major component found in the dried roots of Sophora flavescens Ait. that participates in vital pharmacological activities. Recombinant CYP450 supersomes and liver microsomes were used to study the metabolic profiles of kurarinone and its inhibitory actions against cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes. 100 μM of kurarinone strongly inhibited more than 90% of UGT1A1, UGT1A6, CYP1A2, and CYP2C9. CYP1A2 and CYP2D6 played important roles in catalyzing the biotransformation of kurarinone. Moreover, metabolism of kurarinone considerably differs among species, and metabolic characteristics were similar between monkey and human. Kurarinone demonstrated moderate permeability at values of pH 4.0 and 7.4. Our findings offer a clearer idea to understand the pharmacological and toxicological mechanisms of kurarinone. 1. Introduction The dry root of Sophora flavescens Ait. has been an important species in traditional Chinese medicine since the Qin and Han dynasties. S. flavescens has been documented in editions of the Pharmacopoeia of the People’s Republic of China since 1977. Novel dosage forms in terms of tablets, capsules, and injections were developed, recently [1]. Currently, S. flavescens is widely used to treat dysentery [1], fever [2], skin and mucosal ulcers [3], diarrhea [4], and reduce edema by inducing diuresis [5]. Besides, S. flavescens is known to exhibit varied pharmacological properties including antitumor [6, 7], anti-inflammatory [8], and antibacterial [9, 10] activities. Kurarinone (showed in Figure 1) is a major constituent of S. flavescens with the content ranging from 4.79 mg/g to 16.07 mg/g [11]. Kurarinone exhibits antitumor [12, 13], anti-inflammatory [8], antioveractive bladder [14], antioxidant [15], and antityrosinase [16] activities. It also induced remarkable cytotoxicity in primary rat hepatocytes and HL-7702 cells [17, 18]. ... Trifolirhizin is another active principle extracted from S. flavescens root, which has demonstrated noteworthy effects on Helicobacter pylori infection and diminished amounts of gastric secretion and acid yield in an animal model. [112][113] [114] Withania somnifera Withania somnifera Dunal or Ashwagandha (Family: Solanaceae) is distributed in northern areas of India, the Mediterranean region and in Africa. It has been widely used as a home remedy for several ailments. ... Gastroprotective effects of herbal medicines (Roots) Article Full-text available May 2018 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Solmaz Asnaashari <here is a image 7d7395bed6d1b7a8-720a182512388093> Siavoush Dastmalchi <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Yousef Javadzadeh Herbal medicines are now commonly used all over the world and this has increased global demand. Quality, safety, and efficacy of these drugs have become a serious concern. This review presents the medicinal plants cited in folklore that are used to treat gastrointestinal ulcers. Electronic databases, that is, Web of Science, PubMed, Scopus, and Google Scholar were searched to identify the gastroprotective effects of each plant. Ethnopharmacological studies have reported various botanical products with antiulcer activities, but there has been limited scientific research, presenting clinical data to validate the efficacy and safety of medicinal herbs as gastroprotective agents. Most studies centered on pharmacological properties of medicinal herbs as used animals models. This information has prompted us to compile a list of the medicinal herbs cited in folklore with gastroprotective activity. ... SF has been used for treatment of fever, pain, inflammation, ulcer, numbness and several skin diseases as traditional medicine in China, South Korea and Japan (Kim et al., 2012;He et al., 2015). Moreover, SF or its compounds have been shown to have anti-oxidative (Piao et al., 2006), anti-cancer (Sun et al., 2007;Liu et al., 2010), anti-arthritic (Jin et al., 2010), anti-ulcerative (Yamahara et al., 1990) and anti-dermatitis (Kim et al., 2012) effects, and recent studies have shown that it has neuroprotective effects. Extract of SF suppressed sodium nitroprusside-induced apoptosis in SH-SY5Y cells, while focal cerebral ischemia induced neuronal death in rats ) and enhanced axonal growth in mice (Tanabe et al., 2015), and oxymatrine extracted from SF prevented neuronal cell death in rat brains subjected to cerebral ischemia-reperfusion damage (Li et al., 2011). ... Sophora flavescens Aiton Decreases MPP+-Induced Mitochondrial Dysfunction in SH-SY5Y Cells Article Hee-Young Kim <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hyongjun Jeon <here is a image a4e6e6cafaaea460-1181323e9f50efad> Hyungwoo Kim Seungtae Kim Sophora flavescens Aiton (SF) has been used to treat various diseases including fever and inflammation in China, South Korea and Japan. Several recent reports have shown that SF has anti-inflammatory and anti-apoptotic effects, indicating that it is a promising candidate for treatment of Parkinson’s disease (PD). We evaluated the protective effect of SF against neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+)-induced mitochondrial dysfunction in SH-SY5Y human neuroblastoma cells, an in vitro PD model. SH-SY5Y cells were incubated with SF for 24 h, after which they were treated with MPP+. MPP+-induced cytotoxicity and apoptosis were confirmed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay. MitoSOX red mitochondrial superoxide indicator, tetramethylrhodamine methyl ester perchlorate and Parkin, PTEN-induced putative kinase 1 (PINK1), and DJ-1 immunofluorescent staining were conducted to confirm the mitochondrial function. In addition, western blot was performed to evaluate apoptosis factors (Bcl-2, Bax, caspase-3 and cytochrome c) and mitochondrial function-related factors (Parkin, PINK1 and DJ-1). SF suppressed MPP+-induced cytotoxicity, apoptosis and collapse of mitochondrial membrane potential by inhibiting the increase of reactive oxidative species (ROS) and DNA fragmentation, and controlling Bcl-2, Bax, caspase-3 and cytochrome c expression. Moreover, it attenuated Parkin, PINK1 and DJ-1 expression from MPP+-induced decrease. SF effectively suppressed MPP+-induced cytotoxicity, apoptosis and mitochondrial dysfunction by regulating generation of ROS, disruption of mitochondrial membrane potential, mitochondria-dependent apoptosis and loss or mutation of mitochondria-related PD markers including Parkin, PINK1 and DJ-1. ... They are used to treat jaundice, leucorrhea, carbuncles, pyogenic infections of the skin, scabies, enteritis, and dysentery [12]. Additionally, a recent study found that quinolizidine alkaloids, flavonoids, benzofuran, and triterpenoid could be isolated from the roots of SR [8][9][10][11][12][13][14][15][16] [17] [18][19][20][21][22][23][24]. However, no studies have examined the combined effect of SR and other chemotherapeutic agents on gastric and colorectal adenocarcinoma cells. ... Effects of Sophorae Radix on Human Gastric and Colorectal Adenocarcinoma Cells -Sophorae Radix and Cancer Cells- Min-Chul Kim Bo-Ra Lim Hee-Jung Lee Byung-Joo Kim The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix (SR) and doxorubicin (DOX) in human gastric and colorectal adenocarcinoma cells. We used the human gastric and colorectal adenocarcinoma cell lines (MKN-45 and WIDR cells, respectively). We examined cell death by using the MTT(3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay and the caspase 3 assay with SR. To examine the inhibitory effects of SR, we performed a cell cycle (sub G1) analysis for the MKN-45 and WIDR cells after three days with SR. The reversibility of SR was examined for one-day to five-day treatments with SR. SR inhibited the growth of MKN-45 and WIDR cells in a dosedependent manner. Also, we showed that SR induced apoptosis in MKN-45 and WIDR cells by using the MTT assay, the caspase 3 assay and the sub-G1 analysis. SR combined with DOX markedly inhibited the growth of MKN-45 and WIDR cells compared to SR or DOX alone. After 3 days of treating MKN-45 and WIDR cells with SR, the fraction of cells in the sub-G1 phase was much higher than that of the control group. Our findings provide insights into unraveling the effects of SR on human gastric and colorectal adenocarcinoma cells and into developing therapeutic agents for use against gastric and colorectal adenocarcinomas. ... Verxibinol (23), a flavanol isolated from Sophora flavescens Ait. (Leguminosae), at a dose of 50 mg/kg (p.o.) also inhibited the formation of lesions induced by HCl/ethanol in rats ( Yamahara et al. 1990 ). ... The therapeutic lead potential of metabolites obtained from natural sources for the treatment of peptic ulcer For over a century, ulcer has been a major cause of morbidity and mortality. Its treatment has progressed from vagotomy to proton pump inhibitors. However, the drugs used produce many adverse effects and are less effective than they ought to be. Therefore, there is a growing interest in alternative therapies and the use of natural products. This review emphasizes recent studies involving naturally occurring antiulcer metabolites, categorized according to their chemical structure. Both terrestrial and marine sources are included. More than a hundred and fifty different compounds are presented, and where possible, their main mechanisms of action are summarized. Considering that Helicobacter pylori is an important causal factor in the pathogenesis of ulcer disease, an overview of some natural compounds with anti-H. pylori activity is presented. ... It is known that different compounds from plant origin, such as terpenes, anthraquinones and flavonoids, have shown inhibitory effect on gastric acid secretion and/or antiulcer activity against several experimental models (Pillai and Santhakumari, 1984;Murakami et al., 1992). In an attempt to correlate the effects of the extract observed in this study with chemical compounds present in B. pilosa, we carried out a literature review and found that flavonoids present in many plant species have a broad scale of biological activities, mainly, antiinflammatory and antiulcer (Yamahara et al., 1990; Murakami et al., 1990; Alarcón de la Lastra et al., 1993). Quercetin is a flavonoid which has been isolated from B. pilosa (Geissberger and Séquin, 1991) and of which antiulcer and antisecretory effects have been reported (Alarcó n de la Lastra et al., 1994b). ... Gastric antisecretory and antiulcer activities of an ethanolic extract of Bidens pilosa L. var. radiata Schult. Bip J ETHNOPHARMACOL A Alvarez F Pomar Sevilla <here is a image 09f1b0aff96075ac-fd5699d50b2ed1a6> María José Montero Bidens pilosa var. radiata Schult. Bip. is used in folk medicine to treat stomach disorders including peptic ulcers. The ethanolic extract (0.5-2 g/kg) decreased the gastric juice volume, acid secretion, as well as pepsin secretion in pylorus ligated rats. B. pilosa extract showed antiulcer activity against indomethacin-induced gastric lesions. The extract effectively inhibited gastric haemorrhagic lesions induced by ethanol, and with an effective dose of 2 g/kg being more potent than sucralfate (400 mg/kg). In contrast, ranitidine (50 mg/kg) failed to reduce these lesions. These results indicate that B. pilosa ethanolic extract exerts a cytoprotective effect in addition to its gastric antisecretory activity that could be due, partly at least, to the presence of flavonoids of which quercetin was identified by HPLC. ... For the preventive studies, ulcer was induced according to the method of Yamahara et al 9 . ... Anti-ulcer and Anti-inflammatory Effects of Hydroalcohol Extract of Aloe buettneri A. Berger (Lilliaceae) Kwashie Eklu-Gadegbeku M. Gbeassor Purpose: Aloe buettneri A. Berger is commonly used in Togolese folk medicine to treat inflammation and gastric ulcer. In this study we investigated the anti-oedema, analgesic, antipyretic and ulcer healing properties of the hydro-alcohol extract of their leaves. Methods: Rat oedema paw were induced by the injection of 0.1 ml of formaldehyde 1%, tail flick method is used to study analgesic property, hyperthermia was induced by subcutaneous injection of 15% of a brewers' yeast suspension at dose of 10 ml/kg and ulcers were induced by ethanol or HCl/ethanol mixture. Results: The extract showed anti-inflammatory properties at doses between 250-500 mg/kg. It inhibited, in a dose- dependent manner, the oedema induced by 0.1 ml of formaldehyde 1%. Scores of 73.70% and 83.63% were obtned when the doses of extract administered were 100 and 500 mg/kg, respectively. The tail flick analgesic index showed an increase of 36.56% when the dose was 500 mg/kg. The extract decreased significantly the hyperthermia induced by the injection of yeast. 1000 mg/kg of the extract inhibited 63.77% of the gastric lesion induced by acid-water-ethanol mixture while daily administration of the same dose accelerated the cicatrisation of gastric ulcer induced by 95% ethanol. Conclusion: The results obtained show that the hydro-alcohol extract of Aloe buettneri A. Berger (Lilliaceae) has anti-inflammatory, anti-ulcer and wound healing properties ... Hypolaetin-8-glucoside Stress, ethanol, acetylsalicylic acid Alcaraz and Hoult, 1985; Villar et al., 1984 Kaempferol Ethanol Izzo et al., 1994 Leucocyanidin Aspirin Lewis et al., 1999 Luteolin-7-glycoside, Pylorus-ligated, stress, reserpine, phenylbutazone, serotonin Rainova et al., 1988 5-Methoxy¯avone Indomethacin Blank et al., 1997 Myricetin 3-O-D-galactoside Stress, pylorus-ligated, ethanol Reyes et al., 1996 Naringin Ethanol, stress, pylorus-ligated Martin et al., 1993; Motilva et al., 1993 Quercetin Stress, ethanol, reserpine Izzo et al., 1994; Di Carlo et al., 1994; Martin et al., 1993 Rutin Ethanol Izzo et al., 1994 Silymarin Stress Alarcon de la Lastra, 1992 Ternatin Ethanol, indomethacin, stress Rao et al., 1997 Vexibinol HCl, ethanol Yamahara et al., 1990 582 F. BORRELLI AND A. A. IZZO ... Plant kingdom as a source of anti-ulcer remedies <here is a image 7a53c29382727813-b4cc408c5b0dbda3> Angelo Izzo Phytogenic agents have traditionally been used by herbalists and indigenous healers for the prevention and treatment of peptic ulcer. This article reviews the anti-acid/anti-peptic, gastro-protective and/or anti-ulcer properties of the most commonly employed herbal medicines and their identified active constituents. Botanical compounds with anti-ulcer activity include flavonoids (i.e. quercetin, naringin, silymarin, anthocyanosides, sophoradin derivatives) saponins (i.e. from Panax japonicus and Kochia scoparia), tannins (i.e. from Linderae umbellatae), gums and mucilages (i.e. gum guar and myrrh). Among herbal drugs, liquorice, aloe gel and capsicum (chilli) have been used extensively and their clinical efficacy documented. Also, ethnomedical systems employ several plant extracts for the treatment of peptic ulcer. Despite progress in conventional chemistry and pharmacology in producing effective drugs, the plant kingdom might provide a useful source of new anti-ulcer compounds for development as pharmaceutical entities or, alternatively, as simple dietary adjuncts to existing therapies. ... Sophora flavescens , one of long-been used medicinal plants in oriental medicine, was well known to have a variety of activities against many diseases. These include anti-bacterial, anti-ulceral and vasodilatorial activities [21, 24, 25] . Furthermore , it has been also reported that Sophora flavescens extract has an apoptogenic effect and an inhibitory role in phospholipase C pathway [26,27]. ... The hair growth promoting effect of Sophora flavescens extract and its molecular regulation Seok-Seon Roh Chang Deok Kim Min-Ho Lee Yeo-Kyeong Yoon In search of natural extracts for hair growth, we found that the extract of dried root of Sophora flavescens has outstanding hair growth promoting effect. After topical application of Sophora flavescens extract onto the back of C57BL/6 mice, the earlier conversion of telogen-to-anagen was induced. The growth of dermal papilla cells cultured in vitro, however, was not affected by Sophora flavescens extract treatment. RT-PCR analysis showed that Sophora flavescens extract induced mRNA levels of growth factors such as IGF-1 and KGF in dermal papilla cells, suggesting that the effects of Sophora flavescens extract on hair growth may be mediated through the regulation of growth factors in dermal papilla cells. In addition, the Sophora flavescens extract revealed to possess potent inhibitory effect on the type II 5alpha-reductase activity. Taken together, these results suggest that Sophora flavescens extract has hair growth promoting potential and can be used for hair growing products. Anti-ulcer Activities of Herbal Remedies as Alternative Therapy Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of Sophora flavescens The roots of Sophora flavescens have long been used in Chinese medicine for the treatment of fever, inflammatory disorders, ulcers and skin burns. Sophora flavescens contains flavonoids and alkaloids. This study was conducted to develop a plant-based anti-inflammatory agent focused on chronic inflammatory disorders. To accomplish this, the alkaloid-free prenylated flavonoid-enriched fraction (PFS) of rhizomes of Sophora flavescens was prepared and its in vitro and in vivo anti-inflammatory activities were then evaluated for the first time. The inhibitory activity of PFS on PGE(2), NO, IL-6 and TNF-alpha production of lipopolysaccharide (LPS)-treated RAW 264.7 cells was measured. Additionally, adjuvant-induced arthritis in rats was used as an animal model of chronic inflammation to establish the in vivo anti-inflammatory effects of PFS. PFS inhibited cyclooxygenase-2 (COX-2)-catalyzed PGE(2) and inducible nitric oxide synthase (iNOS)-catalyzed NO production by lipopolysaccharide (LPS)-treated RAW 264.7 cells at 10-50 microg/ml, and these effects primarily occurred via COX-2 inhibition and iNOS down-regulation, respectively. PFS also inhibited IL-6 and TNF-alpha production. When tested against adjuvant-induced arthritis in rats (chronic inflammation), PFS strongly inhibited arthritic inflammation when administered orally at doses of 10-100mg/kg/day. In addition, PFS administered orally potently inhibited acetic acid-induced writhing in mice. Our results suggest that PFS inhibits chronic inflammatory response and the inhibition of proinflammatory molecules such as COX-2, iNOS and IL-6 may contribute, at least in part, to the anti-inflammatory activity in vivo. Overall, these results indicate that PFS from Sophora flavescens may have the potential for treatment of chronic inflammatory disorders such as rheumatoid arthritis. Differential inductive profiles of hepatic cytochrome P450s by the extracts of Sophora flavescens in male and female C57BL/6JNarl mice Sophora flavescens has been used as an antipyretic and analgesic agent. To assess the possible herb-drug interaction, effects of S. flavescens extracts on hepatic cytochrome P450 (P450, CYP) enzymes were studied. Effects of the extracts prepared by three different pharmaceutical companies on P450 enzymes were investigated in male and female C57BL/6JNarl mice. In male mice, extract 1 caused a dose- and time-dependent increase of 7-ethoxyresorufin O-deethylation (EROD) activity. Three-day treatment with 3g/kg extracts 1-3 elevated EROD, 7-pentoxyresorufin O-dealkylation (PROD), coumarin hydroxylation, and nifedipine oxidation (NFO) activities. In female mice, extracts 1 and 2 increased EROD and PROD activities without affecting coumarin hydroxylation and NFO activities. However, extract 3, which lacked prenylated flavonoids, caused an induction profile in females the same as in males. Treatment with extract 3 fortified with prenylated flavonoids restored the gender difference. An alkaloid, oxymatrine was present in all extracts and increased EROD and PROD activities. At a human equivalent dose (0.18 g/(kg day)), all extracts increased EROD activity. These results revealed that Cyp1a had a lower induction response threshold. Oxymatrine contributed at least partly to the P450 induction by S. flavescens. At a higher dose, Cyp2a, Cyp2b, and Cyp3a could be induced and the male-specific induction of Cyp2a and Cyp3a was associated with the presence of prenylated flavonoids. Effects of Anchusa strigosa root aqueous extract on gastric ethanol-induced ulcer in laboratory animals Anchusa strigosa Banks et Sol (Boraginaceae) root extracts (ASRE) were prepared by soaking the dry material in boiling water. The clear soluble extract was dried and found to be 0.238 g/g dry roots. A gastric ulcer was induced in fastened animals by oral ingestion of ethanol. Administration of 0.080 g of ASRE prior to ethanol ingestion protected the stomach of the rat from ulcer formation. The ulcer index values, expressed as a percentage of total stomach surface area affected by the ulcer, were lowered from 34.0+/-4.0 to 6.0+/-0.7 and 32.5+/-9.4 to 2.2+/-1.4 by the morphometric and the planimetric methods, respectively. Treatment of the induced ulcer in guinea pigs was achieved by oral administration of ASRE at the therapeutic dose of extract of 0.286 g/kg body weight/day for 24 days. The intraperitoneal LD50 of ASRE in mice was 0.080 g extract/kg body weight. Replacing water intake by ASRE at 75 ml of variable extract concentrations of 2.865, 3.57 and 4.284 g/l per animal per day for 90 days showed no histopathological changes in all organs of the rat. However, a clear depression effect on the central nervous system and anemia were observed particularly with extract of 3.57 g/l or more. Phenolic Constituents of the Roots of Sophora f lavescens From the roots of Sophora flavescens collected in Taiwan, four new prenylflavonoids, sophoraflavanone K (1), sophoraflavanone L (2), 8-lavandulylkaempferol (3), and cyclokuraridin (4), a new arylbenzofuran, 2-(2,4-dihydroxy-5-prenylphenyl)-5,6-methylenedioxybenzofuran (5), and a new prenyldibenzoyl derivative, sophoradione (6), were isolated. The structures of 1-6 were determined by spectroscopic data analysis. Compounds 2-6 were evaluated for cytotoxic activity against the KB epidermoid carcinoma cell line. Na+-Glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens The methanol extract of Sophora flavescens, which is used in traditional Chinese medicine (sophorae radix), showed potent Na(+)-glucose cotransporter (SGLT) inhibitory activity. Our search for active components identified many well-known flavonoid antioxidants: kurarinone, sophoraflavanone G, kushenol K, and kushenol N. Effect of methanolic extract of Terminalia arjuna against Helicobacter pylori 26695 lipopolysaccharide-induced gastric ulcer in rats Helicobacter pylori lipopolysaccharide (HP-LPS) is a potent virulence factor in the causation of gastric ulcer and gastritis. H. pylori-induced gastric pathology is prevalent throughout the world. Herbal medicines are attracting attention because of their traditional values, popularity and belief, as well as for their advantages such as less toxicity, affordability and medicinal value. The present study aimed to evaluate the anti-ulcer effect of a methanolic extract of Terminalia arjuna (TA) against HP-LPS-induced gastric damage in rats. Ulcers were induced with HP-LPS (50 mug per animal) administered orally daily for 3 days. The efficacy of TA on gastric secretory parameters such as volume of gastric juice, pH, free and total acidity, pepsin concentration, and the cytoprotective parameters such as protein-bound carbohydrate complexes in gastric juice and gastric mucosa was assessed. The protective effect of TA was also confirmed by histopathological examination of gastric mucosa. HP-LPS-induced alterations in gastric secretory parameters were altered favourably in rats treated with TA, suggesting that TA has an anti-secretory role. Furthermore, HP-LPS-induced impairments in gastric defence factors were also prevented by treatment with TA. These results suggest that the severe cellular damage and pathological changes caused by HP-LPS are mitigated by TA; these effects are comparable with those of sucralfate. The anti-ulcer effect of TA may reflect its ability to combat factors that damage the gastric mucosa, and to protect the mucosal defensive factors. Anti-ulcer effect of Magnolia cortex and its active constituents Studies on the constituents of Sophora species Studies on the Constituents of Sophora Species. V. Constituents of the Root of Sophora angustifolia SIEB. et ZUCC. (2) Article From the root of Sophora angustifolia SIEB. et ZUCC., three new flavonoids, named nor-kurarinone, kurarinone and kuraridin, were isolated, whose structures have been established to be I, II and VII, respectively, by spectral and chemical data. Studies on the constituents of Sophora species. XXII. Constituents of the root of Sophora moorcroftiana BENTH. ex BAKER.(1). Article	https://www.researchgate.net/publication/20782521_Antiulcer_action_of_Sophora_flavescens_root_and_an_active_constituent_I
Granton Locals (10 Jun 1910) Granton Locals (10 Jun 1910) News: Granton Locals (10 Jun 1910) Surnames: Gerzemehl, Frei, Kintzele, Witte, Cattanach, Kimball, Fraser, Stallman, Wood, Brooks, Grasser, Neinas, Peters, Schoengarth, Kihn, Canfield, Blake, Riedel, Amidon, Henning, Hart, Woelffer, Rose, Bergeman, Davis, Kemmeter, Brown, Snyder, Dost, Howard, Campman, Beaver, Budge, Carnupp, Pierce, Wage, Thiede, Breed, Lapp, Denham, Page, Moench, Fulwiler, Wonser, Marsh, Slocomb, Schaefer, Kurth, Roder, Reiff, Uhlman, Kuechenmeister, Hantke, Lavey, Hefty, Ross, Whitcomb, Kelicut, Moh, Guk, Hammler, Kemena, Lange, Schulz, Opelt, ----Source: The Granton News (Granton, Clark Co., WI.) June 10, 1910 Granton Locals (10 June 1910) Ernest Gerzemehl went to Marshfield Tuesday. Geo. Frei is having his new barn painted. Mrs. John P. Kintzele is reported to be on the sick list. New goods at Witte’s Cash Store daily Mr. and Mrs. John Cattanach of Nasonville visited relatives here last Sunday. Gertrude Kimball came home from Crandon late last week where she has been teaching the past year. Jessie Fraser is here from Chili visiting her brother George and his wife. Arthur Stallman came home from Altoona late last week on a short vacation visit. If you want a good smoke try Special Londres, The Little Wm. Penn, or Cinco at the drug store. Miss Vada Wood returned to Neillsville Tuesday, after a several days visit to friends here. Miss Pearl Brooks went to Neillsville Wednesday for an indefinite stay with her grandma Brooks. Men’s dress shirts value up to 85c, going at 39c, at Witte’s. For headache, neuralgia, etc., use Shac. Never fails to give relief. Mrs. Mike Grasser and daughter Mollie spent Sunday with friends at Neillsville. Mr. Chas. Neinas and daughter Lydia went to Appleton, Wed., for a weeks visit with Mrs. Mary Peters. Judge O. W. Schoengarth autoed out from Neillsville with his parents and spent Sunday with friends. Mrs. Ernest Kihn of Park Falls attended the funeral of her brother Judson Canfield here last week and remained until Saturday visiting among relatives. Mrs. W. F. Blake of Chicago arrived here on Monday for an extended visit with her mother Mrs. Riedel and other relatives. Try Amidon’s fly dope at my expense. If not satisfied, your money will be refunded. Ila Fraser and her niece Gladys Henning came over from Chili last Saturday and made a several days visit at Geo. Fraser’s. Fred Hart went to Humbird Tuesday and joined his family who went over late last week for a weeks visit among relatives. Mr. and Mrs. Victor Woelffer and little daughters drove out from Neillsville and spent Sunday picnicking with Rev. Reiff’s congregation and their many friends. Chas Neinas, George Rose and Gus Bergeman drove to Greenwood on a business trip, Tuesday. Lew Davis came up from Madison Wednesday morning and will remain until Saturday, when he goes to Montana. Mrs. P. J. Kemmeter entertained the Circle, Wednesday afternoon. Pineapple at Witte’s cheap; get your supply now. Mrs. Laura Brown left on Tuesday for a several weeks visiting and pleasure trip to various Minnesota and Dakota points. Miss Clara Snyder of Milwaukee joined Mr. and Mrs. J. P. Dost here last week Thursday and will accompany them to Minneapolis in a few days. The Mesdames L. H. Howard and W. A. Campman drove over from Neillsville and spent Tuesday here among relatives. Mr. and Mrs. Geo Beaver drove to Loyal Tuesday and attended the wedding of one of Mr. Beaver’s brothers there that day. Nothing like Nyal’s Kidney pill for a lame back, rheumatism, etc., every box guaranteed by Amidon New Idea patterns 10c only at Witte’s Mrs. Geo. Budge, Mrs. Carnupp and daughter Helen of St. Paul came last Friday and spent several days at the W. S. Davis home. Mrs. Norman Pierce came down from Duluth Monday night on a visit to her parents, Mr. and Mrs. T. D. Wage. Miss Margueritha Thiede went to Milwaukee on Wednesday where she is to join friends and with them go to the Atlantic coast to spend the summer. Mr. and Mrs. W.D. Rose will leave today for Sheboygan County on a combination business and pleasure trip. Mr. Rose has secured the agency for a portable bath apparatus and has that county in his territory. Now is the time to use fly dope. Get the best at Amidon’s Drug Store Big Bargains in toilet soap; get your supply as long as the lot lasts, 5c bars Castile soap, 4 for 10c at Witte’s Mrs. Gusta Breed who came home from Chili last week Wednesday has been under the doctor’s care and confined to her bed most of the time since, suffering with heart trouble. Last Saturday night a Royal Neighbor Lodge was constituted here by Mrs. Almira Lapp of Neillsville, the assistant district deputy. Mrs. Sarah Denham of Downsville, district deputy, who visited at W. W. Page’s some two weeks since instituted the lodge at that time. Mrs. Bertha Riedel left Monday for Milwaukee on a visit to relatives and friends. She will stop off at Clintonville to visit Mrs. Leo Moench. Israel Fulwiler a well known and highly respected farmer of the Town of York died last Saturday at the age of 71 years, after being confined to his bed for a long time, suffering from Bright’s disease. Doc Wonser who has been suffering with a fever commonly known as the auto fever, is O. K. at this writing. He purchased a Reo roadster of Len Howard last Monday. Little Marjorie Lapham the other day when she appeared at Marsh’s ice cream parlors with a dime which was 5c more than her daily allowance, was asked how she happened to have so much money, to which she replied in a childish but earnest manner "I guess my grandpa is stuck on me." And nobody doubts it. Otis Slocomb sold his farm in the Town of Grant to a party from Chicago last week. Consideration was $3,000. The farm is at present operated by his brother Austin. The new owner will take possession next fall. Wm. Schaefer who recently bought the Robert Kurth farm has again invested in Town of Grant real estate by purchasing the August Roder farm south of here. We understand Mr. Schafer’s son who is to be married in the near future will occupy this farm. The picnic given by Rev. Reiff’s congregation last Sunday was well attended and greatly enjoyed by all present. The weather was perfect and the rain the night before laid the dust sufficient to put the roads and grounds in perfect condition. These picnics and especially the dinners served there are annually looked for with great anticipation by young and old. For Sale: 40 acre farm in Town of York, 30 acres clear, good buildings. Cheap! Inquire of Wm. Uhlman, Neillsville R. 4. Everyone has its share of troubles, even the man who owns an automobile. The other day when Len Howard was speeding along on a country highway he met a man with horse and buggy, and upon receiving the sign of distress the auto came to a halt and the engine was stopped. "Why", remarked Len as the horse passed the auto without paying the slightest attention to it, "your horse doesn’t seem to be a bit afraid." "No, this one here isn’t afraid, but I got one at home that is," was the man’s reply. Professor Lloyd Davis left last Saturday morning for his home at Red Granite, Wis., after closing his second successful term as principal of our schools. Mr. Davis has decided not to return next fall, a fact very much regretted by his friends, and those who were aware of his ability as a teacher. During his two terms of principal-ship he has brought out school to a degree of perfection and it is hoped that his successor, whoever he may be. will be able to continue the work where Mr. Davis has left it. Mrs. Clemens Kuechenmeister and daughter Anita with little Lillian Hantke went to Eau Claire on Sat. to visit Grandma Hantke and master Irving Kurth. They found master Kurth "Sunshine" very happy and contented, very glad to have this visit with his auntie and little cousins and uncomplainingly bade them good bye at parting, but grandma Hantke was so homesick that they were obliged to bring her home for a few weeks visit when she will return and resume her course of treatment. For Sale: A surrey in good condition. I would take stock in exchange. Frank Lavey Mrs. John Hefty who lives a few miles northwest of here met with a severe accident Wednesday afternoon while assisting her husband in pulling stumps. She was driving the team which in some way became frightened and ran away. Mrs. Hefty got tangled up in the lines and being unable to free herself was dragged about the field and violently thrown against stumps and rocks until the team could be brought to a standstill. A piece of scalp about 6 inches square was severed from her head and besides many other bruises about the body; she suffered also a fracture of the left leg near the hip. Dr. Ross pronounces her condition as serious. Town and school order books, also teacher’s contracts for sale at this office. The Woodmen will give a dance at the Granton Opera House Tuesday evening, June 14 th . Whitcomb’s Orchestra will furnish the music. Invitations are issued to various members of the neighboring camps and each member of this Camp is permitted to invite two friends. Kenneth, the 10 year old son of H. Kelicut about 6 miles south of town suffered a fracture of his left arm Sunday afternoon while playing ball with a number of his comrades. The boy fell and another one accidentally jumped on the arm, thus causing the fracture. Dekko, a new walls’ finish; it is cheap and much better than whitewashing walls. See color card at Amidon’s Monday L. E. Moh sold his beautiful pure bred Percheron Stallion "Avalanche" to Chas. Guk of the Town of Lynn who intends to develop him for breeding purposes. This colt was just one year old on June 2 nd , last week, and weighed exactly 1,000 pounds on that day. He should mature at a ton at 5 years. Farmers keep an eye on him and see him grow. Rev. J. Reiff was pleasantly surprised by a large number of his parishioners and friends at his home last Sunday evening, the occasion being his 40 th birthday. As a token of their esteem they presented him with an elegant office chair purchased of August Hammler. It is needless to say that the evening was enjoyed by all, for Mr. Reiff as well as his better half are very pleasant and capable entertainers, in whose presence anyone is bound to feel at home. Among those present from away were Rev. Kemena and family of Nasonville and Rev. Lange and family of Loyal. While Dr. Schulz was returning home last week Wednesday night he noticed a light in Max Opelt’s store and upon investigation found that burglars were at work within. Securing his shot gun and on returning he noticed three men leaving the store. He commanded them to halt and refusing to do so he opened fire which they promptly returned. In all about 15 shots were exchanged, the burglars finally taking to their heels. So far as could be ascertained, little or nothing was missing from the store. Card of Thanks: We wish to express our thanks for the many courtesies and great kindness shown us by our neighbors and friends through the death of our beloved husband and father. Mrs. Eva Canfield, Mr. and Mrs. Fred Frank, and Howard and Ray Canfield	https://wiclarkcountyhistory.org/3data/74/74119.htm
Effect of Heat Exchange Transient Conditions With Moving Water-Air Interface on Space Charge Accumulation in Undersea HVdc Cables \| Request PDF Request PDF \| Effect of Heat Exchange Transient Conditions With Moving Water-Air Interface on Space Charge Accumulation in Undersea HVdc Cables \| The accumulation of space charge inside the dielectric layer of an HVDC cable is one of the most important issue to be considered in the design... \| Find, read and cite all the research you need on ResearchGate Effect of Heat Exchange Transient Conditions With Moving Water-Air Interface on Space Charge Accumulation in Undersea HVdc Cables IEEE Transactions on Industry Applications PP(99):1-1 DOI: 10.1109/TIA.2021.3099087 Authors: Abstract The accumulation of space charge inside the dielectric layer of an HVDC cable is one of the most important issue to be considered in the design stage and during the operating conditions. The separation of space charge is due to several factors including the dependence on temperature of the electrical conductivity of the insulation and the establishment of a thermal gradient under load conditions. This research is focused on the investigation of the effect of an axial heat transmission on the space charge and electric field distributions in an HVDC cable. In order to assess the impact of this phenomenon, a case study involving a cable immersed partly in water and partly in air has been simulated by means of a 2-D thermal and electrical model in time domain. The electric field calculation is based on the quasi-static Maxwell model and the current continuity equation. To simulate the effect of waves, a moving water-air interface is considered, with time varying sinusoidal law. The results show the establishment of an electrical field peak near the water-air interface due to an increased temperature drop over the insulation in this area. The approach and the findings described in this article attempt to improve the knowledge in the relationship between thermal and electrical phenomena in HVDC cables. Moreover, this article focuses on the advisability of appropriately considering the impact of the axial heat transfer in the standards on the thermal rating of HVDC cables. ... HVdc Cables" [14] . ... ... In particular, attention is focused on local phenomena conditioned both by the temporal variation of the current and by the variation along the axis of the heat exchange conditions between the surface of the cable and the outside. In Figure 1 [14] As it can be seen in Figure 1 As it can be observed from the figures, the maximum electric field value is reached just below the air-water average interface level. ... ... In the case of a cable having a copper core and XLPE insulation, the thermal conductivities are 390 W/(mK) and 0.287 W/(mK) respectively. Therefore, the axial thermal resistance can be approximated as which of the conductor RA that can be calculated as follows [14] : ... PULSED ELECTRO-ACOUSTIC SPACE CHARGE APPARATUS - QUALIFYING, TESTING AND MONITORING OF INSULATION FOR HVDC CABLES AND ACCESSORIES Thesis Full-text available This document refers to the activities carried out in the framework of the PhD with industrial characterization funded from the Italian Ministry of University and Research (MIUR) with scholarship code DOT1320917, CUP B77I18065610001. The activities were aimed to develop a research project called "Pulsed Electro-Acoustic Space Charge Apparatus". This project was focused on the study of the role of space charge accumulation on the reliability and aging of the insulation of HVDC (High Voltage Direct Current) cables and accessories. With this aim, the phenomenon of space charge accumulation was investigated through bibliographic research and through the implementation of models to simulate such phenomena in HVDC cables and accessories in different scenarios. These simulations essentially concerned the study of the effect of axial heat transmission on the achievement of local electric field peaks in HVDC cables and joints as well as the time trend of the electric field during transients such as Polarity Reversal or Transient Over-Voltages. In addition to this, the state-of-the-art of the Pulsed Electro-Acoustic (PEA) method was studied. This technique is considered one of the most reliable for measuring the distribution of space charge. In addition to the bibliographic research on the PEA method, space charge measurements were carried out on both flat and cable samples using commercial equipments at the LEPRE high voltage laboratory of the University of Palermo. Following this study, as part of the collaboration with Prysmian Electronics, the industrial partner of this PhD, an innovative PEA apparatus was designed for measuring the distribution of space charge in flat specimens up to 5 mm thick under temperature gradient. In addition to the design of the PEA cell, a pulse generator suitable for the range of specimens to test as well as the heating and cooling systems of the two surfaces of the sample were designed. In order to evaluate the interaction between space charge and partial discharge phenomena, studies were carried out both by means of models and experimental campaigns. Part of these studies were conducted in cooperation with Chalmers University of Technology using the experience of its staff in the measurement and analysis of partial discharges. The comparison between these experimental and computational results led to optimizing the conductivity models used and improving the predictability of the phenomenon of partial discharges under DC voltage. Predictability of PD inception in defects included in HVDC cables by conductivity models calibrated through experiments Giuseppe Rizzo Vincenzo Li Vigni Antonino Imburgia Guido Ala To date, there are several methods for calculating the electric field distribution within a dielectric layer subjected to HVDC voltage. However, experimental techniques for evaluating the accuracy of models for calculating the electric field, such as space charge measurement, are often not precise enough to be used for this purpose. At the same time, the knowledge of Partial Discharge (PD) phenomenon occurring under HVDC stress is also not as developed as that of PD under HVAC voltage. The main goal of this research is to study the effectiveness of dielectric conductivity models to forecast the inception condition for PD under load and HVDC voltage stress. This study has been carried out by means of comparison between computer simulation and experimental results. The simulations have been carried out by means of a dielectric conductivity model implemented in the FEM software Comsol Multiphysics. The experimental setup consist of a model cable insulated with XLPE with an artificial defect created at the outer surface of the dielectric layer. Although the definition of the electric field inside a cavity is affected by several parameters which are also mutually dependent, the analysis performed demonstrates the predictability of the PD activity within certain voltage and temperature ranges. The Effect of the Axial Heat Transfer on Space Charge Accumulation Phenomena in HVDC Cables Pietro Romano Antonino Imburgia To date, it has been widespread accepted that the presence of space charge within the dielectric of high voltage direct current (HVDC) cables is one of the most relevant issues that limits the growing diffusion of this technology and its use at higher voltages. One of the reasons that leads to the establishment of space charge within the insulation of cables is the temperature dependence of its conductivity. Many researchers have demonstrated that high temperature drop over the insulation layer can lead to the reversal of the electric field profile. In certain conditions, this can over-stress the insulation during polarity reversal (PR) and transient over voltages (TOV) events accelerating the ageing of the dielectric material. However, the reference standards for the thermal rating of cables are mainly thought for alternating current (AC) cables and do not adequately take into account the effects related to high thermal drops over the insulation. In particular, the difference in temperature between the inner and the outer surfaces of the dielectric can be amplified during load transients or near sections with axially varying external thermal conditions. For the reasons above, this research aims to demonstrate how much the existence of “hot points” in terms of temperature drop can weaken the tightness of an HVDC transmission line. In order to investigate these phenomena, a two-dimensional numerical model has been implemented in time domain. The results obtained for some case studies demonstrate that the maximum electric field within the dielectric of an HVDC cable can be significantly increased in correspondence with variations along the axis of the external heat exchange conditions and/or during load transients. This study can be further developed in order to take into account the combined effect of the described phenomena with other sources of introduction, forming, and accumulation of space charge inside the dielectric layer of HVDC cables. Space Charge Accumulation at Material Interfaces in HVDC Cable Insulation Part II—Simulations of Charge Transport	https://www.researchgate.net/publication/353472905_Effect_of_Heat_Exchange_Transient_Conditions_With_Moving_Water-Air_Interface_on_Space_Charge_Accumulation_in_Undersea_HVdc_Cables
PRIME PubMed \| Synthesis and characterization of chitosan oligosaccharide-capped gold nanoparticles as an effective antibiofilm drug against the Pseudomonas aeruginosa PAO1 PubMed journal article: Synthesis and characterization of chitosan oligosaccharide-capped gold nanoparticles as an effective antibiofilm drug against the Pseudomonas aeruginosa PAO1. Download Prime PubMed App to iPhone, iPad, or Android Tags Type your tag names separated by a space and hit enter Synthesis and characterization of chitosan oligosaccharide-capped gold nanoparticles as an effective antibiofilm drug against the Pseudomonas aeruginosa PAO1. Microb Pathog . 2019 Oct; 135:103623. MP Abstract The infection caused by Pseudomonas aeruginosa is a serious concern in human health. The bacterium is an opportunistic pathogen which has been reported to cause nosocomial and chronic infections through biofilm formation and synthesis of several toxins and virulence factors. Furthermore, the formation of biofilm by P. aeruginosa is known as one of the resistance mechanisms against conventional antibiotics. Natural compounds from marine resources have become one of the simple, cost-effective, biocompatible and non-toxicity for treating P. aeruginosa biofilm-related infections. Furthermore, hybrid formulation with nanomaterials such as nanoparticles becomes an effective alternative strategy to minimize the drug toxicity problem and cytotoxicity properties. For this reason, the present study has employed chitosan oligosaccharide for the synthesis of chitosan oligosaccharide-capped gold nanoparticles (COS-AuNPs). The synthesized COS-AuNPs were then characterized by using UV-Visible spectroscopy, Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), Field emission transmission electron microscopy (FE-TEM), and Energy dispersive X-ray diffraction (EDX). The synthesized COS-AuNPs were applied for inhibiting P. aeruginosa biofilm formation. Results have shown that COS-AuNPs exhibited inhibition to biofilm as well as eradication to pre-existing mature biofilm. Simultaneously, COS-AuNPs were also able to reduce bacterial hemolysis and different virulence factors produced by P. aeruginosa. Overall, the present study concluded that the hybrid nanoformulation such as COS-AuNPs could act as a potential agent to exhibit inhibitory properties against the P. aeruginosa pathogenesis arisen from biofilm formation. Links Publisher Full Text (DOI) Authors +Show Affiliations Khan F Marine-Integrated Bionics Research Center, Pukyong National University, Busan, 48513, Republic of Korea. Lee JW Department of Food Science and Technology, Pukyong National University, Busan, 48513, Republic of Korea. Manivasagan P Marine-Integrated Bionics Research Center, Pukyong National University, Busan, 48513, Republic of Korea. Pham DTN Department of Food Science and Technology, Pukyong National University, Busan, 48513, Republic of Korea. Oh J Marine-Integrated Bionics Research Center, Pukyong National University, Busan, 48513, Republic of Korea; Department of Biomedical Engineering, Pukyong National University, Busan, 48513, Republic of Korea. Kim YM Marine-Integrated Bionics Research Center, Pukyong National University, Busan, 48513, Republic of Korea; Department of Food Science and Technology, Pukyong National University, Busan, 48513, Republic of Korea. Electronic address: [email protected]. MeSH Anti-Bacterial Agents Biofilms Chitosan Gold Kinetics Metal Nanoparticles Microbial Sensitivity Tests Microscopy, Electron, Transmission Oligosaccharides Particle Size Pseudomonas aeruginosa Spectroscopy, Fourier Transform Infrared Virulence Factors X-Ray Diffraction Pub Type(s) Journal Article Language eng PubMed ID 31325574 Citation Khan, Fazlurrahman, et al. "Synthesis and Characterization of Chitosan Oligosaccharide-capped Gold Nanoparticles as an Effective Antibiofilm Drug Against the Pseudomonas Aeruginosa PAO1." Microbial Pathogenesis, vol. 135, 2019, p. 103623. Khan F, Lee JW, Manivasagan P, et al. Synthesis and characterization of chitosan oligosaccharide-capped gold nanoparticles as an effective antibiofilm drug against the Pseudomonas aeruginosa PAO1. Microb Pathog . 2019;135:103623. Khan, F., Lee, J. W., Manivasagan, P., Pham, D. T. N., Oh, J., & Kim, Y. M. (2019). Synthesis and characterization of chitosan oligosaccharide-capped gold nanoparticles as an effective antibiofilm drug against the Pseudomonas aeruginosa PAO1. Microbial Pathogenesis , 135 , 103623. https://doi.org/10.1016/j.micpath.2019.103623 Khan F, et al. Synthesis and Characterization of Chitosan Oligosaccharide-capped Gold Nanoparticles as an Effective Antibiofilm Drug Against the Pseudomonas Aeruginosa PAO1. Microb Pathog. 2019;135:103623. PubMed PMID: 31325574. * Article titles in AMA citation format should be in sentence-case Copy Download MLA AMA APA VANCOUVER TY - JOUR T1 - Synthesis and characterization of chitosan oligosaccharide-capped gold nanoparticles as an effective antibiofilm drug against the Pseudomonas aeruginosa PAO1. AU - Khan,Fazlurrahman, AU - Lee,Jang-Won, AU - Manivasagan,Panchanathan, AU - Pham,Dung Thuy Nguyen, AU - Oh,Junghwan, AU - Kim,Young-Mog, Y1 - 2019/07/17/ PY - 2019/05/03/received PY - 2019/06/14/revised PY - 2019/07/16/accepted PY - 2019/7/22/pubmed PY - 2020/1/14/medline PY - 2019/7/21/entrez KW - Antibiofilm KW - Chitosan oligosaccharide KW - Nanoparticles KW - P. aeruginosa KW - Pathogen KW - Virulence SP - 103623 EP - 103623 JF - Microbial pathogenesis JO - Microb Pathog VL - 135 N2 - The infection caused by Pseudomonas aeruginosa is a serious concern in human health. The bacterium is an opportunistic pathogen which has been reported to cause nosocomial and chronic infections through biofilm formation and synthesis of several toxins and virulence factors. Furthermore, the formation of biofilm by P. aeruginosa is known as one of the resistance mechanisms against conventional antibiotics. Natural compounds from marine resources have become one of the simple, cost-effective, biocompatible and non-toxicity for treating P. aeruginosa biofilm-related infections. Furthermore, hybrid formulation with nanomaterials such as nanoparticles becomes an effective alternative strategy to minimize the drug toxicity problem and cytotoxicity properties. For this reason, the present study has employed chitosan oligosaccharide for the synthesis of chitosan oligosaccharide-capped gold nanoparticles (COS-AuNPs). The synthesized COS-AuNPs were then characterized by using UV-Visible spectroscopy, Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), Field emission transmission electron microscopy (FE-TEM), and Energy dispersive X-ray diffraction (EDX). The synthesized COS-AuNPs were applied for inhibiting P. aeruginosa biofilm formation. Results have shown that COS-AuNPs exhibited inhibition to biofilm as well as eradication to pre-existing mature biofilm. Simultaneously, COS-AuNPs were also able to reduce bacterial hemolysis and different virulence factors produced by P. aeruginosa. Overall, the present study concluded that the hybrid nanoformulation such as COS-AuNPs could act as a potential agent to exhibit inhibitory properties against the P. aeruginosa pathogenesis arisen from biofilm formation. SN - 1096-1208 UR - https://www.unboundmedicine.com/medline/citation/31325574/Synthesis_and_characterization_of_chitosan_oligosaccharide_capped_gold_nanoparticles_as_an_effective_antibiofilm_drug_against_the_Pseudomonas_aeruginosa_PAO1_ DB - PRIME DP - Unbound Medicine ER - Grapherence [↓21] Links Publisher Full Text (DOI) Authors Khan F Lee JW Manivasagan P Pham DTN Oh J Kim YM MESH Anti-Bacterial Agents Biofilms Chitosan Gold Kinetics Metal Nanoparticles Microbial Sensitivity Tests Microscopy, Electron, Transmission Oligosaccharides Particle Size Pseudomonas aeruginosa Spectroscopy, Fourier Transform Infrared Virulence Factors X-Ray Diffraction 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 [↓21] Related Citations Fucoidan-Stabilized Gold Nanoparticle-Mediated Biofilm Inhibition, Attenuation of Virulence and Motility Properties in Pseudomonas aeruginosa PAO1. Facile green synthesis of baicalein fabricated gold nanoparticles and their antibiofilm activity against Pseudomonas aeruginosa PAO1. Phloroglucinol-Gold and -Zinc Oxide Nanoparticles: Antibiofilm and Antivirulence Activities towards Pseudomonasaeruginosa PAO1. Green synthesis of gold and silver nanoparticles from Cannabis sativa (industrial hemp) and their capacity for biofilm inhibition. Ecofriendly synthesis of silver and gold nanoparticles by Euphrasia officinalis leaf extract and its biomedical applications. Green synthesis of anisotropic gold nanoparticles using hordenine and their antibiofilm efficacy against Pseudomonas aeruginosa. Caffeine-loaded gold nanoparticles: antibiofilm and anti-persister activities against pathogenic bacteria. A novel antimicrobial therapy for the control of Aeromonas hydrophila infection in aquaculture using marine polysaccharide coated gold nanoparticle. Microwave-Assisted Rapid Green Synthesis of Gold Nanoparticles Using Seed Extract of Trachyspermum ammi: ROS Mediated Biofilm Inhibition and Anticancer Activity. The assessment of antibiofilm activity of chitosan-zinc oxide-gentamicin nanocomposite on Pseudomonas aeruginosa and Staphylococcus aureus. More Home Contact Us Help Privacy / Disclaimer Terms of Service Sign In	https://www.unboundmedicine.com/medline/citation/31325574/Synthesis_and_characterization_of_chitosan_oligosaccharide_capped_gold_nanoparticles_as_an_effective_antibiofilm_drug_against_the_Pseudomonas_aeruginosa_PAO1_
Directive 2004/18/EC of the European Parliament and of the Council of 31 March 2004 on the coordination of procedures for the award of public works contracts, public supply contracts and public service contracts (repealed) Directive 2004/18/EC of the European Parliament and of the Council of 31 March 2004 on the coordination of procedures for the award of public works contracts, public supply contracts and public service contracts (repealed) Table of Contents Content More Resources More Resources Access essential accompanying documents and information for this legislation item from this tab. 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Textual Amendments applied to the whole legislation F1 Repealed by Directive 2014/24/EU of the European Parliament and of the Council of 26 February 2014 on public procurement and repealing Directive 2004/18/EC (Text with EEA relevance) . Previous: Division Next: Division Back to top Options/Help You have chosen to open the Whole Directive The Whole Directive you have selected contains over 200 provisions and might take some time to download. You may also experience some issues with your browser, such as an alert box that a script is taking a long time to run. Would you like to continue? Cancel Continue to open You have chosen to open Schedules only The Schedules you have selected contains over 200 provisions and might take some time to download. You may also experience some issues with your browser, such as an alert box that a script is taking a long time to run. Would you like to continue? 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View our list of partners to see the purposes they believe they have legitimate interest for and how you can object to it. Find out more about how your personal data is processed and set your preferences below. Purposes 12 You can set your consent preferences and determine how you want your data to be used based on the purposes below. Each purpose has a description so that you know how we and our partners use your data. You can object to legitimate interest processing per purpose. Purposes 10 Accept all Reject all Store and/or access information on a device Vendors can: Store and access information on the device such as cookies and device identifiers presented to a user. Select basic ads Legitimate Interest To do basic ad selection vendors can: Use real-time information about the context in which the ad will be shown, to show the ad, including information about the content and the device, such as: device type and capabilities, user agent, URL, IP address Use a user’s non-precise geolocation data Control the frequency of ads shown to a user. Sequence the order in which ads are shown to a user. Prevent an ad from serving in an unsuitable editorial (brand-unsafe) context Vendors cannot: Create a personalised ads profile using this information for the selection of future ads without a separate legal basis to create a personalised ads profile. N.B. Non-precise means only an approximate location involving at least a radius of 500 meters is permitted. Create a personalised ads profile Legitimate Interest To create a personalised ads profile vendors can: Collect information about a user, including a user's activity, interests, demographic information, or location, to create or edit a user profile for use in personalised advertising. Combine this information with other information previously collected, including from across websites and apps, to create or edit a user profile for use in personalised advertising. Select personalised ads Legitimate Interest To select personalised ads vendors can: Select personalised ads based on a user profile or other historical user data, including a user’s prior activity, interests, visits to sites or apps, location, or demographic information. Create a personalised content profile Legitimate Interest To create a personalised content profile vendors can: Collect information about a user, including a user's activity, interests, visits to sites or apps, demographic information, or location, to create or edit a user profile for personalising content. Combine this information with other information previously collected, including from across websites and apps, to create or edit a user profile for use in personalising content. Select personalised content Legitimate Interest To select personalised content vendors can: Select personalised content based on a user profile or other historical user data, including a user’s prior activity, interests, visits to sites or apps, location, or demographic information. Measure ad performance Legitimate Interest To measure ad performance vendors can: Measure whether and how ads were delivered to and interacted with by a user Provide reporting about ads including their effectiveness and performance Provide reporting about users who interacted with ads using data observed during the course of the user's interaction with that ad Provide reporting to publishers about the ads displayed on their property Measure whether an ad is serving in a suitable editorial environment (brand-safe) context Determine the percentage of the ad that had the opportunity to be seen and the duration of that opportunity Combine this information with other information previously collected, including from across websites and apps Vendors cannot: *Apply panel- or similarly-derived audience insights data to ad measurement data without a Legal Basis to apply market research to generate audience insights (Purpose 9) Measure content performance Legitimate Interest To measure content performance vendors can: Measure and report on how content was delivered to and interacted with by users. Provide reporting, using directly measurable or known information, about users who interacted with the content Combine this information with other information previously collected, including from across websites and apps. Vendors cannot: Measure whether and how ads (including native ads) were delivered to and interacted with by a user. Apply panel- or similarly derived audience insights data to ad measurement data without a Legal Basis to apply market research to generate audience insights (Purpose 9) Apply market research to generate audience insights Legitimate Interest To apply market research to generate audience insights vendors can: Provide aggregate reporting to advertisers or their representatives about the audiences reached by their ads, through panel-based and similarly derived insights. Provide aggregate reporting to publishers about the audiences that were served or interacted with content and/or ads on their property by applying panel-based and similarly derived insights. Associate offline data with an online user for the purposes of market research to generate audience insights if vendors have declared to match and combine offline data sources (Feature 1) Combine this information with other information previously collected including from across websites and apps. Vendors cannot: Measure the performance and effectiveness of ads that a specific user was served or interacted with, without a Legal Basis to measure ad performance. Measure which content a specific user was served and how they interacted with it, without a Legal Basis to measure content performance. Develop and improve products Legitimate Interest To develop new products and improve products vendors can: Use information to improve their existing products with new features and to develop new products Create new models and algorithms through machine learning Vendors cannot: Conduct any other data processing operation allowed under a different purpose under this purpose Special Purposes 2 Ensure security, prevent fraud, and debug To ensure security, prevent fraud and debug vendors can: Ensure data are securely transmitted Detect and prevent malicious, fraudulent, invalid, or illegal activity. Ensure correct and efficient operation of systems and processes, including to monitor and enhance the performance of systems and processes engaged in permitted purposes Vendors cannot: Conduct any other data processing operation allowed under a different purpose under this purpose. Note: Data collected and used to ensure security, prevent fraud, and debug may include automatically-sent device characteristics for identification, precise geolocation data, and data obtained by actively scanning device characteristics for identification without separate disclosure and/or opt-in. Technically deliver ads or content To deliver information and respond to technical requests vendors can: Use a user’s IP address to deliver an ad over the internet Respond to a user’s interaction with an ad by sending the user to a landing page Use a user’s IP address to deliver content over the internet Respond to a user’s interaction with content by sending the user to a landing page Use information about the device type and capabilities for delivering ads or content, for example, to deliver the right size ad creative or video file in a format supported by the device Vendors cannot: Conduct any other data processing operation allowed under a different purpose under this purpose Features 4 View the required features enabled for the processing of personal data and opt-in separately for any special features. Features 3 Match and combine offline data sources Vendors can: Combine data obtained offline with data collected online in support of one or more Purposes or Special Purposes. Link different devices Vendors can: Deterministically determine that two or more devices belong to the same user or household Probabilistically determine that two or more devices belong to the same user or household Actively scan device characteristics for identification for probabilistic identification if users have allowed vendors to actively scan device characteristics for identification (Special Feature 2) Receive and use automatically-sent device characteristics for identification Vendors can: Create an identifier using data collected automatically from a device for specific characteristics, e.g. IP address, user-agent string. Use such an identifier to attempt to re-identify a device. Vendors cannot: Create an identifier using data collected via actively scanning a device for specific characteristics, e.g. installed font or screen resolution without users’ separate opt-in to actively scanning device characteristics for identification. Use such an identifier to re-identify a device. Special Features 1 Accept all Reject all Use precise geolocation data Vendors can: Collect and process precise geolocation data in support of one or more purposes. N.B. Precise geolocation means that there are no restrictions on the precision of a user’s location; this can be accurate to within several meters. Partners 140 See the partners we work with below. Expand each one to see how they process your data. You can object to legitimate interest processing per vendor. Third Party Vendors 140 Accept all Reject all : Tappx Privacy policy: https://www.tappx.com/en/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Select personalised ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Link different devices Special Features: Use precise geolocation data Your Consent: Consent expiry: 3 hours Tracking method: Cookies only Show details Active Agent (Virtual Minds GmbH) Privacy policy: https://www.adition.com/en/privacy-platform Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details AcuityAds Inc. Legitimate Interest Privacy policy: https://privacy.acuityads.com/corporate-privacy-policy.html Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Measure content performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Link different devices Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details adbility media GmbH Privacy policy: https://www.adbility-media.com/datenschutz Purposes (Consent): Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Your Consent: Consent expiry: 1 year Tracking method: Cookies only Show details AdDefend GmbH Privacy policy: https://www.addefend.com/en/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 30 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Adex (Virtual Minds GmbH) Privacy policy: https://theadex.com/privacy-platform/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 90 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Adform A/S Legitimate Interest Privacy policy: https://site.adform.com/privacy-center/platform-privacy/product-and-services-privacy-policy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 hour 50 seconds Tracking method: Cookies only Show details ADITION (Virtual Minds GmbH) Privacy policy: https://www.adition.com/en/privacy-platform Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Adnami Aps Legitimate Interest Privacy policy: https://www.adnami.io/privacy-policy-services Purposes (Legitimate Interest): Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Tracking method: Cookies only Show details Adnuntius AS Privacy policy: https://adnuntius.com/resources/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 6 years 295 days 12 hours 19 minutes 24 seconds Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details adrule mobile GmbH Privacy policy: https://www.adrule.net/de/datenschutz/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Adtriba GmbH Privacy policy: https://privacy.adtriba.com/ Purposes (Consent): Store and/or access information on a device Measure ad performance Measure content performance Features: Link different devices Your Consent: Consent expiry: 2 years Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details advanced store GmbH Legitimate Interest Privacy policy: https://www.advanced-store.com/en/data-privacy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details ADYOULIKE SA Legitimate Interest Privacy policy: https://www.adyoulike.com/pages/privacy Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Amazon Advertising Privacy policy: https://www.amazon.co.uk/gp/help/customer/display.html?nodeId=201909010 Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 1 year 30 days 17 hours 13 minutes 20 seconds Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Amobee Inc. Legitimate Interest Privacy policy: https://www.amobee.com/trust/gdpr/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 180 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Arbeitsgemeinschaft Media-Analyse Privacy policy: https://www.agma-mmc.de/datenschutz Purposes (Consent): Store and/or access information on a device Apply market research to generate audience insights Features: Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year 1 day Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details AudienceProject Aps Legitimate Interest Privacy policy: https://privacy.audienceproject.com Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Purposes (Legitimate Interest): Select basic ads Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Avantis Video Ltd Privacy policy: https://www.avantisvideo.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Special Purposes: Ensure security, prevent fraud, and debug Your Consent: Consent expiry: 1 year Tracking method: Cookies and others Show details Axel Springer Teaser Ad GmbH Legitimate Interest Privacy policy: https://www.adup-tech.com/privacy Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details bam! interactive marketing GmbH Privacy policy: https://bam-interactive.de/datenschutz/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 day Tracking method: Cookies only Show details Bannernow, Inc. Legitimate Interest Privacy policy: https://bannernow.com/privacy Purposes (Consent): Store and/or access information on a device Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Your Consent: Tracking method: Cookies only Show details BCOVERY SAS Legitimate Interest Privacy policy: https://www.bcovery.com/politique-de-confidentialite.html Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Measure content performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Special Features: Use precise geolocation data Your Consent: Tracking method: Cookies and others Show details Better Ads GmbH Legitimate Interest Privacy policy: https://www.d3sv.net/privacy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 60 days Tracking method: Cookies only Show details BIDSWITCH GmbH Privacy policy: https://www.bidswitch.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Blis Global Limited Privacy policy: https://blis.com/blis-privacy-policy-for-online-advertising-and-related-uses/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year 35 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Cloud Technologies S.A. Privacy policy: https://www.cloudtechnologies.pl/en/internet-advertising-privacy-policy Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details communicationAds GmbH & Co. KG Legitimate Interest Privacy policy: https://www.communicationads.net/de-de/ueberuns/datenschutz/ Purposes (Consent): Store and/or access information on a device Purposes (Legitimate Interest): Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Your Consent: Consent expiry: 90 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Confiant Inc. Privacy policy: https://www.confiant.com/privacy Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Tracking method: Cookies only Show details Criteo SA Privacy policy: https://www.criteo.com/privacy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year 25 days Tracking method: Cookies and others Show details dataXtrade GmbH Privacy policy: https://dataxtrade.com/de/privacy.html Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details DEFINE MEDIA GMBH Legitimate Interest Privacy policy: https://www.definemedia.de/datenschutz-conative/ Purposes (Consent): Store and/or access information on a device Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Tracking method: Cookies and others Show details Delta Projects AB Legitimate Interest Privacy policy: https://deltaprojects.com/data-collection-policy Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Tracking method: Cookies only Show details DoubleVerify Inc. Legitimate Interest Privacy policy: https://doubleverify.com/privacy-notice/solutions-privacy-notice Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Tracking method: Cookies only Show details Dynata LLC Privacy policy: https://www.dynataprivacy.com/ Purposes (Consent): Store and/or access information on a device Measure ad performance Apply market research to generate audience insights Features: Match and combine offline data sources Link different devices Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details EASYmedia GmbH Privacy policy: https://login.rtbmarket.com/gdpr Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Emerse Sverige AB Legitimate Interest Privacy policy: https://www.emerse.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Measure content performance Apply market research to generate audience insights Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Your Consent: Consent expiry: 30 days Tracking method: Cookies only Show details Exactag GmbH Privacy policy: https://exactag.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Measure ad performance Measure content performance Special Purposes: Ensure security, prevent fraud, and debug Features: Link different devices Your Consent: Consent expiry: 180 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Exit Bee Limited Privacy policy: https://www.exitbee.com/privacy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Measure ad performance Develop and improve products Your Consent: Consent expiry: 1 year Tracking method: Cookies and others Show details Factor Eleven GmbH Privacy policy: https://www.factor-eleven.de/datenschutz/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Apply market research to generate audience insights Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 30 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details FeedAd GmbH Legitimate Interest Privacy policy: https://feedad.com/privacy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure content performance Apply market research to generate audience insights Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 30 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Flashtalking, Inc. Privacy policy: https://www.flashtalking.com/privacypolicy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Features: Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 2 years Tracking method: Cookies only Show details GeoEdge Legitimate Interest Privacy policy: https://www.geoedge.com/privacy-policy/ Purposes (Legitimate Interest): Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Features: Match and combine offline data sources Your Consent: Tracking method: Cookies only Show details GfK SE Privacy policy: https://help.sensic.net/privacypolicy_en.html Purposes (Consent): Store and/or access information on a device Measure ad performance Measure content performance Apply market research to generate audience insights Features: Link different devices Your Consent: Consent expiry: 2 years Tracking method: Cookies and others Show details glomex GmbH Legitimate Interest Privacy policy: https://www.glomex.com/en/privacy-policy/privacy-notice-for-the-glomex-player/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Select personalised content Apply market research to generate audience insights Purposes (Legitimate Interest): Select basic ads Measure ad performance Measure content performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Tracking method: Cookies and others Show details Google Advertising Products Legitimate Interest Privacy policy: https://business.safety.google/privacy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Create a personalised content profile Select personalised content Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Your Consent: Consent expiry: 1 year 30 days 17 hours 13 minutes 20 seconds Tracking method: Cookies and others Show details GumGum, Inc. Privacy policy: https://www.gumgum.com/terms-and-policies/privacy-policy Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year Tracking method: Cookies only Show details Hearts and Science München GmbH Privacy policy: https://www.nonstoppartner.net Purposes (Consent): Store and/or access information on a device Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 60 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details ID5 Technology Ltd Privacy policy: https://id5.io/privacy Purposes (Consent): Store and/or access information on a device Features: Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 90 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Impactify SARL Privacy policy: https://impactify.io/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 30 days Tracking method: Cookies and others Show details Improve Digital Legitimate Interest Privacy policy: https://www.improvedigital.com/platform-privacy-policy Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Apply market research to generate audience insights Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 90 days Tracking method: Cookies only Show details Index Exchange, Inc. Privacy policy: https://www.indexexchange.com/privacy Purposes (Consent): Store and/or access information on a device Select basic ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year 30 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details INFOnline GmbH Privacy policy: https://www.infonline.de/en/privacy-policy/ Purposes (Consent): Store and/or access information on a device Measure content performance Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Inskin Media LTD Legitimate Interest Privacy policy: https://www.inskinmedia.com/privacy-policy.html Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Apply market research to generate audience insights Develop and improve products Purposes (Legitimate Interest): Select basic ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year 1 day Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Integral Ad Science, Inc. Legitimate Interest Privacy policy: https://integralads.com/ias-privacy-data-management/policies/ Purposes (Legitimate Interest): Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Your Consent: Tracking method: Cookies only Show details INVIBES GROUP Legitimate Interest Privacy policy: https://www.invibes.com/terms Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Apply market research to generate audience insights Purposes (Legitimate Interest): Select basic ads Measure ad performance Measure content performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Jaduda GmbH Legitimate Interest Privacy policy: https://www.splicky.com/en/web/privacy-delivery Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 30 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Justpremium BV Legitimate Interest Privacy policy: https://justpremium.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Select personalised ads Develop and improve products Purposes (Legitimate Interest): Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Kayzen Legitimate Interest Privacy policy: https://kayzen.io/data-privacy-policy Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Apply market research to generate audience insights Develop and improve products Purposes (Legitimate Interest): Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Receive and use automatically-sent device characteristics for identification Your Consent: Tracking method: Cookies only Show details LiquidM Technology GmbH Privacy policy: https://liquidm.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details LiveRamp Privacy policy: https://liveramp.fr/iab-transparency-consent-framework/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Lucid Holdings, LLC Privacy policy: https://luc.id/privacy-policy/ Purposes (Consent): Store and/or access information on a device Measure ad performance Measure content performance Apply market research to generate audience insights Special Purposes: Ensure security, prevent fraud, and debug Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 2 years Tracking method: Cookies only Show details Magnite, Inc. Legitimate Interest Privacy policy: https://www.magnite.com/legal/advertising-technology-privacy-policy/ Purposes (Consent): Store and/or access information on a device Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Tracking method: Cookies and others Show details Mediakeys Platform Privacy policy: https://mediakeys.io/fr/privacy-cookies-policy Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Select personalised content Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Special Features: Use precise geolocation data Your Consent: Tracking method: Cookies and others Show details MediaMath, Inc. Legitimate Interest Privacy policy: https://www.mediamath.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year 28 days Tracking method: Cookies and others Show details MindTake Research GmbH Privacy policy: https://www.mindtake.com/en/reppublika-privacy-policy Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Features: Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 180 days Tracking method: Cookies and others Show details MiQ Digital Ltd Privacy policy: https://www.wearemiq.com/privacy-and-compliance/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year 1 hour 6 minutes 40 seconds Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Mobile Professionals BV / Sage&Archer BV Privacy policy: https://mobpro.com/privacy.html Purposes (Consent): Store and/or access information on a device Select basic ads Measure ad performance Features: Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Tracking method: Cookies only Show details Mobkoi Ltd Legitimate Interest Privacy policy: https://www.mobkoi.com/advertising-platform-privacy-policy/ Purposes (Legitimate Interest): Select basic ads Develop and improve products Special Purposes: Technically deliver ads or content Your Consent: Tracking method: Cookies only Show details Monet Engine Inc Privacy policy: https://adaptmx.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Measure ad performance Your Consent: Consent expiry: 1 year Tracking method: Cookies and others Show details NEORY GmbH Privacy policy: https://www.neory.com/privacy.html Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 90 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Next Millennium Media INC Privacy policy: https://nextmillennium.io/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Measure content performance Special Purposes: Technically deliver ads or content Features: Match and combine offline data sources Your Consent: Consent expiry: 10 hours Tracking method: Cookies only Show details Nielsen International SA Legitimate Interest Privacy policy: https://www.nielsen.com/eu/en/legal/privacy-statement/digital-measurement/ Purposes (Consent): Store and/or access information on a device Purposes (Legitimate Interest): Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year 25 days Tracking method: Cookies and others Show details Objective Partners BV Privacy policy: https://www.objectiveplatform.com/cookie-policy-and-privacy-statement/ Purposes (Consent): Store and/or access information on a device Measure ad performance Your Consent: Consent expiry: 90 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Ogury Ltd. Legitimate Interest Privacy policy: https://www.ogury.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Purposes (Legitimate Interest): Select basic ads Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details One Tech Group GmbH Privacy policy: https://onetech.group/en/privacy-policy Purposes (Consent): Store and/or access information on a device Select basic ads Measure ad performance Your Consent: Consent expiry: 1 year Tracking method: Cookies only Show details Onfocus (Adagio) Privacy policy: https://adagio.io/privacy Purposes (Consent): Store and/or access information on a device Select basic ads Measure ad performance Measure content performance Special Features: Use precise geolocation data Your Consent: Consent expiry: 60 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Online Media Solutions LTD (BDA: Brightcom) Privacy policy: https://www.brightcom.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Measure ad performance Measure content performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Features: Receive and use automatically-sent device characteristics for identification Your Consent: Tracking method: Cookies only Show details Online Solution Privacy policy: https://adsafety.net/privacy.html Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details OnProspects Ltd Privacy policy: https://onprospects.com/privacy-policy Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details OpenX Legitimate Interest Privacy policy: https://www.openx.com/legal/privacy-policy/ Purposes (Consent): Store and/or access information on a device Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Opinary GmbH Privacy policy: https://opinary.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 60 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Opti Digital SAS Legitimate Interest Privacy policy: https://www.optidigital.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Measure ad performance Develop and improve products Special Purposes: Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 2 years Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details optimise-it GmbH Legitimate Interest Privacy policy: https://optimise-it.de/datenschutz Purposes (Consent): Store and/or access information on a device Purposes (Legitimate Interest): Measure content performance Your Consent: Consent expiry: Session Tracking method: Cookies and others Show details Oracle Data Cloud - Moat Privacy policy: https://www.oracle.com/legal/privacy/services-privacy-policy.html Special Purposes: Ensure security, prevent fraud, and debug Your Consent: Tracking method: Cookies only Show details Otto (GmbH & Co KG) Legitimate Interest Privacy policy: https://www.otto.de/shoppages/service/datenschutz Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Measure ad performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Permodo GmbH Privacy policy: https://permodo.com/de/privacy.html Purposes (Consent): Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Tracking method: Cookies only Show details Platform161 B.V. Privacy policy: https://verve.com/dsp-cookies-privacy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year 30 days 10 hours Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Playhill Limited Legitimate Interest Privacy policy: https://playhill.com/privacy Purposes (Consent): Store and/or access information on a device Purposes (Legitimate Interest): Select basic ads Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 30 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Publicis Media GmbH Privacy policy: https://www.publicismedia.de/datenschutz/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 90 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details PubMatic, Inc Legitimate Interest Privacy policy: https://pubmatic.com/legal/privacy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Purposes (Legitimate Interest): Select basic ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 90 days Tracking method: Cookies and others Show details Pure Local Media GmbH Privacy policy: https://purelocalmedia.de/?page_id=593 Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Apply market research to generate audience insights Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Features: Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 90 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Quality Media Network GmbH Privacy policy: https://www.qualitymedianetwork.de/datenschutz/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Apply market research to generate audience insights Your Consent: Consent expiry: 300 days Tracking method: Cookies only Show details Readpeak Oy Legitimate Interest Privacy policy: https://readpeak.com/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Purposes (Legitimate Interest): Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 90 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Reppublika Data Analytics and Technologies GmbH Privacy policy: https://www.reppublika.com/privacy-policy Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Features: Link different devices Receive and use automatically-sent device characteristics for identification Your Consent: Consent expiry: 180 days Tracking method: Cookies and others Show details Roq.ad Inc. Privacy policy: https://www.roq.ad/privacy-policy Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Apply market research to generate audience insights Develop and improve products Features: Match and combine offline data sources Link different devices Receive and use automatically-sent device characteristics for identification Special Features: Use precise geolocation data Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details RTB House S.A. Privacy policy: https://www.rtbhouse.com/privacy-center/services-privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Your Consent: Consent expiry: 1 year Tracking method: Cookies and others Show details Salesforce.com, Inc. Privacy policy: https://www.salesforce.com/company/privacy/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Create a personalised content profile Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Features: Match and combine offline data sources Link different devices Your Consent: Consent expiry: 180 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies and others Show details Seeding Alliance GmbH Legitimate Interest Privacy policy: https://seeding-alliance.de/datenschutz/ Purposes (Consent): Store and/or access information on a device Create a personalised ads profile Select personalised ads Create a personalised content profile Select personalised content Purposes (Legitimate Interest): Select basic ads Measure ad performance Measure content performance Apply market research to generate audience insights Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Special Features: Use precise geolocation data Your Consent: Consent expiry: 180 days Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Seedtag Advertising S.L Privacy policy: https://www.seedtag.com/en/privacy-policy/ Purposes (Consent): Store and/or access information on a device Select basic ads Create a personalised ads profile Select personalised ads Measure ad performance Develop and improve products Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 1 year Cookie expiry may be refreshed during the lifetime. Tracking method: Cookies only Show details Sharethrough, Inc Legitimate Interest Privacy policy: https://www.sharethrough.com/privacy-center/consumer-privacy-notice Purposes (Consent): Store and/or access information on a device Select basic ads Purposes (Legitimate Interest): Measure ad performance Special Purposes: Ensure security, prevent fraud, and debug Technically deliver ads or content Your Consent: Consent expiry: 30 days Cookie expiry may be refreshed during the lifetime. 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Buildings \| Free Full-Text \| Natural and Mechanical Ventilation Concepts for Indoor Comfort and Well-Being with a Sustainable Design Perspective: A Systematic Review Current literature and guidelines on sustainable design often debate on the advantages of natural ventilation (NV) and mechanical ventilation (MV) on indoor environment and energy consumption. The present systematic review explores the existing literature comparing NV and MV on the indoor comfort and well-being points of view. The findings emphasize that thermo-hygrometric comfort is the main driver of occupants’ ventilation behavior, while ventilation design is mainly led by indoor air quality targets. Moreover, more recent papers (especially after COVID-19 outbreak) emphasize the necessity of a health-based approach, contrasting airborne pathogens transmission. In this sense, MV is more frequently recommended in public spaces, while hybrid ventilation (HV) is often suggested as a solution to both ensure proper indoor conditions and energy savings. The concept of well-being is currently under-explored, as the present literature only refers to comfort. The same happens with topics such as visual, acoustic, and multi-domain comfort, as well as passive techniques such as night cooling, or analysis of specific environments such as healthcare facilities. Current knowledge would benefit from an expansion of future research in these directions. The choice of the best ventilation solution cannot ignore the context, type, and condition of energy efficient buildings, in order to properly take into account occupants’ well-being. Natural and Mechanical Ventilation Concepts for Indoor Comfort and Well-Being with a Sustainable Design Perspective: A Systematic Review by Luca Zaniboni 1,2,* and Rossano Albatici 1 1 Department of Civil, Environmental and Mechanical Engineering, University of Trento, Via Mesiano 77, 38123 Trento, Italy 2 Department of Environmental and Resource Engineering, Indoor Environment, Technical University of Denmark, Koppels Allé, 402, 231, 2800 Kongens Lyngby, Denmark * Author to whom correspondence should be addressed. Buildings 2022 , 12 (11), 1983; https://doi.org/10.3390/buildings12111983 Received: 18 October 2022 / Revised: 2 November 2022 / Accepted: 10 November 2022 / Published: 15 November 2022 (This article belongs to the Special Issue Energy Use and Comfort of the Built Environment ) Abstract : Current literature and guidelines on sustainable design often debate on the advantages of natural ventilation (NV) and mechanical ventilation (MV) on indoor environment and energy consumption. The present systematic review explores the existing literature comparing NV and MV on the indoor comfort and well-being points of view. The findings emphasize that thermo-hygrometric comfort is the main driver of occupants’ ventilation behavior, while ventilation design is mainly led by indoor air quality targets. Moreover, more recent papers (especially after COVID-19 outbreak) emphasize the necessity of a health-based approach, contrasting airborne pathogens transmission. In this sense, MV is more frequently recommended in public spaces, while hybrid ventilation (HV) is often suggested as a solution to both ensure proper indoor conditions and energy savings. The concept of well-being is currently under-explored, as the present literature only refers to comfort. The same happens with topics such as visual, acoustic, and multi-domain comfort, as well as passive techniques such as night cooling, or analysis of specific environments such as healthcare facilities. Current knowledge would benefit from an expansion of future research in these directions. The choice of the best ventilation solution cannot ignore the context, type, and condition of energy efficient buildings, in order to properly take into account occupants’ well-being. Keywords: building ventilation ; indoor comfort ; well-being ; energy saving ; climate-responsive design 1. Introduction It is well-recognized that the building sector has a key role in the framework of energy savings, being responsible for 40% of energy consumption and 36% of emissions of greenhouse gasses in the European Union [ 1 ]. For this reason, design concepts such as net-zero energy buildings (nZEBs), net-positive energy buildings (nPEBs), and climate-responsive architecture are fundamental to reduce the carbon footprint. In fact, in nZEBs the total annual energy balance (produced minus consumed) is equal to zero [ 2 , 3 ], while in nPEBs the balance is even positive [ 4 , 5 ]. On the other hand, climate-responsive design allows the creation of a structure intrinsically connected with building location, using responsive technologies to improve the performance of buildings [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Furthermore, indoor well-being cannot be neglected in buildings’ design. The well-being concept is heterogeneous, and efforts have been made to define it. Nevertheless, the two aspects of environmental comfort and satisfaction, as well as cognitive performance, health, and productivity, emerge in the building context [ 13 ]. Therefore, a good definition of well-being regards it as the combination of feeling good and functioning well [ 14 ]. For these reasons, good indoor air quality (IAQ), thermal, acoustic, and visual conditions, and their interaction (multi-domain approach) as all part of the indoor environmental quality (IEQ), are fundamental not only for health and comfort, but also for other aspects such as physiological and psychological ones (e.g., working performance) and, since occupants tend to take action to make themselves comfortable, energy consumption [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Occupants can suffer from illnesses and complaints related with comfort, health, and safety in several indoor spaces [ 23 ]. Since the World Health Organization (WHO) Sick Building Syndrome declaration in 1986, IAQ, connected with health and comfort, has been strongly considered in indoor design [ 24 , 25 ]. In fact, several pollutants might be present in internal environments, with an adequate air-supply rate necessary to ensure healthy conditions for occupants [ 26 , 27 , 28 ]. In this complex framework, ventilation has a key and fundamental role, since it has high impact on both buildings’ energy consumption and IEQ. Depending on the ventilation technique, which can be used in combination with other passive solutions such as the use of thermal inertia for night cooling and shadings to avoid solar heat peaks, the carbon footprint can be consistently lowered [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Moreover, ventilation choice cannot overlook the well-being of occupants, which needs to be the primary aim of indoor design [ 25 , 31 ]. Generally speaking, ventilation techniques can be divided into three main groups: natural ventilation (NV), mechanical ventilation (MV), and hybrid or mixed mode ventilation (HV or MMV). Each of these categories have different implications on energy consumed and comfort. NV, totally relying on natural forces (wind- or buoyancy-driven), can consistently lower buildings’ carbon footprint [ 36 , 37 , 38 , 39 , 40 ]. Moreover, the acceptable range of thermal comfort was noticed to be enlarged when NV is present, with higher acceptance of high indoor temperatures when outdoor temperatures are high too [ 41 , 42 ]. This led to the introduction of the adaptive model for naturally ventilated buildings on ASHRAE Standard 55, which is now used together with Fanger’s model in naturally ventilated buildings [ 41 , 43 , 44 , 45 ]. In addition to that, NV might be associated with benefits related with environmental and work satisfaction, productivity, and Sick Building Syndrome, as well as improved feeling of control for occupants and access to the outside environment [ 30 , 36 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The use of NV is suggested by Leadership in Energy and Environmental Design (LEED), in order to decrease both the carbon footprint and heating, ventilation, and air conditioning (HVAC) expenses. In this sense, positive correlations between fulfilled LEED rating and satisfaction perceived was demonstrated [ 56 ]. Conversely, the possibility to fully regulate temperature, airflow, and air velocity is a clear advantage of MV, of which performance is perfectly predictable and controllable if compared with NV, with positive implications on the IAQ [ 25 , 47 , 57 , 58 , 59 ]. The use of heat recovery units can partially overcome the drawback of the larger amount of energy with respect to NV [ 60 , 61 , 62 , 63 ]. Finally, HV can be a good compromise between the two techniques, guaranteeing energy savings, but exploiting MV when proper IEQ conditions cannot be met with NV only [ 29 , 30 , 55 , 64 , 65 , 66 , 67 , 68 , 69 ]. Current literature and standards argue on which of the two techniques should be preferred. Controversial opinions about this topic were also highlighted by the COVID-19 pandemic [ 70 ]. In fact, the risk of infection is strongly dependent on relative humidity (RH), temperature (T), and ventilation [ 71 ]. In this framework, ASHRAE recommended to use NV only in homes where MV or air-purifiers were not installed, in order to avoid thermal discomfort [ 72 , 73 , 74 ]. On the other hand, NV was also associated with the buildings’ infection management [ 75 , 76 ]. In fact, CIBSE and REHVA recommended massive use of window openings, even in mechanically ventilated buildings and in winter [ 77 , 78 ]. Moreover, during London’s lockdown, windows were noticed to be associated with positive cross influences of indoor mental well-being due to positive perceived soundscapes, vegetation view, and natural sounds [ 48 , 49 ]. In a global warming condition, the adaptive comfort model might cease to be fulfilled in plenty of indoor spaces in the next ten years [ 79 ], but a higher use of NV in colder climates might be induced by the shifting of climate conditions [ 30 ]. In this framework, it is clear that when dealing with concepts such as nZEBs, nPEBs, and climate-responsive architecture, the choice of ventilation technique is of paramount importance. Moreover, comfort and well-being should be among the main drivers in buildings’ design, and therefore a strong literature background on how each type of ventilation influences comfort at different climates and seasonal conditions constitutes an important basis for proper design choices. The aim of the present review to provide a framework on scientific evidence of papers comparing NV and MV in terms of comfort and well-being, in the perspective of performant and sustainable buildings’ design (e.g., nZEBs, nPEBs, and climate-responsive buildings). The main hypothesis is that ventilation is firstly aimed to provide IEQ, with energy savings as a very important additional aim. For this reason, the following research questions were explored: Which differences are present between IEQ conditions guaranteed by NV and MV? Which ventilation techniques are more suitable at different climatic, seasonal, and outdoor pollution conditions according to both IEQ and energy perspectives? Which ventilation techniques are more suitable with different building types and uses? If integrated with other studies, the articles here summarized can be exploited by policymakers in order to further expand and update ventilation standards and guidelines taking into account both energy consumption and indoor well-being. The development of such guidelines is fundamental for engineers, architects, and planners in order to help them in conscious and contemplated choices during the design process. 2. Methodology 2.1. Research Methodology A systematic review [ 80 ] was performed using AND/OR Boolean operators [ 13 ] in a search on the Web of Science [ 81 ] database. The search was aimed at identifying all the studies regarding an NV-MV comparison in terms of comfort and well-being. Figure 1 reports the detailed search string used. The PRISMA flow diagram was used in the systematic review process [ 82 ]. 2.2. Inclusion Criteria and Screening Process All types of articles (journal papers, reviews, and conference proceedings) were included. In order to refine the research, considering only the relevant works, the following inclusion–exclusion process was applied: Limiting of the research to English-written studies within the following research areas: (a) construction building technology; (b) engineering civil; (c) engineering environmental; (d) green sustainable science technology; (e) environmental sciences; (f) public environmental occupational health; (g) environmental studies; (h) architecture; (i) thermodynamics; (j) engineering mechanical; (k) infectious diseases; (l) regional urban planning; (m) urban studies; Titles and abstracts screening, rejecting all the papers not in compliance with the research questions, thus not comparing NV and MV on a comfort and/or well-being point of view; Rejection of the studies which full text was not available; Full papers’ reading. 2.3. Categorization and Data Analysis Based on the aim of the present research, selected studies were categorized according to different criteria: Type of environment considered (residential, educational, working, healthcare, etc.); Type of paper (journal paper, journal review, and conference proceedings); Comfort domain analyzed by the paper (thermo-hygrometric, visual, IAQ, acoustic, or multi-domain); Type of ventilation recommended, between “NV only”, “MV only”, “HV (or both HV and NV)”, “no clear preference stated”. The geographical area and/or climate the studies were related to were also highlighted when applicable and specified. In the framework of sustainable design such as nZEB, nPEB, and climate-responsive architecture, outcomes in terms of energy consumption and savings were also highlighted. Moreover, when related with NV and when specified, the ventilation aim was also considered, dividing between air change, thermal regulation, and night cooling (as a more specific type of thermal regulation with remarkable passive design applications) [ 32 , 33 , 41 , 75 , 83 , 84 , 85 , 86 ]. Keyword co-occurrence analyses were performed by means of the software VOSviewer 1.6.18 . Further statistics based on the publication year and publication geographic area were also considered. 3. Results 3.1. General Data and Statistics Details about the number of papers found after each screening phase are reported in Figure 2 . A total number of 94 papers was firstly found, with 68 eligible for full paper reading. After this last process, six more papers were rejected, with a final number of 62 papers considered and analyzed in this essay. Further details on the selection process are available in a PRISMA flow diagram in Figure A1 in Appendix A . Most of the included articles (71.0%) are journal papers, followed by reviews (19.4%), and conference papers (9.7%) ( Figure 3 ). Figure A2 shows the number of papers per publication year. It is clear that, starting from 1994, the topic gained a growing interest, with the number of published papers rising year by year (i.e., one in 1994, five in 2021). It is also interesting to notice that year 2020, during the COVID-19 pandemic, showed a peak in the number of papers (9), due to the obvious necessity to deepen the knowledge into ventilation related with infection airborne transmittance. Figure A3 depicts how the majority of the included articles were European (47.0%) and Asian (31.3%). On the other hand, only 4.8% of the papers were African, and none were South American. Details in Figure A4 show that England is the major publisher of included papers (11), followed by China (10), and USA (6). Eventually, Figure 4 shows the co-occurrence keywords analysis (minimum occurrence number set equal to five for the representation) of the articles included in the present review. With 28 and 27 occurrences respectively, “natural ventilation” and “thermal comfort” were the most frequent keywords. “Indoor air quality” (in the three forms of “Indoor air quality”, “Indoor air-quality” and “IAQ”) was found 26 times in total. On the other hand, visual and acoustic comfort domains were not frequently explored (“acoustic” and “noise” appeared respectively one and two times, while “daylighting” appeared only once). Furthermore, it is important to highlight that neither the “well-being” nor the “wellbeing” keywords appeared in the articles included. 3.2. Papers Related with Residential Environments In this subsection, results related with papers discussing NV and MV comfort comparison in residential environments are reported. A total number of eighteen articles were found, mainly journal papers (13) and conference papers (4), with only one literature review (1). The highest number of these research (9) were related to case studies located in Europe, followed by Asia (6), Oceania (2), and Africa (1). Ventilation for thermal regulation and ventilation for air change were analyzed, generally with a direct correspondence with thermo-hygrometric comfort and IAQ respectively. Night cooling was also considered in some cases, even though it was mainly listed as a way to better exploit NV. Thermo-hygrometric was the comfort domain most frequently considered by the papers here analyzed (15 articles out of 18), followed by IAQ (10 articles) and acoustics (6 papers). One paper considering visual and multi-domain comfort was found. Contrasting conclusions on which ventilation type is preferrable on the comfort point of view were found, as well as regarding the system providing higher energy savings. Brief summaries of the main findings are reported in this Subsection, in Table 1 . The details concerning each paper, key data (type of paper, climate, and ventilation considered and suggested), comfort domains treated and main conclusions are present in Table S1 (available as Supplementary Materials) . Table 1. Key findings related with residential environments. Table 1. Key findings related with residential environments. Thermo-Hygrometric Comfort Main findings References Improvement of thermal comfort or temperature control conditions when using MV or HV, especially when hotter or colder outdoor conditions are present [ 87 , 88 , 89 , 90 , 91 , 92 , 93 ] Good or better performance of NV in terms of thermal comfort [ 94 , 95 ] Thermal comfort is one of the main drivers of occupants’ behavior associated with NV, with the air change rate and windows opening being dependent on outdoor temperature [ 88 , 96 , 97 ] Necessity of proper design of buildings where NV is planned to be exploited for thermal comfort (architectural elements, windows, openings, orientation, control, etc.) [ 98 , 99 , 100 , 101 ] In a Chinese students’ dormitory during winter, temperature and humidity decreased to values under 20 °C and 30% after 4 h of night ventilation with ventilation rates of 0.050 m 3 /s and 0.036 m 3 /s, respectively [ 100 ] Too low or too high building tightness is associated with condensation risks [ 96 ] Too low or too high building tightness is associated with draughts or fluctuating temperature [ 101 ] In a temperate continental city of China, humidification was seen as an issue with both NV and MV, and occupants perceived drier conditions with MV [ 95 ] In developing countries, comfort range with NV might be larger (14.6–26.3 °C of comfort range found in an Ethiopian case study), allowing to satisfactorily exploit this ventilation technique [ 94 ] Thermal comfort, health, and energy savings are the three drivers of ventilation behavior [ 97 ] Visual comfort Main findings References A higher probability of windows opening was observed in Italy during 2020 winter lockdown, where a vegetation view was present [ 102 ] IAQ Main findings References Even though their priority is thermal comfort, occupants seem to be more inclined to spend more on energy if healthier environments can be provided [ 97 ] The use of MV is associated with better air quality or sweeping effect [ 87 , 88 , 101 , 103 ] MV can mitigate air-tightness issues (lowering the radon concentration from 412 Bq/m 3 to 70 Bq/m 3 , and the CO 2 concentration to an average around 760 ppm in a Romanian case study) [ 87 ] Direct link between air change rate (and ventilation behavior) and IAQ conditions [ 96 , 100 ] IAQ conditions are strongly dependent on outdoor conditions or air tightness of buildings [ 92 , 95 , 103 ] HV can be a solution when proper IAQ conditions cannot be met with NV alone [ 100 , 104 ] Acoustic comfort Main findings References Noise from both outdoors (NV) and systems (MV) can be a discomfort source [ 91 , 92 , 97 , 101 ] Together with thermal discomfort and stuffy air, noise can be one of the factors reducing the quality of sleep [ 88 ] During 2020 winter lockdown in Italy and UK, tendency by occupants to keep windows open, at least sometimes, even in urban areas. Necessity to include the concept of pleasant acoustic contexts in standards. Proposal of introduction of an “adaptive acoustic comfort” concept [ 102 ] Multi-domain Main findings References Study and application of multi-domain concept would be fundamental for the definition of acoustic criteria in naturally ventilated buildings [ 102 ] Energy consumption and other issues Main findings References MV can allow for reduction in consumption, due to less windows openings [ 96 ] MV can allow for reduction in consumption, due to the use of heat recovery (86% reduction found with respect to NV) [ 87 ] NV allows for less demand of energy [ 91 , 93 , 95 ] NV can be exploited with not extreme temperatures or not too high outdoor PM 2.5 concentration [ 95 ] Increase in energy consumption up to 20% found with MV in simulative study performed in Mediterranean climate: NV with night cooling suggested for smaller residential buildings, and MV or HV for larger residential or commercial ones [ 91 ] NV can allow for large energy savings in developing countries (wide comfort range in a field study in Ethiopia). Further research suggested to confirm this conclusion [ 94 ] Thermal comfort, health, and energy savings are the three drivers of ventilation behavior [ 97 ] Feasibility, safety, and life cycle costs need to be preliminary analyzed in the design process [ 91 ] Computational Fluid Dynamics (CFDs) simulations used or encouraged by a significant amount of studies, in order to study air movement and comfort induced by NV or HV [ 89 , 90 , 98 , 99 ] 3.3. Papers Related with Non-Residential Environments Works related with non-residential environments are here reported. Thirty-one papers were categorized within this group: twenty-five journal papers, two conference papers, and four reviews. Moreover, in this case, most articles were related to case studies located in Europe (12). Five case studies were in Asia and five in North America, while only one case study was in South America, one in Oceania, and one in Africa. One simulative study considered three climate areas, two in Europe and one in Asia. The articles here grouped mainly regard educational (12) and working environments (14). Articles regarding other facilities, such as industrial or healthcare, are also present. Moreover, in the case of non-residential buildings, thermo-hygrometric was the most explored domain (29 papers out of 31), followed by IAQ (21 papers), acoustic (10), and visual (6). Only three articles linkable with the multi-domain concept were found. Present literature is debating whether MV or NV provide better thermo-hygrometric comfort conditions in non-residential buildings. Moreover, similarly to what concerned residential buildings, while papers related with thermo-hygrometric comfort were mainly considering ventilation for thermal regulation, air change was the main focus of studies dealing with IAQ. Visual, acoustic, and multi-domain comfort were only marginally treated. It is finally fundamental to highlight how, after the pandemic, the main focus of the design seems to have changed to the control of pathogens transmission. Key findings are summarized in Table 2 , while specific details about each article are reported in Table S2 (Supplementary Materials) . Table 2. Key findings related with non-residential environments. Table 2. Key findings related with non-residential environments. Thermo-Hygrometric Comfort Main findings References In monitored classrooms in Beijing, both systems provided a too low temperature (below 18 °C) close to the beginning and the end of running heating period [ 105 ] 1.5 ach −1 MV suggested in nucleus-type hospitals, in order to provide comfort conditions [ 106 ] Personalized ventilation suggested in order to have thermal benefits for occupants [ 107 ] NV alone is not sufficient to ensure thermal comfort in a large semi-transparent ceiling ocean park case study [ 108 ] NV or HV can be adequate to provide thermal comfort [ 30 , 55 , 64 , 67 , 109 , 110 , 111 , 112 , 113 , 114 , 115 ] During summer in Dubai, when NV is not sufficient, despite the too high outdoor temperature and too low wind, a reduction of 2–6 °C is possible in office buildings by NV [ 109 ] Definition of 7 °C outdoor temperature as lower boundary for NV to be ineffective [ 115 ] Definition of the range of applicability of NV between 10 °C and 25 °C of outdoor temperature [ 30 ] Preference for NV is often related with the higher degree of control of occupants [ 25 , 30 , 55 , 111 , 116 ] The negative effects of NV on productivity are under debate [ 111 ] A higher productivity by men workers when HV was used instead of MV was found in an office of Tokyo (Japan) [ 114 ] Dependence of thermo-hygrometric comfort on outdoor temperature and users’ behavior [ 29 , 60 , 67 ] Due to global warming, NV use will decrease at warmer climates, simultaneously increasing in colder and mild areas [ 30 ] HV can be used when non-optimal conditions are achievable with NV only [ 67 , 109 , 117 , 118 ] Nighttime ventilation and night cooling can be exploited to enhance daily thermal comfort conditions [ 30 , 67 ] Specific discomfort conditions (draught, too low temperatures) found with colder outdoor conditions [ 117 , 119 , 120 ] The too low temperatures (around 18 °C) measured in Spanish schools during winter 2021 are admissible only during an emergency situation such as the pandemic [ 119 ] Importance of particular solutions such as temperature monitoring in schools, local discomfort avoidance (by means of humidifiers, electric heaters of exhaust heat recoveries), building orientation, proper design of the exhaust velocity [ 66 , 112 , 119 , 120 ] Importance of exhaust velocity optimization (e.g., depending on internal source of heat) in order to maximize thermal comfort and energy efficiency and minimize the short-circuiting risk [ 66 ] Visual comfort Main finding References Together with IAQ and acoustic, lighting is one of the IEQ aspects which needs deeper studies connected with NV [ 111 ] Daylight benefits of similar constructive techniques used for NV exploitation, such as operable skylights or high windows. Direct sunlight and large glazed façades can lead to drawbacks on both sides (i.e., overheating and glare) [ 30 ] Double-skin façades studied for NV have also the capability to provide natural light [ 112 ] Aspect considered in the study, without direct findings related with NV and MV [ 55 , 106 , 117 ] IAQ Main findings References MV can help in providing optimal IAQ [ 25 , 60 , 107 , 120 , 121 , 122 , 123 , 124 ] Higher IAQ satisfaction in NV buildings [ 113 ] Small or no difference in the perception with the two modes [ 125 ] Difference in the indoor environmental conditions perceived and actually present indoor [ 117 ] The presence of operable windows can provide a feeling of fresh air perception [ 55 ] Use of HV recommended, exploiting MV when not sufficient IAQ can be maintained with NV (e.g., too polluted outdoor conditions) [ 67 , 117 , 118 ] NV might not be sufficient in air-tight buildings [ 120 ] NV will benefit from low polluting mobility solutions such ass electric vehicles [ 30 ] Most standards focus on perceived IAQ and CO 2 concentration or energy consumption, but several comfort, performance, and health issues are often reported in buildings: necessity to move from a comfort-based to a health-based design. In this sense, benefits can be obtained by the use of personalized ventilation [ 107 ] Poorly designed or operated ventilation can lead to poor IAQ, which can cause virus airborne transmission due to dry conditions in winter: necessity the adoption of health-based ventilation design [ 25 ] CO 2 concentration reduction (1000 ppm, with a 1400 ppm decrease) in Spanish schools during the pandemic, due to the most frequent airing [ 119 ] Importance of having long and frequent airing periods with NV [ 67 , 118 , 121 , 126 ] Suggestion of automated windows and/or CO 2 and pollutants monitoring devices [ 117 , 118 , 119 , 122 ] Acoustic comfort Main findings References Loud noise reported as one factor preventing the use of MV in Spanish schools [ 119 ] Importance of noise evaluation when designing the ventilation solution [ 67 , 105 , 118 ] Evaluation of noise with measurements or surveys in studies related with NV and MV [ 55 , 117 , 122 , 123 ] In university classrooms, the intermittent noise of intermittent windows was better tolerated than the continuous one of MV [ 117 ] Benefits from less noisy mobility will be provided to NV [ 30 ] Acoustics related with NV will need further studies in the future [ 111 ] Multi-domain Main findings References IAQ has the potential to influence the other comfort domains (e.g., higher noise with higher IAQ due to higher machines regimes, sunlight causing surfaces’ emissions of pollutants). These aspects should be evaluated and studied altogether to assure comfort and health of occupants [ 107 ] Importance of deepening the studies of all the comfort aspects which are related to NV [ 111 ] Direct association of noise level and IAQ with MV [ 123 ] Energy consumption and other issues Main findings References NV or HV allow to save energy [ 29 , 30 , 67 , 105 , 110 , 111 , 114 , 117 , 118 , 119 , 125 , 126 ] Energy savings of ranging from 3.1 to 85% (coupling it with PV- system) reported with the use of NV or HV [ 114 ] Not using adaptive model encouraging NV in green certification systems, might obstruct designers’ and occupants’ change in decision [ 111 ] NV is widely used in schools of developing countries, in order to save energy [ 127 ] If properly designed and with the use of proper techniques (energy storage or heat recovery), reduction in energy consumption can be achieved with MV [ 121 , 124 ] Automatic windows coupled with heat recovery counter-flow system through outside wall slots can reduce the energy consumed in classrooms [ 122 ] Careful design of ventilation (architecture, presence of heat recovery, technological solutions such as occupancy sensors, temperature or CO 2 monitoring, night cooling coupled with massive elements) encouraged in order to reduce the carbon footprint [ 29 , 66 , 67 , 106 , 109 , 118 , 119 , 120 , 123 , 124 , 126 , 127 ]. The use of local climate conditions instead of international standards, with a consequent expansion of upper and lower comfort limits, can lead to higher energy savings [ 110 ] 3.4. Papers Not Linked to a Specific Environment Type (Various, Unspecified, …) This subsection comprises the articles which do not refer to a specific type of environment. This is due to two main reasons: 1. articles (mainly reviews) referred to all the types of environments in general; 2. studies referred to general mock-ups or models. Consequently, seven papers among the ones in this subsection are literature reviews, constituting the majority of all the reviews considered in the present work. The rest of the articles here explored are journal papers (6). No conference papers are present in this subsection. Similarly, several studies (7) were not linkable to a specific continent, country, or climate. Among the others, four studies were related with Asia, one with Europe, and one was referred to tropical climate in general. Twelve articles out of thirteen considered the thermo-hygrometric domain. The domain was again followed by IAQ (9), acoustic and visual (5 each), and multi-domain (2). Moreover, also in this case, the thermo-hygrometric domain was mostly linked with ventilation for thermal regulation and IAQ was mostly linked with air change. Similarly to residential and non-residential sections, night cooling, when considered, was mainly named or implied (e.g., as ventilation performed at night). Brief summaries of the main results are reported in Table 3 , while Table S3 (Supplementary Materials) contains further and specific details about the articles considered in this subsection. Table 3. Key findings related with various or unspecified environments. Table 3. Key findings related with various or unspecified environments. Thermo-Hygrometric Comfort Main Findings References NV can sometimes be inapplicable due to extreme conditions (temperature or running air) [ 128 ] In hot and humid climates (such as Malaysian) MV can be advantageous on the thermal comfort point of view [ 129 ] Well-designed NV is often adequate to maintain acceptable indoor thermo-hygrometric conditions [ 130 , 131 , 132 , 133 , 134 ] Wider ranges of thermal comfort are present in hot, humid climates, than what is generally indicated in international standard [ 131 ] Cooling from MV should be used only when adequate thermal comfort conditions cannot be guaranteed [ 65 ] Ventilation energy can be reduced only if comfort of occupants can be guaranteed [ 31 ] Importance of well-designed ventilation to guarantee occupants’ comfort [ 130 , 135 ] Numerical models can be useful for control strategies [ 133 ] Visual comfort Main findings References Similar constructive techniques such as atriums, double skin façades, and apertures can be exploited for both NV and daylight [ 31 , 132 ] Used together with the other comfort domains to categorize the studies considered in the review [ 136 ] IAQ Main findings References Even though NV is the cheapest and most often used environmental disinfection method against airborne transmittable diseases, proper disinfection is provided by MV [ 128 ] Higher morbidity cases (13–38% increase) and mortality (28% increase) related with NV adoption in residential buildings of Singapore; adoption of technologies such as MV and filtration from current NV in schools would diminish the number of asthma cases; mortality would also be decreased by the use of filtration in workplaces [ 137 ] Importance of taking into account occupants’ behavior and pollutions’ sources in ventilation design [ 31 , 130 , 138 ] Acoustic comfort Main findings References Noise is one of the parameters affecting occupants’ behavior. Atriums and double-skin façades can be used to exploit NV, while protecting from noise [ 31 ] Importance of considering outdoor noise when designing ventilation [ 130 , 133 ] Used for categorization or marginally considered [ 136 , 138 ] Multi-domain Main findings References Elements such as daylight availability (heat-load related), thermal mass, and night ventilation (cooling load related) are essential for thermal comfort [ 138 ] Thermal perception is also influenced by healthy IAQ [ 131 ] Energy consumption and other issues Main findings References Energy savings are associated with passive cooling and NV [ 65 , 128 , 130 , 132 ] Necessity of coupling ventilation techniques with other passive strategies, with the aim of decreasing the carbon footprint of buildings [ 131 ] Climatic design for passive cooling, use of orientation and materials (e.g., for night cooling) and proper MV operations are fundamental for ventilation design [ 130 ] Necessity of studies on vernacular apertures and elements, as well as louvered windows to exploit night cooling, in order to maximize NV efficiency in tropical climate [ 132 ] Importance of more studies in the field of balconies’ design, as well as post-occupancy evaluations, for NV optimization [ 136 ] Remarkable energy savings can be obtained by means of HV: more studies on smart window based HV should be made [ 31 ] Ventilation of unoccupied or low-occupied spaces leads to a significant amount of wasted energy [ 31 ] A combination of mechanical and passive cooling and different control strategies can lead to a reduction of more than the 60% of the system size and associated energy used [ 65 ] Use of models and simulations applied and encouraged in design and evaluation [ 129 , 130 , 133 , 134 ] 3.5. Final Statistics Table 4 , on the left, reports the number of papers suggesting specific ventilation types. Nineteen papers do not express a clear suggestion between MV, NV, and HV. Among the rest of the papers, a relative similar share suggest NV (13) and MV (9), while most studies (21) recommend the use of HV in order to guarantee energy savings with backup mechanical systems when IEQ conditions cannot be maintained by passive techniques only. It is fundamental to stress that papers recommending HV normally suggest it when satisfactory indoor conditions cannot be reached with NV alone. For this reason, it was decided to group together papers recommending HV and both HV and NV, as “HV (and NV)”. In the same table, on the right, the number of papers treating each comfort domain is reported. As previously implied, thermo-hygrometric is the mostly explored domain (56 papers), followed by IAQ (40), acoustic (21), and visual (12). Only six papers consider or name the importance of a multi-domain approach. Figure 5 allows to explore the association between the publication year and the type of ventilation recommended. It is interesting to notice how the share of papers recommending NV or HV (and NV) seem to slightly increase in time, probably in relation with energy efficiency issues. This trend seems to interrupt in 2021, most likely due to the pandemic, causing more research to suggest the use of MV for health reasons and contrast of virus transmission. Similarly, Figure 6 shows association of comfort domain treated and year of publication. The share of domains considered does not seem to be correlated with the publication year. Nevertheless, as previous subparagraphs underline, visual and acoustic domain are mainly treated marginally, especially in older publications. New publications, instead, more often link these two domains with the multi-domain approach, which is actually more frequent in recent years. Nevertheless, the approach is mainly suggested without performing complete studies about it. The number of papers for each building category is reported in Table 5 . Eighteen papers refer to residential environments. On the other hand, thirteen studies are not linked with any specific environment (e.g., laboratory studies) or are referred to various types of buildings (typically reviews). The majority of papers (31) regard non-residential environments. The highest share of these refer to educational (schools or universities) facilities (12) or working (office) facilities (14). The rest regard industrial (1), amusement (1) or non-residential buildings in general (2). Only one paper related with healthcare facilities was found. The details about the type of ventilation recommended depending on the building type are reported in Figure 7 . It is clear that the share of articles suggesting MV or HV is higher in non-residential buildings. 4. Discussions The present literature review focuses on the comparison of IEQ conditions provided by natural ventilation (NV) and mechanical ventilation (MV), with the aim of collecting and offering a framework of scientific evidence to be exploited for sustainable design (e.g., nZEB, nPEB, and climate-responsive architecture). For this reason, the comparison of energy consumption by the two ventilation types was also highlighted, when present in the literature analyzed. When present in the analyzed articles, benefits of HV were also stressed. The study permitted to highlight the following main considerations: The articles comparing NV and MV in terms of indoor comfort and well-being found in literature are not very numerous. Moreover, even though current research is moving to the concept of well-being, this aspect is not explored in the studies included in the present review, as related keywords never appear in the articles analyzed. Most of the papers found regard non-residential facilities, in particular educational and working environments, underlining the key role of ventilation for obtaining healthy and comfortable conditions in highly occupied premises. Surprisingly, only one paper related to healthcare facilities was found. Several papers highlighting the performance of either MV or NV in healthcare facilities are present in the literature, but the comparison between comfort and well-being provided by NV and MV in this type of building is mainly under-explored. This is probably due to the specific field the present review is related with: studies about ventilation in hospitals that mainly deal with sanitation reasons; therefore, the comparison between the ventilation techniques mainly regards that topic instead of indoor comfort. The association between the number of studies and the publication year has been growing in time, with a sudden increase during 2020, due to the COVID-19 pandemic. The highest amount of papers was related to case studies located in Europe and Asia, highlighting a need for more research in other areas of the world. Most papers explored thermo-hygrometric and IAQ domains. When present, other domains were mainly considered only marginally, for instance stating that a relation between them and ventilation (e.g., noise) is present, and that further research in the field is necessary. During the most recent years, some articles highlighting the importance of multi-domain research appeared. Nevertheless, the topic has not been deeply explored yet. Thermal comfort was the most frequently explored domain in all the types of environments. In all cases, contrasting conclusions on whether MV or NV is preferrable were drawn. Confirming what previously found in the literature, the main advantage of MV was recognized to be the ability to precisely set the indoor conditions. Nevertheless, this is not frequently perceived by occupants, who often prefer NV due to a higher degree of control over the environment they occupy and a major air movement, underlining the influence of the sensation of accessing to the outside. In this sense, the thermal environment was observed to be the main driver of occupants’ NV behavior, with outdoor temperature (due to climate or season) being the main parameter affecting windows opening. Moreover, a shift in the usage of NV might be observed due to climate change, with the hours of windows opening potentially decreasing at warmer climates, but increasing at mild or colder ones. Furthermore, some articles highlight the presence of wider comfort ranges in warmer and/or developing countries. This is probably due to reasons dealing with adaptation. The necessity of proper ventilation design to ensure the right indoor thermo-hygrometric conditions without creating local discomfort (such as draught) was stressed by several papers. In this sense, a more local focus, instead of the reference to international standards and the integration of other passive or active technologies such as night cooling or heat recovery, was promoted. No remarkable differences in findings were found among the different environment types. After thermo-hygrometric, IAQ was the second most explored domain by the papers considered. Especially in residential environments, air tightness of refurbished buildings was seen as an issue for IAQ conditions and proper ventilation design. Particularly in non-residential buildings, MV was often associated with better air quality and less CO 2 and particles concentration. Type of ventilation must be carefully chosen depending on several conditions comprising outdoor pollution. In non-residential facilities in particular, a sudden change in perspective was observed after 2020, with a more health-driven vision of ventilation, strongly focused on the stop of airborne transmission of pathogens. Visual and acoustic comfort were mainly explored marginally, as well as multi-domain approach. For instance, some recent works named visual and acoustic domains highlighting that their connection with ventilation, thermo-hygrometric, and IAQ conditions are important for future research, with a multi-domain point of view. Some papers highlighted how daylight and NV often benefit of the same constructive and architectural characteristics, such as high windows or operable skylights. Acoustic comfort was often explored in terms of noise, seen as an issue for the application of NV (when noise from the outside is present) or MV (poorly designed plants). Nevertheless, the effect of outside pleasant sounds or the so called “adaptive acoustic comfort” needs to be further studied and explored. A high number of papers highlighted how energy consumption is the main disadvantage in the use of MV. On the other hand, NV might be too dependent on occupants’ behavior and might lead to a loss of energy at colder or warmer conditions. Most papers, especially when dealing with extreme climates or larger and commercial buildings, proposed HV as a solution. This technique allows to lower the carbon footprint of buildings, while ensuring sufficient air change when proper indoor conditions cannot be met with passive solutions. The higher share of papers suggesting MV or HV in non-residential buildings is due to the fact that these facilities are constituted by environments which are normally studied for a higher number of occupants (i.e., schools, offices). For this reason, automated or semi-automated systems seem to be more adequate to guarantee the right amount of fresh air in these facilities. In order to improve the ventilation efficiency and the energy savings, the use of advanced technologies (e.g., heat recovery or energy storage) and proper and careful ventilation design were often promoted. For instance, focus should be placed on the optimal velocity of the exhaust in order to obtain the maximization of energy and ventilation efficiency without creating supply exhaust short-circuiting. In this sense, the use of CFD simulations was encouraged, helping with architectural characteristics improving NV, such as building orientation and position, façades, size, and location of inlets and outlets. Finally, a change in standards and guidelines was suggested by some authors in order to improve energy consumption and energy savings, for instance encouraging NV when possible. 5. Conclusions Even though ventilation design is often aimed at ensuring adequate IAQ, thermo-hygrometric comfort seems to be the main ventilation behavior driver for occupants. Especially in non-residential buildings and after the COVID-19 pandemic, the approach in ventilation studies has slightly changed to a health-based driven, rather than a comfort- or energy-based one. In general, present research strongly highlights that hybrid ventilation is the most recommended solution in order to guarantee both energy savings and proper IEQ conditions when not achievable with natural ventilation alone. This is particularly true in extreme or polluted climates, where window openings alone can lead to poor indoor conditions, and/or highly occupied or healthcare environments, where NV alone might not be sufficient to maintain an adequate level of IAQ and healthy conditions. The literature analyzed also suggests that, when possible (e.g., residential environments and smaller offices) the hybrid solutions should also consider the necessity of control by occupants, allowing to switch to a total manual system if required. Proper design of ventilation is encouraged, promoting the use of numerical modelling such as CFD analyses, in order to ensure IEQ and avoid issues such as short-circuiting of supply and exhaust air and draught sensation by occupants. From present literature, it was highlighted how some topics remain under-explored. The current tendency in indoor climate studies is to move from the concept of comfort to a more holistic well-being one, considering aspects related with comfort, satisfaction, health, and well-functioning. Nevertheless, the concept of well-being was not explored in the literature here analyzed. Moreover, only marginal attention was provided to visual, acoustic, and multi-domain comfort. Other under-explored topics regard passive technologies such as night cooling, as well as some types of environments such as healthcare facilities. 6. Future Developments Ventilation is a key factor in the field of sustainable design, specifically regarding nZEB, nPEB, and climate-responsive design, as energy savings strongly depend on ventilation techniques. In this framework, the choice of proper ventilation type (to be energy-driven or IEQ-driven) cannot be made regardless of indoor comfort and well-being. The use of either NV, MV, or HV is highly dependent on the climate, the outside pollution, the building type, and the season. In this sense, the ventilation system should be coupled with sensors and smart home solutions, being able to switch from one typology to another whenever the indoor and outdoor conditions allow or require it. Moreover, warning sensors might be useful to advise occupants on the indoor pollutants and CO 2 concentration when NV is used. Studies addressing the topic of well-being related with the comparison of NV and MV are beneficial for human-centered indoor building design. Moreover, the literature, standards, and guidelines would benefit from studies on ventilation exploring comfort with a multi-domain perspective. Ventilation is clearly and directly connected with thermo-hygrometric environment and IAQ, but recent studies agree on how all the comfort aspects interact (e.g., noise-IAQ, emissions of pollutants with higher sunlight, phycological aspects). For this reason, comfort studies coupling subjective surveys with objective measurements, and correlating the comfort perception in terms of the four domains with each other would be necessary. Moreover, some environments such as healthcare facilities need further research in terms of comfort related with comparison of different ventilation techniques. Ventilation studies might be mostly health-driven in these environments, but a significant amount of previous literature underline the relationship between healing processes and indoor well-being [ 52 , 139 , 140 , 141 ]: therefore, this aspect cannot be neglected. The exploitation of night cooling allows to further exploit natural ventilation during nighttime, when lower temperatures are present, using the delay in the heating process of massive elements. Therefore, comparative comfort studies with and without this technique would allow to assess the comfort benefits during morning hours, further encouraging designers and stakeholders to exploit this technique. Other innovative passive solutions have been proposed in the last years, including the use of internal cladding for improving the thermal inertia, the coupling of massive elements with the smart use of shadings, use of compact form to reduce the heat loss through the envelope area, organization of spaces (e.g., non-habitable areas on eastern and western sides to act as additional thermal buffers, living rooms towards south to better exploit solar gains, etc.), air quality control through proper selection of materials in air-tight buildings, etc. [ 34 , 35 , 97 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ]. The use of these techniques should be explored in terms of indoor well-being when coupled with MV and NV systems. 7. Limitations The present paper aims at providing an overview on the comparison of IEQ conditions provided by different ventilation types. For this reason, it was chosen to include only papers comprising and treating both the types of ventilation, in order to highlight the points in common and differences in the indoor conditions and energy savings provided by each ventilation technique. For this reason, the research can be expanded considering the two ventilation types separately. Moreover, as it is common in review processes, the final papers analyzed depend on the search query, the inclusion criteria, and the database considered. Supplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/buildings12111983/s1 . Table S1. Studies related with residential environments: summary of key data, comfort domain treated, approach, main conclusions and type of ventilation recommended. JP = journal paper; R = review; CP = conference paper. A.Ch. = air-change; T.R. = thermal regulation; N.C. = night cooling. “T.H.” = thermo-hygrometric; “Vis.” = visual; “IAQ” = indoor air quality; “Ac.” = acoustic; “M.Do.” = multi-domain. NV = natural ventilation; MV = mechanical ventilation; HV = hybrid ventilation; NP = no preference. “Env.” = environment; “Vent. Rec.” = ventilation recommended; “Res.” = residential. T = temperature; RH = Relative Humidity; ACR=air-change rate. Table S2. Studies related with non-residential environments: summary of key data, comfort domain treated, approach, main conclusions and type of ventilation recommended. JP = journal paper; R = review; CP = conference paper. A.Ch. = air-change; T.R. = thermal regulation; N.C. = night cooling. “T.H.” = thermo-hygrometric; “Vis.” =visual; “IAQ” = indoor air quality; “Ac.” = acoustic; “M.Do.” = multi-domain. NV = natural ventilation; MV = mechanical ventilation; HV = hybrid ventilation; NP = no preference. “Env.” = environment; “Vent. Rec.” = ventilation recommended; “Edu.” = educational; “Hea.” = healthcare; “Wor.” = working; “Ind.” = industrial; “Amu.” = amusement; “Gen.” = non-residential in general. T = temperature; RH = Relative Humidity; ACR=air-change rate. Table S3. Studies not related with a specific type of environment: summary of key data, comfort domain treated, approach, main conclusions and type of ventilation recommended. JP = journal paper; R = review; CP = conference paper. A.Ch. = air-change; T.R. = thermal regulation; N.C. = night cooling. “T.H.” = thermo-hygrometric; “Vis.” =visual; “IAQ” = indoor air quality; “Ac.” = acoustic; “M.Do.” = multi-domain. NV = natural ventilation; MV = mechanical ventilation; HV = hybrid ventilation; NP = no preference. “Env.” = environment; “Vent. Rec.” = ventilation recommended; “Var.” = Various/Inapplicable. T = temperature; RH = Relative Humidity; ACR = air-change rate. Author Contributions Conceptualization, L.Z. and R.A.; Methodology: L.Z. and R.A.; Formal Analysis: L.Z.; Investigation: L.Z.; Resources: R.A.; Data curation and data interpretation: L.Z.; Writing—Original Draft Preparation: L.Z.; Writing—Review and Editing: L.Z. and R.A.; Visualization: L.Z.; Supervision: R.A.; Project Administration: R.A.; Funding Acquisition: R.A. All authors have read and agreed to the published version of the manuscript. Funding The research received support from the project “Climate Positive Circular Communities”—“ARV” funded within the European Union’s Horizon 2020 Research and Innovation Programme, agreement No. 101036723. Conflicts of Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Appendix A Figure A1. 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Keywords on the same column were linked with the “OR” operator, while black lines represent the “AND” operator. Figure 2. Papers found after each phase of the screening process. Figure 2. Papers found after each phase of the screening process. Figure 3. Percentage of papers per type. Figure 3. Percentage of papers per type. Figure 4. Co-occurrence keywords analysis of the articles included performed with VOSviewer 1.6.18 , considering the keywords with a minimum number of occurrence equal to 5. Figure 4. Co-occurrence keywords analysis of the articles included performed with VOSviewer 1.6.18 , considering the keywords with a minimum number of occurrence equal to 5. Figure 5. Association between ventilation type suggested and publication year. Numbers indicate the number of papers recommending each ventilation type. NV: natural ventilation; MV: mechanical ventilation; HV: hybrid ventilation; NP: no preference. Figure 6. Association between comfort domain treated and publication year. Numbers indicate the number of papers considering each comfort domain. Figure 6. Association between comfort domain treated and publication year. Numbers indicate the number of papers considering each comfort domain. Figure 7. Type of ventilation suggested depending on building type. Numbers indicate the number of papers recommending each ventilation type. NV: natural ventilation; MV: mechanical ventilation; HV: hybrid ventilation; NP: no preference. Figure 7. Type of ventilation suggested depending on building type. Numbers indicate the number of papers recommending each ventilation type. NV: natural ventilation; MV: mechanical ventilation; HV: hybrid ventilation; NP: no preference. Table 4. Number of studies suggesting each ventilation type and number of studies treating each comfort domain. NV: natural ventilation; MV: mechanical ventilation; HV: hybrid ventilation; NP: no preference. T.H.: thermo-hygrometric; Vis.: =visual; IAQ: indoor air quality; Ac.: acoustic; M.Do.: multi-domain. Table 4. Number of studies suggesting each ventilation type and number of studies treating each comfort domain. NV: natural ventilation; MV: mechanical ventilation; HV: hybrid ventilation; NP: no preference. T.H.: thermo-hygrometric; Vis.: =visual; IAQ: indoor air quality; Ac.: acoustic; M.Do.: multi-domain. Ventilation Type Suggested Comfort Domain Treated NV MV HV (and NV) NP T.H. Vis. IAQ Ac. M.Do. N. of papers 13 9 21 19 56 12 40 21 6 Table 5. Number of studies per building type. Res.: residential; Non-res.: non-residential; Var.: Various/Inapplicable; Edu.: educational; Hea.: healthcare; Wor.: working; Ind.: industrial; Amu.: amusement; Gen.: non-residential in general. Table 5. Number of studies per building type. Res.: residential; Non-res.: non-residential; Var.: Various/Inapplicable; Edu.: educational; Hea.: healthcare; Wor.: working; Ind.: industrial; Amu.: amusement; Gen.: non-residential in general. Res. Non-Res. Var. TOT Edu. Hea. Wor. Ind. Amu. Gen. N. of papers 18 31 12 1 14 1 1 2 13 MDPI and ACS Style Zaniboni, L.; Albatici, R. Natural and Mechanical Ventilation Concepts for Indoor Comfort and Well-Being with a Sustainable Design Perspective: A Systematic Review. Buildings 2022, 12, 1983. https://doi.org/10.3390/buildings12111983 AMA Style Zaniboni L, Albatici R. Natural and Mechanical Ventilation Concepts for Indoor Comfort and Well-Being with a Sustainable Design Perspective: A Systematic Review. Buildings. 2022; 12(11):1983. https://doi.org/10.3390/buildings12111983 Chicago/Turabian Style Zaniboni, Luca, and Rossano Albatici. 2022. "Natural and Mechanical Ventilation Concepts for Indoor Comfort and Well-Being with a Sustainable Design Perspective: A Systematic Review" Buildings12, no. 11: 1983. https://doi.org/10.3390/buildings12111983	https://www.mdpi.com/2075-5309/12/11/1983/xml
Can contact lens wearers apply wetting solution while wearing cosmetics? It is possible to apply wetting solution drops without damaging eye cosmetics. The best method is to stand upright and pull out the lower eyelid to form a space to place the drops. Can contact lens wearers apply wetting solution while wearing cosmetics? It is possible to apply wetting solution drops without damaging eye cosmetics. The best method is to stand upright and pull out the lower eyelid to form a space to place the drops. Zoe Diana Draelos, M.D.It is possible to apply wetting solution drops without damaging eye cosmetics. The best method is to stand upright and pull out the lower eyelid to form a space to place the drops. This is accomplished by pulling down on the lower eye with the index finger to pull the eyelid away from the eye. Prime the wetting solution bottle such that one drop is hanging on the tip. Move the bottle close the lower eyelid, but do not touch the eyeball and contaminate the bottle tip, placing one drop into the space between the eyeball and the lower eyelid. Release the lower eyelid. Blink several times and repeat until the eye is properly wetted. This method prevents smudging eyeliner, mascara, and eye shadow. In part 2 of this Frontline Forum series, John M. Strasswimmer, MD, PhD; Andrew H. Weinstein, MD; Neal Bhatia, MD; Laura Ferris, MD; and Aaron S. Farberg, MD, discuss solutions for managing and treating patients with basal cell carcinoma. Continued from part 1. Dermatologist Shortages Farberg has researched the accessibility of dermatologic care across the country and emphasizes the need to increase the number of dermatologists to help address BCC. He helped lead a study surveying dermatologists through the American Academy of Dermatology. Results of the survey showed that 38% of clinicians in urban areas reported a low number of dermatologists in their community. More than half of dermatologists in rural areas reported fewer dermatologists than required to serve their populations. More than 70% of regions studied with at least 1 practicing dermatologist have fewer than 4 dermatologists per 100,000 individuals. Study investigators alongside Farberg shared that 4 dermatologists per 100,000 individuals is an estimate of how many are needed to adequately care for a population. 6 Weinstein said the current reimbursement system disincentivizes dermatologists who may be leaving the field or focusing on more lucrative aspects of dermatology, such as antiaging. Multidisciplinary Care Although more aggressive cancers, such as melanoma or Merkel cell carcinoma, often result in the rapid assembly of multidisciplinary teams to treat disease, this happens to a lesser extent with BCC, the panel said. Multiple health organizations in the United States and Europe have set forth multidisciplinary recommendations for patients with BCC. Those guidelines indicate that dermatologists can benefit from working relationships with medical oncologists, surgical oncologists, radiation oncologists, Mohs surgeons, nurse practitioners, physician assistants, pharmacists, and pathologists. 7 The panel recommended talking to patients about creating an interdisciplinary team as quickly as possible. This includes discussions about biologic treatments, especially because patients may have seen advertisements on television or online and will wonder why their doctor has not discussed these options with them. Farberg noted that dermatologists are in a unique position to help guide the team and providea holistic approach. “Each patient is different; they have various individual risk factors,” he said. “So, when I get this pathology report or I see this on a pathology slide, I need to first understand what’s going on with the patient. From there, if we decide this does require a multidisciplinary approach, then I believe it is our job as dermatologists to be a multidisciplinary advocate.” He added that in multidisciplinary treatment groups, the dermatologist must be the patient’s advocate and encourage treatment modalities that dermatologists may rely on another specialist to prescribe, such as immunotherapy. Bhatia agreed that the dermatologist needs to take a lead in determining the best care for the patient, and suggested it may be necessary to reframe the way clinicians approach treatment. “I’m concerned that medical dermatologists especially, but all of us as a whole, don’t think about cancer the way oncologists do. We don’t think about shrinking tumor burden, cutting it out and making it go away,” he said. “I think we need to get back into the model of what are our [colleagues are] doing? What mechanisms of action do they have to improve outcomes?” “I think IV drugs and checkpoint inhibitors can be a much bigger part of our practice,” he added. “There are some tumors that just need chemotherapy or need medical therapy. …We all [need to] find a balance of increasing our interest in getting patients treated—whether it involves us doing the infusions or working with someone who can do the infusions with us.” The experts also emphasized that an excellent working relationship with the dermatopathologist assisting with a patient’s case is essential, as they have deeper knowledge and work with samples on a much more frequent basis. The panel stressed that dermatologists should not be their own dermatopathologists because of this additional expertise. Knowledgeable and trustworthy colleagues are also essential, as multidisciplinary teams get faster and more accurate diagnoses. References 7. Kim JYS, et al; Work Group; Invited Reviewers. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol. 2018;78(3):540-559. doi:10.1016/j.jaad.2017.10.006 Continued in part 3.	https://www.dermatologytimes.com/view/can-contact-lens-wearers-apply-wetting-solution-while-wearing-cosmetics
Snail Kite \| Audubon Field Guide In the wide-open marshes of central Florida, this broad-winged bird glides slowly and low over the sawgrass. It has no need for fast flight, because it seeks only snails -- and only one particular... Adult male. Photo: Allen Hoffacker/Audubon Photography Awards Priority Bird Snail Kite Rostrhamus sociabilis Conservation status The Florida population is endangered; disruption of water flow (with impact on habitat and snail populations) is the main cause. Recently an exotic species of apple snail, larger than the local native species, has become established in Florida. The impact of this exotic on the Snail Kites is still uncertain: it might harm the birds by outcompeting the native snail, or the kites may adapt to feeding mainly on the newly established species. Family Hawks and Eagles Habitat Fresh marshes and canals. In Florida, found at large freshwater lakes and marshes. Favors shallow waters, with stands of sawgrass and cattails mixed with areas of open water and with a few shrubs or low trees. In the American tropics, also in wet savannahs, rice fields, sugarcane fields. In the wide-open marshes of central Florida, this broad-winged bird glides slowly and low over the sawgrass. It has no need for fast flight, because it seeks only snails -- and only one particular sort, the apple snail. This snail is strongly affected by water levels, and drainage of wetlands has hurt populations of both the snail and the kite. The Florida race of this bird, formerly called Everglades Kite, is now endangered. Photo Gallery Feeding Behavior Hunts by gliding slowly and low over marsh, dropping to pick up snail with one foot from surface of water or plants. Sometimes perches low, scanning surrounding area for snails, then flies to catch one. Kite flies to perch, holds snail with one foot while extracting snail from shell with long, curved upper mandible of bill. Eggs Currently in Florida, usually 2-3. Formerly may have laid more eggs there, regularly 4, rarely 5-6; smaller clutches today may be response to lowered food supply. Eggs white, marked with brown. Incubation is by both parents, 26-28 days. Young: Both parents feed the young at first, bringing them snails. After 3-6 weeks, one parent (either one) usually departs, may find another mate and nest again. Remaining parent cares for young until they are 9-11 weeks old. Young may climb out of nest at 4-5 weeks, can fly well at 6-7 weeks. Young Both parents feed the young at first, bringing them snails. After 3-6 weeks, one parent (either one) usually departs, may find another mate and nest again. Remaining parent cares for young until they are 9-11 weeks old. Young may climb out of nest at 4-5 weeks, can fly well at 6-7 weeks. Diet Large snails. Under normal conditions, Florida birds live almost entirely on large apple snails (genus Pomacea). When the snails become scarce, as during drought, the kites may eat many small turtles. Also rarely eat small snails, rodents, crabs. Nesting Usually nests in loose colonies. In courtship, male flies up and dives short distance repeatedly near female; flies with exaggerated deep wingbeats. Male may feed snails to female. Nest site is over water in shrub or low tree, sometimes in cattails or sawgrass, usually 3-15' above water, rarely up to 30' or higher. Nest (built mostly by male) is bulky platform of sticks and twigs, lined with vines and weeds. Illustration ©David Allen Sibley.Learn more about these drawings. Text © Kenn Kaufman, adapted from Lives of North American Birds Migration Apparently not migratory, but nomadic, moving around in response to changing water levels. All Seasons - Common All Seasons - Uncommon Breeding - Common Breeding - Uncommon Winter - Common Winter - Uncommon Migration - Common Migration - Uncommon See a fully interactive migration map for over 450 bird species on the Bird Migration Explorer. Songs and Calls Low cackles and chatters when disturbed. Audio © Lang Elliott, Bob McGuire, Kevin Colver, Martyn Stewart and others. Learn more about this sound collection . How Climate Change Will Reshape the Range of the Snail Kite Audubon’s scientists have used 140 million bird observations and sophisticated climate models to project how climate change will affect this bird’s range in the future. Zoom in to see how this species’s current range will shift, expand, and contract under increased global temperatures. Climate threats facing the Snail Kite Choose a temperature scenario below to see which threats will affect this species as warming increases. The same climate change-driven threats that put birds at risk will affect other wildlife and people, too. Warming scenario: +1.5 ℃ +3.0 ℃ Why these temperatures? Season: Summer Winter What is a season? The species is projected to shift mostly out of the conterminous 48 states, for which threats data are available. These birds need your help Get Audubon in Your Inbox	https://www.audubon.org/field-guide/bird/snail-kite?site=fl&nid=14996&site=fl&nid=14996
People v. Baffi - New York - Case Law - VLEX 884587571 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object] People v. Baffi Court New York Court of Appeals Writing for the Court COOKE, C. J., and GABRIELLI Citation 404 N.E.2d 737,49 N.Y.2d 820,427 N.Y.S.2d 615 Decision Date 18 March 1980 Parties , 404 N.E.2d 737 The PEOPLE of the State of New York, Respondent, v. George BAFFI, Appellant. Page 615 427 N.Y.S.2d 615 49 N.Y.2d 820, 404 N.E.2d 737 The PEOPLE of the State of New York, Respondent, v. George BAFFI, Appellant. Court of Appeals of New York. Richard I. Rosenkranz, Brooklyn, for appellant. Eugene Gold, Dist. Atty. (Morris Harary, Asst. Dist. Atty., of counsel), for respondent. OPINION OF THE COURT MEMORANDUM. Defendant George Baffi appeals, on grounds of ineffective assistance of counsel, from his conviction of possession of gambling records in the first degree, and promoting gambling in the second degree. George and his brothers Albert and Nicholas were identically charged in a single indictment, based on evidence gathered in the search of an apartment pursuant to a warrant. George and Nicholas were present in the apartment when the police, with a no-knock warrant, broke in through a rear window to search for gambling records and paraphernalia; Albert entered the apartment while the search was in progress. The police found various gambling records in the apartment and on the persons of George and Albert, but not on Nicholas. The police also noted certain spontaneous statements made by George during the search. At trial one attorney represented all three defendants. The jury convicted George and Albert, but acquitted Nicholas. During the course of a pretrial suppression hearing the attorney for the three defendants made this statement: "Your Honor, we're going to go ahead but I want to put on the record, I advised these defendants of the possibility of a conflict in this case and they wish (me to) represent each and everyone of them; however, in the event that on further discussions with the defendants, there is a possibility of maybe another attorney representing one or two of them, this will not hinder the trial in any way whatsoever. I just want to put this on the record, of what I advised the defendants of to protect myself. Thank you very much." The trial court gave no response and made no further inquiry, nor did the defendants, who were apparently present, make any statements. Although the trial court may place some reliance on the statement by counsel that he has informed his clients of the pitfalls of joint representation and gotten their consent (People v. Gomberg, 38 N.Y.2d 307 , 379 N.Y.S.2d 769 , 342 N.E.2d 550 ), such a statement alone does not relieve the trial court of the obligation "independent of the attorney's obligation" (People v. Macerola, 47 N.Y.2d 257 , 263, 417... People v. Cortez United States New York Court of Appeals January 21, 2014 ...trial court of the potential pitfalls” posed by the conflict ( id. at 263, 417 N.Y.S.2d 908, 391 N.E.2d 990). And, in People v. Baffi, 49 N.Y.2d 820 , 822, 427 N.Y.S.2d 615, 404 N.E.2d 737 (1980) we reiterated that “[a]lthough the trial court may place some reliance on the statement by couns...... People v. Cortez United States New York Court of Appeals January 21, 2014 ...trial court of the potential pitfalls” posed by the conflict ( id. at 263, 417 N.Y.S.2d 908, 391 N.E.2d 990). And, in People v. Baffi, 49 N.Y.2d 820 , 822, 427 N.Y.S.2d 615, 404 N.E.2d 737 (1980) we reiterated that “[a]lthough the trial court may place some reliance on the statement by couns...... People v. Slavik United States New York County Court April 14, 1986 ...thereof, did exist, a new trial must be ordered ..." (at page 264, 417 N.Y.S.2d 908, 391 N.E.2d 990). See also People v. Baffi, 49 N.Y.2d 820 , 427 N.Y.S.2d 615, 404 N.E.2d 737 Thus, the Macerola Court recognized that a defendant might be hard pressed to show actual prejudice in the trial re...... People v. Recupero United States New York Court of Appeals December 1, 1988 ...that should have been pursued Page 237 for each defendant such that the potential for conflict actually operated (People v. Baffi, 49 N.Y.2d 820 , 822, 427 N.Y.S.2d 615, 404 N.E.2d 737). Notwithstanding the absence of such a showing, however, the dissent would reverse, urging upon the court ...... 20 cases People v. Cortez United States New York Court of Appeals January 21, 2014 ...trial court of the potential pitfalls” posed by the conflict ( id. at 263, 417 N.Y.S.2d 908, 391 N.E.2d 990). And, in People v. Baffi, 49 N.Y.2d 820 , 822, 427 N.Y.S.2d 615, 404 N.E.2d 737 (1980) we reiterated that “[a]lthough the trial court may place some reliance on the statement by couns...... People v. Cortez United States New York Court of Appeals January 21, 2014 ...trial court of the potential pitfalls” posed by the conflict ( id. at 263, 417 N.Y.S.2d 908, 391 N.E.2d 990). And, in People v. Baffi, 49 N.Y.2d 820 , 822, 427 N.Y.S.2d 615, 404 N.E.2d 737 (1980) we reiterated that “[a]lthough the trial court may place some reliance on the statement by couns...... People v. Slavik United States New York County Court April 14, 1986 ...thereof, did exist, a new trial must be ordered ..." (at page 264, 417 N.Y.S.2d 908, 391 N.E.2d 990). See also People v. Baffi, 49 N.Y.2d 820 , 427 N.Y.S.2d 615, 404 N.E.2d 737 Thus, the Macerola Court recognized that a defendant might be hard pressed to show actual prejudice in the trial re...... People v. Recupero United States New York Court of Appeals December 1, 1988 ...that should have been pursued Page 237 for each defendant such that the potential for conflict actually operated (People v. Baffi, 49 N.Y.2d 820 , 822, 427 N.Y.S.2d 615, 404 N.E.2d 737). Notwithstanding the absence of such a showing, however, the dissent would reverse, urging upon the court ......	https://case-law.vlex.com/vid/people-v-baffi-884587571
The Unofficial Dynamic Range Database \| Stereophile.com At the 2012 NYC hi-fi show, I was chastised by a random showgoer for using a “dynamic-less” recording as a reference in the Legacy room. Now with the help of the Unofficial Dynamic Range Database, I can find the dynamic range measurements of many of my favorite recordings, including the record ridiculed by one spiteful audiophile. Was he right about its dynamics? Ariel Bitran \| May 9, 2012 At the 2012 NYC hi-fi show, I was chastised by a random showgoer for using a “dynamic-less” recording as a reference in the Legacy room. Now with the help of the Unofficial Dynamic Range Database, I can find the dynamic range measurements of many of my favorite recordings, including the record ridiculed by one spiteful audiophile. Was he right about its dynamics? The “Unofficial” Dynamic Range Database uses a sliding scale from 1 to 20 (1 being the worst, 20 being the best) to rank the dynamic quality of each of the recordings they list. This number represents the difference between the peak decibel level on a recording and the recording’s average loudness. DRD applies the following descriptors to these ranges: 1-7=bad; 8-13=transition; and 14-20=good. Evaluation for each album on the website includes the album’s average dynamic range, the track with the weakest dynamic range, and the track with the greatest. The Unofficial DRD also provides individual dynamic range measurements for each track on the album. For example, Phish’s Lawn Boy , the record which drew so much resentment out of a fellow audiophile, scored an average of 12 in terms of overall album dynamics, which is considered close to “good” or “in transition” by DRD’s sliding scale. So still a little compressed, but certainly not as bad as that guy made it out to be: my CD made him storm out of the room! The weakest track clocks in at 9 (“Split Open and Melt”) and the most dynamic song on the record, “Bouncing Round the Room”, scores a 14. Interestingly, “Bouncing” is the only song on this record that received a medium level of radio airplay, and it was the most dynamic! Just goes to show that not all radio singles have to be LOUD. Participants on the Dynamic Range Database use the Dynamic Range Meter, a foobar2000 component, to take their measurements. The Dynamic Range Meter is designed to give the same information as the popular Pleasurize Dynamic Range Meter . Any user can submit their test results to the site. On the site, users can search by artist or album. The mainpage allows you to sort alphabetically by Artist or Album or rank their dynamic rankings in ascending or descending order. After sorting the albums by worst dynamic range, I was not surprised to see some of my favorite bands and records at the top of the list, including My Morning Jacket, The Mars Volta, and the Red Hot Chili Peppers. What I found in the ultra-dynamic recordings was also refreshing: Van Halen, Talking Heads, and Rush. Kudos to Stereophile.com user lastgoodbye for the tip. Sites like these give consumers the power of information, and with that comes the power of smarter decision making, which will ultimately lead to better quality by demanding more in what we choose to buy. Log in or register to post comments COMMENTS I wish it was searchable or Submitted by Kal Rubinson on May 9, 2012 - 3:51pm I wish it was searchable or in a coherent order (did I miss it?). Couldn't find anything that I could relate to except some older classical which didn't do too bad. Kal Log in or register to post comments I always look at my music... Submitted by michaelavorgna on May 9, 2012 - 4:42pm ...before listening for the same reason I listen to paintings before determining what's worth viewing. Log in or register to post comments Be wary Submitted by nile49 on May 9, 2012 - 8:35pm of certain formats, I believe the old foobar plugin optmistically miscalculated the dynamic range of mp3's and possibly other formats. Log in or register to post comments Dynamic Range Day Winner scores a "Bad" in this Database Submitted by matt123 on May 10, 2012 - 7:21am Ironic that Elbow's Build A Rocket Boys! , the 2011 Dynamic Range Day winner for best-sounding dynamic album scores a "bad" 7 or 8 in this data. The 2012 winner Björk for “ Biophilia ” scores an 8 also. http://dynamicrangeday.co.uk/award/ I checked the other finalists and only one vinyl copy scores a "good" Laura Marling - 8 LCD Soundsystem’s This Is Happening , 10, 15 (vinyl) The Coral’s Butterfly House , 8, 13 (vinyl) Massive Attack’s Heligoland , 8, 12 (vinyl) Neil Young’s Le Noise , 9 Mumford & Sons’ Sigh No More , 8, 12 (vinyl) Four Tet’s There Is Love In You, 9 Norah Jones’s …Featuring, 9 I think this is a really valuable service, and I don't want to dis what seems to be a volunteer effort - but this has to bring it a bit into question, maybe its the plugin as nile49 says above. Would be interesting to understand why the vinyl scores better - I assume they are vinyl rips, so is it the ripping process, the format itself or mastering? Log in or register to post comments It's not ironic. Submitted by Ladyfingers on May 13, 2012 - 8:48am It's indicative of how little dynamic range the average non-classical recording has at the moment. I use this database very reliably to see which version of a favourite recording to buy, as while a high DR is no guarantee of quality, a low one almost certainly guarantees poor sound for anything with percussion. 8 actually isn't too bad, but the 12s and 13s in comparison really do sparkle and punch. Good late 80s and early 90s CDs sound AMAZING when you turn them up. Using the DB, look for instance at Rush's albums, and compare the modern remasters to the older CDs. They are something of a disgraceful benchmark in overcompressed, clipped remastering, and it's clearly shown there. Standard mastering practice is so abysmal now that it beggars belief. Vinyl scores higher in general because it is now accepted that digital audio MUST sound a certain way. My friend has a audio software from Steinberg whose final step in the recording process is a 0dBFS brickwall limiting with no explanation why it must be done. You'll find that older CDs actually had higher DR than same-era vinyl and that at the time this was a selling point mentioned on the packaging ("may reveal limitations of the master tape"). Now comparatively limited vinyl, hilariously, is the audiophile medium because the better format has been abused. Log in or register to post comments Responses Submitted by Ariel Bitran on May 10, 2012 - 7:46am Kal, you can organize the results either alphabetically or numerically by clicking on the category. You can also search by artist or album in the search toolbar just above all the listings (right corner). ML: are you being sarcastic or was that a typo? just wanna be sure. ("listen" to your paintings) Nile and Matt: the question of the validity of the listings is a great one, and one that I honestly avoided answering b/c I can only assume that some of these listings are incorrect and I just wanted to bring light to what a great idea/site this is. Content is user submitted. As the wikipedia of dynamic ranges, user submitted content is surely up to question. Hopefully if this website grows, they can enlist editors/moderators or a system which ensures accuracy. Re: certain formats -- the listings indicate whether the recordings were measured with lossy or lossless formats, so hopefully that can assist in making a judgment. Re: dyanmic range day winners -- this is crazy! none of those albums really scored above a 14 except the LCD vinyl! Great research. Certainly raises some interesting questions.... Log in or register to post comments No typo Submitted by michaelavorgna on May 10, 2012 - 8:22am I think it’s important to realize that the relationship between these “DR Scale” scores and perceived sound quality is not 1 to 1. In other words, not all dynamic range compression sounds the same even if it gets the same “score” from the Foobar2000 software tool. Or to put it in plainer language, you have to actually listen to music to know if you’ll enjoy it or not. I also think it would be a shame and a mistake if people started to make music purchase decisions based on this information. I’m not promoting dynamic range compression, and we’d all be better off without it, just trying to avoid another unnecessary witch hunt. VILLAGER #1: If... she.. weighs the same as a duck, she's made of wood. BEDEMIR: And therefore--? VILLAGER #1: A witch! Log in or register to post comments Michael, spot on. Submitted by kovan yarrum on May 10, 2012 - 8:52pm Michael, you are spot on. Sometimes how the files "look" have very correlation with how they sound. It can work both ways...one that looks like it has plenty of headroom may sound just ok, and one that looks like it may be clipped can sound good. I sent some Audacity screen caps of the recent Queen remasters to a friend who said they "looked" good and should sound great, when in reality they are as harsh and clipped sounding as any remastering I have had the (dis)pleasure of hearing. Log in or register to post comments Sorting was useless as there Submitted by Kal Rubinson on May 10, 2012 - 11:29am Sorting was useless as there is no naming consistency. I did sort by date and gave up looking when I found no classical in 2012, 2011 and a page or two of 2010. I guess the problems lie elsewhere. Log in or register to post comments Classical Recordings... Submitted by John Atkinson on May 11, 2012 - 9:07am ...tend not to suffer from unnecessary dynamic compression, so the database's problems are less important than in rock, where too many recordings from the past 10 years have had too heavy on a hand on the "Squash-it-to death" knob. As an example, I mentioned in my presentation on this subject at last October's AES Convention the 1932 recording of Elgar's Violin Concerto, which had greater dynamic range than almsot all modern rock recordings - see www.stereophile.com/asweseeit/177/index.html . John Atkinson Editor, Stereophile Log in or register to post comments Agreed, Use your ears Submitted by JItterjaber on May 10, 2012 - 9:01am I appreciate the chief over at Audiostream for speaking up. It is also important to remember that dynamic range is not just a result of an engineer compressing/limiting...It is also a product of the type and style of music being played. More so, It can be over compressed in the mixing stage...before it is then squashed in mastering. Seriously, use YOUR EARS! I explored this topic a bit on my blog: http://bit.ly/IqmDVU I for one appreciate the mastering engineers over at "Dynamic Range Day." They are trying to be advocates in an industry where non-engineers make final sound level decisions. Learn, pass it on. Log in or register to post comments This reminds me of... Submitted by Ariel Bitran on May 10, 2012 - 9:48am the relationship between audio hardware and measurements. there are many times when an amplifier sounds great to the reviewer, but JA finds that it measures terribly! (I'm loooking at you tube amp) I think its more of a question of what do these measurements bring to the table and what can they help us learn and can awareness of the issue positively affect the current standard? If you sort the recordings by worst average dynamic range, almost all of the ones at the top of the list are "new" recordings released in the past 10 years. Just b/c something is compressed surely doesn't mean that we shouldn't buy it, but to ask for better isn't a sin either. like with Metallica's Death Magnetic, fans heard the record, thought it sucked (not the music, but the sound quality), and asked for a better quality release. these measurements are a great form of documentation and community building and education to perpetuate the attitude of wanting better. not a bible but a travel-guide. Log in or register to post comments "...perpetuate the attitude of wanting better." Submitted by michaelavorgna on May 11, 2012 - 5:05am Well put and agreed. But...The notion that we can cleanly and clearly separate sound quality from music quality in order to focus on the former runs the greater risk of losing sight of the latter. Case in point being a lot of the music you hear at hi-fi shows. Log in or register to post comments Question Submitted by Ariel Bitran on May 11, 2012 - 7:37am I agree. My question is the following: Is there any room for absolute measurement in terms of deciding the quality of an audio recording? does this have place or is this a lost cause since the ratio of quality to dynamic range rating is not 1:1? or what is the healthiest way to use these numbers? Log in or register to post comments The short answer Submitted by michaelavorgna on May 11, 2012 - 8:44am It’s music. Just listen. The longer answer… Your Metallica example is an interesting one in that people objected to what they heard and asked for better - the fact that they objected to the amount and severity of dynamic compression used is an important and interesting fact, after the fact. It allows for a common understanding of the issue as well as a solution. An attempt to reverse this order by looking at a list of recordings and their associated “DR Scores” shifts our focus from listening to looking which strikes me as a step in the wrong direction. To reiterate, the ultimate quality of a recording must also take the music into account. Otherwise we’re left with nothing but sound. Since there’s no way to measure musical content to determine value, there’s no way to graphically represent a value that takes both sound and music into account. Just as there’s no way to listen to the value of a painting. So no, I cannot see “any room for absolute measurement in terms of deciding the quality of an audio recording” unless we’re uninterested in the music. Log in or register to post comments There are plenty of things Submitted by Ladyfingers on May 13, 2012 - 10:03am There are plenty of things that indicate objectively poor sound quality, though. Most of the low DR recordings in the database do, in fact, sound pretty terrible. Log in or register to post comments Sure Submitted by michaelavorgna on May 14, 2012 - 4:56am But the only way to know if we're interested in the music is to listen. Some terrible sounding records are certainly worth listening to, just as some great sounding records are not. In my opinion of course because ultimately we're talking about music not sounds. Log in or register to post comments But, given the choice between Submitted by Ladyfingers on May 14, 2012 - 6:18am But, given the choice between a poor and good master of the same recording, which would you choose? Log in or register to post comments Is this a trick question? Submitted by michaelavorgna on May 14, 2012 - 8:31am The one I prefer listening to. Log in or register to post comments Are you aware... Submitted by Ladyfingers on May 14, 2012 - 9:30pm ...how bad any 5-6DR mastering sounds compared to a 12DR version of the same record? There has to be something very seriously wrong with the old mastering for it to sound worse than the modern, compressed-to-hell version. Log in or register to post comments Reissues/remasters Submitted by michaelavorgna on May 15, 2012 - 9:54am I was not thinking about using the DR Ratings to compare reissues/remasters with original recordings. Here I agree – a reduced DR Value in the reissue would indicate something’s not right. Regarding reissues, I tend to prefer the original vinyl (if available). Log in or register to post comments The Healthiest Way to Use These Numbers Submitted by TriodeDave on May 15, 2012 - 9:58am would be to ignore them. If you already have a recording and enjoy it, will you chuck it when you discover that it's not on an Approved Dynamic Range List? Conversely, if you're told that a recording you're considering purchasing 'cause you like the artist or you've heard the tunes are great isn't on the ADRL, will you change your mind buy something "approved" instead? If you do either or both, you'll end up with a shelf of ADRL members, but you'll spend very little time listening to them, perhaps taking up aggregating a giant ball of twine instead. If you do neither, you'll end up with a collection of music you enjoy with varying amounts of dynamic range represented. Unless your favorite thought is, "Well there's two (minutes, hours, days) I'll never get back.", why bother? Log in or register to post comments Vinyl vs. Digital Submitted by roscoeiii on May 10, 2012 - 10:00am Based on a quick search I am also seeing that vinyl copies are tending to have a greater dynamic range than digital, including 24/96 digital. To choose an example of recently recorded albums, check out the dynamic ranges for the the Fleet Foxes: http://www.dr.loudness-war.info/index.php?search_artist=fleet+foxes&search_album= Log in or register to post comments You can't apply the same Submitted by Ladyfingers on May 13, 2012 - 8:55am You can't apply the same brickwall limiting to vinyl. Vinyl mastering needs a certain RMS volume level to sound good because of all the surface noise, and if that is exceeded, then the needle can literally jump out of the groove. It's an inferior medium, but its limitations encourage better mastering. Very sad. Log in or register to post comments Some of my favorite Submitted by PredatorZ on May 15, 2012 - 11:31am Some of my favorite recordings are live , IM assuming that they must have minimal production and tweaking by some "engineer", for example Judas Priest Live, and Muddy Waters Folk Singer, have a real tactile feel of the venue. I wonder how these 2 recordings would rank in the tests. It might be a usefull tool for exploring unfamiliar music and making choices of recordings to audition. Bottom line, as mentioned in prior posts, is listening. Great thing is, thats why we are all here, our love of music and reproducing the best possible experiences with the systems we have. Cheers Bret Edit: Downloaded and ran the foobar2000 component with results now posted on the website, Muddy Waters Folk Singer rated 15 overall, 17 on its hiest track, Judas Priest...Live rated 13 overall, and 14 on its hiest track. Im going to submit my favorite albums as far as my "percieved sound quality" and see how this works out :) Log in or register to post comments Using your ears Submitted by tmsorosk on May 16, 2012 - 3:59am I always chuckle when someone kicks into one of these discussions and says, " use your ears ". doesn't that go without saying, or at least hope everyone partaking in an audio forum understands that by now. I find it interesting to understand a little bit about one perimeter of why we may or may not like the sound of a certain album, musical content aside. Tim Log in or register to post comments seems to be a useless statstic Submitted by james on May 16, 2012 - 4:59pm A Picture of Nectar , which is listed as Phish's most dynamic album is also the worst sounding to my ears. It sounds so thin and brittle. Log in or register to post comments Nectar Submitted by Ariel Bitran on May 18, 2012 - 5:42am haha james! I actually agree. I could never understand why Nectar was so brittle. I think Lawn Boy sounds great. Rift is a little squashed but super clean sounding (like Lawn Boy), and I'm dying to hear the Junta just released on HD tracks. Log in or register to post comments nectar Submitted by james on May 18, 2012 - 6:50pm glad someone agrees. try making it all the way through Cavern. The new Junta sounds great. I got the vinyl copy and it does sound excellent. Quickly A/B'ing back and forth between the original and the new version, it's not jaw dropping, but it does sound very good. I could listen to something like "Anything But Me" from [i]Round Room[/i] all day. The sound of Trey's guitar on that track does it for me. Log in or register to post comments Google "MasVis analysis" for Submitted by Patrik Lundquist on June 2, 2012 - 4:53am Google "MasVis analysis" for more in-depth mastering analyses of CDs. Also, the Dynamic Range DB isn't completely trustworthty due to a bug in the official DR meter: The reason for the usefulness of the DR Meter despite of its flaws had always been that large DR value database /.../ - now because of that bug all the thousands of records scanned from lossy sources are basically rubbish. http://www.hydrogenaudio.org/forums/index.php?showtopic=88373&st=0&p=769036&#entry769036 Log in or register to post comments Very late to the game Submitted by jasenj1 on February 15, 2018 - 6:44am I just recently discovered the DR database. I promptly downloaded the tool and began running a bunch of my albums through it - and submitting entries. Some of the discussion here has pitted audio quality against musicality. I would think anyone reading Stereophile values BOTH, and the balance between them is dynamic. I might have an album/song that really speaks to me and moves me for its lyrics, rhythm, emotion, etc. I would enjoy such music whether it was played through an AM radio or a $100,000 Stereophile-worthy rig. But, because I care about such things, I would choose the expensive rig given a choice. Likewise there may be recordings that are exceptional - great dynamic range, clarity, subtleties, sound stage, etc. In these, I admire the craft of capturing the performance; a high-quality playback rig enhances (and is probably necessary for) that enjoyment. And certainly, certain types of music lend themselves to high DR while others do not. So with all those caveats and qualifiers in mind, a higher DR recording is an indicator of a better recording than a low DR. And if the DR is low enough it is a strong indicator that the recording is severely compromised. Log in or register to post comments Also discoverd some moths ago the DR data base Submitted by Snarf on June 9, 2018 - 2:02am I must say it is a lot off line last few weeks. Furthermore it is for me a very usefull tool. I listen (mostly)to 60 70 80 music based on my CD collection (ha ha i'm 59). I remix an make Dj set based on Deep house beats with 60 70 80 undertones. Now for the latest (Deep house beats) you want to have the opposite of a High DR rating all this Deep House suff is quite compressed. But even so it is an art to compress it such that you can listen for houres. 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Dundas-Rice County Minnesota Education data and school information Dundas-Rice County Minnesota Education data with local analysis and research Dundas-Rice County Minnesota Education Attainment Charts This section of charts contains education data for Dundas-Rice County Minnesota based mainly on the latest year 2022 Census data using the American Community Survey but also the survey from Common Core Data available for Public Elementary through Secondary Schools. In Figure 1 , the percent of all people aged 25 years or older, who have either graduated from high school or completed the Graduate Equivalency Degree (GED) or some equivalent certification/credential. Dundas-Rice County shows it has a High School Grad or higher of 95% which is the third most percent high school graduates or better of all other places in the greater Dundas-Rice County region. The city with the highest percent high school graduates or better in the area is Northfield which shows a high school graduates of 97% ( only slightly larger). In Figure 2 , the percentage of people aged 25 years or older who have graduated from college/university with at least a bachelor's degree is provided. Note that the bachelor's degree is also called a four-year degree because it normally takes four years of full-time study to finish the course curriculum required to obtain the degree. This chart portrays the proportion of the population in this region who are college graduates with at least a bachelor degree or higher. In many ways, this analysis alongside the prior chart are very quick measures of the level of education in any particular area. Dundas-Rice County shows it has a Bachelors Degree or higher of 35% which is the second most of all the places in the metro area. The city with the highest percent with a bachelors degree or higher in the area is Northfield which shows a percent with a bachelors degree of 50% (42.7% larger). Figure 4 shows the percentage of people 25 years of age or older who either have no schooling at all or dropped out of school before being able to complete high school. Additionally, these are people who also do not have a Graduate Equivalency Degree (GED) or some other high school level type credential/student achievement. This analysis, along with the last two charts, provides another high level review and comparative data on the Dundas-Rice County Minnesota educational level. Dundas-Rice County shows it has a School Dropout Rate of 5% which is in the middle range of other places in the greater region. The city with the highest percent who dropped out of school in the area is Faribault which depicts a percent who dropped out of school of 13% (approximately 2.5 times bigger). Figure 5 provides a more detailed look at the educational attainment for Dundas-Rice County Minnesota. This chart provides the proportion of people aged 25 years of age or older and what was their level of educational attainment. The chart provides 5 broad categories including: No Education/No School, Some High School, High School or equivalent, Some college or Associates Degree, and Bachelors Degree or higher. Dundas-Rice County has the percentage of percent of people with less than a high school education less than most other places in the metro area at 23% of the total. Second, it has one of the largest proportions of percent of people with some college or an associates degree at 35% of the total and is ranked #2. The only larger city being Northfield with 50%. The next chart shows a break down of people who have received a bachelor's degree or higher advanced degree generally in a campus learning environment. In particular, Figure 6 , provides the proportional breakdown of all the people who have received a postsecondary education along with what the level of advanced degree that was obtained. Note that these categories do not include any type professional development type activities such as those related to maintaining professional credentials in workshop lessons. Note Professional Degree includes medical, dental, lawyers, etc. Dundas-Rice County has the largest proportion of percent of people with an associate degree at 48% of the total and is ranked #1. The chart in Figure 7 shows the broad area of academic concentration or the discipline for people who have received a bachelors degree. This high level classification is essentially the field of study for which a degree was obtained. Dundas-Rice County has the percentage of percent of people with a science or engineering degree in the middle range of other places in the local area at 6.7% of the total. Figure 9 provides comparative data between the places in the greater Dundas-Rice County Minnesota region for broad educational attainment. This analysis uses provides five broad education attainment categories including: No Education/No School, Some High School, High School or equivalent, Some college or Associates Degree, and Bachelors Degree or higher. Dundas-Rice County has the percentage of percent of people with less than a high school degree less than most other places in the greater region at 23.0% of the total. Second, it has one of the largest proportions of percent of people with some college or an associates degree at 35.3% of the total and is ranked #2. The only larger city being Northfield with 50.4%. A more detailed frequency distribution of educational attainment is provided in Figure 10 . In particular this illustration breaks out the highest levels of university educational opportunities beyond the four year college degree. Included in the breakout are the relative proportion of masters degrees, PhD/Doctorate/Doctorial holders, and professional degrees such as medicine, dentistry, lawyers, etc. Dundas-Rice County has the percentage of percent of people with less than high school less than most other places in the local area at 23.0% of the total. The next exhibit ( Figure 11 ) provides detailed cross tabulation analysis that provides education success data broken out or cross tabulated by age group. Please note that the columns add to 100% and you must use the pagination buttons at the bottom of the table to see all the rows. Figure 12 is a cross tabulation analysis that shows large educational success categories and is broken out or cross tabulated by racial group. Please note that the columns add to 100% and you must use the pagination buttons at the bottom of the table to see all the rows.The final cross tabulation analysis is provided in Figure 13 and shows education success broken out by gender. Please note that the columns add to 100% and you must use the pagination buttons at the bottom of the table to see all the rows. Dundas-Rice County Minnesota School Enrollment Charts The next section of chart resources look at school enrollment by a variety of educational institutions and are categorized into a number of other groupings. Figure 14 provides the overall school enrollment by broad range of school age/level groupings. Dundas-Rice County has one of the largest proportions of percent of children in kindergarten at 28.0% of the total and is ranked #2. The only larger city being Dennison with 44.7%. Second, it has one of the largest proportions of percent of children in grade 1 to 4 at 30.3% of the total and is ranked #2. The only larger city being Lonsdale with 34.4%. Third, it has less than most other places in the area when ranked by percent of children in grades 9 to 12 at 9.6% of the total. Figure 15 provides a simple high level comparison of the proportion of students that are enrolled in public schools versus students enrolled in private schools in the Dundas-Rice County Minnesota region. Dundas-Rice County depicts percent enrolled in public schools quite a bit bigger as the percent enrolled in private schools. The next comparison provided in Figure 16 shows the proportion of students enrolled in private schools versus students enrolled public schools for students enrolled in Kindergarten through 8th grade (grade 8) or (K through 8). Dundas-Rice County depicts percent of children enrolled in public k-8 grades very much bigger as the percent of children enrolled in private k-8 grades. Figure 17 provides a comparative analysis all students enrolled in a public high school versus those students who are enrolled in private high school schools. Dundas-Rice County depicts percent enrolled in a public high school very much bigger as the percent enrolled in a private high school. The next chart ( Figure 18 ) provides a similar analysis to the last chart but provides the data for public post secondary education versus private higher education colleges. Dundas-Rice County shows percent enrolled in a public college markedly bigger as the percent enrolled in a private college. Figure 19 shows another view of students enrolled in public or private schools-postsecondary schools or colleges/universities. This analysis shows the proportion for all graduate and professional schools (such as law or medical school) and whether those students are enrolled in private or public institutions. Dundas-Rice County shows percent enrolled in a public gradudate or professional school approximately half the size as the percent enrolled in a private gradudate or professional school. The next chart in this series of resources shown in Figure 20 looks at the total number of students enrolled in any educational institution for each place in the greater Dundas-Rice County region. (Total enrollment in this case includes all students from preschool all the way through students enrolled in graduate school.) Dundas-Rice County depicts it has a Total Enrolled of 537 which is in the middle range of other places in the local area. The city with the highest total population enrolled in school in the area is Northfield which depicts a total population enrolled in school of 8,924 ( quite a bit bigger). Comparing total population enrolled in school to the United States average of 81,076,829, Dundas-Rice County is only about 0.0% the size. Also, in comparison with the state of Minnesota , total population enrolled in school of 1,411,198, Dundas-Rice County is only about 0.0% the size. The final chart in this series is Figure 22 and provides analysis data for the school year shown. The chart shows the proportion of kids/children that are enrolled in a pre-school public district versus those kids/children who are enrolled in a private pre-school oriented tuition institution (private salary/superintendent/etc.) Dundas-Rice County Minnesota has one of the largest proportions of public preschool enrollment at 40% of the total and is ranked #3. Only #2 Northfield (44%), and #1 Dennison (50%) are larger. Dundas-Rice County Minnesota Area Schools Charts Figure 23 lists all the schools in the area along with the school district, county location and other program information/credential such as if they are a public charter school or private charter school or magnet school. Some of the Area Schools are: Arcadia Charter School, Northfield Middle, Bridgewater Elementary, Northfield Senior High, and Northfield Area Learning Center. The next illustration in Figure 24 shows the total child school enrollment for all grades (through 12th grade) at the school shown using NCES data (Common Core of Data, Public Elementary-Secondary School Universe Survey.) Looking at Enrollment for Area Schools we find that Northfield Senior High ranks the largest with a value of 1,242 enrolled students. The next largest values are for: Northfield Middle (926), Sibley Elementary (566), Roosevelt Elementary (559), and Bridgewater Elementary (550). The difference between the highest value (Northfield Senior High) and the next highest (Northfield Middle) is that the enrolled students is about 34.1% larger. Figure 25 show the ratio of the number of students to the number of teachers in the classroom. A good student to teacher ratio should be low because it indicates that there are less students for any one teacher to educate in a class and generally a better learning environment, better success and optimal teaching excellence. Teachers includes all educational staff such as special education teachers and any other educator. Note that distance learning (online learning/remote learning) is not included in these values. Looking at Student to Teacher Ratio for Area Schools we find that Northfield Area Learning Center ranks the largest with a value of 7.1 student to teacher ratio. The next largest values are for: Discovery Public School Faribault (8.0), Early Childhood Special Education (8.2), Arcadia Charter School (11.1), and Longfellow Elementary (11.3). The difference between the lowest value (Northfield Area Learning Center) and the next lowest (Discovery Public School Faribault) is that the student to teacher ratio is 12.1% larger. The next chart, Figure 26 , shows the racial mix of students at each location in this district of the state of Minnesota department of education. Dundas-Rice County, MinnesotaEducation Data Demographics Housing Economy Education Education Attainment School Enrollment Area Schools Healthcare <table><tr><th> Figure 1: Dundas-Rice County, MN At least High School Education<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th><th> Figure 2: Dundas-Rice County, MN Bachelors Degree or Better Education<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th></tr><tbody><tr><td> 0% 50% 100% Faribault United States Dennison Minnesota Minneapolis-St Paul Lonsdale Dundas-Rice County Dundas Nerstrand Northfield<table><tr><th> Place</th><th> High School Grad or higher</th></tr><tbody><tr><td> Faribault</td><td> 87%</td></tr><tr><td> United States</td><td> 89%</td></tr><tr><td> Dennison</td><td> 91%</td></tr><tr><td> Minnesota</td><td> 94%</td></tr><tr><td> Minneapolis-St Paul</td><td> 94%</td></tr><tr><td> Lonsdale</td><td> 95%</td></tr><tr><td> Dundas-Rice County</td><td> 95%</td></tr><tr><td> Dundas</td><td> 95%</td></tr><tr><td> Nerstrand</td><td> 95%</td></tr><tr><td> Northfield</td><td> 97%</td></tr></tbody></table> ...</td><td> 0% 50% 100% Nerstrand Faribault Dennison Lonsdale United States Dundas-Rice County Dundas Minnesota Minneapolis-St Paul Northfield<table><tr><th> Place</th><th> Bachelors Degree or higher</th></tr><tbody><tr><td> Nerstrand</td><td> 15%</td></tr><tr><td> Faribault</td><td> 18%</td></tr><tr><td> Dennison</td><td> 18%</td></tr><tr><td> Lonsdale</td><td> 21%</td></tr><tr><td> United States</td><td> 34%</td></tr><tr><td> Dundas-Rice County</td><td> 35%</td></tr><tr><td> Dundas</td><td> 35%</td></tr><tr><td> Minnesota</td><td> 38%</td></tr><tr><td> Minneapolis-St Paul</td><td> 42%</td></tr><tr><td> Northfield</td><td> 50%</td></tr></tbody></table> ...</td></tr></tbody></table> <table><tr><th> Figure 3: Advertisement<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th><th> Figure 4: Dundas-Rice County, MN School Dropout Rate<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th></tr><tbody><tr><td></td><td> 0% 10% 20% Northfield Nerstrand Dundas-Rice County Dundas Lonsdale Minneapolis-St Paul Minnesota Dennison United States Faribault<table><tr><th> Place</th><th> School Dropout Rate</th></tr><tbody><tr><td> Northfield</td><td> 3%</td></tr><tr><td> Nerstrand</td><td> 5%</td></tr><tr><td> Dundas-Rice County</td><td> 5%</td></tr><tr><td> Dundas</td><td> 5%</td></tr><tr><td> Lonsdale</td><td> 5%</td></tr><tr><td> Minneapolis-St Paul</td><td> 6%</td></tr><tr><td> Minnesota</td><td> 6%</td></tr><tr><td> Dennison</td><td> 9%</td></tr><tr><td> United States</td><td> 11%</td></tr><tr><td> Faribault</td><td> 13%</td></tr></tbody></table> ...</td></tr></tbody></table> <table><tr><th> Figure 5: Dundas-Rice County, MN Education Attainment Breakdown<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th><th> Figure 6: Higher Education Attainment (100%=All People with Bachelor or better)<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th></tr><tbody><tr><td> Some college or Associates Degree Bachelors Degree or higher High School or GED Less than High School No schooling 36.6% 23% 35.3%<table><tr><th> Place</th><th> Dundas-Rice County</th></tr><tbody><tr><td> Some college or Associates Degree</td><td> 0.366</td></tr><tr><td> Bachelors Degree or higher</td><td> 0.353</td></tr><tr><td> High School or GED</td><td> 0.23</td></tr><tr><td> Less than High School</td><td> 0.048</td></tr><tr><td> No schooling</td><td> 0.003</td></tr></tbody></table> No schooling</td><td> Bachelors degree % Associate degree % Masters degree % Professional school degree % Doctorate degree % 47.7% 15.3% 30.8%<table><tr><th> Place</th><th> Dundas-Rice County</th></tr><tbody><tr><td> Bachelors degree %</td><td> 0.477</td></tr><tr><td> Associate degree %</td><td> 0.308</td></tr><tr><td> Masters degree %</td><td> 0.153</td></tr><tr><td> Professional school degree %</td><td> 0.036</td></tr><tr><td> Doctorate degree %</td><td> 0.026</td></tr></tbody></table> Doctorate degree</td></tr></tbody></table> Figure 7: Dundas-Rice County, MN Bachelors Degrees Field of Study<here is a image 377931e4a21edf85-24ad93d40e2d87d9> Science & Engineering Science and Engineeri… Arts, Humanities, Other Business Education Dundas-Rice County Dundas Northfield Dennison Nerstrand Faribault Lonsdale United States Minnesota Minneapolis-St Paul 0% 50% 100%<table><tr><th> Place</th><th> Science & Engineering</th><th> Science and Engineering Related</th><th> Arts, Humanities, Other</th><th> Business</th><th> Education</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 31.9%</td><td> 6.7%</td><td> 23.2%</td><td> 17.5%</td><td> 20.7%</td></tr><tr><td> Dundas</td><td> 31.9%</td><td> 6.7%</td><td> 23.2%</td><td> 17.5%</td><td> 20.7%</td></tr><tr><td> Northfield</td><td> 36.5%</td><td> 6.5%</td><td> 31.9%</td><td> 9.5%</td><td> 15.7%</td></tr><tr><td> Dennison</td><td> 38.7%</td><td> 6.5%</td><td> 22.6%</td><td> 29%</td><td> 3.2%</td></tr><tr><td> Nerstrand</td><td> 37.9%</td><td> 24.1%</td><td> 24.1%</td><td> 6.9%</td><td> 6.9%</td></tr><tr><td> Faribault</td><td> 24.5%</td><td> 12.8%</td><td> 25.5%</td><td> 14%</td><td> 23.2%</td></tr><tr><td> Lonsdale</td><td> 37.5%</td><td> 8%</td><td> 24.8%</td><td> 15%</td><td> 14.7%</td></tr><tr><td> United States</td><td> 35.8%</td><td> 9.7%</td><td> 23.7%</td><td> 19.6%</td><td> 11.2%</td></tr><tr><td> Minnesota</td><td> 34.8%</td><td> 9.7%</td><td> 24.1%</td><td> 18.9%</td><td> 12.5%</td></tr><tr><td> Minneapolis-St Paul</td><td> 35.7%</td><td> 8.8%</td><td> 24.9%</td><td> 20%</td><td> 10.7%</td></tr></tbody></table> Science and Engineerin… Figure 8: Dundas-Rice County, MN Bachelors Degree Obtained<here is a image 377931e4a21edf85-24ad93d40e2d87d9> Computers, Mathemat… Biological, Agricultura… Physical and Related S… Psychology Social Sciences Engineering Multidisciplinary Studies Science and Engineering Related Business Education Literature and Languages Liberal Arts and History 1/2 Dundas-Rice County 0% 5% 10% 15% 20% 25%<table><tr><th> Place</th><th> Computers, Mathematics and Statistics</th><th> Biological, Agricultural, and Environmental Sciences</th><th> Physical and Related Sciences</th><th> Psychology</th><th> Social Sciences</th><th> Engineering</th><th> Multidisciplinary Studies</th><th> Science and Engineering Related</th><th> Business</th><th> Education</th><th> Literature and Languages</th><th> Liberal Arts and History</th><th> Visual and Performing Arts</th><th> Communications</th><th> Other</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 2.7%</td><td> 12.6%</td><td> 2%</td><td> 2.2%</td><td> 9.1%</td><td> 3.2%</td><td> 0%</td><td> 6.7%</td><td> 17.5%</td><td> 20.7%</td><td> 4.4%</td><td> 5.7%</td><td> 1.7%</td><td> 3.5%</td><td> 7.9%</td></tr></tbody></table> 0/0 Figure 9: Dundas-Rice County, MN Education Attainment by Level Comparison (Age 25+)<here is a image 377931e4a21edf85-24ad93d40e2d87d9> No schooling Less than High School High School or GED Some college or Associates Degree Bachelors Degree or higher Dundas-Rice County Dundas Northfield Dennison Nerstrand Faribault Lonsdale United States Minnesota Minneapolis-St Paul 0% 50% 100%<table><tr><th> Place</th><th> No schooling</th><th> Less than High School</th><th> High School or GED</th><th> Some college or Associates Degree</th><th> Bachelors Degree or higher</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 0.3%</td><td> 4.8%</td><td> 23%</td><td> 36.6%</td><td> 35.3%</td></tr><tr><td> Dundas</td><td> 0.3%</td><td> 4.8%</td><td> 23%</td><td> 36.6%</td><td> 35.3%</td></tr><tr><td> Northfield</td><td> 0.4%</td><td> 2.8%</td><td> 20.9%</td><td> 25.4%</td><td> 50.4%</td></tr><tr><td> Dennison</td><td> 0.6%</td><td> 8.8%</td><td> 33.1%</td><td> 39.4%</td><td> 18.1%</td></tr><tr><td> Nerstrand</td><td> 2.3%</td><td> 2.3%</td><td> 36%</td><td> 44.6%</td><td> 14.9%</td></tr><tr><td> Faribault</td><td> 3.1%</td><td> 9.7%</td><td> 41.4%</td><td> 28.1%</td><td> 17.7%</td></tr><tr><td> Lonsdale</td><td> 0.8%</td><td> 4.4%</td><td> 30.3%</td><td> 43%</td><td> 21.4%</td></tr><tr><td> United States</td><td> 1.6%</td><td> 9.5%</td><td> 26.5%</td><td> 28.7%</td><td> 33.7%</td></tr><tr><td> Minnesota</td><td> 1.4%</td><td> 5.1%</td><td> 23.9%</td><td> 32.1%</td><td> 37.6%</td></tr><tr><td> Minneapolis-St Paul</td><td> 1.6%</td><td> 4.6%</td><td> 21.4%</td><td> 30.5%</td><td> 42%</td></tr></tbody></table> Bachelors Degree or higher Figure 10: Dundas-Rice County, MN Education Attainment Detailed Comparison (Age 25+)<here is a image 377931e4a21edf85-24ad93d40e2d87d9> No schooling Less than High School High School or GED Some college Not Graduate Associate degree Bachelors degree Masters degree Professional school degree Doctorate degree Dundas-Rice County 0% 10% 20% 30%<table><tr><th> Place</th><th> No schooling</th><th> Less than High School</th><th> High School or GED</th><th> Some college Not Graduate</th><th> Associate degree</th><th> Bachelors degree</th><th> Masters degree</th><th> Professional school degree</th><th> Doctorate degree</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 0.3%</td><td> 4.8%</td><td> 23%</td><td> 20.8%</td><td> 15.8%</td><td> 24.4%</td><td> 7.8%</td><td> 1.8%</td><td> 1.3%</td></tr></tbody></table> Doctorate degree Figure 11: Dundas-Rice County, MN Detailed Education Attainment Breakout by Age Group (Age 18+)<here is a image 377931e4a21edf85-24ad93d40e2d87d9><table><tr><th> Education</th><th> 18 to 24 years</th><th> 25 to 34 years</th><th> 35 to 44 years</th><th> 45 to 64 years</th><th> 65 years and over</th></tr><tbody><tr><td colspan=1> 9th to 12th grade, no diploma</td><td colspan=1>12%</td><td colspan=1>2%</td><td colspan=1>3%</td><td colspan=1>4%</td><td colspan=1>3.5%</td></tr><tr><td colspan=1> Associates degree</td><td colspan=1>7%</td><td colspan=1>19%</td><td colspan=1>16%</td><td colspan=1>15%</td><td colspan=1>14.5%</td></tr><tr><td colspan=1> Bachelors degree</td><td colspan=1>9%</td><td colspan=1>27%</td><td colspan=1>30%</td><td colspan=1>21%</td><td colspan=1>23.7%</td></tr><tr><td colspan=1> Graduate or professional degree</td><td colspan=1>0%</td><td colspan=1>10%</td><td colspan=1>19%</td><td colspan=1>8%</td><td colspan=1>12.7%</td></tr></tbody></table> 1 2 Figure 12: Dundas-Rice County, MN Detailed Education Attainment Breakout by Race (Age 25+)<here is a image 377931e4a21edf85-24ad93d40e2d87d9><table><tr><th> Education</th><th> White</th><th> Black</th><th> American Indian</th><th> Asian</th><th> Native Hawaiian</th><th> Hispanic</th></tr><tbody><tr><td colspan=1> Bachelors degree or higher</td><td colspan=1>37%</td><td colspan=1>0%</td><td colspan=1>0%</td><td colspan=1>14%</td><td colspan=1>0%</td><td colspan=1>4.3%</td></tr><tr><td colspan=1> High school graduate or GED</td><td colspan=1>23%</td><td colspan=1>0%</td><td colspan=1>0%</td><td colspan=1>24%</td><td colspan=1>0%</td><td colspan=1>21.7%</td></tr><tr><td colspan=1> Less than high school diploma</td><td colspan=1>4%</td><td colspan=1>0%</td><td colspan=1>0%</td><td colspan=1>11%</td><td colspan=1>0%</td><td colspan=1>63.0%</td></tr><tr><td colspan=1> Some college or associates degree</td><td colspan=1>36%</td><td colspan=1>100%</td><td colspan=1>0%</td><td colspan=1>51%</td><td colspan=1>0%</td><td colspan=1>10.9%</td></tr></tbody></table> Figure 13: Dundas-Rice County, MN Detailed Male and Female breakdown of Educational Attainment<here is a image 377931e4a21edf85-24ad93d40e2d87d9><table><tr><th> Education</th><th> Total</th><th> Male</th><th> Female</th></tr><tbody><tr><td colspan=1> Associates Degree</td><td colspan=1>16%</td><td colspan=1>16%</td><td colspan=1>15.2%</td></tr><tr><td colspan=1> Bachelors Degree</td><td colspan=1>24%</td><td colspan=1>23%</td><td colspan=1>25.9%</td></tr><tr><td colspan=1> Doctorate degree</td><td colspan=1>1%</td><td colspan=1>2%</td><td colspan=1>0.5%</td></tr><tr><td colspan=1> High school/GED</td><td colspan=1>23%</td><td colspan=1>23%</td><td colspan=1>22.7%</td></tr><tr><td colspan=1> Less than High School</td><td colspan=1>5%</td><td colspan=1>6%</td><td colspan=1>3.9%</td></tr><tr><td colspan=1> Masters degree</td><td colspan=1>8%</td><td colspan=1>8%</td><td colspan=1>7.9%</td></tr><tr><td colspan=1> No schooling completed</td><td colspan=1>0%</td><td colspan=1>1%</td><td colspan=1>0%</td></tr><tr><td colspan=1> Professional school degree</td><td colspan=1>2%</td><td colspan=1>1%</td><td colspan=1>2.9%</td></tr><tr><td colspan=1> Some college-No Degree</td><td colspan=1>21%</td><td colspan=1>21%</td><td colspan=1>21.1%</td></tr><tr><td colspan=1> Total</td><td colspan=1>100%</td><td colspan=1>47%</td><td colspan=1>53.5%</td></tr></tbody></table> Figure 14: Dundas-Rice County, MN School Enrollment by Aggregate Categories<here is a image 377931e4a21edf85-24ad93d40e2d87d9> Kindergarten Grade 1 to 4 Grade 5 to 8 Grade 9 to 12 College, undergraduate Graduate or prof school Dundas-Rice County Dundas Northfield Dennison Nerstrand Faribault Lonsdale United States Minnesota Minneapolis-St Paul 0% 50% 100%<table><tr><th> Place</th><th> Kindergarten</th><th> Grade 1 to 4</th><th> Grade 5 to 8</th><th> Grade 9 to 12</th><th> College, undergraduate</th><th> Graduate or prof school</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 4.8%</td><td> 28%</td><td> 30.3%</td><td> 23.8%</td><td> 9.6%</td><td> 3.6%</td></tr><tr><td> Dundas</td><td> 4.8%</td><td> 28%</td><td> 30.3%</td><td> 23.8%</td><td> 9.6%</td><td> 3.6%</td></tr><tr><td> Northfield</td><td> 1.6%</td><td> 7.6%</td><td> 12.1%</td><td> 8.9%</td><td> 68%</td><td> 1.9%</td></tr><tr><td> Dennison</td><td> 15.8%</td><td> 44.7%</td><td> 10.5%</td><td> 26.3%</td><td> 2.6%</td><td> 0%</td></tr><tr><td> Nerstrand</td><td> 6.2%</td><td> 6.2%</td><td> 29.2%</td><td> 29.2%</td><td> 22.9%</td><td> 6.2%</td></tr><tr><td> Faribault</td><td> 10.3%</td><td> 26.5%</td><td> 22.4%</td><td> 27.8%</td><td> 12.3%</td><td> 0.8%</td></tr><tr><td> Lonsdale</td><td> 4.2%</td><td> 19%</td><td> 34.4%</td><td> 23.8%</td><td> 14%</td><td> 4.7%</td></tr><tr><td> United States</td><td> 5.3%</td><td> 21.1%</td><td> 22.3%</td><td> 22.6%</td><td> 23%</td><td> 5.8%</td></tr><tr><td> Minnesota</td><td> 5.6%</td><td> 21.9%</td><td> 22.8%</td><td> 23%</td><td> 21.3%</td><td> 5.4%</td></tr><tr><td> Minneapolis-St Paul</td><td> 5.6%</td><td> 21.9%</td><td> 22.7%</td><td> 23.1%</td><td> 20.9%</td><td> 5.9%</td></tr></tbody></table> Graduate or prof school <table><tr><th> Figure 15: Dundas-Rice County, MN Overall Public vs. Private School Enrollment<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th><th> Figure 16: Dundas-Rice County, MN Public vs. Private K-8 School Enrollment<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th></tr><tbody><tr><td> Public Sc… Private S… 0% 50% 100% Dundas-Rice County Dundas Northfield Dennison Nerstrand Faribault Lonsdale United States Minnesota Minneapolis-St Paul<table><tr><th> Place</th><th> Public School Enrollment</th><th> Private School Enrollment</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 91%</td><td> 9%</td></tr><tr><td> Dundas</td><td> 91%</td><td> 9%</td></tr><tr><td> Northfield</td><td> 33%</td><td> 67%</td></tr><tr><td> Dennison</td><td> 95%</td><td> 5%</td></tr><tr><td> Nerstrand</td><td> 92%</td><td> 8%</td></tr><tr><td> Faribault</td><td> 86%</td><td> 14%</td></tr><tr><td> Lonsdale</td><td> 94%</td><td> 6%</td></tr><tr><td> United States</td><td> 83%</td><td> 17%</td></tr><tr><td> Minnesota</td><td> 85%</td><td> 15%</td></tr><tr><td> Minneapolis-St Paul</td><td> 84%</td><td> 16%</td></tr></tbody></table> Private Sc…</td><td> Public K-… Private K… 0% 50% 100% Dundas-Rice County Dundas Northfield Dennison Nerstrand Faribault Lonsdale United States Minnesota Minneapolis-St Paul<table><tr><th> Place</th><th> Public K-8 Enrollment</th><th> Private K-8 Enrollment</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 95%</td><td> 5%</td></tr><tr><td> Dundas</td><td> 95%</td><td> 5%</td></tr><tr><td> Northfield</td><td> 92%</td><td> 8%</td></tr><tr><td> Dennison</td><td> 100%</td><td> 0%</td></tr><tr><td> Nerstrand</td><td> 100%</td><td> 0%</td></tr><tr><td> Faribault</td><td> 84%</td><td> 16%</td></tr><tr><td> Lonsdale</td><td> 95%</td><td> 5%</td></tr><tr><td> United States</td><td> 88%</td><td> 12%</td></tr><tr><td> Minnesota</td><td> 89%</td><td> 11%</td></tr><tr><td> Minneapolis-St Paul</td><td> 89%</td><td> 11%</td></tr></tbody></table> Private K-…</td></tr></tbody></table> <table><tr><th> Figure 17: Dundas-Rice County, MN Public vs. Private High School Enrollment<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th><th> Figure 18: Dundas-Rice County, MN Public vs. Private College Enrollment<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th></tr><tbody><tr><td> Public Hi… Private… 0% 50% 100% Dundas-Rice County Dundas Northfield Dennison Nerstrand Faribault Lonsdale United States Minnesota Minneapolis-St Paul<table><tr><th> Place</th><th> Public High School Enrollment</th><th> Private High School Enrollment</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 94%</td><td> 6%</td></tr><tr><td> Dundas</td><td> 94%</td><td> 6%</td></tr><tr><td> Northfield</td><td> 97%</td><td> 3%</td></tr><tr><td> Dennison</td><td> 100%</td><td> 0%</td></tr><tr><td> Nerstrand</td><td> 93%</td><td> 7%</td></tr><tr><td> Faribault</td><td> 89%</td><td> 11%</td></tr><tr><td> Lonsdale</td><td> 100%</td><td> 0%</td></tr><tr><td> United States</td><td> 89%</td><td> 11%</td></tr><tr><td> Minnesota</td><td> 92%</td><td> 8%</td></tr><tr><td> Minneapolis-St Paul</td><td> 92%</td><td> 8%</td></tr></tbody></table> Private H…</td><td> Public C… Private C… 0% 50% 100% Dundas-Rice County Dundas Northfield Dennison Nerstrand Faribault Lonsdale United States Minnesota Minneapolis-St Paul<table><tr><th> Place</th><th> Public College Enrollment</th><th> Private College Enrollment</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 86%</td><td> 14%</td></tr><tr><td> Dundas</td><td> 86%</td><td> 14%</td></tr><tr><td> Northfield</td><td> 5%</td><td> 95%</td></tr><tr><td> Dennison</td><td> 0%</td><td> 100%</td></tr><tr><td> Nerstrand</td><td> 73%</td><td> 27%</td></tr><tr><td> Faribault</td><td> 92%</td><td> 9%</td></tr><tr><td> Lonsdale</td><td> 92%</td><td> 8%</td></tr><tr><td> United States</td><td> 78%</td><td> 22%</td></tr><tr><td> Minnesota</td><td> 77%</td><td> 23%</td></tr><tr><td> Minneapolis-St Paul</td><td> 75%</td><td> 25%</td></tr></tbody></table> Private Co…</td></tr></tbody></table> <table><tr><th> Figure 19: Dundas-Rice County, MN Public vs. Private Graduate or Professional School Enrollment<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th><th> Figure 20: Dundas-Rice County, MN Total Enrolled in Schools<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th></tr><tbody><tr><td> Public Gr… Private… 0% 50% 100% Dundas-Rice County Dundas Northfield Nerstrand Faribault Lonsdale United States Minnesota Minneapolis-St Paul<table><tr><th> Place</th><th> Public Gradudate or Pro school enrollment</th><th> Private Gradudate or Pro school enrollment</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 37%</td><td> 63%</td></tr><tr><td> Dundas</td><td> 37%</td><td> 63%</td></tr><tr><td> Northfield</td><td> 51%</td><td> 49%</td></tr><tr><td> Nerstrand</td><td> 100%</td><td> 0%</td></tr><tr><td> Faribault</td><td> 76%</td><td> 24%</td></tr><tr><td> Lonsdale</td><td> 81%</td><td> 19%</td></tr><tr><td> United States</td><td> 60%</td><td> 40%</td></tr><tr><td> Minnesota</td><td> 64%</td><td> 36%</td></tr><tr><td> Minneapolis-St Paul</td><td> 63%</td><td> 37%</td></tr></tbody></table> Private G…</td><td> 0 5,000 10,000 Dennison Nerstrand Dundas-Rice County Dundas Lonsdale Faribault Northfield<table><tr><th> Place</th><th> Total Enrolled</th></tr><tbody><tr><td> Dennison</td><td> 40</td></tr><tr><td> Nerstrand</td><td> 48</td></tr><tr><td> Dundas-Rice County</td><td> 537</td></tr><tr><td> Dundas</td><td> 537</td></tr><tr><td> Lonsdale</td><td> 1,578</td></tr><tr><td> Faribault</td><td> 5,330</td></tr><tr><td> Northfield</td><td> 8,924</td></tr></tbody></table> ...</td></tr></tbody></table> <table><tr><th> Figure 21: Advertisement<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th><th> Figure 22: Dundas-Rice County, MN Public vs. Private Preschool<here is a image 377931e4a21edf85-24ad93d40e2d87d9></th></tr><tbody><tr><td></td><td> Public pr… Private p… 0% 50% 100% Dundas-Rice County Dundas Northfield Dennison Faribault Lonsdale United States Minnesota Minneapolis-St Paul<table><tr><th> Place</th><th> Public preschool enrollment</th><th> Private preschool enrollment</th></tr><tbody><tr><td> Dundas-Rice County</td><td> 60%</td><td> 40%</td></tr><tr><td> Dundas</td><td> 60%</td><td> 40%</td></tr><tr><td> Northfield</td><td> 56%</td><td> 44%</td></tr><tr><td> Dennison</td><td> 50%</td><td> 50%</td></tr><tr><td> Faribault</td><td> 77%</td><td> 23%</td></tr><tr><td> Lonsdale</td><td> 81%</td><td> 19%</td></tr><tr><td> United States</td><td> 59%</td><td> 41%</td></tr><tr><td> Minnesota</td><td> 66%</td><td> 34%</td></tr><tr><td> Minneapolis-St Paul</td><td> 62%</td><td> 38%</td></tr></tbody></table> Private pr…</td></tr></tbody></table> Figure 23: List of Schools in the Dundas-Rice County, MN Area (2013)<here is a image 377931e4a21edf85-24ad93d40e2d87d9><table><tr><th> School Name</th><th> School District</th><th> School Level</th><th> Grade Range</th><th> Magnet School</th><th> Charter School</th></tr><tbody><tr><td colspan=1> Sibley Elementary</td><td colspan=1> Northfield Public School District</td><td colspan=1> Primary School</td><td colspan=1> K to 5</td><td colspan=1> No</td><td colspan=1> No</td></tr><tr><td colspan=1> Roosevelt Elementary</td><td colspan=1> Faribault Public School District</td><td colspan=1> Primary School</td><td colspan=1> K to 5</td><td colspan=1> No</td><td colspan=1> No</td></tr><tr><td colspan=1> Prairie Creek Community School</td><td colspan=1> Prairie Creek Community School</td><td colspan=1> Primary School</td><td colspan=1> K to 5</td><td colspan=1> No</td><td colspan=1> Yes</td></tr><tr><td colspan=1> Northfield Senior High</td><td colspan=1> Northfield Public School District</td><td colspan=1> High School</td><td colspan=1> 9 to 12</td><td colspan=1> No</td><td colspan=1> No</td></tr><tr><td colspan=1> Northfield Middle</td><td colspan=1> Northfield Public School District</td><td colspan=1> Middle School</td><td colspan=1> 6 to 8</td><td colspan=1> No</td><td colspan=1> No</td></tr><tr><td colspan=1> Northfield Area Learning Center</td><td colspan=1> Northfield Public School District</td><td colspan=1> Other</td><td colspan=1> 6 to 12</td><td colspan=1> No</td><td colspan=1> No</td></tr><tr><td colspan=1> Nerstrand Charter School</td><td colspan=1> Nerstrand Charter School</td><td colspan=1> Primary School</td><td colspan=1> K to 5</td><td colspan=1> No</td><td colspan=1> Yes</td></tr><tr><td colspan=1> Longfellow Elementary</td><td colspan=1> Northfield Public School District</td><td colspan=1> Primary School</td><td colspan=1> PK to PK</td><td colspan=1> No</td><td colspan=1> No</td></tr><tr><td colspan=1> Greenvale Park Elementary</td><td colspan=1> Northfield Public School District</td><td colspan=1> Primary School</td><td colspan=1> K to 5</td><td colspan=1> No</td><td colspan=1> No</td></tr><tr><td colspan=1> Faribault Area Learning Center</td><td colspan=1> Faribault Public School District</td><td colspan=1> High School</td><td colspan=1> 9 to 12</td><td colspan=1> No</td><td colspan=1> No</td></tr></tbody></table> 1 2 Figure 24: Dundas-Rice County, MN School Enrollment (2013)<here is a image 377931e4a21edf85-24ad93d40e2d87d9> Enrollment Northfield Area Learning Center Discovery Public School Faribault Longfellow Elementary Early Childhood Special Education Faribault Area Learning Center Arcadia Charter School Nerstrand Charter School Prairie Creek Community School Cannon River Stem School Greenvale Park Elementary Bridgewater Elementary Roosevelt Elementary Sibley Elementary Northfield Middle Northfield Senior High 0 1000 2000<table><tr><th> School Name</th><th> Enrollment</th></tr><tbody><tr><td> Northfield Area Learning Center</td><td> 44</td></tr><tr><td> Discovery Public School Faribault</td><td> 51</td></tr><tr><td> Longfellow Elementary</td><td> 71</td></tr><tr><td> Early Childhood Special Education</td><td> 92</td></tr><tr><td> Faribault Area Learning Center</td><td> 108</td></tr><tr><td> Arcadia Charter School</td><td> 126</td></tr><tr><td> Nerstrand Charter School</td><td> 153</td></tr><tr><td> Prairie Creek Community School</td><td> 180</td></tr><tr><td> Cannon River Stem School</td><td> 255</td></tr><tr><td> Greenvale Park Elementary</td><td> 502</td></tr><tr><td> Bridgewater Elementary</td><td> 550</td></tr><tr><td> Roosevelt Elementary</td><td> 559</td></tr><tr><td> Sibley Elementary</td><td> 566</td></tr><tr><td> Northfield Middle</td><td> 926</td></tr><tr><td> Northfield Senior High</td><td> 1,242</td></tr></tbody></table> Enrollment Figure 25: Student to Teacher Ratios (2013) - Low Scores Are Better<here is a image 377931e4a21edf85-24ad93d40e2d87d9> Student to Teacher Ratio Northfield Area Learning Center Discovery Public School Faribault Early Childhood Special Education Arcadia Charter School Longfellow Elementary Faribault Area Learning Center Greenvale Park Elementary Bridgewater Elementary Roosevelt Elementary Cannon River Stem School Sibley Elementary Prairie Creek Community School Nerstrand Charter School Northfield Middle Northfield Senior High 0 20 40<table><tr><th> School Name</th><th> Student to Teacher Ratio</th></tr><tbody><tr><td> Northfield Area Learning Center</td><td> 7.1</td></tr><tr><td> Discovery Public School Faribault</td><td> 8</td></tr><tr><td> Early Childhood Special Education</td><td> 8.2</td></tr><tr><td> Arcadia Charter School</td><td> 11.1</td></tr><tr><td> Longfellow Elementary</td><td> 11.3</td></tr><tr><td> Faribault Area Learning Center</td><td> 12.3</td></tr><tr><td> Greenvale Park Elementary</td><td> 13.2</td></tr><tr><td> Bridgewater Elementary</td><td> 13.7</td></tr><tr><td> Roosevelt Elementary</td><td> 13.7</td></tr><tr><td> Cannon River Stem School</td><td> 13.8</td></tr><tr><td> Sibley Elementary</td><td> 14.9</td></tr><tr><td> Prairie Creek Community School</td><td> 16.1</td></tr><tr><td> Nerstrand Charter School</td><td> 18.4</td></tr><tr><td> Northfield Middle</td><td> 19.5</td></tr><tr><td> Northfield Senior High</td><td> 20.7</td></tr></tbody></table> Student to Teacher Ratio Figure 26: Dundas-Rice County, MN School Racial Mix (2013)<here is a image 377931e4a21edf85-24ad93d40e2d87d9> White Black Hispanic Asian Pacific Islander American Indian Two or More Races Roosevelt Elementary Early Childhood Special Education Faribault Area Learning Center Greenvale Park Elementary Longfellow Elementary Discovery Public School Faribault Northfield Area Learning Center Northfield Middle Sibley Elementary Northfield Senior High Cannon River Stem School Bridgewater Elementary Arcadia Charter School Prairie Creek Community School Nerstrand Charter School 0% 50% 100%<table><tr><th> School Name</th><th> White</th><th> Black</th><th> Hispanic</th><th> Asian</th><th> Pacific Islander</th><th> American Indian</th><th> Two or More Races</th></tr><tbody><tr><td> Roosevelt Elementary</td><td> 57.4%</td><td> 6.1%</td><td> 34.7%</td><td> 1.3%</td><td> 0%</td><td> 0.2%</td><td> 0.4%</td></tr><tr><td> Early Childhood Special Education</td><td> 65.2%</td><td> 4.3%</td><td> 25%</td><td> 1.1%</td><td> 0%</td><td> 1.1%</td><td> 3.3%</td></tr><tr><td> Faribault Area Learning Center</td><td> 68.5%</td><td> 4.6%</td><td> 25%</td><td> 0.9%</td><td> 0%</td><td> 0.9%</td><td> 0%</td></tr><tr><td> Greenvale Park Elementary</td><td> 68.7%</td><td> 0.6%</td><td> 26.7%</td><td> 2.2%</td><td> 0%</td><td> 0%</td><td> 1.8%</td></tr><tr><td> Longfellow Elementary</td><td> 71.8%</td><td> 0%</td><td> 25.4%</td><td> 0%</td><td> 0%</td><td> 0%</td><td> 2.8%</td></tr><tr><td> Discovery Public School Faribault</td><td> 72.5%</td><td> 5.9%</td><td> 11.8%</td><td> 0%</td><td> 0%</td><td> 3.9%</td><td> 5.9%</td></tr><tr><td> Northfield Area Learning Center</td><td> 79.5%</td><td> 2.3%</td><td> 18.2%</td><td> 0%</td><td> 0%</td><td> 0%</td><td> 0%</td></tr><tr><td> Northfield Middle</td><td> 83.7%</td><td> 1.6%</td><td> 11.6%</td><td> 1.7%</td><td> 0%</td><td> 0.1%</td><td> 1.3%</td></tr><tr><td> Sibley Elementary</td><td> 84.3%</td><td> 1.9%</td><td> 10.1%</td><td> 1.9%</td><td> 0%</td><td> 0.2%</td><td> 1.6%</td></tr><tr><td> Northfield Senior High</td><td> 86.6%</td><td> 0.9%</td><td> 8.8%</td><td> 2.3%</td><td> 0%</td><td> 0.2%</td><td> 1.3%</td></tr><tr><td> Cannon River Stem School</td><td> 86.7%</td><td> 2%</td><td> 6.3%</td><td> 0.4%</td><td> 0%</td><td> 0.4%</td><td> 4.3%</td></tr><tr><td> Bridgewater Elementary</td><td> 86.7%</td><td> 1.5%</td><td> 7.8%</td><td> 1.6%</td><td> 0%</td><td> 0.5%</td><td> 1.8%</td></tr><tr><td> Arcadia Charter School</td><td> 88.9%</td><td> 0%</td><td> 4.8%</td><td> 3.2%</td><td> 0%</td><td> 0%</td><td> 3.2%</td></tr><tr><td> Prairie Creek Community School</td><td> 91.7%</td><td> 0%</td><td> 2.2%</td><td> 1.7%</td><td> 1.7%</td><td> 0.6%</td><td> 2.2%</td></tr><tr><td> Nerstrand Charter School</td><td> 98.7%</td><td> 0%</td><td> 0%</td><td> 1.3%</td><td> 0%</td><td> 0%</td><td> 0%</td></tr></tbody></table> Two or More Races 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<here is a image 81d2476066588f4e-267363bb7eb3110b>icon in upper right corner of each chart for information.	https://www.towncharts.com/Minnesota/Education/Dundas-city-Rice-County-MN-Education-data.html
Internet Engineering Task Force T. Fossati Internet-Draft KoanLogic Intended status: Standards Track P. Giacomin Expires: September 11, 2012 Freelance S. Loreto Ericsson March 10, 2012 Publish and Monitor Options for CoAP draft-fossati-core-publish-monitor-options-01 Abstract This memo defines two additional Options for the Constrained Application Protocol (CoAP) especially targeted at sleepy sensors: Publish and Monitor. The Publish Option enables opportunistic updates of a given resource state, by temporarily delegating the authority of the Publish'ed resource to a Proxy node. The whole process is driven by the (sleepy) origin -- which may actually never need to listen. The Monitor Option complements the typical Observe pattern, enabling the tracking of a resource hosted by a node sleeping most of the time, by taking care of establishing and maintaining an Observe relationship with the (sleepy) origin on behalf of the (sleepy) client. Status of this Memo This Internet-Draft is submitted in full conformance with the provisions of BCP 78 and BCP 79. Internet-Drafts are working documents of the Internet Engineering Task Force (IETF). Note that other groups may also distribute working documents as Internet-Drafts. The list of current Internet- Drafts is at http://datatracker.ietf.org/drafts/current/. Internet-Drafts are draft documents valid for a maximum of six months and may be updated, replaced, or obsoleted by other documents at any time. It is inappropriate to use Internet-Drafts as reference material or to cite them other than as "work in progress." This Internet-Draft will expire on September 11, 2012. Copyright Notice Fossati, et al. Expires September 11, 2012 [Page 1] Internet-Draft Publish and Monitor Options for CoAP March 2012 Copyright (c) 2012 IETF Trust and the persons identified as the document authors. All rights reserved. This document is subject to BCP 78 and the IETF Trust's Legal Provisions Relating to IETF Documents (http://trustee.ietf.org/license-info) in effect on the date of publication of this document. Please review these documents carefully, as they describe your rights and restrictions with respect to this document. Code Components extracted from this document must include Simplified BSD License text as described in Section 4.e of the Trust Legal Provisions and are provided without warranty as described in the Simplified BSD License. Table of Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.1. Requirements Language and Motivation . . . . . . . . . . . 3 2. Options . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.1. Publish Option . . . . . . . . . . . . . . . . . . . . . . 4 2.1.1. Publishing a Resource . . . . . . . . . . . . . . . . 4 2.1.2. Updating a Resource . . . . . . . . . . . . . . . . . 5 2.1.3. Unpublishing a Resource . . . . . . . . . . . . . . . 6 2.1.4. Value Format . . . . . . . . . . . . . . . . . . . . . 6 2.1.5. Discovery . . . . . . . . . . . . . . . . . . . . . . 6 2.1.5.1. Publishing the /.well-known/core Resource . . . . 6 2.1.5.2. Resource Directory . . . . . . . . . . . . . . . . 7 2.2. Monitor Option . . . . . . . . . . . . . . . . . . . . . . 7 2.2.1. Public Monitor Registration . . . . . . . . . . . . . 8 2.2.2. Monitor De-registration . . . . . . . . . . . . . . . 9 2.2.2.1. Explicit De-registration . . . . . . . . . . . . . 10 2.2.2.2. Implicit De-registration . . . . . . . . . . . . . 10 2.2.3. Resource Refresh . . . . . . . . . . . . . . . . . . . 10 3. Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . 10 4. IANA Considerations . . . . . . . . . . . . . . . . . . . . . 10 5. Security Considerations . . . . . . . . . . . . . . . . . . . 11 6. References . . . . . . . . . . . . . . . . . . . . . . . . . . 11 6.1. Normative References . . . . . . . . . . . . . . . . . . . 11 6.2. Informative References . . . . . . . . . . . . . . . . . . 12 Authors' Addresses . . . . . . . . . . . . . . . . . . . . . . . . 12 Fossati, et al. Expires September 11, 2012 [Page 2] Internet-Draft Publish and Monitor Options for CoAP March 2012 1. Introduction The proposal described in this memo covers the following use case: a node N, which is sleeping most of the time, depends one or more resources hosted at another sleepy node M. In cases as such, the probability of an empty intersection between their respective wake periods is very high, making it hard for the two to synchronize. In this scenario, using the basic observe [I-D.ietf-core-observe] functionality is not enough, as it could lead to lost state updates in case N is offline while M pushes its notifications; further, the observation may never bootstrap since its initialization needs both client and origin awake at the same time. This memo introduces two extensions to the Proxy caching functionality that give the Proxy an explicit mediation role in the sleepy-to-sleepy CoAP [I-D.ietf-core-coap] communication. 1.1. Requirements Language and Motivation The key words "MUST", "MUST NOT", "REQUIRED", "SHALL", "SHALL NOT", "SHOULD", "SHOULD NOT", "RECOMMENDED", "MAY", and "OPTIONAL" in this document are to be interpreted as described in [RFC2119]. This specification makes use of the following terminology: Sleepy Device: a sensor/actuator (usually battery operated) that powers down its radio beyond the normal radio duty cycle in order to save energy. and tries to provide an in-protocol solution for the requirement REQ3 stated in [I-D.shelby-core-coap-req]: The ability to deal with sleeping nodes. Devices may be powered down at any point in time but periodically "wake up" for brief periods of time. 2. Options +-----+----------+---------+--------+--------+---------+ \| No. \| C/E \| Name \| Format \| Length \| Default \| +-----+----------+---------+--------+--------+---------+ \| YY \| Critical \| Publish \| uint \| 1 B \| 0x2 \| \| XX \| Critical \| Monitor \| (none) \| 0 B \| (none) \| +-----+----------+---------+--------+--------+---------+ Fossati, et al. Expires September 11, 2012 [Page 3] Internet-Draft Publish and Monitor Options for CoAP March 2012 2.1. Publish Option The Publish Option enables the sleepy origin to temporarily (i.e. for a specified "lease" time) delegate the authority of one of its hosted resources to a Proxy node that will start to behave as the origin for the Publish'ed resource. This allows a sleepy sensor to use the Proxy as the rendezvous point for one-way sleepy to sleepy signaling. 2.1.1. Publishing a Resource P S \| PUT \| Proxy-URI: coap://sleepy.example.org/res \|<--------+ Publish: 0110 \| r \| Content-Type: text/plain \| \| ETag: 0xabcd \| \| Max-Age: 1200 \| \| \| 2.01 \| +-------->\| \| \| Figure 1 The origin server publishes one of its hosted resources, specified by the enclosed Proxy-URI, by PUT'ing it to the Proxy with a Publish Option attached. The Publish Option value specifies the CoAP methods that clients are allowed to use on the resource (see Section 2.1.4). The example in Figure 1 shows a delegation where the GET and PUT methods are allowed while POST and DELETE are explicitly prohibited, meaning that the resource can be read and updated by clients, but it can't be deleted nor created. The Proxy, which is voluntarily charged by the resource owner to act as the delegated origin for the "lease" time specified by Max-Age, replies with a 2.01 if the authority transfer has succeeded. An exact duplicate of the submitted representation is created, and from now on it can be accessed using the original URI provided that clients go through the delegated Proxy. If the Publish operation does not succeed, the origin transfer fails, and an appropriate response code is returned. An ETag MAY be supplied as a metadata to be included in responses involving the Publish'ed representation. If no Max-Age is given, a default of 3600 seconds MUST be assumed. The Max-Age value, either implicit or explicit, determines the lifetime of the origin delegation. When the Max-Age value is elapsed, the Proxy MUST delete the Publish'ed resource value and fall back to its usual proxying Fossati, et al. Expires September 11, 2012 [Page 4] Internet-Draft Publish and Monitor Options for CoAP March 2012 function. The Publish Option is critical and MUST be present in the request only. If the Proxy does not recognize it, a 4.02 (Bad Option) MUST be returned to the client. If the option value is not correctly formatted (see Section 2.1.4), a 4.00 (Bad Request) MUST be returned to the client. It is sufficient for any client wishing to access the resource to do so using the Proxy node that, following the Publish operation, will start behaving a the origin, satisfying requests on behalf of the sleeping node. The Proxy MUST save the identity of the resource Publish'er in order to distinguish "maintainance" operations such as update and explicit deletion, from "regular" access to the published resource by clients. An interesting outcome of this communication strategy is that the sleepy origin may really never need to listen on its radio interface. 2.1.2. Updating a Resource P S \| PUT \| Proxy-URI: coap://sleepy.example.org/res \|<--------+ Publish: 0110 \| r \| Content-Type: text/plain \| \| ETag: 0xdcba \| \| Max-Age: 1200 \| \| \| 2.04 \| +-------->\| \| \| Figure 2 In order to update the delegated resource state, the sleepy node shall send the very same request to the Proxy, which in turn replies with a 2.04 (Changed) status code in case the update operation has succeeded, or an appropriate error code in case it fails. Fossati, et al. Expires September 11, 2012 [Page 5] Internet-Draft Publish and Monitor Options for CoAP March 2012 2.1.3. Unpublishing a Resource P S \| DELETE \| Proxy-URI: coap://sleepy.example.org/res \|<---------+ Publish: 0x0 \| \| \| \| \| 2.02 \| +--------->\| \| \| The delegation of a given resource can be explicitly revoked by the real origin at any time before the lease time expires, by issuing a DELETE request to the Proxy hosting the resource duplicate with a Publish Option with value 0x0. On successful deletion of the delegation a 2.02 (Deleted) response code is returned by the Proxy. 2.1.4. Value Format 0 1 2 3 4 5 6 7 +-+-+-+-+-+-+-+-+ \|C R U D 0 0 0 0\| +-+-+-+-+-+-+-+-+ Each of the first 4 bits is a flag field indicating whether the associated CoAP method (respectively: POST, GET, PUT and DELETE) is allowed on the Publish'ed resource. The remaining 4 bits are unused and MUST be set to 0. In case the value is missing, the default is assumed to be 0x2, i.e. the resource is read-only. An all-0 value is used to explicitly revoke the delegation (see Section 2.1.3.) If the delegated Proxy receives a request with a method that is not compatible with the supplied mask, it MUST respond with a 4.05 (Method Not Allowed) response code. 2.1.5. Discovery 2.1.5.1. Publishing the /.well-known/core Resource The [I-D.ietf-core-link-format] has no explicit text about "well- known" discovery of devices through a Proxy, nor about the cacheability rules for such resource. Even if it seems reasonable to Fossati, et al. Expires September 11, 2012 [Page 6] Internet-Draft Publish and Monitor Options for CoAP March 2012 assume that the /.well-known/core URI is both query-able and cacheable through a Proxy, on the contrary the situation is not very much so. In fact, since the "well-known" interface relies on the resource origin being implicitly defined by the source address of the UDP packet carrying the response, quering the "well-known" interface (either unicast or multicast) through a Proxy-URI has little hope to be fully functional. The (ab)use of a an implicit L3 locator as the identifier of the resource authority makes "well-known" discovery generally incompatible with Proxy mediated communication, unless each target URI in a link is given as a URI and not as a relative-ref (section 4.1 of [RFC3986]). Consequently, in this proposal we assume that the /.well-known/core of a sleepy node can be Publish'ed if and only if the target URI in the each link is not a relative-ref. Its registration is the same as in Figure 1, but the Proxy MAY need to treat it in a way that is slightly different from other "normal" delegated resources. In fact, while delegation is in place (i.e. the lease period is not elapsed, and neither explicit revocation has happened) the Proxy MAY be able to respond to filtered queries (section 4.1 of [I-D.ietf-core-link-format]) regarding the Publish'ed /.well-known/core. 2.1.5.2. Resource Directory Given the strong requirement on the link formatting given in Section 2.1.5.1, it could be preferable (or even necessary) to use the Resource Directory [I-D.shelby-core-resource-directory] as a means of delegating the discovery of the resources hosted at a sleepy node. This can be done either by the sleepy node, or automatically by the delegated Proxy when a Publish request is received. [[Automatic push to RD: check it out]] 2.2. Monitor Option The Monitor Option is a variant of the Observe Option that is aimed at solving some issues that may occur when sleepy sensors are involved. Suppose that the resource of interest is not in cache, and a sleepy endpoint wants to Observe it through the Proxy. If the origin of the requested resource is sleeping at the time the observation is Fossati, et al. Expires September 11, 2012 [Page 7] Internet-Draft Publish and Monitor Options for CoAP March 2012 requested, the requesting node gets an error, and may need to stay awake and retry until the target node gets ready -- which is clearly not an option in case the sensor has a very small duty cycle. The Monitor Option is used to ask a Proxy to keep a given resource fresh by observing it, while the requesting node is sleeping. Thus the sleepy sensor can possibly get the latest representation published by the monitored resource when it wakes up, even if the origin is sleeping -- and was sleeping at the time the Monitor has been requested. The Monitor Option is critical and MUST be present in the request only. If the Proxy does not recognize it, a 4.02 (Bad Option) MUST be returned to the client. 2.2.1. Public Monitor Registration P C \| POST \| Proxy-URI: coap://sleepy.example.org/res \|<-------+ Monitor: <empty> \| \| Max-Age: 86400 \| \| Content-Type: application/json \| 2.01 \| +------->\| Location-Path: temp \| \| Location-Path: res \| \| Figure 3 The client POST's the resource to be monitored, identified by the Proxy-URI. The request message contains an empty Monitor Option, and possibly specifies a TTL (i.e. an implicit de-registration indication) for the monitor through Max-Age. One or more content types for the acceptable representations of the resource are optionally specified via the Accept option. In case no TTL is supplied, a default value of 3600 seconds is assumed. The operation creates a "monitor" resource at the Proxy, that MUST maintain a fresh carbon copy of one or more representations of the requested resource depending on the supplied Content-Type's. For convenience, multiple "monitor" resources corresponding to the same target resource, can be coalesced into the same monitor object at the Proxy -- possibly with the same URI. In such case, a set containing one entry for each registered client is kept, which holds the client identities, their expiry and one or more preferred media types for their representation(s). When all entries are deleted (either because clients have explicitly deregistered the monitor, or the monitor period has expired), the corresponding "monitor" object is Fossati, et al. Expires September 11, 2012 [Page 8] Internet-Draft Publish and Monitor Options for CoAP March 2012 deleted. Note that an underlying cache entry MAY still be kept in case the cached representation(s) are still fresh (i.e. the Max-Age of the "monitor" resource and Max-Age of the target resource have completely different semantics.) If the monitor resource is successfully created, the server MUST return a 2.01 response containing one or more Location-Path and/or Location-Query Options to identify the monitored resource instance, which can be used from now on by the requester as an alias to the target resource. At a later time, the client wakes up and wants to access the monitored resource. It does so by requesting the Proxy monitor resource that has been previously created. P C \| GET \| URI-Path: temp \|<-------+ URI-Path: res \| \| Accept: application/json \| \| \| 2.05 \| +------->\| (Content) \| \| \| \| Figure 4 In case the observation on the target node has not been started because the Proxy has not yet been able to contact the origin, the Proxy will return a [TBD] error code. In case the requested resource was not present on the origin, the Proxy will return an empty response (i.e. one with no payload.) [[XXX: add an explicit response code perhaps like HTTP 204 ?]] In case the monitor resource is not found in the Proxy, either because the Proxy has rebooted and lost its state, or the monitor resource has been de-registered (see Section 2.2.2), a 4.04 response code is returned to the client -- that can recreate it, if needed. 2.2.2. Monitor De-registration The monitor object MUST be deleted at the Proxy when all its associated resources have been de-registered or have expired. In order to save storage, a Proxy MAY decide to delete a monitor resource in case it has not been requested for a sufficiently long Fossati, et al. Expires September 11, 2012 [Page 9] Internet-Draft Publish and Monitor Options for CoAP March 2012 time, or for any other reason. Note that the Proxy may also reboot and lose its state, including the state associated to any monitored resource. The requester can realize that the state at the Proxy has been lost, and re-instantiate the monitor, when it receives an unexpected 4.04 from the "monitor" resource. 2.2.2.1. Explicit De-registration P C \| DELETE \| Path: temp \|<-------+ Path: res \| \| \| 2.02 \| +------->\| \| \| Figure 5 Explicit de-registration is performed by a client, with a DELETE on the URI returned by the Proxy on the corresponding registration. 2.2.2.2. Implicit De-registration Implicit de-registration MUST occur when the monitoring period specified by the client via Max-Age expires. If no Max-Age was supplied at registration time, a default of 3600 seconds MUST be assumed. 2.2.3. Resource Refresh In order to minimize the number of messages used by the monitoring process, the Proxy MUST try to install an observation on the requested resource. In case this first attempt fails, the Proxy MAY fall back to repeated poll whose duration is upper bounded by the Max-Age value indicated by the client during registration. Usual cache validation MUST be applied to the cached copy of the monitored resource. 3. Acknowledgements Bruce Nordman. 4. IANA Considerations The following entries are added to the CoAP Option Numbers registry: Fossati, et al. Expires September 11, 2012 [Page 10] Internet-Draft Publish and Monitor Options for CoAP March 2012 .------------------------------. \| Number \| Name \| Reference \| :--------:---------:-----------: \| 2n+1 \| Publish \| RFC XXXX \| +--------+---------+-----------+ \| 2m+1 \| Monitor \| RFC XXXX \| `------------------------------' 5. Security Considerations Threat: cache poisoning. Countermeasure: authenticate sender. Threat: unauthorized de-registration Countermeasure: authenticate requester. Threat: Proxy resources' exhaustion. Countermeasure: authenticate requester + quota limit. Threat: global state loss. Countermeasure: cache redundancy. 6. References 6.1. Normative References [I-D.ietf-core-coap] Frank, B., Bormann, C., Hartke, K., and Z. Shelby, "Constrained Application Protocol (CoAP)", draft-ietf-core-coap-08 (work in progress), October 2011. [I-D.ietf-core-link-format] Shelby, Z., "CoRE Link Format", draft-ietf-core-link-format-11 (work in progress), January 2012. [I-D.ietf-core-observe] Hartke, K., "Observing Resources in CoAP", draft-ietf-core-observe-04 (work in progress), February 2012. [RFC2119] Bradner, S., "Key words for use in RFCs to Indicate Requirement Levels", BCP 14, RFC 2119, March 1997. [RFC3986] Berners-Lee, T., Fielding, R., and L. Masinter, "Uniform Resource Identifier (URI): Generic Syntax", STD 66, Fossati, et al. Expires September 11, 2012 [Page 11] Internet-Draft Publish and Monitor Options for CoAP March 2012 RFC 3986, January 2005. 6.2. Informative References [I-D.shelby-core-coap-req] Shelby, Z., Stuber, M., Sturek, D., Frank, B., and R. Kelsey, "CoAP Requirements and Features", draft-shelby-core-coap-req-02 (work in progress), October 2010. [I-D.shelby-core-resource-directory] Krco, S. and Z. Shelby, "CoRE Resource Directory", draft-shelby-core-resource-directory-02 (work in progress), October 2011. Authors' Addresses Thomas Fossati KoanLogic Via di Sabbiuno, 11/5 Bologna 40100 Italy Email: [email protected] Pierpaolo Giacomin Freelance Email: [email protected] Salvatore Loreto Ericsson Hirsalantie 11 Jorvas 02420 Finland Email: [email protected] Fossati, et al. Expires September 11, 2012 [Page 12]	https://www.potaroo.net/ietf/all-ids/draft-fossati-core-publish-monitor-options-01.txt
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We use beauty to raise hearts and minds to God, faithful to the traditions of St Philip Neri and St John Henry Newman. Saturday 1 July 2023 Congratulations to Dom Stanislaus on his ordination to the priesthood yesterday at St Michael’s Abbey, Farnborough! We look forward to welcoming him back to celebrate the Solemn Mass in our church on Sunday 9 July at 11am. #oxfordoratory View on Instagram Thursday 29 June 2023 July Music Sunday 2 July Solemn Mass 11:00 13th Sunday of the Year Missa Tu es Petrus Palestrina Sicut in holocaustis Palestrina Laudibus in sanctis Byrd Final from Organ Symphony No. 6 Widor Sunday 9 July Solemn Mass 11:00 14th Sunday of the Year Missa Octavi toni Lassus Simile est regnum caelorum Guerrero Beati omnes qui timent Dominum Purcell Prelude in A minor BWV 543i Bach Sunday 16 July Solemn Mass 11:00 15th Sunday of the Year Mass for Four Voices Byrd Ad te Domine levavi de Monte Ave verum Byrd A fancy Byrd Sunday 23 July Solemn Mass 11:00 16th Sunday of the Year Missa simile est regnum caelorum Victoria Tota pulchra es Vals Salve Regina Palestrina Fugue sur le nom d’Alain Op. 7ii Duruflé Sunday 30 July Solemn Mass 11:00 17th Sunday of the Year Missa Quarti toni Victoria Exaltabo te Domine Lassus Tantum ergo de Severac Prelude and Fugue in C BWV 547 Bach Wednesday 28 June 2023 Two different men, one same Faith Tomorrow we celebrate the feast of the two great pillars of the church, Peter and Paul. They were very different men from very different backgrounds. Peter was a fisherman from rural Galilee. Paul was a learned Pharisee from the university city of Tarsus. Peter’s first language was Aramaic; Paul’s first language was Greek. Peter knew Jesus from the time of his baptism and was with Jesus until the time of the Lord’s passion and death; Paul only ever met the risen Lord, in that famous incident, his conversion, on the road to Damascus. For all their differences, they had that which is most important in common. Both of these men found themselves at odds with the Lord. Jesus called Peter “satan”, an obstacle in his path, when the Apostle tried to persuade the Lord away from his cross and passion — and then Peter would go on to deny his Master publicly three times. Paul had a hand in the death of the first Christian martyr, St Stephen, and violently persecuted Christ’s followers, and in doing that persecuted Christ himself. And yet, in each case, it was Jesus who had the last word. Their resistance to the Lord did not prevent him from working powerfully through them. Peter was chosen to be the leader of the twelve, the rock on which Jesus would build his church. Paul was chosen to be the great apostle to the Gentiles, to take the faith out beyond Israel to the whole world. They were very different people and the Lord worked through each of them in different ways. But they were united in one faith and in love for the Lord and for the little community of those who followed the Lord. They were certainly united in death: a very early tradition recalls that both were executed in Rome during the Emperor Nero’s persecution of Christians after the great fire of Rome. The feast of Saints Peter and Paul reminds us that the way the Lord works through us is unique to each one of us. We each have our part in the great story of salvation, and each have our place in the great family of God which is the Church. The feast also reassures us that our many resistances to the Lord will not be a hindrance to his working through us. Peter, who denied the Lord, and Paul, who persecuted the Lord, would become his greatest servants and Apostles, and the very foundation of the Church. Our failings, even our greatest failings, do not define who we are. St Paul would go on to say, ‘the Lord’s grace toward me has not been in vain’. The Lord’s grace towards us in our weakness and frailty and our waywardness will never be in vain if we continue to open ourselves to the workings of that grace and the path that the Lord has prepared for us. May St Peter and St Paul pray for us, and for God’s church, as we each play our part in the preaching of the Gospel, the growth of the flock of Christ, and the building up of the kingdom. 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 24 June 2023 Congratulations to Andrew and Nina, baptised this morning! Today, the birthday of St John the Baptist, is a fitting day to baptise, and not just because he is famous for baptising people. His birth marks the end of the Old Testament and the beginning of the New. Today is about looking forward to the future. Baptism can sometimes feel like an ending after the period of preparation and catechesis, but it is of course only the beginning of the Christian life. The big work lies before us. As St Philip used to say, “The great thing is to become saints.” #oxfordoratory View on Instagram Thursday 22 June 2023 Yesterday we welcomed Fr William Pearsall of the Society of Jesus to preach for the feast of St Aloysius. “What Aloysius did is what many saints have done — many who are condemned for not being useful. They explored the frontiers of the spiritual life. They were heroic in the sense that those who went to the North Pole or the South Pole or climbed the highest mountains, they were heroic… They were heroic because they were living with the discovery of God and how the limits between nature and grace will always be an expanding horizon.” St Aloysius, pray for us! #oxfordoratory View on Instagram Wednesday 21 June 2023 Happy feast of St Aloysius! Two relics of his are displayed this month in our relic chapel, including a letter bearing his signature. #oxfordoratory View on Instagram Wednesday 21 June 2023 Flos paradisi Today we celebrate the great solemnity of the patron of our church: St Aloysius Gonzaga of the Society of Jesus. St Aloysius is, together with St Gabriel Possenti, patron of young people, students, and seminarians and thus was a natural choice as patron for our church in this university city. He is also the patron of our parish school and we entrust to his loving intercession all our children who are able to learn the love of God from his example. We have his shrine in the chapel of Our Lady of Oxford, his statue is there on the reredos, and his initials guide our eyes towards his heavenly home as we look up at the sanctuary ceiling. Our patrons are important — St Aloysius has been given to us in this parish by God, through his Church, to watch over us in a particular manner, to intercede for all those who live and worship here, and to encourage us in our own quest for holiness. Born the eldest son of the Marquis of Castiglione, St Aloysius seemed destined for a life of political intrigue and secular affairs, but, as with St Ignatius before him, it was the lives of the saints that really captivated him and placed in his heart the desire to strive for something better. This was not some childish caprice; he had seen the reality of life at court with its violence, frivolity, and degradation of human dignity, and desired not only to turn his back on it, but to embrace with all his heart a life given wholly to God. He began in earnest, adopting severe penances and teaching the local children their catechism. Hearing about the missions of St Francis Xavier, he set his heart on becoming a Jesuit — much to the horror of his family. Eventually, having not overcome family opposition but at least its concrete obstacles, and having renounced his rights of inheritance, he entered the Jesuit novitiate in Rome in 1585. He had much to learn and much to which to adapt himself, but whatever he had to do he simply did it with all his heart — trusting in the sure knowledge that God was at work. Would he have met St Philip in Rome? Concrete evidence is hard to find, though these two saints of Rome are often depicted in art. We know they had mutual friends and these no doubt would have told them of Rome’s Third Apostle and of the holy Jesuit novice. One can imagine St Aloysius on a novitiate walk popping in to the Chiesa Nuova to see Mister Father Philip whom all Rome spoke of and revered or of St Philip blessing a crowd of passing Jesuit novices and knowing the heart of one of them that would see them both in glory. St Aloysius’ real work in Rome was that which St Philip had embarked upon at the beginning — the care of the sick and the destitute. When plague broke out he volunteered to go with the other novices to pick people off the streets, to wash them, to prepare them for the sacraments and care for their souls. At first, he admitted to his director St Robert Bellarmine, this revolted him, but he soon learnt to see the image of Christ in these people, and to love them, not only in caring for them, but in seeing Christ in them. Never one to enjoy good health, Aloysius himself fell ill of plague, and died at the age of 23 on 21 June 1591, just a few years before St Philip’s death. When we look at images of St Aloysius we normally see a rather pale young man who looks like so many other sickly young saints, distinguished perhaps only by the great ruff that he wears about his neck. But he was more than that. He was a young man who bothered about God and thus about other people. He was not yet in his mid-twenties, when he had discovered that real freedom comes from serving God with all ones heart; that Christian love has to be lived in the real, strength-sapping, heart-breaking, service of others; that there is joy in taking people off the streets, washing them, bandaging their wounds and restoring them to the dignity that is theirs as children of God. The image attached to these words is a depiction of St Aloysius in Milan in the Chiesa di Santa Maria presso San Satiro . The saint looks rather weak and malnourished, but what strength he has is used to hold up a man who is either dying or dead, with St Aloysius pressing the Cross to him and holding the man’s head up with his hands. The look on St Aloysius’ face is one, simply, of love — of love for God and neighbour, and of joy found in bringing the love of God to others. How much this young man, St Aloysius, still has left to teach 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. Friday 16 June 2023 Heart of Jesus, all-holy! Fountain of all blessings, I adore thee, I love thee, and with a lively sorrow for my sins, I offer thee this poor heart of mine. Make me humble, patient, pure, and wholly obedient to thy will. Good Jesus, grant that I may live in thee and for thee. Protect me in the midst of danger; comfort me in my afflictions; give me health of body, assistance in my temporal needs, thy blessing on all that I do, and the grace of a holy death. Amen. #oxfordoratory View on Instagram Thursday 15 June 2023 A photo from Sunday’s Solemn Mass for Corpus Christi. #oxfordoratory View on Instagram Thursday 15 June 2023 June Music Sunday 4 June Solemn Mass 11:00 The Most Holy Trinity Kyrie Mundy Missa Euge bone Tye Libera nos Sheppard Honor, virtus et potestas Tallis Sunday 11 June Solemn Mass 11:00 Corpus Christi Missa Pange lingua Josquin Lauda Sion Palestrina Oculi omnium Byrd Friday 16 June Solemn Mass 18:00 The Most Sacred Heart of Jesus Missa Dormendo un giorno Guerrero Improperium Palestrina Sancte Deus Tallis Sunday 18 June Solemn Mass 11:00 11th Sunday of the Year Missa Brevis in F Op.117 Rheinberger Benedicam Dominum Victoria Salve Regina Poulenc Wednesday 21 June Solemn Mass 18:00 St Aloysius Gonzaga Missa O quam gloriosum Victoria Justitiae Domini A Scarlatti O bone Jesu Anchieta Sunday 25 June Solemn Mass 11:00 12th Sunday of the Year Missa Repleatur os meum Palestrina Perfice gressus meos Lassus Homo quidam fecit coenam magnam Mouton Thursday 29 June Solemn Mass 18:00 St Peter and St Paul Missa Petre ego pro te rogavi Lobo Petre ego pro te rogavi Guerrero Janitor caeli Ortiz Wednesday 14 June 2023 The Sacred Heart Love is a funny thing. Materialists will tell us that it is purely the result of a series of electro-chemical responses in the brain, and yet others will tell us that it is the result of fate, the conspiracy of the alignment of the planets or the times we find ourselves in. The heart has long been understood as the centre of a person, a place of knowledge as much as will. It makes us do unreasonable things like acts of unwarranted kindness and altruism and by the edge of its blade we can be hurt in ways that we just can’t speak about. And yet none of these express what love is in itself — only God does that. On Friday we venerate the Heart of our Lord as the symbol of his human love in which God’s divine love is revealed to us. In most of the prayers to or the meditations on the Sacred Heart, even those very ancient prayers, the woundedness of our Lord’s heart comes to the fore. That heart pierced with a lance and bruised with outrages and blasphemies is a stark and realistic image of the extent to which Christ loves us. Christ, who is the image of the unseen God, the Icon of the Father, shows us precisely what God’s love for us looks like. And it looks like a heart pierced and bruised on account of our sins, yet burning with ardent love for you and for me. This divine love is not for softies. The time when we celebrate this feast is very fitting. We have come to the end of the Church’s celebration of the mysteries of our redemption: the Passion, the Cross, the Resurrection, the Ascension, Pentecost, the Feast of the Blessed Trinity and Corpus Christi. But today we commemorate the divine-human love which motivated them all. In adoring the Sacred Heart, we adore the totality of Christ’s saving work — it represents the way in which God holds nothing back from us. And in order to share his divine life with us, he reaches down into the very depths of our life, even — and especially — where it is painful, difficult to speak of, hidden. By taking it all and joining it to himself, he scoops us up, he enables us to become like him. By sharing our life, and by sharing our pains, he heals us, he sanctifies us, and he strengthens us. It is also true that his heart welcomes us precisely so that we might become like it. The whole thrust of our Christian life is that we might be conformed to our Saviour, that we might resemble him, and in this sense, in the life of faith, we should ask ourselves continually whether our heart resembles his. His Sacred Heart is both the example and the cause of our becoming like him. His love is attractive. The more we consider the love with which Jesus acted, and spoke and gave of himself for us, the more we can begin, by his grace, to imitate him — it is truly the school of Christian perfection. And we begin in that school by prayer. When St John Henry Newman, our Cardinal, chose his motto, he looked to St Francis de Sales’ Treatise on the Love of God . The phrase he chose and paraphrased, Cor ad Cor loquitur represents for us the central mystery of the prayer that can begin to transform us. St Francis de Sales wrote: Truly the chief exercise in mystical theology is to speak to God and to hear God speak in the bottom of the heart; and because this discourse passes in most secret aspirations and inspirations, we term it a silent conversing. Eyes speak to eyes, and heart to heart, and none understand what passes save those who speak. We may be no great shakes at the spiritual life, or prayer, or we may feel that excelling in virtue is beyond us, but if we can in the simplest of ways open our poor heart to his Sacred Heart, and speak to him as to a friend, if we can entrust our lives to him and ask him devoutly and sincerely to shape us after the model of his Heart, then our Christian life will be all the more graced. 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 13 June 2023 The Corpus Christi procession concluded with Benediction at the University Chaplaincy. #oxfordoratory View on Instagram Tuesday 13 June 2023 The procession finished at the University’s Catholic Chaplaincy. #oxfordoratory View on Instagram Tuesday 13 June 2023 The numbers caught the attention of the local media: https://www.oxfordmail.co.uk/news/23582016.oxfords-catholic-congregations-take-part-corpus-christi-procession/ #oxfordoratory View on Instagram Tuesday 13 June 2023 Children scattered flower petals before the Blessed Sacrament all the way. #oxfordoratory View on Instagram Tuesday 13 June 2023 Our route now passes through the city in a straight line, taking us directly through the busiest shopping areas. #oxfordoratory View on Instagram Tuesday 13 June 2023 The canopy was carried by members of the University of Oxford wearing their academic dress. #oxfordoratory View on Instagram Tuesday 13 June 2023 Fr Robert Ombres OP preached a sermon. #oxfordoratory View on Instagram Tuesday 13 June 2023 We paused at Blackfriars. #oxfordoratory View on Instagram Tuesday 13 June 2023 We were joined by local clergy and religious orders as we processed through the streets to the Dominican Priory at Blackfriars. #oxfordoratory View on Instagram	https://www.oxfordoratory.org.uk/tour/blog/post/10029-10029/blog/post/10008-10008/mass-times.php
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Barry Schwabsky on Tony Cragg - Artforum International BARRY SCHWABSKY: When I first started seeing your work in the early to mid-’80s, it was related to the new figuration. In fact, that’s the title you gave to one of your found-plastic wall pieces from 1985. Was that maybe a misreading of what your work was about?TONY CRAGG: One has to see it in terms of bigger movements. I was born in 1949, went into art school twenty years later, in 1969. The first art that I saw and was interested in was the art of the Conceptualists, the Minimalists, the Land artists, arte povera, Joseph Beuys. I realized that there were already people who had a certain ’80s THEN Tony Cragg BARRY SCHWABSKY: When I first started seeing your work in the early to mid-’80s, it was related to the new figuration. In fact, that’s the title you gave to one of your found-plastic wall pieces from 1985. Was that maybe a misreading of what your work was about? TONY CRAGG: One has to see it in terms of bigger movements. I was born in 1949, went into art school twenty years later, in 1969. The first art that I saw and was interested in was the art of the Conceptualists, the Minimalists, the Land artists, arte povera, Joseph Beuys. I realized that there were already people who had a certain sensibility, these ideas and formal solutions for something that I’d already started to do on my own, like tying up bits of string, and knotting it, and other sorts of practical exercises with material. I was still a student, and these were people five, ten, fifteen years older than me. In Europe this was the postwar generation that moved into positions of responsibility in all walks of life, simply because of the vacuum that was in front of them due to the war. My life has been spent with this big wave of people in front of me. So at the time I was very influenced by these artists’ work, but I realized I didn’t want to make their work. I even had problems with a lot of that work. I was already kind of antagonistic toward the idea of making straight lines and flat surfaces. I didn’t like the romanticism of certain things I admired. I didn’t feel like I had my own position yet, and I didn’t want to be the tail end of something. So it took most of the ’70s, student times and after, to work out something that wasn’t too heavily influenced. I wanted to use materials that weren’t romantic, that were typically used in an urban situation, I wanted more complicated references rather than reducing everything down to a minimal gesture. I didn’t want work that stayed always on a gestural, conceptual level. I wanted to challenge the geometry of a lot of the work of the time, as well as the very aestheticized purist sense of much of it. At the end of the ’70s, in Europe anyway, you had the feeling that the preceding generation had dominated the decade in such a way that something had to change. That was even expressed in the fact that there were a lot of exhibitions whose explicit purpose was to look for a new generation of artists. And you immediately saw that it wasn’t going to be a linear continuity, but a real break. BS: Can you define the nature of the break? BS: Your references are primarily to European artists. TC: That was absolutely an aspect of the end of the ’70s and into the ’80s, an awareness, a new consciousness of European art. It started with these apparently national groups, but there was a European identity. Europe had been downtrodden since World War II, but now there was a new self-confidence. The idea of political union came later, but it was very much felt in terms of art. Even the opening of Spain, for instance—that happened first on a cultural level. Culture was a real vehicle in the ’80s for the unity of Europe, and not in the sense of homogenizing it. BS: So you felt as connected to the Italian painters and the German painters as you did to the English sculptors? TC: I had great sympathy, great relationships with them. We knew we made very different things, that our origins and our interests were very different. But alongside those national groupings, there was another structure that is much more difficult to describe and therefore less well known, which has to do with sympathies and spiritual affinities. BS: Did these relationships with painters help you see your way toward using images in sculpture? TC: Obviously. I felt very free to use the plastic fragments I’d started using in ’77 in new forms. That was almost a kind of punk gesture at the time, a little bit aimed against the pieties of Land art, Minimalism, or whatever. BS: The story that usually gets told these days about those times says that the return of recognizable, representational images was a kind of regressive move, a betrayal of the innovations of the ’60s and ’70s, so it’s interesting that you recall the subversive thrust of it. TC: I always have rules about what I’m doing, and the game becomes to break the rules, but on my own terms. The first things I did that you’d call representational—they actually represented a fragment of what I’d found as a material. For instance, a little plastic Indian that I’d found on the banks of the Rhine would become the motif for a work made of plastic fragments. So I was very conscious of the relationship between the image, the material, and the object. That’s the eternal triangle. It was premised on a conceptual basis rather than a subjective gesture. But it still allowed for complicated thoughts and a richer emotional palette or atmosphere around the work. It wasn’t just about going back to figuration. BS: What about the change that took place in your work, during the ’80s, from accumulations of separate elements to works where the elements were fixed together in a way that made them more like sculptural objects in a traditional sense—works in cast bronze, for instance? TC: First, this process I’d come to—running around, finding the material, finding images, dealing with a given situation, the challenge of the time and the space—was something that was a great enrichment to me. I traveled the world, encountered materials I could use, widened my understanding of what I wanted to do. BS: So those early pieces were essentially made on site. TC: Absolutely, site-specific. And then at the end of that period of time a whole set of considerations slid into place for me. One was the fact that I was physically tired of doing that. What had started as an adventure and a challenge had become a repertoire. Two, at the same time and parallel to that, I realized that while you could make gestures that were exciting, you couldn’t get past a certain level with the material; the engagement with the material was too limited. You could never actually impose your will; you could make images, but you couldn’t influence very much the form of the object. I needed to go back to the studio and to remake things and learn more skills. Third, I also had a sense for the first time then that what I call the Duchampesque strategy was reaching its limits. In the nineteenth century there’s so little material for making sculpture. There’s plaster, wood, stone, very traditional materials, and most of the sculpture was figurative. Suddenly, because of the discovery of new materials, industrial materials, new techniques and tools that had to be invented for each material, you suddenly had an enormous expansion of the vocabulary of art, of sculpture. I think the twentieth century is just that—the process of artists rushing through the world and finding some part of the non-art world and bringing it into the art world, minus its context. At the beginning of the twentieth century there was still a lot of non-art world, and a small art world. By the time the ’80s came, Gilbert & George and Richard Long and Joseph Beuys had made their work; they’d reduced enormously the difference between the art world and the non-art world. So what was I going to do? Rush around looking for another new material to make art with? We have a finite world, so the possibilities were diminishing. This palette or vocabulary of materials is big; you can use anything from shit to gold to make art with, but what do we want to express with it? What do we want to make? The nominative Duchampian strategy was running out of energy. My decision in the early ’80s made me go back into the studio and adopt another strategy. BS: Which was a return to something more like the traditional art object. TC: The artists of the ’70s were the first generation that globalized art, really. The material was very intelligent, they were very intelligent, because it allowed them to do simultaneous exhibitions around the world. They could work with any kind of space and accommodate the work to the architecture or the situation. My attitude is, I make the sculpture in the studio on my own terms on my own time, and I want to see it go out of the studio and have its own existence whether it’s noticed or not. BS: What about the rebirth of the art market in the ’80s? We have the sense that in the ’70s the materials used were very adaptable to the physical situations but recalcitrant to the market, which was in a recession anyway. In the ’80s the market had its resurgence. TC: In the ’70s you could buy substantial works by extraordinary artists for a few thousand dollars. There was hardly any contemporary work that cost more than that. There were very few galleries. There were no television programs about art, nor was it covered by every newspaper. Art was not perceived in a very big public framework. By the middle of the ’80s, there was a growth of interest. I don’t really want to talk about the market because I never understand it very well, but the growth of public interest through the ’80s changed substantially the number of exhibition spaces and the number of artists who could have their work seen. It enabled a pluralization in art. You didn’t have to make Minimalism your religion, or Conceptualism, or arte povera. Suddenly you realized that there were the paintings of Baselitz or Twombly and also the texts and installations of Lawrence Weiner and also the steel sculptures of Richard Serra, and all these things lived together and just made life more interesting, in fact. It was public interest that made things more pluralized. The market came out of this interest, it wasn’t the cause of it. Art became a really vital and interesting story, and there was a public that was interested in looking at exhibitions and that eventually became the basis for some people to make collections. But most of the people going to exhibitions didn’t have the money to make collections. That’s the thing that’s important, that the history of painting and sculpture in the last thirty, forty years is an ever-growing, fantastically interesting picture. Critic and curator Barry Schwabsky is a frequent contributor toArtforum andBookforum.	https://www.artforum.com/print/200304/tony-cragg-4474
Aviation Accident Summary ANC01LA057 In-Depth Access to the NTSB Aviation Accident Database and Final Reports from international accident investigation branches on iPhone/iPad. Aviation Accident Summaries Aviation Accident Summary ANC01LA057 Stebbins, AK, USA Aircraft #1 N756DJ Cessna 206 Analysis The solo certificated commercial pilot was departing for another airport about 5 miles away. During the takeoff roll, as the airplane's airspeed approached 60 knots, the pilot applied aft control yoke pressure to rotate the nose of the airplane. When the desired pitch angle for takeoff was attained, she released the back pressure, but the yoke failed to move forward. The airplane then pitched-up uncontrollably, and she disengaged the electric trim, as she was concerned about a runaway trim condition. She regained control of the airplane, noted that she had very limited aileron and elevator range of motion available, and elected to continue straight ahead to her next scheduled stop. She added that she tried to transmit a "mayday" to other airplane’s in the area, but the radio transmit button, located on the pilot's control yoke, was now inoperative. During the short flight, she was able to adjust the altitude and airspeed by adjusting engine power. During approach to the accident airport, while using a combination of engine power, rudder, and the remaining amount of aileron control, she was able to maneuver the airplane for landing on runway 05. As the airplane passed over the approach end of the runway, she attempted to flare just before touchdown. The nose of the airplane failed to rise, and the nose wheel struck the gravel-covered runway. The nose landing gear collapsed, and the airplane bounced off the right side of the runway. A postaccident examination of the control yoke mechanism, behind the instrument panel, revealed that a wiring harness had become entangled in a series of roller bearings associated with the control yoke mechanism. A subsequent inspection revealed that the accident airplane's control column did not have a required STA-Strap, part number S-2209-2, installed. The proper installation of the required STA-Strap would provide proper clearance between the wiring harness, and the control yoke roller bearings. The roller bearing assembly was disassembled, and the entangled wiring harness was removed. The correct length for the factory installed wiring harness is 49 inches. The wiring harness that was removed from the roller bearing assembly measured at 34 inches. A review of the airplane's maintenance history disclosed no maintenance activity concerning the control yoke assembly. A review of the FAA's aircraft registry database disclosed that the operator owned the airplane for about 11 years. The airplane had been added to the operator's Approved Aircraft Inspection Program (AAIP), on February 11, 2001. In order for an airplane to be initially placed on the AAIP, it must be inspected in accordance with AAIP Events1, 2, 3, and 4. According to the operator's AAIP inspection schedule, an inspection of the control wheels, columns, pulleys, and cables, for condition is required during the Event 4 inspection. Factual Information On May 15, 2001, about 1534 Alaska daylight time, a wheel-equipped Cessna 206 airplane, N756DJ, sustained substantial damage during an emergency landing at Stebbins Airport, Stebbins, Alaska. The airplane was being operated as a visual flight rules (VFR) scheduled domestic commuter flight under Title 14, CFR Part 135, when the accident occurred. The airplane was registered to, and operated by, Warbelow's Air Ventures, Inc., Fairbanks, Alaska, as Flight 911-2. The solo certificated commercial pilot was not injured. Visual meteorological conditions prevailed, and a VFR flight plan was filed. The flight originated at the St. Michael Airport, St. Michael, Alaska, about 1450, and was en route to Stebbins. The intended routing of Flight 911-2 was from Unalakleet, Alaska, to St. Michael, to Stebbins, and then return to Unalakleet. During a telephone conversation with the National Transportation Safety Board investigator-in-charge on May 17, the pilot reported that the first leg of her flight between Unalakleet and St. Michael was uneventful. She said that after deplaning the one passenger in St. Michael, she had about 256 pounds of US mail/cargo remaining in the airplane that was destined for Stebbins. She added that as she entered runway 02, she conducted a pretakeoff control continuity check, and noted no deficiencies. During the takeoff roll, as the airplane's airspeed approached 60 knots, she applied aft control yoke pressure to rotate the nose of the airplane. When the desired pitch angle for takeoff was attained, she released the back pressure, but the yoke failed to move forward. She said, in part: " ... the nose of the airplane then pitched-up uncontrollably. I tried to push the yoke forward, but it just wouldn’t move, so I disengaged the electric trim for fear that I had a runaway trim." She said that when she tried to move the control yoke left or right, she had a very limited range of motion available in both directions. The pilot said that after she regained control of the airplane, she elected to continue straight ahead to her next scheduled stop, located about 5 miles from her departure airport. She added that she tried to transmit a "mayday" to other airplane’s in the area, but the radio transmit button, located on the pilots control yoke, was now inoperative. She said by using the limited amount of aileron control she had remaining, in conjunction with the rudder, she was able to make a very shallow left turn to the west, and headed to Stebbins, her previously intended destination. She said that during the 5 mile flight to Stebbins, she was able to adjust the altitude and airspeed by adjusting engine power. As she approached the Stebbins Airport, she noted that the wind was favoring a northerly approach for landing on runway 05. Using a combination of engine power, rudder, and the remaining amount of aileron control, she was able to maneuver the airplane for landing on runway 05, at Stebbins. As the airplane passed over the approach end of the runway, the pilot attempted to flare just before touchdown. The nose of the airplane failed to rise, and the nose wheel struck the gravel-covered runway. The nose landing gear collapsed, and the airplane bounced off the right side of the runway. The airplane sustained substantial damage to the wings and fuselage. A Federal Aviation Administration (FAA) airworthiness inspector, Fairbanks Flight Standards District Office, traveled to the accident scene on May 15, and examined the airplane wreckage before recovery efforts were started. The FAA inspector reported that his initial examination of the control yoke confirmed the pilot's report of not being able to move the control yoke. A closer examination of the control yoke mechanism, behind the instrument panel, revealed that a wiring harness had become entangled in a series of roller bearings associated with the control yoke mechanism. The airplane was recovered by the operator and transported to the operator's maintenance facility in Fairbanks. On May 25, 2001, in the presence of an FAA airworthiness inspector from the Fairbanks Flight Standards District Office, the control yoke assembly was removed from the accident airplane, along with the entangled wiring harness. The control yoke assembly was shipped to the FAA's Wichita Aircraft Certification Office, Wichita, Kansas, for further examination and inspection. The FAA inspector added that after reviewing the accident airplane's maintenance records, he was unable to find any maintenance log entry concerning the control yoke assembly. A review of the FAA's aircraft registry database disclosed that the operator owned the airplane for about 11 years. The FAA airworthiness inspector reported that the accident airplane was maintained under the operator's Approved Aircraft Inspection Program (AAIP). This program requires inspections be performed approximately every 100 hours. He said that the accident airplane was initially placed on the AAIP on February 11, 2001, and added that in order for an airplane to be initially placed on the approved aircraft inspection program, it must be inspected in accordance with AAIP Events 1, 2, 3, and 4. According to the operator's AAIP inspection schedule, an inspection of the control wheels, columns, pulleys, and cables for condition, is required during the Event 4 inspection. The most recent inspection (event 2), was accomplished on May 9, 2001, 7.3 hours before the accident. On June 4, 2001, in the presence of a senior airframe/structures engineer from the FAA's Aircraft Certification Office in Wichita, and an Air Safety Investigator from Cessna Aircraft Company, a detailed inspection and teardown of the accident airplane's control yoke assembly was conducted. An initial inspection revealed that the accident airplane's control column did not have a required STA-Strap, part number S-2209-2, installed. The installation of the required STA-Strap would provide proper clearance between the wiring harness, and the control yoke roller bearings. The roller bearing assembly was disassembled, and the entangled wiring harness was removed. The correct length for the factory installed wiring harness is 49 inches. The wiring harness that was removed from the roller bearing assembly measured at 34 inches. Probable Cause and Findings A jammed control yoke during landing, an entangled wiring harness, and inadequate maintenance by company personnel. A factor associated with the accident was the pilot's inability to flare the airplane during landing, due to the mechanical malfunction. Source:NTSB Aviation Accident Database	https://www.accidents.app/summaries/accident/20010605X01079
Boeing CH-47D Chinook helicopter 90-00183. Boeing CH-47D Chinook helicopter 90-00183. 90-00183 90-00183 on the ramp near Hangar 1 at Fort Wainwright, Alaska, 16 April 2003. 90-00183, Boeing D model kit number M3335, was a CH-47D helicopter. The U.S. Army acceptance date was 30 November 1990, at 4,391.5 aircraft hours. The administrative strike date was 20 April 2004. As of 28 September 2001, 90-00183 had accumulated 1,640.8 D model hours and 6,027.8 total aircraft hours. 90-00183 was a conversion from the original C model Chinook 68-15816 . On 21 December 1989, 90-00183 was inducted into the D model program, conversion complete on 15 November 1990, and initially assigned to the unit that would eventually become B Company - "Sugar Bears North", 4th Battalion, 123rd Aviation Regiment, located at Fort Wainwright, Alaska. Fort Wainwright was the former historic Ladd Field of World War Two era fame. B Company was the former C Company, 228th Aviation Regiment (16 October 1987 - 24 June 1994). 90-00183 was received by C Company on 18 January 1991. C Company was the former 242nd Assault Support Helicopter Company (ASHC) - "Muleskinners" (located in Alaska from November 1971 through 16 October 1987). When United States involvement in the Vietnam conflict ended, 242nd ASHC was re-located from the Republic of Vietnam (RVN) to Alaska. The aviation unit in Alaska at the time was designated the 236th ASHC, 19th Aviation Battalion (April 1971 - November 1971). When the 242nd ASHC re-located to Alaska and re-formed, the unit name changed from "Muleskinners" to "Sugar Bears" and the unit designation went from the 236th ASHC to the 242nd ASHC. At some point, the unit was split into two companies. One company remained in Alaska and became known as " Sugar Bears North ". The other company, C Company, 1st Battalion, 228th Aviation Regiment, was relocated to Fort Kobbe, Panama and became known as "Sugar Bears South". 90-00183 remained assigned to the Sugar Bears until 20 April 2004, where it was lost due to an accident. While conducting Pathfinder insertion and extraction operations in the Yukon Training Area, approximately 25 miles east of Fort Wainwright, 90-00183 landed hard at Bravo Battery LZ (UTM Grid coordinate 6W WG12357105). The indications were the aircraft experienced a condition known as settling-with-power and then struck the ground very hard twice. The left aft landing gear struck first and the aircraft became airborne. Then the right aft landing gear struck and the aircraft became airborne. The double strike more than likely induced an out-of-balance condition in the rotor system similar to ground resonance . The aft pylon was torn from the airframe and the fuselage landed in an upright position. The cockpit section was partially torn loose from the main cabin section along the top portion and the bottom of the airframe, forward of the center cargo hook, was displaced upward. There were only minor injuries reported by the crew of four in the way of lower and upper back pain. There were no passengers aboard the aircraft. There was no post crash fire. Virtually every section of the airframe aft of STA 90 was damaged to some extent. The airframe was eventually classified as being damaged beyond economical repair - the cost of repair would exceed the purchase price of a new build helicopter (roughly $30 million dollars (2004)). Data from Historical Records. As of 20 April 2004, this aircraft was 35.53 years old. As of 20 April 2004, the last known location of 90-00183 was in Alaska. Aircraft status: Crashed. A map showing the approximate location of the site where 90-00183 crashed. The photographs below show 90-00183 at the crash site on or about 20 April 2004: The Fuselage At the termination of its final flight, 90-00183 sits on the western edge of the landing zone (LZ) Bravo Battery in the Yukon Training Area (YTA). The road leading off the the left side of the photograph is oriented 295 degrees magnetic. The aft pylon was jettisoned during the crash sequence and placed off to the side. Note the crack. This crack runs from the right forward landing gear, across the belly to the left forward landing gear, up to the top of the fuselage and over to the main cabin door, where it starts down towards the right forward landing gear. The crack almost completely separates the front portion of the fuselage from the aft portion. About the only thing holding the fuselage together at this point was some wiring, hydraulic lines, and the internal Robertson Extended Range Fuel System tank (ERFS II) that was squeezed between the cabin floor and the roof when the forward landing gear were displaced upward during the crash sequence. Note the line in the snow leading to the right forward landing gear. It is evidence that the airframe slid left and forward after the final landing was made. Believe it or not, when the aft pylon was jettisoned the forward rotor system didn't receive a single scratch, not even during the final landing event and rotor system coast down. The Aft Pylon A pretty amazing set-down for the aft pylon. Once jettisoned, the pylon just floated off to the side and gently set itself down in the snow. Even after the rotor blades contacted the ground, the pylon never moved (or even rotated) from the point of touchdown. The rotor blades simply coasted down and then beat themselves to a stop. All of the aft pylon mount and skin bolts were intact. The photograph shows an aft blade dampener outboard lug damaged during the crash sequence. The Kevlar windings were broken by forces that exceeded design limits. The Main Cabin For the purposes of the airframe recovery, the cockpit and cabin sections were cargo strapped together to minimize any further damage. A single ERFS II tank was installed. As the forward landing gear was shoved upward, the tank was squeezed between the cabin floor and roof. The Station 534 bulkhead was compressed downward during the crash sequence. The Move The photographs below show 90-00183 in the process of moving from the crash site in the Yukon Training Area to Fort Wainwright for further examination and final disposition: Above: A SCAMP is used to remove the forward rotor blades. Below, a HEMMT Wrecker vehicle's winch is used to prevent the airframe from rolling over on its side. Due to the damaged landing gear and airframe twist, there was a high probability that the aircraft would roll down the hill. Note the 4 foot ladder in the photo above. Until the wrecker was in-place, the ladder (wedged under the main cabin door handle) was the only thing preventing the aircraft from rolling on its side. A 55 ton crane was moved into the site to lift the airframe onto a flat bed truck for transport back to Fort Wainwright. The photographs below show 90-00183 after the move to Hangar 7 and 8 at Fort Wainwright: Note the severed break-away fuel system fittings. No fuel was lost during the crash or post crash sequence even though most fittings were extensively damaged. On the day following the accident, some seepage was noted coming from the left main fuel tank forward brake-away fittings, but was more of an environmental rather than a crash safety issue. The above photograph also shows the right forward landing gear torque box displaced upwards approximately 6 to 12 inches as a result of the accident. This aircraft was piloted by: CPT Russell J. Elizondo, PI, 1995-1998. CW2/3 Dennis Busch, PC, 1994-1997 - PC/MTP/ME, 1998-2001. CW4 Mark S. Morgan, PC/MTP/ME, 2000-2003. This aircraft was crewed by: SSG Bert Lagasse, FE, 1996-1999. SGT Rich Pittman, FE, 1999-2000. SGT Joe Dillenburg, CE, 1999-2000. SSG Ryan Galovics, FE, 2000-2003. SSG Mike Ruffner, CE 2002-2004. A similar fate - 66-19110	http://www.chinook-helicopter.com/history/aircraft/D_Models/90-00183/90-00183.html
Commission on AIDS and is a member of the Board of Directors of the HIV Medicine Association. Bruce Kuhlik, who will serve as the new vice chair, is the former chief legal officer of Pathfinder International, an NGO focused on improving sexual and reproductive health and rights globally by mobilizing communities. Bruce has been a member of the board for six years serving on the Executive Committee and as chair of the Audit Committee. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Tue, 01 Mar 2022 10:18:26 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-announces-new-chair-and-vice-chair-for-board-directors</guid> </item> <item> <title>Power To Decide Thanks Senate Supporters of the Women’s Health Protection Act</title> <link>https://powertodecide.org/about-usnewsroom/power-decide-thanks-senate-supporters-womens-health-protection-act</link> <description>(Washington, D.C.) – The U.S. Senate held a historic vote today on the Women’s Health Protection Act (WHPA), a measure that would codify into federal law the rights of people to receive abortion care without medically unnecessary restrictions, such as mandatory waiting periods, ultrasounds or biased counseling. While the measure was unable to overcome procedural hurdles to passage, today’s vote nonetheless represents an important step forward as the Senate’s first ever on stand-alone, proactive abortion legislation. The following statement can be attributed to Power to Decide CEO Dr. Raegan McDonald-Mosley, MD, MPH: “We at Power to Decide cheer the historic step forward that today’s vote represents and applaud the many legislative champions standing up for reproductive health, rights and justice for all. Despite this historic effort on the Women’s Health Protection Act, millions of people remain at the mercy of a patchwork of state laws designed only to make abortion care difficult if not possible to access. “State legislatures across the country have passed nearly 500 laws to restrict or ban abortion care since 2011, culminating with the passage of Texas’s draconian SB 8. “The health crisis sparked by SB 8 is reflected in visits to Power to Decide’s clinic locator, which has surged almost 600% in the past six months among Texas women seeking abortion care. This sharp increase highlights the urgent need for federal policies that can protect the rights of people to get the abortion care they need, when they need it, without medically unnecessary restrictions. “As an OBGYN who has provided abortion care the past 20 years, I’ve seen first-hand the devastating harm abortion restrictions can have on a pregnant person’s reproductive well-being and mental health. These politically-motivated restrictions are particularly devastating to people who already face daily, systemic barriers to health care, people struggling to make ends meet, people in rural areas or communities of color. “We are encouraged by the strong showing of support for the Women’s Health Protection Act and look forward to future efforts to pass this urgently-needed legislation. We can and must help ensure all people have the ability to decide their futures and live life on their own terms.” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant or have a child. </description> <pubDate>Mon, 28 Feb 2022 17:51:23 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-thanks-senate-supporters-womens-health-protection-act</guid> </item> <item> <title>POWER TO DECIDE HAILS NOMINATION OF JUDGE BROWN JACKSON TO UNITED STATES SUPREME COURT</title> <link>https://powertodecide.org/about-usnewsroom/power-decide-hails-nomination-judge-brown-jackson-united-states-supreme-court</link> <description>(Washington, D.C.) — Today, President Joe Biden nominated Judge Ketanji Brown Jackson to the U.S. Supreme Court. If confirmed, Judge Jackson will be the first African American woman to serve on the nation’s highest court. Judge Jackson presently sits on the U.S. Court of Appeals for the District of Columbia Circuit, and previously served as a federal district court judge for the District of Columbia. The following statement can be attributed to Power to Decide CEO, Dr. Raegan McDonald-Mosley, MD, MPH: “This Supreme Court has signaled its willingness to revisit settled law and potentially roll back reproductive rights and health for generations to come. The consequences of the court’s decisions have far-reaching effects on the reproductive well-being, health and rights of people in every part of the country. “We are encouraged by the nomination of Judge Jackson, whose background and experience—including her rulings protecting the Teen Pregnancy Prevention Program—suggest that she understands the barriers women of color and people with low incomes face every day, such as accessing basic, reproductive health care. “Judge Jackson’s nomination is monumental, particularly for Black women and girls who may soon, finally, see themselves represented on the nation’s highest court. Moreover, it is another step toward having the highest court in the land better represent the country and the broad support for reproductive health care access that exists within it. “We urge the Senate to fairly consider Judge Jackson as the next Supreme Court justice.” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant and have a child. </description> <pubDate>Fri, 25 Feb 2022 10:37:43 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-hails-nomination-judge-brown-jackson-united-states-supreme-court</guid> </item> <item> <title>ESTIMATED 180,000 WOMEN IN CONNECTICUT LIVE IN CONTRACEPTIVE DESERTS</title> <link>https://powertodecide.org/about-usnewsroom/estimated-180000-women-connecticut-live-contraceptive-deserts</link> <description>(Washington, D.C.)—According to data released by Power to Decide, an estimated 180,000 women living at or below 250% of the poverty level in Connecticut live in contraceptive deserts, counties in which there is not reasonable access to a health center offering the full range of contraceptive methods. Currently, across the country more than 19 million U.S. women of low income live in contraceptive deserts. “In Connecticut, 180,000 women must overcome significant barriers to access the contraception they need and deserve in order to decide if, when and under what circumstances to get pregnant and have a child,” said Raegan McDonald-Mosley, MD, MPH, CEO of Power to Decide. “The challenge of covering costs associated with obtaining family planning services—such as transportation, child care and unpaid time off from work—may be too great a burden for those already struggling to make ends meet.” Additional data from Power to Decide show that more than 151,000 Connecticut women of reproductive age (13-44) in need of publicly funded contraception live in the five counties that lost resources due to the Title X Family Planning Program “domestic gag rule.” The rule was lifted on November 8, 2021, after more than two years of harm. Despite these challenges, family planning providers have been making every effort to provide contraceptive services to patients across the state. Connecticut has also taken several steps to expand access to contraception. This includes expanding Medicaid to low-income adults, which helps decrease the percentage of uninsured women, and by extension, give them the contraceptive coverage they need to help live healthy lives. In addition, Connecticut requires insurance to cover an extended supply of prescription contraceptives, as well as the full range of contraceptive methods. Connecticut can also guard against additional barriers to access by enacting policies that allow pharmacists to prescribe contraception. More information about these policies can be found here. In addition, information about Connecticut’s telehealth policies relevant to contraceptive access can be found here. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Tue, 22 Feb 2022 10:05:33 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/estimated-180000-women-connecticut-live-contraceptive-deserts</guid> </item> <item> <title>MORE THAN 217,000 WOMEN IN OKLAHOMA LIVE IN CONTRACEPTIVE DESERTS</title> <link>https://powertodecide.org/about-usnewsroom/more-217000-women-oklahoma-live-contraceptive-deserts</link> <description>(Washington, D.C.)—According to data released by Power to Decide, an estimated 217,460 women living at or below 250% of the poverty level in Oklahoma live in contraceptive deserts, counties in which there is not reasonable access to a health center offering the full range of contraceptive methods. Currently, across the country more than 19 million U.S. women of low income live in contraceptive deserts. “In Oklahoma, more than 217,000 women must overcome significant barriers to access the contraception they need and deserve in order to decide if, when and under what circumstances to get pregnant and have a child,” said Raegan McDonald-Mosley, MD, MPH, CEO of Power to Decide. “The challenge of covering costs associated with obtaining family planning services—such as transportation, child care and unpaid time off from work—may be too great a burden for those already struggling to make ends meet.” Oklahoman women are also far less likely to have health coverage than women in other parts of the country, which limits their ability to get the birth control method that is right for them. In Oklahoma, 21.5% of women of reproductive age (13-44) are uninsured, almost double the national average of 12.1%. Despite these challenges, family planning providers are making every effort to provide contraceptive services to patients across the state. States like Oklahoma can also take proactive steps to expand access to contraception. Oklahoma recently expanded Medicaid to low-income adults, which will help decrease the percentage of uninsured women, and by extension, give them contraceptive coverage. In addition, allowing pharmacists to prescribe contraception and requiring insurance to cover an extended supply of prescription contraceptives can make it easier to access some contraceptive methods. Oklahoma can also guard against additional barriers to access by enacting policies that protect insurance coverage of the full range of contraceptive methods. More information about these policies can be found here. In addition, information about Oklahoma’s telehealth policies relevant to contraceptive access can be found here. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Wed, 09 Feb 2022 09:55:36 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/more-217000-women-oklahoma-live-contraceptive-deserts</guid> </item> <item> <title>MORE THAN 284,000 WOMEN IN MARYLAND LIVE IN CONTRACEPTIVE DESERTS</title> <link>https://powertodecide.org/about-usnewsroom/more-284000-women-maryland-live-contraceptive-deserts</link> <description>(Washington, D.C.)—According to data released by Power to Decide, an estimated 284,640 women living at or below 250% of the poverty level in Maryland live in contraceptive deserts, counties in which there is not reasonable access to a health center offering the full range of contraceptive methods. Of those in need living in contraceptive deserts, 1,720 live in counties without a single health center that provides the full range of contraceptive methods. Currently, across the country more than 19 million U.S. women of low income live in contraceptive deserts. “In Maryland, nearly 285,000 women must overcome significant barriers to access the contraception they need and deserve in order to decide if, when and under what circumstances to get pregnant and have a child,” said Raegan McDonald-Mosley, MD, MPH, CEO of Power to Decide. “The challenge of covering costs associated with obtaining family planning services—such as transportation, child care and unpaid time off from work—may be too great a burden for those already struggling to make ends meet.” The Title X Family Planning Program “domestic gag rule” presented further challenges to contraceptive access. After more than one year of harm, the gag rule was permanently blocked from going into effect in Maryland in September 2020. Despite these difficulties, family planning providers have been making every effort to provide contraceptive services to patients across the state. Maryland has also taken proactive steps to alleviate the impact of the domestic gag rule and to expand access to contraception. In addition to providing state funds to supplement the loss of federal Title X funds, Maryland has already expanded Medicaid to low-income adults, which helps decrease the percentage of uninsured women, and by extension, give them the contraceptive coverage they need to help live healthy lives. Maryland requires insurance to cover an extended supply of prescription contraceptives, as well as the full range of contraceptive methods. The state has also enacted policies that allow pharmacists to prescribe contraception. More information about these policies can be found here. In addition, information about Maryland’s telehealth policies relevant to contraceptive access can be found here. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Wed, 02 Feb 2022 09:45:50 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/more-284000-women-maryland-live-contraceptive-deserts</guid> </item> <item> <title>POWER TO DECIDE MARKS 49TH ANNIVERSARY OF ROE V. WADE</title> <link>https://powertodecide.org/about-usnewsroom/power-decide-marks-49th-anniversary-roe-v-wade</link> <description>(Washington, D.C.) — Today marks the 49th anniversary of the landmark 1973 U.S. Supreme Court decision in Roe v. Wade, which empowered people to be the stewards of their life’s course and enabled them to exert their reproductive freedom. In response, Power to Decide CEO, Dr. Raegan McDonald Mosley issued the following statement: “The decision allowed women and people capable of reproduction to experience economic and professional vitality. While today we recognize what Roe made possible, we also recognize the millions who cannot access abortion care despite Roe. Policies such as the Hyde Amendment and efforts to restrict access by state legislatures have consistently kept abortion care out of reach for people struggling to make ends meet and communities of color who face systemic barriers to health care access. “If Roe v. Wade is struck down, it’s estimated that 26 states would immediately move to outlaw abortion with “trigger laws” that make abortion immediately illegal. Other states have pre-Roe abortion bans on the books or have legislatures that would immediately pass laws to ban abortion. The result would be devastating for those who lack the resources to travel to a state where abortion remains legal. “Throughout my career as an OBGYN specializing in family planning and providing abortion care, I have counseled people from different backgrounds, creeds and nationalities regarding their reproductive health. I know the impact to a person’s reproductive well-being and mental health that result from being denied abortion care. “It is fundamentally wrong to have access to safe and essential abortion care dependent on what state you live in and/or how much money you make. It is time we pass the Women’s Health Protection Act (WHPA), which would establish a right to abortion care across the country. This bill enshrines the right for people to receive abortion care without medically unnecessary restrictions, such as mandatory waiting periods, biased counseling and mandatory ultrasounds. The bill passed the House last Fall and must now pass the Senate. “We urge the immediate passage of this critical legislation in order to prevent states from turning the clock back on all the progress made since Roe v. Wade was decided. We must also demand that state policymakers protect coverage and access to abortion care. This is how we can ensure that all people can achieve reproductive well-being.” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant or have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Sat, 22 Jan 2022 09:00:00 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-marks-49th-anniversary-roe-v-wade</guid> </item> <item> <title>NEARLY 429,000 WOMEN IN INDIANA LIVE IN CONTRACEPTIVE DESERTS</title> <link>https://powertodecide.org/about-usnewsroom/nearly-429000-women-indiana-live-contraceptive-deserts</link> <description>(Washington, D.C.) —According to data released by Power to Decide, an estimated 428,540 women living at or below 250% of the poverty level in Indiana live in contraceptive deserts, counties in which there is not reasonable access to a health center offering the full range of contraceptive methods. Of those in need living in contraceptive deserts, nearly a quarter live in counties without a single health center that provides the full range of contraceptive methods. Currently, across the country more than 19 million U.S. women of low income live in contraceptive deserts. “In Indiana, nearly 429,000 women must overcome significant barriers to access the contraception they need and deserve in order to decide if, when and under what circumstances to get pregnant and have a child,” said Raegan McDonald-Mosley, MD, MPH, CEO of Power to Decide. “The challenge of covering costs associated with obtaining family planning services—such as transportation, child care and unpaid time off from work—may be too great a burden for those already struggling to make ends meet.” Additional data from Power to Decide show that nearly 66,000 Indianan women of reproductive age (13-44) in need of publicly funded contraception live in the five counties that lost resources due to the Title X Family Planning Program “domestic gag rule” that was lifted on November 8, 2021, after more than two years of harm. Despite these challenges, family planning providers are making every effort to provide contraceptive services to patients across the state. Still, Indiana can take additional proactive steps to expand access to contraception. This is more important than ever, as the pandemic continues to devastate people’s lives in various ways. Indiana has already expanded Medicaid to low-income adults, which helps decrease the percentage of uninsured women, and by extension, give them the contraceptive coverage they need to live healthy lives. In addition, Indiana provides Medicaid reimbursement for postpartum long-acting reversible contraception. Indiana can also guard against additional barriers to access by enacting policies that allow pharmacists to prescribe contraception, extend the supply of prescription contraceptives and protect contraceptive coverage. More information about these policies can be found here. In addition, information about Indiana’s telehealth policies relevant to contraceptive access can be found here. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Mon, 13 Dec 2021 10:30:22 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/nearly-429000-women-indiana-live-contraceptive-deserts</guid> </item> <item> <title>NEARLY 242,000 WOMEN IN OREGON LIVE IN CONTRACEPTIVE DESERTS</title> <link>https://powertodecide.org/about-usnewsroom/nearly-242000-women-oregon-live-contraceptive-deserts</link> <description>(Washington, D.C.) —According to data released by Power to Decide, an estimated 241,690 women living at or below 250% of the poverty level in Oregon live in contraceptive deserts, counties in which there is not reasonable access to a health center offering the full range of contraceptive methods. Currently, across the country more than 19 million U.S. women of low income live in contraceptive deserts. “In Oregon, nearly 242,000 women must overcome significant barriers to access the contraception they need and deserve in order to decide if, when and under what circumstances to get pregnant and have a child,” said Raegan McDonald-Mosley, MD, MPH, CEO of Power to Decide. “The challenge of covering costs associated with obtaining family planning services—such as transportation, child care and unpaid time off from work—may be too great a burden for those already struggling to make ends meet.” Additional data from Power to Decide show that 257,950 Oregonian women of reproductive age (13-44) in need of publicly funded contraception live in the 29 counties that were impacted by the Title X Family Planning Program “domestic gag rule” that was lifted on November 8, 2021, after more than two years of harm. Despite these challenges, family planning providers have been making every effort to provide contraceptive services to patients across the state. In this challenging landscape, Oregon took proactive steps to partially alleviate the impact of the domestic gag rule and to expand access to contraception in various ways. In addition to providing state funds to supplement the loss of federal Title X funds, Oregon has already expanded Medicaid to low-income adults, which helps decrease the percentage of uninsured women, and by extension, give them the contraceptive coverage they need to live healthy lives. In addition, Oregon has enacted state policies that allow pharmacists to prescribe contraception, require insurance to cover an extended supply of prescription contraceptives and protect insurance coverage of the full range of contraceptive methods. More information about these policies can be found here. In addition, information about Oregon’s telehealth policies relevant to contraceptive access can be found here. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Mon, 13 Dec 2021 10:15:53 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/nearly-242000-women-oregon-live-contraceptive-deserts</guid> </item> <item> <title>SUPREME COURT HEARS ORAL ARGUMENTS IN CASE THAT COULD IMPACT ABORTION CARE ACCESS FOR MILLIONS</title> <link>https://powertodecide.org/about-usnewsroom/supreme-court-hears-oral-arguments-case-could-impact-abortion-care-access-for</link> <description>(Washington, D.C.) — Today, the U.S. Supreme Court will hear oral arguments in Dobbs v. Jackson Women's Health Organization, a case that directly challenges Roe v. Wade. At issue is a Mississippi law that would ban abortion care after 15 weeks of pregnancy. If Roe v. Wade is overturned, 24 states are poised to ban access to abortion care immediately. The state of Mississippi’s efforts are in direct conflict with popular opinion. Recent polling from Power to Decide shows that 74% of respondents (including 75% of white, 80% of Black and 65% of Hispanics respondents) believe abortion care should remain legal. In addition, two-thirds (66%) are concerned that people may not be able to access abortion care now and in the future. “Abortion care is an essential part of the full spectrum of reproductive health services and a common part of the reproductive life-course for many people,” said Dr. Raegan McDonald-Mosley, CEO of Power to Decide. “Despite public support for abortion care, the state of Mississippi is asking the court to reverse Roe which would threaten people’s ability to manage their reproductive health and endanger their physical and emotional well-being.” Research shows that abortion care restrictions and bans impact people’s financial status and emotional health. Women denied abortion care are four times as likely to live below the federal poverty line compared to those who were able to access abortion care when needed, according to data. In addition, they are more likely to experience serious health complications from pregnancy and experience poor physical health for years after the pregnancy. “We only have to look to Texas to see what is at stake before the court today,” continued McDonald-Mosley. “The harmful Texas ban has forced people with lower incomes, people of color and people in rural areas to travel to other states for abortion care. Many have been unable to surmount these barriers and are unable to receive the care they need. The ability to access the full spectrum of reproductive health services should not depend on your income level or where you live. Everyone – regardless of background or economic status – deserves the opportunity to decide if, when and under what circumstances to get pregnant and have a child.” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant or have a child. Please visit us our follow us on Facebook and Twitter. </description> <pubDate>Wed, 01 Dec 2021 06:00:00 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/supreme-court-hears-oral-arguments-case-could-impact-abortion-care-access-for</guid> </item> <item> <title>POWER TO DECIDE APPLAUDS HOUSE PASSAGE OF THE BUILD BACK BETTER ACT </title> <link>https://powertodecide.org/about-usnewsroom/power-decide-applauds-house-passage-build-back-better-act</link> <description>(Washington, D.C.) — Today, the U.S. House of Representatives in a 220-213 vote passed the Build Back Better Act, H.R. 5376. The bill would expand access to health care for millions of people giving them greater power to decide their futures. The Build Back Better Act would close the Medicaid coverage gap, enhance subsidies for health insurance plans offered as part of the Affordable Care Act, expand Medicaid post-partum coverage to 12 months and invest in addressing maternal health disparities and birth equity. These provisions will ensure that everyone has the health coverage they need and the ability to achieve their own reproductive well-being. In response, Power to Decide, CEO, Dr. Raegan McDonald-Mosley issued the following statement: “We thank our Congressional champions for passing this historic legislation investing in the health of our country. Key provisions of the legislation will expand health insurance coverage for roughly 800,000 women of reproductive age, of whom two-thirds are women of color. “For many years, the health care system has disproportionately harmed people who already face systemic barriers to access health care including people of color, people living in rural areas and those working to make ends meet. The provisions of this bill that address maternal health disparities and advance birth equity are steps in the right direction to address the systemic barriers pregnant people of color face. “By expanding health insurance coverage and affordability more people will gain access to the reproductive health care they deserve. We urge the U.S. Senate to pass the Build Back Better Act in order to ensure that everyone has the ability to access the health care they deserve so they can live life on their own terms.” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Fri, 19 Nov 2021 10:05:43 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-applauds-house-passage-build-back-better-act</guid> </item> <item> <title>CONCERN GROWING ABOUT FUTURE ACCESS TO BIRTH CONTROL</title> <link>https://powertodecide.org/about-usnewsroom/concern-growing-about-future-access-birth-control</link> <description>(Washington, DC)—Concern is on the rise about the ability of people to access the full range of birth control methods, according to a new nationally representative survey of adults age 18-45 released today by Power to Decide. Nearly seven in ten (69%) say they are concerned about future access to birth control (up from 51% in 2020). Democrats (74%), Independents (72%) and Republicans (55%) are all concerned about access to birth control. In addition, 85% of respondents—including 93% of Independents, 85% of Democrats and 76% of Republicans—believe all people, regardless of who they are, where they live or what their economic status may be deserve access to all methods of birth control. This and other survey findings were released today from Power to Decide in honor of its ninth annual Thanks, Birth Control Day. “It’s not surprising that a growing number of people are concerned about access to birth control given the ongoing efforts from some elected officials to restrict access to it,” said Raegan McDonald-Mosley, MD, CEO, Power to Decide. “The ability to plan and space out a pregnancy and pursue one’s goals should belong to all people, regardless of who they are or where they live.” Fully 74% of survey respondents (up from 45% in 2020)—including 71% of Republicans, 74% of Independents and 77% of Democrats—report using some form of contraception to avoid an unplanned pregnancy. Further, more than half (55% overall, 59% Democrat, 53% Independent and 51% Republican) agree birth control has allowed them to manage health conditions and 67% agree (including 72% of Democrats, 68% of Independents and 60% of Republicans) birth control has helped them work towards educational or professional goals. Finally, 76% (including 79% of Independents, 75% of Democrats and 74% of Republicans) are thankful birth control allowed them to decide if, when and under what circumstances to get pregnant and have a child. “Today, we proudly celebrate contraception for all it allows us to accomplish for ourselves and our families and for the opportunity to decide if, when and under what circumstances to get pregnant and have a child,” continued Dr. McDonald-Mosley. Power to Decide’s Thanks, Birth Control survey results are being released in conjunction with the ninth annual Thanks, Birth Control Day, taking place today, Wednesday, Nov. 17. The Centers for Disease Control and Prevention cites birth control as one of the 10 greatest public health achievements of the 20th century because of its profoundly positive impact on women, families, and society. When more people talk openly about why they use—and are grateful for—birth control, everybody wins. Here are three quick and easy ways to say, “Thanks, Birth Control” with us today: Join us today, from 2-3pm ET for our Twitter Storm using #ThxBirthControl. Spread the word on social media sharing why you are thankful for birth control, what birth control gives you the power to decide or how birth control allows people to live their best worry-free sex life. You can browse our toolkit to see pre-written social copy or write your own to help us dominate the conversation online. Check out our Thanks, Birth Control swag on our store and rock it year-round, as we celebrate birth control all-day, everyday! Snap a selfie to post on social media with your #ThxBirthControl swag. Share your story about the benefits of birth control, why you love birth control and how birth control allows people to live their best worry-free sex life. Our work would not be possible without generous support from our partners. Power to Decide would like to thank the following for their support and commitment to people’s reproductive health. Thank you for helping us say, Thanks, Birth Control: PRJKT Ruby, Agile Therapeutics, Twentyeight Health, Organon, Mayne Pharma, Bayer Pharmaceuticals, Nurx and the JPB Foundation. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. About the Survey: The study was conducted for Power to Decide via telephone by SSRS, an independent research company. Interviews were conducted on September 21, 2021 – October 7, 2021 among adults ages 18 to 45. A total of 1,005 interviews were conducted, with a margin of error for total respondents of +/-3.95% adjusted for design effect, at the 95% confidence level. </description> <pubDate>Wed, 17 Nov 2021 08:00:00 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/concern-growing-about-future-access-birth-control</guid> </item> <item> <title>AUMENTA LA PREOCUPACIÓN EN CUANTO AL ACCESO A MÉTODOS ANTICONCEPTIVOS EN EL FUTURO</title> <link>https://powertodecide.org/about-usnewsroom/aumenta-la-preocupacion-en-cuanto-al-acceso-metodos-anticonceptivos-en-el-futuro</link> <description>(Washington, DC) — La preocupación en cuanto a que las personas puedan tener acceso a todos los métodos anticonceptivos ha aumentado, según una nueva encuesta representativa a nivel nacional de adultos de entre las edades de 18 y 45 años publicada hoy día por Power to Decide. Casi siete de cada diez (el 69 %) de los encuestados dice estar preocupados por el acceso de los métodos anticonceptivos en el futuro (un aumento del 51% en el 2020). Los demócratas (el 74%), los independientes (el 72%) y los republicanos (el 55%) están todos preocupados por el acceso a los métodos anticonceptivos. Además, el 85% de los encuestados, incluyendo el 93% de los independientes, el 85% de los demócratas y el 76% de los republicanos, creen que todas las personas, independientemente de quiénes sean, dónde vivan o cuál sea su situación económica deben tener acceso a todos los métodos anticonceptivos. Este y otros resultados de dicha encuesta fueron publicados hoy por Power to Decide como parte de su noveno día anual dedicado a dar las gracias por los métodos anticonceptivos conocido en inglés como el Thanks, Birth Control Day. “No es sorprendente que un creciente número de personas estén preocupadas por el acceso a los métodos anticonceptivos dados los esfuerzos para restringir el acceso a los mismos que llevan a cabo algunos funcionarios electos”, dijo Raegan McDonald-Mosley, MD y CEO de Power to Decide. “La habilidad para planificar y espaciar los embarazos y poder perseguir las metas propias debe ser posible para todas las personas, independientemente de quiénes sean o dónde vivan”. El 74% de los encuestados (en comparación con el 45% en el 2020) incluyendo el 71% de los republicanos, el 74% de los independientes y el 77% de los demócratas, han reportado que utilizan algún tipo de contraceptivo para evitar un embarazo no planificado. Además, más de la mitad (el 55% del total, el 59% de los demócratas, el 53% de los independientes y el 51% de los republicanos) están de acuerdo con que los métodos anticonceptivos les han permitido manejar mejor sus condiciones de salud y el 67% (incluyendo el 72% de los demócratas, el 68% de les independientes, el 60% de los republicanos) está de acuerdo con que los métodos anticonceptivos los han ayudado a encaminarse hacia sus metas de trabajo y estudios. Por último, el 76% (incluyendo el 79% de los independientes, el 75% de los demócratas y el 74% de los republicanos) están agradecidos porque los métodos anticonceptivos les han ayudado a decidir si quieren y en cuáles circunstancias quieren quedar embarazados y tener un hijo. “Hoy, estamos orgullosos de celebrar los métodos anticonceptivos por todo lo que nos permiten lograr para nosotros mismos y para nuestras familias, y por la oportunidad de decidir si queremos, cuándo queremos y en qué circunstancias quedar embarazadas y tener un hijo”, continuó diciendo la Dr. McDonald-Mosley. Los resultados de la encuesta Thanks, Birth Control de Power to Decide están siendo publicados durante el noveno día anual dedicado a dar las gracias por los métodos anticonceptivos o Thanks, Birth Control Day, el cual se celebra hoy día, miércoles 17 de noviembre. El Centro para el Control y la Prevención de las Enfermedades indica que los métodos anticonceptivos son uno de los 10 logros más importantes del siglo XX, en cuanto a la salud pública, debido al inmenso impacto positivo que han tenido para las mujeres, las familias y la sociedad. Cuando más personas discuten abiertamente lo que utilizan y por lo que están agradecidas en cuánto a los métodos anticonceptivos, todos salimos ganando. A continuación, encontrarán tres maneras fáciles y rápidas para dar las gracias y decir junto a nosotros: “Anticonceptivos, muchas gracias” o “Thanks, Birth Control”: Únete a nosotros hoy, de 2 a 3pm ET para nuestro esfuerzo en Twitter y utiliza #ThxBirthControl. Comparte en los medios sociales el motivo por el cual estás agradecida de los métodos anticonceptivos, qué tipo de método anticonceptivo te ofrece el poder de decidir o cómo los anticonceptivos ayudan a las personas a vivir la mejor versión de sus vidas sin preocuparse por su vida sexual. Puedes buscar más información en nuestro toolkit donde aparecen ideas para copiar en tu muro o para ayudarte a escribir tu propio mensaje y que nos puedas ayudar a dominar la conversación online. Mira todos los artículos que tenemos disponible de swag de Thanks, Birth Control en nuestra tienda y úsalos todo en año, para celebrar el día de dar las gracias por los anticonceptivos todos los días. Póntelos, tómate un selfie y postéalo en los medios sociales con la etiqueta #ThxBirthControl. Comparte tu historia sobre los beneficios de los métodos anticonceptivos, por qué te encantan, y cómo los anticonceptivos ayudan a las personas a vivir la mejor versión de sus vidas sin tener que preocuparse por sus vidas sexuales. Nuestro trabajo no sería posible sin la generosa contribución de nuestros socios. Power to Decide desdea agradecer a los siguientes por su apoyo y compromiso con la salud reproductiva de las personas. Muchas gracias por ayudarnos a decir “Thanks, Birth Control” a: PRJKT Ruby, Agile Therapeutics, Twentyeight Health, Organon, Mayne Pharma, Bayer Pharmaceuticals, Nurx y al JPB Foundation. Power to Decide es una organización privada, no partidista y sin fines de lucro que trabaja para asegurar que todas las personas, sin importar quiénes sean, dónde vivan o cuál sea su situación económica, tengan el poder de decidir si quieren, cuándo y bajo qué circunstancias quedar embarazadas y tener un hijo. Favor de visitarnos a través de www.PowerToDecide.org o síguenos a través de Facebook y Twitter. Información sobre la encuesta: Esta encuesta telefónica ha sido llevada a cabo para Power to Decide por SSRS, una compañía independiente de investigación. Las entrevistas se llevaron a cabo entre el 21 de septiembre de 2021 y el 7 de octubre de 2021 y se entrevistó a adultos entre las edades de 18 y 45 años. Se llevaron a cabo un total de 1,005 entrevistas, con un margen de error para el total de los encuestados del +/-3.95% ajustados para el efecto del diseño y con un índice de confianza del 95%. </description> <pubDate>Wed, 17 Nov 2021 08:00:00 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/aumenta-la-preocupacion-en-cuanto-al-acceso-metodos-anticonceptivos-en-el-futuro</guid> </item> <item> <title>POWER TO DECIDE APPLAUDS THE BIDEN-HARRIS ADMINISTRATION’S NATIONAL STRATEGY ON GENDER EQUITY AND EQUALITY</title> <link>https://powertodecide.org/about-usnewsroom/power-decide-applauds-biden-harris-administrations-national-strategy-gender-equity</link> <description>Washington, D.C. — Today, the White House Gender Policy Council released the National Strategy on Gender Equity and Equality, a broad strategy that includes a roadmap to help people achieve their reproductive well-being. The strategy on gender equity and equality includes strong commitments to programs and policies that will protect, improve and expand access to the full spectrum of reproductive and sexual health care. “We applaud the administration’s ambitious agenda to improve people’s ability to achieve their goals regardless of who they are, where they live or how much money they make,” said Dr. Raegan McDonald-Mosley, CEO of Power to Decide. “Measures such as restoring and expanding the Title X Family Planning Program and closing disparities in maternal health care center the needs for equity and address systemic barriers. This is an important step in the right direction to improve access to reproductive health for all.” Among other important commitments, the strategy also ensures people can get their reproductive health care from the provider of their choice, regardless of what health program they use. In addition, it supports medically accurate, inclusive, age-appropriate sex education. Further, it commits to protecting Roe v. Wade and eliminating barriers in coverage of abortion care by repealing the harmful Hyde Amendment. “This unprecedented national strategy will lay out the necessary work to help ensure all people have the opportunity to decide if, when and under what circumstances to get pregnant and have a child,” continued McDonald-Mosley. “We look forward to working with the administration to make this vision a reality for all” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Fri, 22 Oct 2021 16:11:00 -0400</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-applauds-biden-harris-administrations-national-strategy-gender-equity</guid> </item> <item> <title>POWER TO DECIDE STATEMENT ON SENATE FY 2022 LABOR, HEALTH AND HUMAN SERVICES AND EDUCATION SPENDING BILL</title> <link>https://powertodecide.org/about-usnewsroom/power-decide-statement-senate-fy-2022-labor-health-and-human-services-and</link> <description>(Washington, D.C.) — Yesterday, the U.S. Senate Appropriations Committee released draft spending bills for Fiscal Year (FY) 2022, including those that fund Labor, Health and Human Services and Education (LHHS) and Financial Services and General Government (FSGG). The LHHS spending bill includes $500 million for the Title X Family Planning Program, an increase of $213.5 million over the current funding level. The bill also includes $130 million for the evidence-based Teen Pregnancy Prevention (TPP) Program, an increase of $29 million over the current funding level. It also eliminates funding for abstinence-only programs in appropriations. Finally, neither the harmful Hyde Amendment nor the ban on coverage of abortion care for Medicaid beneficiaries in DC are included. In response, Dr. Raegan McDonald-Mosley, CEO of Power to Decide issued the following statement: “We are thrilled by the bold action taken by the Senate Appropriations Committee to provide robust funding increases for the TPP and Title X Programs. The increased investments would help ensure more people have access to the reproductive health services and information they need and deserve. In addition, the historic boost in funding for the Title X program would help reverse the damage done by the domestic gag rule. “We are also thankful that the bills eliminate restrictions on abortion care that have resulted in too many being denied the care they need solely because of their income and zip code. “We thank the members of the Senate who championed these programmatic increases and significant policy changes. We urge the Senate to pass these bills with the current funding levels for the TPP and Title X programs and without restrictions on access to abortion care. Such action will help ensure more people have the information and access to care they need to achieve the futures they want for themselves and their families.” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant or have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Tue, 19 Oct 2021 09:41:24 -0400</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-statement-senate-fy-2022-labor-health-and-human-services-and</guid> </item> <item> <title>POWER TO DECIDE HAILS FEDERAL COURT DECISION TEMPORARILY BARRING ENFORCEMENT OF HARMFUL ABORTION RESTRICTION</title> <link>https://powertodecide.org/about-usnewsroom/power-decide-hails-federal-court-decision-temporarily-barring-enforcement-harmful</link> <description>(Washington, D.C.) — Yesterday, a federal district judge granted a temporary injunction barring enforcement of Texas Senate Bill 8, a The 2019 honorees successfully protected the Teen Pregnancy Prevention (TPP) Program, preventing the Trump administration from circumventing Congress and abolishing the TPP program. The award is named after Sarah S. Brown, the founding CEO of Power to Decide, and was established to recognize innovative leaders who have been strong, smart and bold in making significant contributions to the mission of Power to Decide. “We are proud to honor these three organizations that worked tirelessly to protect and defend the TPP Program with the 2019 Sarah S. Brown Award,” said Ginny Ehrlich, CEO, Power to Decide. “These legal groups have demonstrated tremendous courage and unwavering commitment in fighting against actions that would have adversely impacted the most vulnerable among us. By not backing down, they stood squarely on the side of science and successfully defeated an effort that would have reversed the progress we have made in reducing unplanned pregnancies.” “Democracy Forward is proud to stand with all of the communities, advocates and legal teams committed to defending the TPP program,” said Democracy Forward Executive Director Anne Harkavy. “We are honored to receive this recognition and we will keep fighting to protect these critical programs against unlawful attacks.” “Planned Parenthood is proud to celebrate the incredible work of our Public Policy Litigation & Law team as an honoree of Power to Decide’s 2019 Sarah S. Brown Award for their work to protect the TPP program,” said Dr. Leana Wen, President of Planned Parenthood Federation of America. “Because of the best in class work from our litigation team and allies, including the partnership with our friends at Arnold & Porter, millions of young people across the country will not be left with a critical gap in health education. As the nation’s largest provider of sex education, Planned Parenthood looks forward to continuing to provide, protect and expand evidence-based, comprehensive sexual and reproductive health education.” “Public Citizen appreciates this recognition of our work to restore TPP program funding to 66 grantees, after the administration—for ideological reasons unsupported by facts or the law—tried to terminate these important programs,” said Allison Zieve, Director, Public Citizen Litigation Group. Since peaking in 1991, the teen birth rate has declined 70 percent, as a result, in part, of bipartisan policies and programs, such as the TPP program. The program provides high-quality, evidenced-based sexual health information to young people most in need. Yet, despite its proven success, the administration tried to abolish the TPP program by cutting short all of its existing grants. In response, the awardee organizations joined efforts and filed suits against the U.S. Department of Health and Human Services to challenge the administration’s actions. Specifically, 11 lawsuits were filed by these groups against the shortening of grants, including one class action suit. The plaintiffs won all 11 lawsuits and the government has since dropped its appeals in all the cases. Andrea Kane currently serves as the Vice President for Policy and Strategic Partnerships at Power to Decide. The award recognizes Kane’s distinguished career and her on-going work on behalf of women, young people and families. Kane has successfully identified systems gaps among vulnerable populations, such as youth in foster care and community college students and helped to initiate innovative policy and programmatic efforts, which specifically met the needs of these populations. In addition, Kane played a key role in maintaining support for the TPP program. “Andrea is a fearless and bold advocate who has made a difference in the lives of millions of youth and families throughout her distinguished career. It gives me great pleasure to recognize our esteemed colleague and friend Andrea Kane with the 2018 Sarah S. Brown Award. During her distinguished and ongoing career, Andrea has been a leading force in bringing forth smart and innovative policies that help to ensure all young people have the power to decide, if, when and under what circumstances to get pregnant and have a child,” Ehrlich said. From 2001 through 2008, Kane was a visiting fellow with the Brookings Institution’s Center on Children and Families. Before joining Power to Decide in 2001, Kane served at the White House Domestic Policy Council as a special assistant to President Clinton and worked at the National Governors’ Association and at the state and local level in California, Texas and Virginia. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Mon, 11 Feb 2019 11:11:17 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-recognizes-efforts-safeguard-teen-pregnancy-prevention-program-sarah</guid> </item> <item> <title>POWER TO DECIDE APPLAUDS PRELIMINARY INJUNCTION ON RULES THAT WOULD LIMIT ACCESS TO BIRTH CONTROL</title> <link>https://powertodecide.org/about-usnewsroom/power-decide-applauds-preliminary-injunction-rules-would-limit-access-birth</link> <description>(Washington, D.C.) — Yesterday, a federal court in Pennsylvania issued a preliminary nationwide injunction temporarily blocking the implementation of the Trump Administration’s final rules that would have limited the availability of birth control coverage through the Affordable Care Act (ACA). The finalized rules were issued by the Trump Administration last November and would have allowed employers to opt out of covering birth control in their insurance plans based on religious or moral objections. Ginny Ehrlich, CEO, Power to Decide responded to the injunction saying: “All women deserve access to the full spectrum of reproductive health services. No co-pay birth control coverage as a part of their insurance plans is a critical part of that access. Birth control is basic health care. We are pleased that at least for now, women will continue to have access to this essential component of care. The Trump Administration’s rules that will not be taking effect would limit impacted women’s access to birth control and as importantly, limit their ability to decide what’s best for their health. All women deserve the power to decide for themselves if, when and under what circumstances to get pregnant and have a child.” The injunction issued yesterday follows the decision from a federal court in California on Sunday, Jan. 13, which issued a limited injunction blocking these rules from going into effect in 13 states. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Tue, 15 Jan 2019 16:03:24 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-applauds-preliminary-injunction-rules-would-limit-access-birth</guid> </item> <item> <title>A NEW REPORT FROM THE CENTERS FOR DISEASE CONTROL AND PREVENTION FINDS AN INCREASE IN BIRTH CONTROL USE AMONG WOMEN IN THE U.S.</title> <link>https://powertodecide.org/about-usnewsroom/new-report-centers-for-disease-control-and-prevention-finds-increase-birth-control</link> <description>(Washington, D.C.) — According to a report from the U.S. Centers for Disease Control and Prevention's National Center for Health Statistics (CDC NCHS), the number of women using a method of contraception to avoid an unplanned pregnancy has increased. Specifically, in 2015-2017, nearly 65% of women aged 15 to 49 in the United States used a method of contraception, which is an increase from the 61.1% of women who were previously surveyed from 2011 to 2015. In response to the report, Dr. Colleen Crittenden Murray, Senior Science Officer, Power to Decide, issued the following statement: “Unquestionably, we believe our efforts to provide medically accurate information, and increase opportunity among women to access the full spectrum of contraceptive options has positively contributed to the higher prevalence of birth control use in this country. Eliminating copay and expanding Medicaid coverage has also contributed to making access to contraception more readily available and thus increasing overall use, as indicated in the report. Today, the consistent attacks on reproductive health, which include reducing access to reproductive health services and quality sexual health information for people who need it most, threaten women’s ability to achieve their reproductive goals on their own terms. We will continue our efforts to ensure that all women— regardless of who they are or where they live—have access to the information and services they need to decide if, when, and under what circumstances to get pregnant and have a child.” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Fri, 21 Dec 2018 14:18:16 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/new-report-centers-for-disease-control-and-prevention-finds-increase-birth-control</guid> </item> <item> <title>POWER TO DECIDE AND MEDICINES360 ANNOUNCE PARTNERSHIP TO EXPAND ACCESS TO CONTRACEPTION</title> <link>https://powertodecide.org/about-usnewsroom/power-decide-and-medicines360-announce-partnership-expand-access-contraception</link> <description> (Washington, D.C.) —Today, millions of women in need of contraception struggle with access to this basic part of women’s health care. To help women access this needed service, Power to Decide and Medicines360, a mission-driven nonprofit women’s health pharmaceutical, will partner to help expand access to contraception for all women. This partnership aims especially to help the more than 19 million women who live in contraceptive deserts—meaning that they live in counties without reasonable access to the full range of contraceptive methods. Medicines360 and Power to Decide will work together to ensure that all women have access to the information and services they need in order to align their intentions with their actions and live life on their own terms. They will offer information about clinics that provide low cost IUD options via Power to Decide’s Bedsider program; support low income women’s transportation and child care costs via the contraceptive access fund, which will launch in 2019 and educate providers about quality contraceptive care. “We are excited to work with Medicines360 to ensure that women can access the birth control method that’s right for them,” said Ginny Ehrlich, CEO, Power to Decide. “All women deserve the power to decide if, when and under what circumstances to get pregnant and have a child. However, many women struggle to access the care they need to achieve their goals due to financial and other barriers. Medicines360 has led the way to put low cost IUDs on the market and shares our goal to reduce barriers to access.” “In partnership with Power to Decide, we can help respond to the challenges women face when trying to access contraception,” said Jessica Grossman, MD, Chief Executive Officer, Medicines360. “Our goal is to close critical access gaps for women and we look forward to working with Power to Decide to accelerate progress in this arena.” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at powertodecide.org or follow us on Facebook and Twitter. Medicines360, located in San Francisco, California, is a nonprofit global women’s health pharmaceutical company with a mission to expand access to quality medicines for all women regardless of their socioeconomic status, insurance coverage, or geographic location. Medicines360 is committed to working with healthcare providers, advocacy groups and patients to deliver innovative and meaningful treatments that help women around the world have greater access to the medicines they need. For more information, visit www.medicines360.org.</description> <pubDate>Fri, 21 Dec 2018 12:55:47 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-and-medicines360-announce-partnership-expand-access-contraception</guid> </item> <item> <title>BEDSIDER AND TWENTYEIGHT HEALTH PARTNER TO INCREASE WOMEN’S ACCESS TO CONTRACEPTION</title> <link>https://powertodecide.org/about-usnewsroom/bedsider-and-twentyeight-health-partner-increase-womens-access-contraception</link> <description>(Washington, D.C.) — Twentyeight Health, a mission-driven digital health platform that focuses on women’s access to high quality health care, will donate one percent of its revenues to Bedsider. This will enable Bedsider to continue to provide high quality information and access to tools on birth control so that all women have the power to decide if, when and under what circumstances to get pregnant and have a child. “We are so grateful to Twentyeight Health for their vision and partnership,” said Ginny Ehrlich, CEO, Power to Decide. “This generous support from Twentyeight Health will allow us to expand upon our award winning Bedsider program, which provided more than 7 million young people valuable information and resources on sex, love, relationships and birth control in 2018 alone.” Access to reproductive and sexual health care is still a challenge in the United States. More than 19 million women live in contraceptive deserts—meaning they do not have reasonable access to the full range of contraceptive methods. In addition, 7 out of 10 pregnancies among unmarried women 18-29 are described by women themselves as unplanned and 43% of women report having no exposure to sexual education by the time they become sexually active. “We believe that all women should have access to high quality health care. Our mission is to make services such as filling on-line prescriptions, coordinating home deliveries for birth control or consulting with a doctor through secure messaging, available to everyone in need,” said Amy Fan, co-founder, Twentyeight Health. “We are passionate about ensuring all women have the resources they need in order to manage their reproductive health and we are proud to be working with Bedsider in this effort,” said Bruno Van Tuykom, co-founder, Twentyeight Health. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. Bedsider.org is an evidence-informed, digital intervention aimed at supporting young women (age 18-29) to learn about access and using birth control effectively. Bedsider is the first reproductive health digital intervention in the U.S. for adults that has been shown to prevent unplanned pregnancy. Bedsider offers medically accurate information on all current methods of contraception and includes the most comprehensive database of health center locations offering reproductive health services in the U.S. Bedsider also offers extensive content on sexual health and relationships, as well as content and tools to support consistent and reliable use of contraception. Bedsider had more than 6.25 million unique users in 2017. To access the new feature on Bedsider’s clinic finder, go here. Twentyeight Health is a mission-driven women’s health platform focused on increasing access to healthcare services, starting with birth control. We provide online doctors evaluations for birth control prescriptions, quick home deliveries and secure messaging with doctors. We also have sex ed content vetted by doctors so women can learn about all their options. Learn more at TwentyeightHealth.com.</description> <pubDate>Tue, 18 Dec 2018 12:21:33 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/bedsider-and-twentyeight-health-partner-increase-womens-access-contraception</guid> </item> <item> <title>POWER TO DECIDE EARNS 4-STAR RATING FROM CHARITY NAVIGATOR </title> <link>https://powertodecide.org/about-usnewsroom/power-decide-earns-4-star-rating-charity-navigator</link> <description>(Washington, D.C.)— Power to Decide, the campaign to prevent unplanned pregnancy, was awarded its 12th consecutive 4-star rating by Charity Navigator, which is a streak that can be claimed by less than 1% of all charities reviewed. The 4-star rating is the highest rating a charitable non-profit can receive. Charity Navigator is an independent, non-profit organization that provides donors with essential information in order to make informed decisions about charitable giving. For more than 20 years, Power to Decide has been a recognized as a leader in ensuring that young people have what they need to decide if, when, and under what circumstances to get pregnant. Power to Decide provides reliable, relevant, and resonant sexual and reproductive health information via its direct to consumer property, Bedsider.org. The organization also has been a leader in advocating for greater access to contraceptive methods in order to avoid unplanned pregnancies. Power to Decide also serves as a trusted source for research-based solutions and works with mentors, policymakers, and entertainment media in order to further its mission. “We are so proud to have received this prestigious recognition from Charity Navigator for the 12th consecutive time,” said Ginny Ehrlich, CEO, Power to Decide. “This special recognition validates our work and recognizes our efforts to ensure that every dollar of support we receive is used wisely in order to maximize our impact for young people. Our goal remains to help ensure that all young people—regardless of who they are or where they live—have access to quality sexual health information and the full range of contraceptive methods.” Power to Decide was founded in 1996 when teen pregnancy and birth rates were significantly higher. Although unplanned and teen pregnancies rates have declined significantly, women of color and women living in poverty continue to experience unplanned pregnancies at unacceptably high rates. In addition, recent research conducted by Power to Decide shows that nearly 20 million American women live in contraceptive deserts—defined by their lack of reasonable access to public health care sites offering the full range of contraceptive methods. “Despite significant progress, we cannot declare victory. We must continue our efforts until all young people have the power to decide if, when, and under what circumstances to get pregnant and have a child,” concluded Ehrlich. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant and have a child. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter. </description> <pubDate>Mon, 19 Nov 2018 10:44:22 -0500</pubDate> <dc:creator>MLeDuc</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-earns-4-star-rating-charity-navigator</guid> </item> <item> <title>Power To Decide Joins 100 Reproductive Health, Rights, and Justice Groups to Advance Reproductive Health for All </title> <link>https://powertodecide.org/about-usnewsroom/power-decide-joins-100-reproductive-health-rights-and-justice-groups-advance</link> <description>(Washington, D.C.) —On Thursday November 15, Power to Decide joined 100 reproductive health, rights, and justice groups in outlining a bold and proactive vision for policymakers to advance sexual and reproductive health. This vision statement is the first step in a larger process in which these groups will work collectively to provide legislative and administrative policy recommendations that advance our shared goals. Ginny Ehrlich, CEO, Power to Decide, issued the following in regards to the vision statement: “At Power to Decide, we believe that everyone - regardless of who they are or where they live - should have the power to decide if, when, and under what circumstances to get pregnant and have a child. Unfortunately, we have a long way to go to make that a reality – especially among those who face other forms of systematic oppression. Just one indicator of the work we need to do relates to contraceptive access. More than 19 million women in need of publicly funded birth control live in contraceptive deserts, or counties without reasonable access to a clinic offering the full range of methods. Power to Decide is committed to reducing these disparities by working towards policies and programs that build a system of support that enables everyone to live life on their own terms.”</description> <pubDate>Fri, 16 Nov 2018 14:21:13 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-joins-100-reproductive-health-rights-and-justice-groups-advance</guid> </item> <item> <title>Historic 70% Decline in U.S. Teen Birth Rate</title> <link>https://powertodecide.org/about-us/newsroom/historic-70-decline-us-teen-birth-rate</link> <description>(Washington, D.C.) —The U.S. teen birth rate has declined 70% since peaking in 1991 and is at a new record low according to a new study from the Center for Disease Control (CDC). The historic declines include: 70% decline in teen births between 1991 and 2017. 55% decline in teen births between 2009 and 2017. 7% decline in teen births between 2016 and 2017 The report also notes significant declines in teen births between 2016 and 2017 among all racial/ethnic groups, including: 15% decline among non-Hispanic Asian teens 11% decline among non-Hispanic Native Hawaiian or other Pacific Islander teens 9% decline among Hispanic teens 8% decline among non-Hispanic white teens 6% decline among non-Hispanic Black and American Indian/Alaska Native teens In response, Colleen Crittenden Murray, Senior Science Officer, Power to Decide, issued the following statement: “It is highly probable that the historic decline in teen birth rates can be explained by the combination of improved access to and consistent use of birth control. In addition, we know that teenagers are having less sex, which has also contributed to the declines. The new data is significant for what it represents for young women across the country. Young people who do not have children are more likely to finish high school and pursue higher education opportunities or join the workforce.” “A recent poll conducted by Power to Decide revealed that access and information about birth control received considerable public support. Unfortunately, this access is under attack. Misguided policies by the current Presidential Administration would further limit women’s ability to access birth control methods that are right for them. Notably, this limitation will be more pronounced among lower income and rural communities, thus continuing to restrict the basic health care they deserve.” “The Affordable Care Act and the expansion of Medicaid increased access to affordable and quality contraception for women and as a result have also contributed to the steady decline in teen birth rates. Any attempt to curtail these important resources would discontinue the progress we have made, and hurt the most vulnerable among us.” </description> <pubDate>Fri, 16 Nov 2018 14:01:29 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-us/newsroom/historic-70-decline-us-teen-birth-rate</guid> </item> <item> <title>En El Día De Gracias, Día De Los Anticonceptivos, Una Encuesta Nacional Confirma Que Los Anticonceptivos Continúan Teniendo Un Apoyo Generalizado Como Parte Fundamental Del Cuidado De Salud De La Mujer</title> <link>https://powertodecide.org/about-usnewsroom/en-el-dia-de-gracias-dia-de-los-anticonceptivos-una-encuesta-nacional-confirma-que</link> <description>(Washington, D.C.) —Casi 8 de cada 10 (78%) adultos en los Estados Unidos, incluyendo el 66% de los republicanos y el 93% de los demócratas, consideran a los anticonceptivos como una parte fundamental del cuidado de salud de la mujer, de acuerdo a una nueva encuesta telefónica de más de 1,000 adultos de 18 años o más publicada hoy por Power to Decide. La encuesta además demuestra que una conversación más abierta sobre la amplia gama de métodos y los beneficios a la salud incrementaría el uso de anticonceptivos en los EE.UU. “En el día de Gracias, Día de los Anticonceptivos, agradecemos las muchas oportunidades que los anticonceptivos han hecho posible y continúan haciéndolo en las vidas personales y profesionales de las mujeres,” dijo Ginny Ehrlich, CEO de Power to Decide. “Nuestra encuesta muestra que la mayoría de las personas en los Estados Unidos comprenden que necesitamos ampliar el acceso a los anticonceptivos e incrementar la información y el entendimiento referente a los muchos beneficios de salud de los anticonceptivos. Ampliar el poder de decidir sí, cuando y bajo qué circunstancias embarazarse y tener un hijo es nuestro grito de lucha para todas las mujeres y niñas independientemente de quienes son o donde viven.” Los resultados de la encuesta están siendo dados a conocer para coincidir con el 6to día anual de Gracias, Día de los Anticonceptivos, que se celebra el día de hoy, martes 13 de noviembre. El día de Gracias, Día de los Anticonceptivos celebra los múltiples beneficios que los anticonceptivos proporcionan a las mujeres, a las familias y a la sociedad. A pesar del amplio apoyo a los esfuerzos por proteger el financiamiento público para los anticonceptivos entre los encuestados (75%), los anticonceptivos continúan siendo esquivos para más de 19 millones de mujeres en los Estados Unidos que viven en desiertos de anticonceptivos. Estos son condados en donde existe una falta de acceso razonable a una clínica que proporcione toda la gama de opciones de anticonceptivos en sus respectivos condados. Los resultados de la encuesta incluyeron: El 81% de los encuestados apoyan políticas que le facilitarían a personas de 18 años de edad o más obtener toda la gama de métodos anticonceptivos. 75% de los encuestados apoyan los esfuerzos para proteger el financiamiento federal, estatal y local para anticonceptivos para mujeres de 18 años o más. El 76% de todos los encuestados dicen que, si supieran que no todos tienen acceso a toda la gama de métodos anticonceptivos, abogarían por el acceso completo a anticonceptivos. El 56% de los encuestados estuvieron de acuerdo en que, si las personas tuvieran un más fácil acceso a una amplia gama de métodos anticonceptivos, el número de personas tomando anticonceptivos aumentaría. “Al abogar por el pleno acceso a anticonceptivos, podemos ayudar a aumentar la conciencia sobre su importancia en la vida de las personas e incrementar la aceptación de los anticonceptivos como un cuidado de salud fundamental para todas las mujeres,” dijo Ginny Ehrlich, CEO de Power to Decide. “Abogar por un mayor acceso también ayuda a asegurar que todas las mujeres puedan alinear sus intenciones con sus acciones y vivir sus mejores vidas.” Para aquellos interesados en compartir sus razones por las que están agradecidos con los anticonceptivos o en abogar por un mayor acceso de los mismo, el día de Gracias, Día de los Anticonceptivos es una plataforma perfecta. Empieza con estos 6 pasos fáciles y rápidos: El 13 de noviembre, tomate una selfi y di Gracias, Anticonceptivos, y etiquétala en las redes sociales con #ThxBirthControl. Comparte tu amor por los anticonceptivos mediante una gráfica.¡Lastarjetas postales digitalesde Bedsiderson perfectas para desparramar el amor por los anticonceptivos en las redes sociales! ¿Sintiéndote artística? Crea tu propio letrero de Gracias, Anticonceptivos comentando porque estás agradecida por los anticonceptivos, tómate una foto y publícala en las redes sociales con #ThxBirthControl. ¿Te han permitido los anticonceptivos lograr algo grande n tu vida? Cuéntale a Bedsider tu historia! Envía tu historia (escrita o en video) en su página web para gritar por todos los aires porque son importantes los anticonceptivos. Extiende tu mano para ayudar. ¡Has una donación a Power to Decide y ayuda a mujeres que viven en los desiertos de anticonceptivos a obtener los anticonceptivos que merecen! ¡Por último, pero no menos importante… demuestra tu amor por los anticonceptivos no solo el día de hoy sino todos los días del año! Visita Bedsider.org y PowertoDecide.org para ver otras ideas y contenido que puedes compartir. Power to Decidees una organización privada, no partidista y sin fines de lucro que trabaja para garantizar que todas las personas, independientemente de quienes son, donde viven o cuál es su estatus económico, tengan el poder de decidir sí, cuando y bajo qué circunstancias embarazarse y tener un hijo. Por favor visítenos en www.PowerToDecide.org o síganos en Facebook y Twitter. Acerca de la Encuesta:La información presentada aquí fue obtenida de una encuesta telefónica nacional realizada por Power to Decide por SSRS, una compañía de investigación independiente. Las entrevistas telefónicas se llevaron a cabo del 21 de agosto al 26 de agosto de 2018 entre una muestra representativa nacional de 1,016 encuestados estadounidenses de 18 años de edad y mayores. El margen de error por el total de encuestados es de +/- 3.69% a un nivel de confianza del 95%.</description> <pubDate>Tue, 13 Nov 2018 01:02:54 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/en-el-dia-de-gracias-dia-de-los-anticonceptivos-una-encuesta-nacional-confirma-que</guid> </item> <item> <title>On Thanks, Birth Control Day, A National Poll Confirms That Birth Control Remains Widely Supported As A Basic Part Of Women’s Health Care</title> <link>https://powertodecide.org/about-usnewsroom/thanks-birth-control-day-national-poll-confirms-birth-control-remains-widely</link> <description>(Washington, D.C.) — Nearly 8 in 10 (78%) adults in the United States—including 66% of Republicans and 93% of Democrats—consider birth control a basic part of women’s health care, according to a new telephone survey of more than 1,000 adults 18 and older released today by Power to Decide. The survey also showed that more open discussion regarding the full range of methods and health benefits would increase use of birth control in the U.S. “On Thanks Birth Control Day, we give thanks for the many opportunities birth control has and continues to make possible in women’s lives,” said Ginny Ehrlich, CEO, Power to Decide. “Our polling reconfirms what we already know that the majority of people in the United States support broad-based access and public funding for birth control.” The survey results are b of men and women ages 18 and older who are internet users. Google’s reports state a margin of error of +/- 2.1% at the 95% confidence level, which provides a helpful indication of the variability in these results; however, we note that because the sample is based on those who initially self-selected for participation, this estimate rests on a specific set of statistical assumptions about the selected sample, rather than the standard methodology for random probability sampling. Numbers may not sum to 100 due to rounding.</description> <pubDate>Tue, 13 Mar 2018 17:20:25 -0400</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/new-polling-shows-young-women-seek-sex-and-relationship-advice-their-fathers</guid> </item> <item> <title>Power To Decide Raises Concerns About Title X Funding </title> <link>https://powertodecide.org/about-usnewsroom/power-decide-raises-concerns-about-title-x-funding</link> <description>(Washington, D.C.) — Power to Decide, the campaign to prevent unplanned pregnancy, expressed concerns about The Trump Administration’s recent announcement regarding the Title X Family program because of its emphasis on natural family planning (also known as fertility awareness methods) and abstinence over other FDA approved methods of contraception. The $260 million funding opportunity announcement (FOA) for Title X does not include support for more effective methods of contraception, such as hormonal and long-acting methods. The announcement also fails to mention the Quality Family Planning recommendations, which are the national standard of clinical care for family planning services produced by the Centers for Disease Control and Prevention (CDC) and the U.S. Office of Population Affairs. In response, Ginny Ehrlich, CEO of Power to Decide, issued the following statement: “For nearly 5 decades, Title X has played a critical role in preventing unplanned pregnancy by offering low-income and uninsured individuals access to high-quality contraceptive services, preventive screenings, and health education and information. The Family Planning Program funding announcement issued this past Friday has the potential to weaken high quality contraceptive care, which would be a major step backwards in a woman’s ability to decide if, when, and under what circumstances to get pregnant.” “We are concerned that the Administration’s shifts in program priorities towards less effective methods, namely natural family planning, could result in funding going to providers that offer only a limited range of contraceptive methods, and away from the providers able to offer high quality contraceptive care that includes the full range of methods. Already, more than 19 million U.S. women in need of publicly funded birth control live in contraceptive deserts, where they do not have reasonable access to a public clinic that offers the full range of methods in the counties in which they live. Let’s not exacerbate this already challenging situation for millions more women.” For more information about the Title X Family Planning Program, please go here. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Tue, 27 Feb 2018 15:10:58 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-raises-concerns-about-title-x-funding</guid> </item> <item> <title>Power to Decide Dismayed By Critical Program Eliminations In President’s Budget</title> <link>https://powertodecide.org/about-us/newsroom/power-decide-dismayed-by-critical-program-eliminations-in-presidents-budget</link> <description>(Washington, D.C.)—Power to Decide, the campaign to prevent unplanned pregnancy, is dismayed that the President’s budget for fiscal year 2019 severely cuts or eliminates the following programs critical to ensuring that all young people have the power to decide if, when, and under what circumstances to get pregnant: Prohibits those covered by Medicaid or receiving services through the Title X program from accessing high quality family planning providers, including Planned Parenthood. Proposes a repeal of the Affordable Care Act (ACA) and changes to Medicaid that could result in fewer people having health coverage, and as a result coverage for contraception. Eliminates the evidence-based Teen Pregnancy Prevention (TPP) Program, currently funded at $101 million annually. “The cuts in the President’s budget are harmful to young people and women of all ages. They will severely restrict access to quality health services, including contraception, as well as access to evidence-based teen pregnancy prevention programs for hundreds of thousands of youth,” said Ginny Ehrlich, Chief Executive Officer, Power to Decide. “These cuts would threaten the historic progress the nation has made in reducing rates of unplanned pregnancy. We urge Congress to work with the President to restore funding for these programs at their current levels in order to ensure that all young people have the information and access to services they need to decide if, when, and under what circumstances to get pregnant.” Power to Decide applauds the fact that the proposed budget provides level funding for the Title X Family Planning Program at $286 million. The proposed budget does include $75 million annually for both the Personal Responsibility Education Program (PREP) and state abstinence education grants. However, the budget proposes shifting programs like PREP and the state abstinence grants from mandatory to discretionary funding. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Tue, 13 Feb 2018 18:37:28 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-us/newsroom/power-decide-dismayed-by-critical-program-eliminations-in-presidents-budget</guid> </item> <item> <title>Power to Decide Encouraged By Bi-Partisan Funding of Key Programs</title> <link>https://powertodecide.org/about-us/newsroom/power-decide-encouraged-bi-partisan-funding-key-programs</link> <description>(Washington, D.C.) — Early this morning, Congress passed a spending package that includes funding for key programs which support young people’s power to decide if, when, and under what circumstances to become pregnant. Specifically, the bi-partisan spending measure does the following: Extends funding for the Teen Pregnancy Prevention (TPP) Program and the Title X Family Planning Program through March 23 at their current funding levels. Extends funding for the Personal Responsibility Education Program (PREP) through FY 2019 at $75 million annually and funding for the state Sexual Risk Avoidance Education, with some programmatic changes, through FY 2019 at $75 million annually. The spending measure also includes multi-year funding for community health centers, the Maternal Infant and Early Childhood Home Visiting Program, and provides key extensions of important health programs. The bill also includes a broader budget deal that paves the way for Congress to finally finish its work on appropriations for fiscal year 2018. “Now that this budget deal is in place, congressional appropriators will be negotiating final spending levels for the TPP Program and Title X,” said Ginny Ehrlich, Chief Executive Officer, Power to Decide. “The TPP Program and Title X make critical contributions to ensuring that young people have the information, access and opportunity to decide if, when, and under what circumstances to become pregnant. We urge Congress to fully fund these programs, and to ensure that they are administered in the same high quality manner as they have been in the past. These programs help to ensure that hundreds of thousands of young people receive quality sex education and that millions of women, especially those in need, can continue to access high quality contraceptive care and supplies.” Recently, Power to Decide released new analysis showing that as a result of over two decades of investments made in prevention programs and services, unplanned pregnancies and birth rates among teens in the U.S. declined significantly, resulting in public savings of $4.4 billion in 2015 alone. “As our recent study indicates, investments in access to contraception and quality sex education are not only beneficial to young people, but also result in a positive return on investment and saves taxpayers billions of dollars annually. We are encouraged that Congress has provided funding, which will allow the federal government to play a key role in ongoing efforts to ensure that all young people have the power to decide if, when and under what circumstances to become pregnant,” concluded Ehrlich. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Fri, 09 Feb 2018 17:41:58 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-us/newsroom/power-decide-encouraged-bi-partisan-funding-key-programs</guid> </item> <item> <title>Declines In Teen Pregnancy And Childbearing Lead To Billions In Public Savings</title> <link>https://powertodecide.org/about-us/newsroom/declines-teen-pregnancy-and-childbearing-means-billions-in-public-savings</link> <description>Washington, D.C. — More than two decades of investments in prevention programs and services have led to significant declines in unplanned pregnancies and birth rates among teens in the United States. New analysis from Power to Decide, the campaign to prevent unplanned pregnancy, shows that these declines resulted in public savings of $4.4 billion in 2015 alone. “Ensuring that all young people have the power to decide if, when and under what circumstances to get pregnant helps them achieve the futures they want,” said Ginny Ehrlich, Chief Executive Officer, Power to Decide. “Over the past two decades, we have invested in access to contraception and quality sex education. These prevention programs have been strong investments, as they have contributed to ever declining teen pregnancy and birth rates, and have consequently saved the public billions of dollars. If further investments were made in these vital programs, we estimate that an additional $1.9 billion could be saved each year.” Since peaking in 1991, the teen birth rate has declined 67%, and the related savings to taxpayers have been significant. The new Power to Decide analysis reflects the public sector savings that are directly tied to medical and economic supports provided during pregnancy and infancy for teen mothers specifically through Medicaid and the Women Infant and Children (WIC), Temporary Assistance for Needy Families (TANF), and Supplemental Nutrition Assistance (SNAP) programs. Yet despite the impressive record of success as well as significant savings to taxpayers, the current Administration has recently issued directives that threaten continued efforts in this area including access to quality sex education and contraceptive care. “Although the nation has made historic strides, we cannot mistake this progress for victory,” Ehrlich added. “We must maintain and expand investments that offer young people the support they need to align their intentions and their actions. Most importantly, we need to protect women’s access to no- or low-cost contraception. We also must continue to advocate for public financing through the Title X family planning program and Medicaid. These efforts help ensure that all women, especially those in need, can continue to access high quality contraceptive care and supplies. These efforts allow young people to live life on their own terms, and it also happens to be sound economic policy. Studies suggest that we save $7 for every $1 invested in reproductive health care.” Despite declines in all 50 states and among all racial/ethnic groups, persistent disparities remain—teen pregnancy rates for Latina and African American women are still more than twice as high as compared to their white counterparts. In addition, more than 19 million women in need of publicly funded contraception live in contraceptive deserts, where they do not have reasonable access in their county to a public clinic that offers the full range of contraceptive methods. Power to Decide compiled and analyzed the most recent data available on teen childbearing (national and state) as well as from public assistance programs, including Medicaid, WIC, TANF and SNAP where young mothers are likely participants. To view the complete results of our analysis—including state by state results visit https://PowerToDecide.org/savings. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Wed, 31 Jan 2018 13:41:25 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-us/newsroom/declines-teen-pregnancy-and-childbearing-means-billions-in-public-savings</guid> </item> <item> <title>New Analysis From Power To Decide Shows Declines In Teen Pregnancy and Childbearing Lead To Billions In Savings</title> <link>https://powertodecide.org/about-us/newsroom/new-analysis-shows-teen-pregnancy-and-childbearing-declines-save-billions</link> <description>Washington, D.C. — More than two decades of investments in prevention programs and services have led to significant declines in unplanned pregnancies and birth rates among teens in the United States. New analysis from Power to Decide, the campaign to prevent unplanned pregnancy, shows that these declines resulted in public savings of $4.4 billion in 2015 alone. On Wednesday, January 31, 2018, at 1:00 p.m. Power to Decide will host a telephonic press conference to discuss the new analysis. Investments in prevention programs empower young people to decide if, when and under what circumstances to get pregnant—and help them live life on their own terms. As reflected in the new analysis, these investments also save the public billions of dollars each year. If further investments were made in these vital programs, the organization estimates an additional $1.9 billion could be saved each year. The new analysis from Power to Decide reflects the public sector savings that are directly tied to medical and economic supports provided during pregnancy and infancy for teen mothers specifically through Medicaid and the Women Infant and Children (WIC), Temporary Assistance for Needy Families (TANF), and Supplemental Nutrition Assistance (SNAP) programs. WHO: Ginny Ehrlich, Chief Executive Officer, Power to Decide Kelleen Kaye, Vice President, Research and Evaluation, Power to Decide WHAT: Telephonic press conference to discuss the new analysis released by Power to Decide WHEN: Wednesday, January 31, 2018 at 1:00 p.m. EST WHERE: 1-877-888-4291 or 1-785-424-1878 Conference ID: Pregnancy Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Mon, 29 Jan 2018 10:57:23 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-us/newsroom/new-analysis-shows-teen-pregnancy-and-childbearing-declines-save-billions</guid> </item> <item> <title>Administration Establishes “Conscience and Religious Freedom Division” That Threatens Women’s Power to Decide</title> <link>https://powertodecide.org/about-usnewsroom/administration-establishes-conscience-and-religious-freedom-division-threatens</link> <description>(Washington, D.C.) —The U.S. Department of Health and Human Services (HHS) recently created a new office that will allow health care providers to deny services based on the provider’s moral or religious convictions. The new office, the Conscience and Religious Freedom Division, was established to “protect” health care providers who feel pressured to “perform, accommodate or assist with” procedures and services that contradict their religious beliefs. In response to this announcement, Power to Decide’s CEO Ginny Ehrlich issued the following statement: “HHS’s core mission is to enhance the health and well-being of all Americans. Enabling health care providers to refuse to provide health services and support based on their beliefs rather than the health needs of their clients runs counter to HHS’s mission and violates a person’s power to decide what health services and support is right for them. This is yet another example of the Administration’s recent efforts to deny access to basic health care for women, LGBTQ individuals, and other vulnerable populations. We are most concerned about the impact this will have on access to the full range of birth control methods and emergency contraception. We urge health care providers to do what’s best for their clients—no matter who they are or where they live—by honoring their rights to make their own decisions about their sexual and reproductive health.” Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Wed, 24 Jan 2018 12:30:28 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/administration-establishes-conscience-and-religious-freedom-division-threatens</guid> </item> <item> <title>Power to Decide CEO Ginny Ehrlich Participates in 2018 Women’s March in Washington, D.C.</title> <link>https://powertodecide.org/about-usnewsroom/power-decide-ceo-ginny-ehrlich-participates-2018-womens-march-washington-dc</link> <description>Washington, D.C. — In response to the threats to civil rights, healthcare reform, reproductive health, LGBTQ rights and much more, millions participated in the women’s march last year. Power to Decide will continue to fight so that all young people—no matter who they are or where they live—have access to quality sex education and to no-cost or low-cost contraception. In anticipation of the march, Ginny Ehrlich, CEO, Power to Decide, issued the following statement: “I know that I stand with millions of people when expressing my grave concerns about the actions that this Administration has taken to cut and restrict programs that support young people in accessing the information and services they need to decide if, when, and under what circumstances to get pregnant. We must remember that there is strength in numbers and together we can support all young people – no matter who they are or where they live – to decide their futures on their own terms. As we march this weekend, let’s remember that access to birth control is basic health care and has made so much possible for millions of women over the past four decades. Our young people deserve the same opportunities that existed for my generation. We must fight for their futures by protecting their access to information and contraception so they can all live life on their own terms.” WHO: Ginny Ehrlich, CEO, Power to Decide WHAT: Available for comment regarding the following: Continued access to no co-pay contraception for millions of women; Sustaining a strong network of safety-net clinics providing high-quality contraceptive care through the Title X family planning program and Medicaid; Making certain that all young people have the sexual health information they need to plan their futures; The strong support for birth control across all political, religious and racial/ethnic groups; The more than 19 million women in need living in contraceptive deserts – meaning that they lack reasonable access to the full range of contraceptive methods. WHEN: Saturday, January 20, 2018, from 9:00 a.m. to 3:00 p.m. WHERE: Please contact Julian Teixeira at 202-365-2273 or Paloma Zuleta at 202-812-4477 Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Fri, 19 Jan 2018 12:25:58 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/power-decide-ceo-ginny-ehrlich-participates-2018-womens-march-washington-dc</guid> </item> <item> <title>Seven Organizations Promoting Women’s Health Launch a New Campaign</title> <link>https://powertodecide.org/about-usnewsroom/seven-organizations-promoting-womens-health-launch-new-campaign</link> <description>WASHINGTON D.C. - Today, a partnership of organizations that promote women’s health announced the launch of a new campaign called Care Women Deserve, which aims to educate people about the vital preventive services available to women with no out-of pocket costs. The American College of Obstetricians and Gynecologists, Black Women’s Health Imperative, March of Dimes, National Women’s Law Center, Power to Decide, the campaign to prevent unplanned pregnancy, UnidosUS, and the United State of Women have come together to inform people that the Affordable Care Act requires insurance plans to provide coverage for recommended preventive services without copay, coinsurance or deductible that are essential to women’s overall health. Many women are not aware of these benefits or believe they have been rolled back. “The women’s preventive services guidelines are a set of science and evidence based services that improve the well-being of women across the country,” said American College of Obstetricians and Gynecologists President, Haywood L. Brown, M.D. “These guidelines help providers determine which screenings and other preventive health services they should routinely offer, so women can get the care they need and deserve.” “Under the Affordable Care Act, women gained access to a host of important preventive health services without having to pay out of pocket,” stated March of Dimes President Stacey D. Stewart. “We want all women to understand these benefits, so they can be as healthy as possible at every stage of life.” “Preventive care helps women stay healthy and improves overall well-being,” said Power to Decide CEO Ginny Ehrlich. “Without access to recommended preventive care, including contraceptive care, women can experience health-related barriers that can negatively impact their lives, as well as the lives of their family.” The following recommended preventive services are available to most women across the United States at no cost, if they are insured: Well-woman visits Contraception, counseling and follow-up care Sexually Transmitted Infections (STI) counseling Cervical cancer screening Human Immunodeficiency Virus (HIV) screening Breast cancer screening Interpersonal and domestic violence screening Gestational diabetes screening Breastfeeding services and supplies Women’s Preventive Services Guidelines are supported by the Health Resources and Services Administration (HRSA) and based on a rigorous review of evidence conducted by a committee of women’s health experts. After reviewing the entire body of research on women’s preventive care, the committee agreed on a set of services that women should receive across their lifespan. This list of services reflects that process and the evidence-based consensus of a range of women’s health experts. The Care Women Deserve campaign has a number of resources for the public to use, including to raise awareness of the Women’s Preventive Services Guidelines. Supporters can use the following hashtags: #CareWomenDeserve and #GetTheCare Website: CareWomenDeserve.org Facebook: facebook.com/CareWomenDeserve Twitter: twitter.com/CareWeDeserve Instagram: @carewomendeserve ### Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Tue, 09 Jan 2018 08:00:00 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/seven-organizations-promoting-womens-health-launch-new-campaign</guid> </item> <item> <title>Power to Decide Strongly Opposes Administration's Directives That Place Ideology Over Evidence</title> <link>https://powertodecide.org/about-us/newsroom/power-to-decide-concerned-over-administrations-word-ban</link> <description>Washington, D.C.—According to reports, the Trump Administration has recently banned the U.S. Centers for Disease Control and Prevention (CDC) from using the following seven terms: "evidence,” "science-based," "diversity," "vulnerable," "entitlement," "transgender" and "fetus" in their FY 2019 budget proposal. Reports also indicate that other agencies within the Department of Health and Human Services are banned from using "diversity" and "vulnerable," as well as other words. Power to Decide strongly opposes these bans and is deeply concerned about their impact on people in the United States receiving vital and accurate health information, as well as, the impact on health equity. Ginny Ehrlich, CEO, Power to Decide issued the following statement regarding the Trump Administration's directives: "We are dismayed and alarmed by the efforts of the Trump Administration to ban the use of words that help people access accurate information about their health, as well as, prohibiting terms that respect and include the diversity of the people in the United States. These bans put ideology over evidence, and the effect is nothing short of playing politics with people's lives. Rest assured, Power to Decide will continue to provide access to science-based and reliable information on sexual health so that everybody - no matter who they are or where they live - has the power to decide if, when, and under what circumstances to get pregnant." Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Mon, 18 Dec 2017 11:03:11 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-us/newsroom/power-to-decide-concerned-over-administrations-word-ban</guid> </item> <item> <title>Power to Decide Awarded Four-Star Rating By Charity Navigator</title> <link>https://powertodecide.org/about-us/newsroom/power-decide-awarded-four-star-rating-by-charity-navigator</link> <description>Washington, D.C. — For the 11th year in a row, Power to Decide, the campaign to prevent unplanned pregnancy, was awarded a four-star rating by Charity Navigator, the independent, non-profit organization that provides donors with essential information they need to make informed decisions about charitable giving. The four-star rating is the highest rating a charitable non-profit can receive. Power to Decide has been awarded the four-star rating for 11 consecutive years. Only 1% of rated charities can claim this honor. For more than 20 years, Power to Decide has been a recognized source for high-quality, accurate information on sexual health, contraception, and related topics. The organization serves as a trusted source for research-based solutions. It also supports professionals, mentors and works with policymakers, advocates, the press, entertainment media and key influencers. Lastly, Power to Decide serves as convener and catalyst, creating partnerships and offering a place for everyone. “We are so proud to receive this recognition from Charity Navigator for the 11th year in a row,” said Ginny Ehrlich, CEO, Power to Decide. “This special recognition puts us among the top 1% of organizations from a quality perspective and it reinforces the fact that every dollar of support will be maximized to ensure that all young people have access to quality sexual health information and the full range of contraceptive methods so that they can live life on their own terms.” Power to Decide was founded in 1996 when teen pregnancy and birth rates were significantly higher. Although unplanned and teen pregnancies rates have declined significantly, women of color and women living in poverty continue to experience unplanned pregnancies at unacceptably high rates. In addition, recent research conducted by Power to Decide shows that nearly 20 million American women live in contraceptive deserts—defined by their lack of reasonable access to public health care sites offering the full range of contraceptive methods. “Despite significant progress, we must continue our efforts so that all women, regardless of their race, ethnicity, or socioeconomic status have the power to decide if, when, and under what circumstances to get pregnant,” concluded Ehrlich. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Wed, 13 Dec 2017 12:38:33 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-us/newsroom/power-decide-awarded-four-star-rating-by-charity-navigator</guid> </item> <item> <title>Hormonal Contraception Remains Effective Option For Millions of Women</title> <link>https://powertodecide.org/about-usnewsroom/hormonal-contraception-remains-effective-option-for-millions-women</link> <description>Washington, D.C.– A study recently released by the New England Journal of Medicine compared the breast cancer rates in 1.8 million Danish women age 15 to 49 who used hormonal birth control to breast cancer rates in women who relied on non-hormonal methods. Per the study, for every 100,000 women, the use of hormonal birth control resulted in an additional 13 cases of breast cancer a year. Specifically, there were 68 cases of breast cancer for hormonal contraceptive users as compared to 55 cases for non-hormonal contraceptive users. The study was conducted over the course of 11 years and filtered out women who had previously been diagnosed with cancer, had undergone infertility treatments, and had experienced blood clots. “Like most medications, the risks of using hormonal contraception should be balanced carefully against the benefits, to include lowering the risk of other forms of cancer such as ovarian and endometrial. The risks also need to be considered in the context of other health benefits, not least of which is their effectiveness in preventing an unplanned pregnancy,” said Ginny Ehrlich, Chief Executive Officer, Power to Decide. “Experts agree that by in large, hormonal contraception continues to be a safe and effective option for millions of women in this country, The implications of this research need to be assessed carefully for any individual woman. This is all the more reason why it is essential that all women have access to high quality contraceptive counseling and care without barriers, so they can discuss and select the method of birth control that makes most sense for them. For those looking for non-hormonal methods of contraception, today’s consumer can also choose from a variety of methods that are consistent with their needs and lifestyle.” We also hope that there will be further analysis of the data, as the study did not consider alcohol use, limited physical activity, or breast-feeding as possible contributors to breast cancer among hormonal birth control users. To learn more about the full range of contraceptive methods, visit https://www.bedsider.org/methods. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Mon, 11 Dec 2017 14:19:15 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/hormonal-contraception-remains-effective-option-for-millions-women</guid> </item> <item> <title>The National Campaign Se Convierte En Power to Decide</title> <link>https://powertodecide.org/about-usnewsroom/national-campaign-se-convierte-en-power-decide</link> <description>(Washington, D.C.) — Power to Decide, (El Poder de Decidir) la campaña para prevenir el embarazo no planificado en adolescentes, se ha cambiado oficialmente el nombre anterior The National Campaign to Prevent Teen and Unplanned Pregnancy (también conocida como el The National Campaign). Este cambio enfatiza el enfoque de la organización en asegurarse que todos los jóvenes, no importa quiénes sean ni dónde vivan, puedan tomar decisiones en cuanto a su futuro reproductivo. “Power to Decide no es solamente nuestro nuevo nombre, es también nuestra visión para la gente joven —no importa quienes sean ni donde vivan”, dijo Ginny Ehrlich, director ejecutivo. “Power to Decide está basada en 21 años de éxito en llegar a los jóvenes mediante The National Campaign. Ahora, como Power to Decide, nos enfocamos en ayudar a que las personas jóvenes tengan el poder de decidir su futuro y trabajamos para asegurarnos que cuentan con la información, el acceso y las oportunidades necesarias para decidir si quieren quedar embarazadas, cuándo y en qué circunstancias”. Una nueva encuesta a nivel nacional publicada hoy día por Power to Decide confirma el abrumador apoyo que tiene el tener acceso a todos los tipos de métodos anticonceptivos como una manera importante de aumentar las oportunidades de los jóvenes. La encuesta, en la cual participaron más de 2,000 personas de 18 años o mayores, reveló: Que el 94 % de los encuestados está de acuerdo con que todas las personas deberían tener el poder de decidir si quieren quedar embarazadas, cuándo y en qué circunstancias. 9 de cada 10 encuestados está de acuerdo con que las personas jóvenes con el poder decidir si quedar embarazadas y cuándo quedar embarazadas tienen más oportunidades y son más capaces de alcanzar su máximo potencial. El 87 % de los encuestados cree que los métodos anticonceptivos le dan a las personas el poder de decidir su futuro. El 87 % de los encuestados está de acuerdo con que todo el mundo se merece tener acceso a la gama completa de métodos anticonceptivos, no importa quiénes sean, dónde vivan, ni cuál sea su situación económica. Aunque ha habido una disminución histórica en la cantidad de embarazos de adolecentes y no planificados en los Estados Unidos, todavía sigue siendo desigual el acceso a la información sobre salud sexual de buena calidad y a los métodos anticonceptivos. Todavía una de cada cuatro mujeres quedará embarazada ante de cumplir los 20 años, y los Estados Unidos sigue teniendo el porciento más alto de embarazo de adolecentes de todos los países industrializados. Más aún, más de 19 millones de mujeres en el país vive en áreas que se conocen como desiertos anticonceptivos (contraceptive deserts)— dónde hay una falta de acceso razonable a lugares públicos para cuidado que ofrezcan toda la variedad de métodos anticonceptivos. “La mayoría de las personas jóvenes dicen que no quieren quedar embarazadas en un futuro cercano, y cada uno de estos jóvenes debe poder tomar los pasos necesarios para que esa intención se convierta en una realidad”, dijo Stephen A. Weiswasser, presidente de la junta de directores de Power to Decide. “Nuestro nuevo nombre refleja nuestro compromiso con proveer información confiable y precisa, así como con terminar con la diferencia que existe en cuanto al acceso a los métodos anticonceptivos y la disparidad en los porcentajes de embarazos no planificados”. Para obtener más información sobre Power to Decide visite la página www.PowerToDecide.org. Power to Decide es una organización privada, no partidista, sin fines de lucro que trabaja para asegurar que todas las personas—no importa quienes sean, dónde vivan, ni cuál sea su estatus económico— tengan el poder de decidir si quieren, cuándo quieren y bajo qué circunstancias quieren quedar embarazadas. Favor de visitar nuestra página www.PowerToDecide.org o síganos por Facebook y Twitter. </description> <pubDate>Mon, 04 Dec 2017 11:45:29 -0500</pubDate> <dc:creator>dboyd</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-usnewsroom/national-campaign-se-convierte-en-power-decide</guid> </item> <item> <title>The National Campaign Becomes Power to Decide</title> <link>https://powertodecide.org/about-us/newsroom/national-campaign-becomes-power-to-decide</link> <description>New Name Reflects National Sentiment of Nation’s Youth (Washington, D.C.) — Power to Decide, the campaign to prevent unplanned pregnancy, has officially become the new name of The National Campaign to Prevent Teen and Unplanned Pregnancy (The National Campaign). The change makes unmistakable the organization’s focus on ensuring that all young people, no matter who they are or where they live, have the power to decide their futures. “Power to Decide is not just our new name, it is our vision for young people—no matter who they are or where they live,” said Ginny Ehrlich, Chief Executive Officer. “Power to Decide builds on 21 years of success reaching young people as The National Campaign. Now, as Power to Decide, we will focus on helping young people harness the power to decide their futures by ensuring that they have the information, access, and opportunity necessary to decide if, when, and under what circumstances to get pregnant.” New national polling released today by Power to Decide confirms overwhelming support for access to the full range of birth control methods as a critical way to build opportunity for young people. The survey of more than 2,000 individuals age 18 and older also revealed that: 94% of respondents agree that everyone should have the power to decide if, when, and under what circumstances to get pregnant. 9 out of 10 respondents agree that young people with the power to decide if and when to get pregnant have more opportunities and are better able to realize their full potential. 87% of respondents believe birth control gives people the power to decide their futures. 87% of respondents agree that everyone deserves access to the full range of birth control methods, no matter who they are, where they live, and what their economic status is. Although there have been historic declines in rates of teen and unplanned pregnancy, access to quality sexual health information and birth control in the U.S. remains uneven. Consequently, it is still the case that one in four young women will become pregnant before age 20, and the U.S. still has the highest rate of teen pregnancy in the industrialized world. More than 19 million women in need live in contraceptive deserts—defined by their lack of reasonable access to public health care sites that offer the full range of contraceptive methods. “Most young people say they do not want to become pregnant anytime soon, and every one of them should be able to take the steps to make that intention a reality,” said Stephen A. Weiswasser, Chair, Power to Decide Board of Directors. “Our new name exemplifies our commitment to providing trusted and accurate information and to end gaps in contraceptive access and therefore disparities in rates of unplanned pregnancy.” To learn more about Power to Decide, visit www.PowerToDecide.org. Power to Decide is a private, non-partisan, non-profit organization that works to ensure all people—no matter who they are, where they live, or what their economic status might be—have the power to decide if, when, and under what circumstances to get pregnant. Please visit us at www.PowerToDecide.org or follow us on Facebook and Twitter.</description> <pubDate>Mon, 04 Dec 2017 08:30:00 -0500</pubDate> <dc:creator>mrosst</dc:creator> <guid isPermaLink="true">https://powertodecide.org/about-us/newsroom/national-campaign-becomes-power-to-decide</guid> </item> </channel> </rss>	https://powertodecide.org/press-releases/rss.xml?f%5B0%5D=tags%3A157&f%5B1%5D=tags%3A196&f%5B2%5D=tags%3A233&node=1381
Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC (Text with EEA relevance) Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC (Text with EEA relevance) Regulation (EC) No 396/2005 of the European Parliament and of the Council Show full title Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC (Text with EEA relevance) This is a legislation item that originated from the EU After exit day there will be three versions of this legislation to consult for different purposes. The legislation.gov.uk version is the version that applies in the UK. The EU Version currently on EUR-lex is the version that currently applies in the EU i.e you may need this if you operate a business in the EU. The web archive version is the official version of this legislation item as it stood on exit day before being published to legislation.gov.uk and any subsequent UK changes and effects applied. The web archive also captured associated case law and other language formats from EUR-Lex. Changes over time for: Regulation (EC) No 396/2005 of the European Parliament and of the Council (without Annexes) 23/02/2005 - Amendment 10/04/2008 - Amendment 13/11/2014 - Amendment 14/12/2019 - Amendment Exit day: start of implementation period 31/01/2020 11pm - Amendment End of implementation period 31/12/2020 - Amendment Changes to legislation: There are outstanding changes not yet made to Regulation (EC) No 396/2005 of the European Parliament and of the Council. 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CHAPTER IU.K. SUBJECT MATTER, SCOPE AND DEFINITIONS Article 1U.K. Subject matter This Regulation establishes, in accordance with the general principles laid down in Regulation (EC) No 178/2002, in particular the need to ensure a high level of consumer protection and harmonised Community provisions relating to maximum levels of pesticide residues in or on food and feed of plant and animal origin. Article 2U.K. Scope 1. This Regulation shall apply to products of plant and animal origin or parts thereof covered by Annex I to be used as fresh, processed and/or composite food or feed in or on which pesticide residues may be present. 2. This Regulation shall not apply to the products covered by Annex I where it may be established by appropriate evidence that they are intended for: (a) the manufacture of products other than food or feed; or (b) sowing or planting; or (c) activities authorised by national law for the testing of active substances. 3. Maximum residue levels for pesticides set in accordance with this Regulation shall not apply to products covered by Annex I intended for export to third countries and treated before export, where it has been established by appropriate evidence that the third country of destination requires or agrees with that particular treatment in order to prevent the introduction of harmful organisms into its territory. 4. This Regulation shall apply without prejudice to Directives 98/8/EC(1), 2002/32/EC and Regulation (EEC) No 2377/90(2). Article 3U.K. Definitions 1. For the purpose of this Regulation, the definitions in Regulation (EC) No 178/2002, and the definitions in Article 2, points 1 and 4 of Directive 91/414/EEC shall apply. 2. The following definitions shall also apply: (a) ‘good agricultural practice’ (GAP) means the nationally recommended, authorised or registered safe use of plant protection products under actual conditions at any stage of production, storage, transport, distribution and processing of food and feed. It also implies the application, in conformity with Directive 91/414/EEC, of the principles of integrated pest control in a given climate zone, as well as using the minimum quantity of pesticides and setting MRLs/temporary MRLs at the lowest level which allows the desired effect to be obtained; (b) ‘critical GAP’ means the GAP, where there is more than one GAP for an active substance/product combination, which gives rise to the highest acceptable level of pesticide residue in a treated crop and is the basis for establishing the MRL; (c) ‘pesticide residues’ means residues, including active substances, metabolites and/or breakdown or reaction products of active substances currently or formerly used in plant protection products as defined in Article 2, point 1 of Directive 91/414/EEC, which are present in or on the products covered by Annex I to this Regulation, including in particular those which may arise as a result of use in plant protection, in veterinary medicine and as a biocide; (d) ‘maximum residue level’ (MRL) means the upper legal level of a concentration for a pesticide residue in or on food or feed set in accordance with this Regulation, based on good agricultural practice and the lowest consumer exposure necessary to protect vulnerable consumers; (e) ‘CXL’ means an MRL set by the Codex Alimentarius Commission; (f) ‘limit of determination’ (LOD) means the validated lowest residue concentration which can be quantified and reported by routine monitoring with validated control methods; (g) ‘import tolerance’ means an MRL set for imported products to meet the needs of international trade where: (g) the use of the active substance in a plant protection product on a given product is not authorised in the Community for reasons other than public health reasons for the specific product and specific use; or a different level is appropriate because the existing Community MRL was set for reasons other than public health reasons for the specific product and specific use; (h) ‘proficiency test’ means a comparative test in which several laboratories perform analyses on identical samples, allowing an evaluation of the quality of the analysis performed by each laboratory; (i) ‘acute reference dose’ means the estimate of the amount of substance in food, expressed on a body weight basis, that can be ingested over a short period of time, usually during one day, without appreciable risk to the consumer on the basis of the data produced by appropriate studies and taking into account sensitive groups within the population (e.g. children and the unborn); (j) ‘acceptable daily intake’ means the estimate of the amount of substances in food expressed on a body weight basis, that can be ingested daily over a lifetime, without appreciable risk to any consumer on the basis of all known facts at the time of evaluation, taking into account sensitive groups within the population (e.g. children and the unborn). Article 4U.K. List of groups of products for which harmonised MRLs shall apply [ F1 1. The products, product groups and/or parts of products referred to in Article 2(1) to which harmonised MRLs shall apply shall be defined in and covered by Annex I. That measure, designed to amend non-essential elements of this Regulation, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(3). Annex I shall include all products for which MRLs are set, as well as the other products for which it is appropriate to apply harmonised MRLs, in particular in view of their relevance in the diet of consumers or in trade. Products shall be grouped in such a way that MRLs may as far as possible be set for a group of similar or related products. ] 2. Annex I shall be first established within three months from the entry into force of this Regulation and shall be revised when appropriate, in particular, at the request of a Member State. Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. Article 5U.K. Establishment of a list of active substances for which no MRLs are required [ F1 1. Active substances of plant protection products evaluated under Directive 91/414/EEC for which no MRLs are required shall be defined and listed in Annex IV to this Regulation, taking into account the uses of those active substances and the matters referred to in points (a), (c) and (d) of Article 14(2). Those measures, designed to amend non-essential elements of this Regulation, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(4). ] 2. Annex IV shall be first established within 12 months from the entry into force of this Regulation. Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. CHAPTER IIU.K. PROCEDURE FOR APPLICATIONS FOR MRLS SECTION 1U.K. Submission of applications for MRLs Article 6U.K. Applications 1. Where a Member State envisages granting an authorisation or a provisional authorisation for the use of a plant protection product in accordance with Directive 91/414/EEC, that Member State shall consider whether, as a result of such use, an existing MRL set out in Annex II or III to this Regulation needs to be modified, whether it is necessary to set a new MRL, or whether the active substance should be included in Annex IV. If necessary it shall require the party requesting the authorisation to submit an application in accordance with Article 7. 2. All parties demonstrating, through adequate evidence, a legitimate interest in health, including civil society organisations, as well as commercially interested parties such as manufacturers, growers, importers and producers of products covered by Annex I may also submit an application to a Member State in accordance with Article 7. 3. Where a Member State considers that the setting, modification or deletion of an MRL is necessary, that Member State may also compile and evaluate an application for setting, modifying, or deleting the MRL in accordance with Article 7. 4. Applications for import tolerances shall be submitted to rapporteur Member States designated pursuant to Directive 91/414/EEC or, if no such rapporteur has been designated, applications shall be made to Member States designated by the Commission in accordance with the procedure referred to in Article 45(2) of this Regulation at the request of the applicant. Such applications shall be made in accordance with Article 7 of this Regulation. Article 7U.K. Requirements relating to applications for MRLs 1. The applicant shall include in an application for an MRL the following particulars and documents: (a) the name and address of the applicant; (b) a presentation of the application dossier including: (i) a summary of the application; (ii) the main substantive arguments; (iii) an index of the documentation; (iv) a copy of the relevant GAP applying to the specific use of that active substance; (c) a comprehensive overview of relevant concerns raised in the available scientific literature about the plant protection product and/or its residue; (d) the data listed in Annexes II and III to Directive 91/414/EEC relating to data requirements for the setting of MRLs for pesticides including, where appropriate, toxicological data and data on routine analytical methods for use in control laboratories, as well as plant and animal metabolism data. However, where relevant data are already publicly available, in particular when an active substance has already been evaluated under Directive 91/414/EEC or when a CXL exists and such data are submitted by the applicant, a Member State may also use such information in evaluating an application. In such cases, the evaluation report shall include a justification for using or not using such data. 2. The evaluating Member State may, where appropriate, request the applicant to provide supplementary information in addition to information required under paragraph 1 within a time limit specified by the Member State. In no event may this period exceed two years. Article 8U.K. Evaluation of applications 1. A Member State to which an application complying with Article 7 is submitted pursuant to Article 6 shall immediately forward a copy to the Authority and the Commission and draw up an evaluation report without undue delay. [ F1 2. Applications shall be evaluated in accordance with the relevant provisions of the Uniform Principles for the Evaluation and Authorisation of Plant Protection Products set out in Annex VI to Directive 91/414/EEC or specific evaluation principles to be laid down in a Commission regulation. That regulation, designed to amend non-essential elements of this Regulation by supplementing it, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(3). ] 3. By way of derogation from paragraph 1 and by agreement between the Member States concerned, evaluation of the application may be carried out by the rapporteur Member State designated pursuant to Directive 91/414/EEC for that active substance. 4. Where a Member State encounters difficulties in evaluating an application or in order to avoid duplication of work, it may be decided in accordance with the procedure referred to in Article 45(2) which Member State shall evaluate particular applications. Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. Article 9U.K. Submission of evaluated applications to the Commission and the Authority 1. After completion of the evaluation report, the Member State shall forward it to the Commission. The Commission shall without delay inform the Member States and forward the application, the evaluation report and the supporting dossier to the Authority. 2. The Authority shall acknowledge in writing receipt of the application to the applicant, the evaluating Member State and the Commission without delay. The acknowledgement shall state the date of receipt of the application and the accompanying documents. SECTION 2U.K. Consideration of applications concerning MRLs by the authority Article 10U.K. The Authority's opinion on applications concerning MRLs 1. The Authority shall assess the applications and the evaluation reports and give a reasoned opinion on, in particular, the risks to the consumer and where relevant to animals associated with the setting, modification or deletion of an MRL. That opinion shall include: (a) an assessment of whether the analytical method for routine monitoring proposed in the application is appropriate for the intended control purposes; (b) the anticipated LOD for the pesticide/product combination; (c) an assessment of the risks of the acceptable daily intake or acute reference dose being exceeded as a result of the modification of the MRL; the contribution to the intake due to the residues in the product for which the MRLs was requested; (d) any other element relevant to the risk assessment. 2. The Authority shall forward its reasoned opinion to the applicant, the Commission and the Member States. The reasoned opinion shall clearly define the basis for each conclusion reached. 3. Without prejudice to Article 39 of Regulation (EC) No 178/2002, the Authority shall make its reasoned opinion public. Article 11U.K. Time limits for the Authority's opinion on applications concerning MRLs 1. The Authority shall give its reasoned opinion as provided for in Article 10 as soon as possible and at the latest within three months from the date of receipt of the application. In exceptional cases where more detailed evaluations need to be carried out, the time limit laid down in the first subparagraph may be extended to six months from the date of receipt of the valid application. 2. Where the Authority requests supplementary information, the time limit laid down in paragraph 1 shall be suspended until that information has been provided. Such suspensions are subject to Article 13. Article 12U.K. Assessment of existing MRLs by the Authority 1. The Authority shall, within a period of 12 months from the date of the inclusion or non-inclusion of an active substance in Annex I to Directive 91/414/EEC after the entry into force of this Regulation, submit a reasoned opinion based in particular on the relevant assessment report prepared under Directive 91/414/EEC to the Commission and the Member States on: (a) existing MRLs for that active substance set out in Annex II or III to this Regulation; (b) the necessity of setting new MRLs for that active substance, or its inclusion in Annex IV to this Regulation; (c) specific processing factors as referred to in Article 20(2) of this Regulation that may be needed for that active substance; (d) MRLs which the Commission may consider including in Annex II and/or Annex III to this Regulation and on those MRLs which may be deleted related to that active substance. 2. For substances included in Annex I to Directive 91/414/EEC before the entry into force of this Regulation, the reasoned opinion referred to in paragraph 1 of this Article shall be delivered within 12 months of the entry into force of this Regulation. Article 13U.K. Administrative review Any decision taken under, or failure to exercise, the powers vested in the Authority by this Regulation may be reviewed by the Commission on its own initiative or in response to a request from a Member State or from any person directly and individually concerned. For that purpose, a request shall be submitted to the Commission within two months after the day on which the party concerned became aware of the act or omission in question. The Commission shall take a decision within two months requiring, if appropriate, the Authority to withdraw its decision or to remedy its failure to act within a set time-limit. SECTION 3U.K. Setting, modifying or deletion of MRLs Article 14U.K. Decisions on applications concerning MRLs [ F1 1. Upon receipt of the opinion of the Authority and taking account of that opinion, one of the following shall be prepared by the Commission without delay and at the latest within three months: (a) a regulation on the setting, modification or deletion of an MRL. That regulation, designed to amend non-essential elements of this Regulation, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(4). On imperative grounds of urgency, the Commission may have recourse to the urgency procedure referred to in Article 45(5) in order to ensure a high level of consumer protection; (b) a decision rejecting the application, which shall be adopted in accordance with the regulatory procedure referred to in Article 45(2). ] 2. With regard to the acts referred to in paragraph 1, account shall be taken of: (a) the scientific and technical knowledge available; (b) the possible presence of pesticide residues arising from sources other than current plant protection uses of active substances, and their known cumulative and synergistic effects, when the methods to assess such effects are available; (c) the results of an assessment of any potential risks to consumers with a high intake and high vulnerability and, where appropriate, to animals; (d) the results of any evaluations and decisions to modify the uses of plant protection products; (e) a CXL or a GAP implemented in a third country for the legal use of an active substance in that country; (f) other legitimate factors relevant to the matter under consideration. 3. The Commission may request at any time that supplementary information be provided by the applicant or by the Authority. The Commission shall make available any supplementary information received to the Member States and the Authority. Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. Article 15U.K. Inclusion of new or modified MRLs in Annexes II and III 1. The Regulation referred in Article 14(1) shall: (a) set new or modified MRLs and list them in Annex II to this Regulation where the active substances have been included in Annex I to Directive 91/414/EEC; or (b) where the active substances have not been included in Annex I to Directive 91/414/EEC and where they are not included in Annex II to this Regulation, set or modify temporary MRLs and list them in Annex III to this Regulation; or (c) in the cases mentioned in Article 16, set temporary MRLs and list them in Annex III to this Regulation. [ F1 2. Where a temporary MRL is set as provided for in paragraph 1(b), it shall be deleted from Annex III by a regulation one year after the date of the inclusion or non-inclusion in Annex I to Directive 91/414/EEC of the active substance concerned. That regulation, designed to amend non-essential elements of this Regulation, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(4). On imperative grounds of urgency, the Commission may have recourse to the urgency procedure referred to in Article 45(5) in order to ensure a high level of consumer protection. However, where one or more Member States so request, the temporary MRL may be maintained for an additional year pending confirmation that any scientific studies necessary for supporting an application for setting a MRL have been undertaken. In cases where such confirmation is provided, the temporary MRL shall be maintained for a further two years, provided that no unacceptable safety concerns for consumers have been identified. ] Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. Article 16U.K. Procedure for setting temporary MRLs in certain circumstances 1. The Regulation referred to in Article 14(1) may also set a temporary MRL to be included in Annex III in the following circumstances: (a) in exceptional cases, in particular where pesticide residues may arise as a result of environmental or other contamination or from uses of plant protection products pursuant to Article 8(4) of Directive 91/414/EEC; or (b) where the products concerned constitute a minor component of the diet of consumers, and do not constitute a major part of the diet of relevant subgroups, and, where relevant, of animals; or (c) for honey; or (d) for herbal infusions; or (e) where essential uses of plant protection products have been identified by a Decision to delete an active substance from, or not to include an active substance in, Annex I to Directive 91/414/EEC; or (f) where new products, product groups and/or parts of products have been included in Annex I, and one or more Member States so request, in order to allow any scientific studies necessary for supporting an MRL to be undertaken and evaluated, provided that no unacceptable safety concerns for the consumer have been identified. 2. The inclusion of temporary MRLs as referred to in paragraph 1 shall be based on the opinion of the Authority, monitoring data and an assessment demonstrating that there are no unacceptable risks to consumers or animals. The continued validity of the temporary MRLs referred to in paragraphs 1(a), (b), (c) and (d) shall be reassessed at least once every 10 years and any such MRLs shall be modified or deleted as appropriate. The MRLs referred to in paragraph 1(e) shall be reassessed at the expiry of the period for which the essential use was authorised. The MRLs referred to in paragraph 1(f) shall be reassessed when the scientific studies have been completed and evaluated, but no later than four years after their inclusion in Annex III. Article 17U.K. Modifications of MRLs following revocation of authorisations of plant protection products Amendments to Annexes II or III needed to delete an MRL following the revocation of an existing authorisation for a plant protection product may be adopted without seeking the opinion of the Authority. CHAPTER IIIU.K. MRLS APPLICABLE TO PRODUCTS OF PLANT AND ANIMAL ORIGIN [ F1 Article 18U.K. Compliance with MRLs 1. The products covered by Annex I shall not contain, from the time they are placed on the market as food or feed, or fed to animals, any pesticide residue exceeding: (a) the MRLs for those products set out in Annexes II and III; (b) 0,01 mg/kg for those products for which no specific MRL is set out in Annexes II or III, or for active substances not listed in Annex IV unless different default values are fixed for an active substance while taking into account the routine analytical methods available. Such default values shall be listed in Annex V. That measure, designed to amend non-essential elements of this Regulation, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(4). On imperative grounds of urgency, the Commission may have recourse to the urgency procedure referred to in Article 45(5) in order to ensure a high level of consumer protection. 2. Member States may not prohibit or impede the placing on the market or the feeding to food-producing animals within their territories of the products covered by Annex I on the grounds that they contain pesticide residues provided that: (a) such products comply with paragraph 1 and Article 20; or (b) the active substance is listed in Annex IV. 3. By way of derogation from paragraph 1, Member States may authorise, further to a post-harvest treatment with a fumigant on their own territory, residue levels for an active substance which exceed the limits specified in Annexes II and III for a product covered by Annex I where the active substance/product combinations are listed in Annex VII provided that: (a) such products are not intended for immediate consumption; (b) appropriate controls are in place to ensure that such products cannot be made available to the end user or consumer, if they are supplied directly to the latter, until the residues no longer exceed the maximum levels specified in Annexes II or III; (c) the other Member States and the Commission have been informed of the measures taken. Measures designed to amend non-essential elements of this Regulation and defining the active substance/product combinations listed in Annex VII shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(3). 4. In exceptional circumstances, and in particular further to the use of plant protection products in accordance with Article 8(4) of Directive 91/414/EEC or pursuant to obligations set out in Directive 2000/29/EC(3) , a Member State may authorise the placing on the market and/or the feeding to animals within its territory of treated food or feed not complying with paragraph 1, provided that such food or feed does not constitute an unacceptable risk. Such authorisations shall immediately be notified to the other Member States, the Commission and the Authority, together with an appropriate risk assessment for consideration without undue delay with a view to setting a temporary MRL for a specified period or taking any other necessary measure in relation to such products. Those measures, designed to amend non-essential elements of this Regulation by supplementing it, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(4). On imperative grounds of urgency, the Commission may have recourse to the urgency procedure referred to in Article 45(5) in order to ensure a high level of consumer protection. ] Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. Article 19U.K. Prohibition concerning processed and/or composite products The processing, and/or mixing for dilution purposes with the same or other products, of the products covered by Annex I not complying with Articles 18(1) or 20 with a view to placing them on the market as food or feed or feeding them to animals shall be prohibited. Article 20U.K. MRLs applicable to processed and/or composite products 1. Where MRLs are not set out in Annexes II or III for processed and/or composite food or feed, the MRLs applicable shall be those provided in Article 18(1) for the relevant product covered by Annex I, taking into account changes in the levels of pesticide residues caused by processing and/or mixing. [ F1 2. Specific concentration or dilution factors for certain processing and/or mixing operations or for certain processed and/or composite products may be included in the list in Annex VI. That measure, designed to amend non-essential elements of this Regulation, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(3). ] Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. CHAPTER IVU.K. SPECIAL PROVISIONS RELATING TO THE INCORPORATION OF EXISTING MRLS INTO THIS REGULATION Article 21U.K. First establishment of MRLs [ F1 1. MRLs for products covered by Annex I shall be first established and listed in Annex II, incorporating the MRLs provided for under Directives 86/362/EEC, 86/363/EEC and 90/642/EEC, taking into account the criteria listed in Article 14(2) of this Regulation. Those measures, designed to amend non-essential elements of this Regulation, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(3). ] 2. Annex II shall be established within 12 months from the entry into force of this Regulation. Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. Article 22U.K. First establishment of temporary MRLs [ F1 1. Temporary MRLs for active substances for which a decision on inclusion or non-inclusion in Annex I to Directive 91/414/EEC has not yet been taken shall be first established and listed in Annex III to this Regulation, unless already listed in Annex II, taking into account the information provided by the Member States, where relevant the reasoned opinion referred to in Article 24, the factors referred to in Article 14(2) and the following MRLs: (a) remaining MRLs in the Annex to Directive 76/895/EEC; and (b) hitherto unharmonised national MRLs. Those measures, designed to amend non-essential elements of this Regulation, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(3). ] 2. Annex III shall be established within 12 months from the entry into force of this Regulation in accordance with Articles 23, 24 and 25. Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. Article 23U.K. Information to be provided by the Member States on national MRLs Where an active substance is not yet included in Annex I to Directive 91/414/EEC and where a Member State has set, by the date of entry into force of Annex I to this Regulation at the latest, a national MRL for that active substance for a product covered by Annex I to this Regulation, or has decided that no MRL is required for that active substance, the Member State concerned shall notify the Commission, in a format and by a date to be established in accordance with the procedure referred to in Article 45(2), of the national MRL, or the fact that no MRL is required for an active substance, and where relevant and at the request of the Commission: (a) the GAP; (b) where the critical GAP is applied in the Member State and, where available, summary data on supervised trials and/or monitoring data; (c) the acceptable daily intake and, if relevant, the acute reference dose used for the national risk assessment, as well as the outcome of the assessment. Article 24U.K. Opinion of the Authority on data underlying national MRLs 1. The Authority shall provide a reasoned opinion to the Commission on potential risks to consumer health arising from: (a) temporary MRLs that may be included in Annex III; (b) active substances that may be included in Annex IV. 2. In preparing the reasoned opinion referred to in paragraph 1, the Authority shall take into account the scientific and technical knowledge available, and in particular, information provided by the Member States as required by Article 23. Article 25U.K. Setting of temporary MRLs Taking into account the opinion of the Authority, if such an opinion is necessary, temporary MRLs for active substances referred to in Article 23 may be set and listed in Annex III pursuant to Article 22(1) or, as appropriate, the active substance may be included in Annex IV pursuant to Article 5(1). Temporary MRLs shall be set at the lowest level that can be achieved in all Member States on the basis of good agricultural practice. CHAPTER VU.K. OFFICIAL CONTROLS, REPORTS AND SANCTIONS SECTION 1U.K. Official controls of MRLs Article 26U.K. Official controls 1. Without prejudice to Directive 96/23/EC(4), Member States shall carry out official controls on pesticide residues in order to enforce compliance with this Regulation, in accordance with the relevant provisions of Community law relating to official controls for food and feed. 2. Such controls on pesticide residues shall, in particular, consist of sampling and subsequent analysis of the samples and identification of the pesticides present and their respective residue levels. Such controls shall also be carried out at the point of supply to the consumer. Article 27U.K. Sampling 1. Each Member State shall take a sufficient number and range of samples to ensure that the results are representative of the market, taking into account the results of previous control programmes. Such sampling shall be carried out as close to the point of supply as is reasonable, to allow for any subsequent enforcement action to be taken. F22. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Textual Amendments F2 Deleted byRegulation (EU) 2017/625 of the European Parliament and of the Council of 15 March 2017 on official controls and other official activities performed to ensure the application of food and feed law, rules on animal health and welfare, plant health and plant protection products, amending Regulations (EC) No 999/2001, (EC) No 396/2005, (EC) No 1069/2009, (EC) No 1107/2009, (EU) No 1151/2012, (EU) No 652/2014, (EU) 2016/429 and (EU) 2016/2031 of the European Parliament and of the Council, Council Regulations (EC) No 1/2005 and (EC) No 1099/2009 and Council Directives 98/58/EC, 1999/74/EC, 2007/43/EC, 2008/119/EC and 2008/120/EC, and repealing Regulations (EC) No 854/2004 and (EC) No 882/2004 of the European Parliament and of the Council, Council Directives 89/608/EEC, 89/662/EEC, 90/425/EEC, 91/496/EEC, 96/23/EC, 96/93/EC and 97/78/EC and Council Decision 92/438/EEC (Official Controls Regulation) (Text with EEA relevance). Article 28U.K. Methods of analysis F21. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . F22. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. All laboratories analysing samples for the official controls on pesticide residues shall participate in the Community proficiency tests for pesticide residues organised by the Commission. Textual Amendments F2 Deleted byRegulation (EU) 2017/625 of the European Parliament and of the Council of 15 March 2017 on official controls and other official activities performed to ensure the application of food and feed law, rules on animal health and welfare, plant health and plant protection products, amending Regulations (EC) No 999/2001, (EC) No 396/2005, (EC) No 1069/2009, (EC) No 1107/2009, (EU) No 1151/2012, (EU) No 652/2014, (EU) 2016/429 and (EU) 2016/2031 of the European Parliament and of the Council, Council Regulations (EC) No 1/2005 and (EC) No 1099/2009 and Council Directives 98/58/EC, 1999/74/EC, 2007/43/EC, 2008/119/EC and 2008/120/EC, and repealing Regulations (EC) No 854/2004 and (EC) No 882/2004 of the European Parliament and of the Council, Council Directives 89/608/EEC, 89/662/EEC, 90/425/EEC, 91/496/EEC, 96/23/EC, 96/93/EC and 97/78/EC and Council Decision 92/438/EEC (Official Controls Regulation) (Text with EEA relevance). SECTION 2U.K. Community control programme Article 29U.K. Community control programme 1. The Commission shall prepare a coordinated multiannual Community control programme, identifying specific samples to be included in the national control programmes and taking into account problems that have been identified regarding compliance with the MRLs set out in this Regulation, with a view to assessing consumer exposure and the application of current legislation. 2. The Community control programme shall be adopted and updated every year in accordance with the procedure referred to in Article 45(2). The draft Community control programme shall be presented to the Committee referred to in Article 45(1) at least six months before the end of each calendar year. SECTION 3U.K. National control programmes Article 30U.K. National control programmes for pesticide residues 1. Member States shall establish multiannual national control programmes for pesticide residues. They shall update their multiannual programme every year. Those programmes shall be risk-based and aimed in particular at assessing consumer exposure and compliance with current legislation. They shall specify at least the following: (a) the products to be sampled; (b) the number of samples to be taken and analyses to be carried out; (c) the pesticides to be analysed; (d) the criteria applied in drawing up such programmes, including: (i) the pesticide-product combinations to be selected; (ii) the number of samples taken for domestic and non-domestic products respectively; (iii) consumption of the products as a share of the national diet; (iv) the Community control programme; and (v) the results of previous control programmes. 2. Member States shall submit their updated national control programmes for pesticide residues, as mentioned in paragraph 1, to the Commission and to the Authority at least three months before the end of each calendar year. 3. Member States shall participate in the Community control programme as provided for in Article 29. They shall, on an annual basis, publish all results of national residue monitoring on the Internet. Where MRLs are exceeded, Member States may name the retailers, traders or producers concerned. SECTION 4U.K. Information by the Member States and annual report Article 31U.K. Information by the Member States 1. Member States shall submit the following information concerning the previous calendar year to the Commission, the Authority and the other Member States by 31 August each year: (a) the results of the official controls provided for in Article 26(1); (b) the LODs applied in the national control programmes referred to in Article 30 and under the Community control programme referred to in Article 29; (c) details of the participation of the analytical laboratories in the Community proficiency tests referred to in Article 28(3) and other proficiency tests relevant to the pesticide-product combinations sampled in the national control programme; (d) details of the accreditation status of the analytical laboratories involved in the controls referred to in point (a); (e) where permitted by national legislation, details of enforcement measures taken. 2. Implementing measures relating to the submission of information by the Member States may be established in accordance with the procedure referred to in Article 45(2) after consultation with the Authority. Article 32U.K. The Annual Report on Pesticide Residues 1. On the basis of the information provided by the Member States under Article 31(1) the Authority shall draw up an Annual Report on pesticide residues. 2. The Authority shall include information on at least the following in the Annual Report: (a) an analysis of the results of the controls provided for in Article 26(2); (b) a statement of the possible reasons why the MRLs were exceeded, together with any appropriate observations regarding risk management options; (c) an analysis of chronic and acute risks to the health of consumers from pesticide residues; (d) an assessment of consumer exposure to pesticide residues based on the information provided under point (a) and any other relevant available information, including reports submitted under Directive 96/23/EC. 3. Where a Member State has not provided information in accordance with Article 31, the Authority may disregard the information relating to that Member State when compiling the Annual Report. 4. The format of the Annual Report may be decided in accordance with the procedure referred to in Article 45(2). 5. The Authority shall submit the Annual Report to the Commission by the last day of February each year. 6. The Annual Report may include an opinion on the pesticides to be covered in future programmes. 7. The Authority shall make public the Annual Report, as well as any comments by the Commission or Member States. Article 33U.K. Submission of the Annual Report on Pesticide Residues to the Committee The Commission shall submit the Annual Report on Pesticide Residues to the Committee referred to in Article 45(1) without delay, for review and recommendations on any necessary measures to be taken regarding reported infringements of the MRLs set out in Annexes II and III. SECTION 5U.K. Sanctions Article 34U.K. Sanctions The Member States shall lay down rules on the sanctions applicable to infringements of the provisions of this Regulation and shall take all measures necessary to ensure that they are implemented. The sanctions provided for must be effective, proportionate and dissuasive. The Member States shall notify those rules and any subsequent amendment to the Commission without delay. CHAPTER VIU.K. EMERGENCY MEASURES Article 35U.K. Emergency measures Articles 53 and 54 of Regulation (EC) No 178/2002 shall apply where, as a result of new information or of a reassessment of existing information, pesticide residues or MRLs covered by this Regulation may endanger human or animal health requiring immediate action. The time limit within which the Commission must take its decision shall be reduced to seven days in the case of fresh produce. F3CHAPTER VIIU.K. [ F3 SUPPORT MEASURES RELATING TO HARMONISED PESTICIDE MRLS F3Article 36U.K. Support measures relating to harmonised pesticide MRLs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . F3Article 37U.K. Community contribution to the support measures for harmonised pesticide MRLs ] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Textual Amendments F3 Deleted byRegulation (EU) No 652/2014 of the European Parliament and of the Council of 15 May 2014 laying down provisions for the management of expenditure relating to the food chain, animal health and animal welfare, and relating to plant health and plant reproductive material, amending Council Directives 98/56/EC, 2000/29/EC and 2008/90/EC, Regulations (EC) No 178/2002, (EC) No 882/2004 and (EC) No 396/2005 of the European Parliament and of the Council, Directive 2009/128/EC of the European Parliament and of the Council and Regulation (EC) No 1107/2009 of the European Parliament and of the Council and repealing Council Decisions 66/399/EEC, 76/894/EEC and 2009/470/EC. CHAPTER VIIIU.K. COORDINATION OF APPLICATIONS FOR MRLS Article 38U.K. Designation of national authorities Each Member State shall designate one or more national authorities to coordinate cooperation with the Commission, the Authority, other Member States, manufacturers, producers and growers for the purposes of this Regulation. Where more than one authority is designated by a Member State, it shall indicate which of the designated authorities shall act as a contact point. The national authorities may delegate tasks to other bodies. Each Member State shall inform the Commission and the Authority of the names and addresses of the designated national authorities. Article 39U.K. Coordination by the Authority of information on MRLs The Authority shall: (a) coordinate with the rapporteur Member State designated in accordance with Directive 91/414/EEC for an active substance; (b) coordinate with the Member States and the Commission regarding MRLs, in particular for the purpose of fulfilling the requirements of Article 41. Article 40U.K. Information to be submitted by the Member States Member States shall submit to the Authority, at its request, any available information necessary for the assessment of the safety of MRLs. Article 41U.K. Database of the Authority on MRLs Without prejudice to the applicable provisions of Community and national law on access to documents, the Authority shall develop and maintain a database, accessible to the Commission and to the competent authorities of the Member States, containing the relevant scientific information and GAPs relating to the MRLs, the active substances and the processing factors set out in Annexes II, III, IV and VII. In particular it shall contain dietary intake assessments, processing factors and toxicological endpoints. Article 42U.K. Member States and fees 1. Member States may recover the costs of work associated with setting, modifying or deleting MRLs, or with any other work arising from obligations under this Regulation, by means of a fee or charge. 2. Member States shall ensure that the fee or charge referred to in paragraph 1: (a) is established in a transparent manner; and (b) corresponds to the actual cost of the work involved. It may include a scale of fixed charges based on average costs for the work referred to in paragraph 1. CHAPTER IXU.K. IMPLEMENTATION Article 43U.K. Scientific opinion of the Authority The Commission or the Member States may request from the Authority a scientific opinion on any measure related to the assessment of risks under this Regulation. The Commission may specify the time limit within which such an opinion shall be provided. Article 44U.K. Procedure for the adoption of the Authority's opinions 1. When the Authority's opinions pursuant to this Regulation require only scientific or technical work involving the application of well-established scientific or technical principles they may, unless the Commission or a Member State objects, be issued by the Authority without consulting the scientific committee or the scientific panels mentioned in Article 28 of Regulation (EC) No 178/2002. 2. The implementing rules pursuant to Article 29(6)(a) of Regulation (EC) No 178/2002 shall specify the cases in which paragraph 1 of this Article shall apply. [ F1 Article 45U.K. Committee procedure 1. The Commission shall be assisted by the Standing Committee on the Food Chain and Animal Health established by Article 58 of Regulation (EC) No 178/2002. 2. Where reference is made to this paragraph, Articles 5 and 7 of Decision 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof. The period laid down in Article 5(6) of Decision 1999/468/EC shall be set at three months. 3. Where reference is made to this paragraph, Article 5a(1) to (4) and Article 7 of Decision 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof. 4. Where reference is made to this paragraph, Article 5a(1) to (4) and (5)(b), and Article 7 of Decision 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof. The time limits laid down in Article 5a(3)(c) and (4)(b) and (e) of Decision 1999/468/EC shall be set at two months, one month and two months respectively. 5. Where reference is made to this paragraph, Article 5a(1), (2), (4) and (6) and Article 7 of Decision 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof. ] Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. [ F1 Article 46U.K. Implementing measures 1. Implementing measures to ensure the uniform application of this Regulation, technical guidance documents to assist in its application and detailed rules concerning the scientific data required for the setting of MRLs shall be established or may be amended in accordance with the regulatory procedure referred to in Article 45(2), taking into account, where appropriate, the opinion of the Authority. 2. Measures designed to amend non-essential elements of this Regulation and relating to the establishment or amendment of the dates referred to in Article 23, Article 29(2), Article 30(2), Article 31(1) and Article 32(5) shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(3), taking into account, where appropriate, the opinion of the Authority. ] Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. Article 47U.K. Report on implementation of this Regulation Not later than 10 years after the entry into force of this Regulation, the Commission shall forward to the European Parliament and to the Council a report on its implementation and any appropriate proposals. CHAPTER XU.K. FINAL PROVISIONS Article 48U.K. Repeal and adaptation of legislation 1. Directives 76/895/EEC, 86/362/EEC, 86/363/EEC and 90/642/EEC are hereby repealed with effect from the date referred to in the second paragraph of Article 50. 2. Article 4(1)(f) of Directive 91/414/EEC shall be replaced by the following: ‘(f) where appropriate, the MRLs for the agricultural products affected by the use referred to in the authorisation have been set or modified in accordance with Regulation (EC) No 396/2005(5) ’ [ F1 Article 49U.K. Transitional measures 1. The requirements of Chapter III shall not apply to products lawfully produced or imported into the Community before the date referred to in the second paragraph of Article 50. However, in order to ensure a high level of consumer protection, appropriate measures concerning those products may be taken. Those measures, designed to amend non-essential elements of this Regulation by supplementing it, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(5). 2. Where necessary to allow for the normal marketing, processing and consumption of products, further transitional measures may be laid down for the implementation of certain MRLs provided for in Articles 15, 16, 21, 22, and 25. Those measures, designed to amend non-essential elements of this Regulation by supplementing it, and without prejudice to the obligation to ensure a high level of consumer protection, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 45(4). ] Textual Amendments F1 Substituted byRegulation (EC) No 299/2008 of the European Parliament and of the Council of 11 March 2008 amending Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, as regards the implementing powers conferred on the Commission. Article 50U.K. Entry into force This Regulation shall enter into force on the twentieth day following its publication in the Official Journal of the European Union. Chapters II, III and V shall apply as from six months from the publication of the last of the Regulations establishing Annexes I, II, III and IV. This Regulation shall be binding in its entirety and directly applicable in all Member States.	https://www.legislation.gov.uk/eur/2005/396/body?view=extent
The Oxford Oratory <here is a image 28c7aaa09adc6928-993bfc2584d55164> 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. Saturday 24 June 2023 <here is a image 27cf3de6da8734ca-8bdf209a246426e8> Congratulations to Andrew and Nina, baptised this morning! Today, the birthday of St John the Baptist, is a fitting day to baptise, and not just because he is famous for baptising people. His birth marks the end of the Old Testament and the beginning of the New. Today is about looking forward to the future. Baptism can sometimes feel like an ending after the period of preparation and catechesis, but it is of course only the beginning of the Christian life. The big work lies before us. As St Philip used to say, “The great thing is to become saints.” #oxfordoratory <here is a image 1615bff70a2a651f-8de8fa8c0f919e3d> Yesterday we welcomed Fr William Pearsall of the Society of Jesus to preach for the feast of St Aloysius. “What Aloysius did is what many saints have done — many who are condemned for not being useful. They explored the frontiers of the spiritual life. They were heroic in the sense that those who went to the North Pole or the South Pole or climbed the highest mountains, they were heroic… They were heroic because they were living with the discovery of God and how the limits between nature and grace will always be an expanding horizon.” St Aloysius, pray for us! #oxfordoratory <here is a image cb5c3e10fabbd958-c54beffc6a81f76c> Happy feast of St Aloysius! Two relics of his are displayed this month in our relic chapel, including a letter bearing his signature. #oxfordoratory Flos paradisi <here is a image 08882fe692d4b4e9-cf8cbef9fe53c26d> Today we celebrate the great solemnity of the patron of our church: St Aloysius Gonzaga of the Society of Jesus. St Aloysius is, together with St Gabriel Possenti, patron of young people, students, and seminarians and thus was a natural choice as patron for our church in this university city. He is also the patron of our parish school and we entrust to his loving intercession all our children who are able to learn the love of God from his example. We have his shrine in the chapel of Our Lady of Oxford, his statue is there on the reredos, and his initials guide our eyes towards his heavenly home as we look up at the sanctuary ceiling. Our patrons are important — St Aloysius has been given to us in this parish by God, through his Church, to watch over us in a particular manner, to intercede for all those who live and worship here, and to encourage us in our own quest for holiness. Born the eldest son of the Marquis of Castiglione, St Aloysius seemed destined for a life of political intrigue and secular affairs, but, as with St Ignatius before him, it was the lives of the saints that really captivated him and placed in his heart the desire to strive for something better. This was not some childish caprice; he had seen the reality of life at court with its violence, frivolity, and degradation of human dignity, and desired not only to turn his back on it, but to embrace with all his heart a life given wholly to God. He began in earnest, adopting severe penances and teaching the local children their catechism. Hearing about the missions of St Francis Xavier, he set his heart on becoming a Jesuit — much to the horror of his family. Eventually, having not overcome family opposition but at least its concrete obstacles, and having renounced his rights of inheritance, he entered the Jesuit novitiate in Rome in 1585. He had much to learn and much to which to adapt himself, but whatever he had to do he simply did it with all his heart — trusting in the sure knowledge that God was at work. Would he have met St Philip in Rome? Concrete evidence is hard to find, though these two saints of Rome are often depicted in art. We know they had mutual friends and these no doubt would have told them of Rome’s Third Apostle and of the holy Jesuit novice. One can imagine St Aloysius on a novitiate walk popping in to the Chiesa Nuovato see Mister Father Philip whom all Rome spoke of and revered or of St Philip blessing a crowd of passing Jesuit novices and knowing the heart of one of them that would see them both in glory. St Aloysius’ real work in Rome was that which St Philip had embarked upon at the beginning — the care of the sick and the destitute. When plague broke out he volunteered to go with the other novices to pick people off the streets, to wash them, to prepare them for the sacraments and care for their souls. At first, he admitted to his director St Robert Bellarmine, this revolted him, but he soon learnt to see the image of Christ in these people, and to love them, not only in caring for them, but in seeing Christ in them. Never one to enjoy good health, Aloysius himself fell ill of plague, and died at the age of 23 on 21 June 1591, just a few years before St Philip’s death. When we look at images of St Aloysius we normally see a rather pale young man who looks like so many other sickly young saints, distinguished perhaps only by the great ruff that he wears about his neck. But he was more than that. He was a young man who bothered about God and thus about other people. He was not yet in his mid-twenties, when he had discovered that real freedom comes from serving God with all ones heart; that Christian love has to be lived in the real, strength-sapping, heart-breaking, service of others; that there is joy in taking people off the streets, washing them, bandaging their wounds and restoring them to the dignity that is theirs as children of God. The image attached to these words is a depiction of St Aloysius in Milan in the Chiesa di Santa Maria presso San Satiro. The saint looks rather weak and malnourished, but what strength he has is used to hold up a man who is either dying or dead, with St Aloysius pressing the Cross to him and holding the man’s head up with his hands. The look on St Aloysius’ face is one, simply, of love — of love for God and neighbour, and of joy found in bringing the love of God to others. How much this young man, St Aloysius, still has left to teach 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. Friday 16 June 2023 <here is a image 90de54d35c43d015-336827041ffdf36d> Heart of Jesus, all-holy! Fountain of all blessings, I adore thee, I love thee, and with a lively sorrow for my sins, I offer thee this poor heart of mine. Make me humble, patient, pure, and wholly obedient to thy will. Good Jesus, grant that I may live in thee and for thee. Protect me in the midst of danger; comfort me in my afflictions; give me health of body, assistance in my temporal needs, thy blessing on all that I do, and the grace of a holy death. Amen. #oxfordoratory Thursday 15 June 2023 <here is a image 23a01f392d19c2db-79e05d63b135cb12> A photo from Sunday’s Solemn Mass for Corpus Christi. #oxfordoratory June Music Sunday 4 JuneSolemn Mass 11:00 The Most Holy Trinity Kyrie Mundy Missa Euge bone Tye Libera nos Sheppard Honor, virtus et potestas Tallis Sunday 11 JuneSolemn Mass 11:00 Corpus Christi Missa Pange lingua Josquin Lauda Sion Palestrina Oculi omnium Byrd Friday 16 JuneSolemn Mass 18:00 The Most Sacred Heart of Jesus Missa Dormendo un giorno Guerrero Improperium Palestrina Sancte Deus Tallis Sunday 18 JuneSolemn Mass 11:00 11th Sunday of the Year Missa Brevis in F Op.117 Rheinberger Benedicam Dominum Victoria Salve Regina Poulenc Wednesday 21 JuneSolemn Mass 18:00 St Aloysius Gonzaga Missa O quam gloriosum Victoria Justitiae Domini A Scarlatti O bone Jesu Anchieta Sunday 25 JuneSolemn Mass 11:00 12th Sunday of the Year Missa Repleatur os meum Palestrina Perfice gressus meos Lassus Homo quidam fecit coenam magnam Mouton Thursday 29 JuneSolemn Mass 18:00 St Peter and St Paul Missa Petre ego pro te rogavi Lobo Petre ego pro te rogavi Guerrero Janitor caeli Ortiz The Sacred Heart Love is a funny thing. Materialists will tell us that it is purely the result of a series of electro-chemical responses in the brain, and yet others will tell us that it is the result of fate, the conspiracy of the alignment of the planets or the times we find ourselves in. The heart has long been understood as the centre of a person, a place of knowledge as much as will. It makes us do unreasonable things like acts of unwarranted kindness and altruism and by the edge of its blade we can be hurt in ways that we just can’t speak about. And yet none of these express what love is in itself — only God does that. On Friday we venerate the Heart of our Lord as the symbol of his human love in which God’s divine love is revealed to us. In most of the prayers to or the meditations on the Sacred Heart, even those very ancient prayers, the woundedness of our Lord’s heart comes to the fore. That heart pierced with a lance and bruised with outrages and blasphemies is a stark and realistic image of the extent to which Christ loves us. Christ, who is the image of the unseen God, the Icon of the Father, shows us precisely what God’s love for us looks like. And it looks like a heart pierced and bruised on account of our sins, yet burning with ardent love for you and for me. This divine love is not for softies. The time when we celebrate this feast is very fitting. We have come to the end of the Church’s celebration of the mysteries of our redemption: the Passion, the Cross, the Resurrection, the Ascension, Pentecost, the Feast of the Blessed Trinity and Corpus Christi. But today we commemorate the divine-human love which motivated them all. In adoring the Sacred Heart, we adore the totality of Christ’s saving work — it represents the way in which God holds nothing back from us. And in order to share his divine life with us, he reaches down into the very depths of our life, even — and especially — where it is painful, difficult to speak of, hidden. By taking it all and joining it to himself, he scoops us up, he enables us to become like him. By sharing our life, and by sharing our pains, he heals us, he sanctifies us, and he strengthens us. It is also true that his heart welcomes us precisely so that we might become like it. The whole thrust of our Christian life is that we might be conformed to our Saviour, that we might resemble him, and in this sense, in the life of faith, we should ask ourselves continually whether our heart resembles his. His Sacred Heart is both the example and the cause of our becoming like him. His love is attractive. The more we consider the love with which Jesus acted, and spoke and gave of himself for us, the more we can begin, by his grace, to imitate him — it is truly the school of Christian perfection. And we begin in that school by prayer. When St John Henry Newman, our Cardinal, chose his motto, he looked to St Francis de Sales’ Treatise on the Love of God. The phrase he chose and paraphrased, Cor ad Cor loquiturrepresents for us the central mystery of the prayer that can begin to transform us. St Francis de Sales wrote: Truly the chief exercise in mystical theology is to speak to God and to hear God speak in the bottom of the heart; and because this discourse passes in most secret aspirations and inspirations, we term it a silent conversing. Eyes speak to eyes, and heart to heart, and none understand what passes save those who speak. We may be no great shakes at the spiritual life, or prayer, or we may feel that excelling in virtue is beyond us, but if we can in the simplest of ways open our poor heart to his Sacred Heart, and speak to him as to a friend, if we can entrust our lives to him and ask him devoutly and sincerely to shape us after the model of his Heart, then our Christian life will be all the more graced. 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 13 June 2023 <here is a image 0a219f870ecdb4fc-b05f991df4b80b21> The Corpus Christi procession concluded with Benediction at the University Chaplaincy. #oxfordoratory Tuesday 13 June 2023 <here is a image 7de58cf2c953cb02-cb3593d95e5b3a6e> The procession finished at the University’s Catholic Chaplaincy. #oxfordoratory Tuesday 13 June 2023 <here is a image 0050feb12853a7a4-e287d4d3b316a4ac> The numbers caught the attention of the local media: https://www.oxfordmail.co.uk/news/23582016.oxfords-catholic-congregations-take-part-corpus-christi-procession/ #oxfordoratory <here is a image 1e8c5e41dbace8b3-f13de7a94ba50876> Children scattered flower petals before the Blessed Sacrament all the way. #oxfordoratory <here is a image 02e446a06b4967e9-123a471760af1c47> Our route now passes through the city in a straight line, taking us directly through the busiest shopping areas. #oxfordoratory <here is a image 45b1a6dec1ee3e34-60982a346c615b61> The canopy was carried by members of the University of Oxford wearing their academic dress. #oxfordoratory <here is a image 4c21fcc6046f1d97-c6c0f60e89d6f0fa> Fr Robert Ombres OP preached a sermon. #oxfordoratory <here is a image c73a2603b5ae0424-6890548d25e67261> We paused at Blackfriars. #oxfordoratory <here is a image f4bb2cd78aee371a-1526fe4846c634e0> We were joined by local clergy and religious orders as we processed through the streets to the Dominican Priory at Blackfriars. #oxfordoratory <here is a image 1f061f62b565c7a0-bd18972461334585> The processions sets off… #oxfordoratory <here is a image af05b5ea533ed86d-fb13d73ce04d81a6> We had record numbers for the procession this year. There wasn’t space in church for everyone at the beginning! There were more people outside too. #oxfordoratory <here is a image 6203782e1c176a92-1deadb6e817fbb0e> The beginning of our Corpus Christi procession last Sunday. #oxfordoratory	https://www.oxfordoratory.org.uk/campaign/blog/post/9975-9975/blog/post/10029-10029/oratory-bookshop.php
Population Pharmacokinetics of Paritaprevir, Ombitasvir, and Ritonavir in Japanese Patients with Hepatitis C Virus Genotype 1b Infection \| Request PDF Request PDF \| Population Pharmacokinetics of Paritaprevir, Ombitasvir, and Ritonavir in Japanese Patients with Hepatitis C Virus Genotype 1b Infection \| Background and Objective Hepatitis C virus (HCV) infection is of considerable clinical concern in Japan. We modeled the population... \| Find, read and cite all the research you need on ResearchGate Population Pharmacokinetics of Paritaprevir, Ombitasvir, and Ritonavir in Japanese Patients with Hepatitis C Virus Genotype 1b Infection Clinical Pharmacokinetics 56(1) DOI: 10.1007/s40262-016-0423-2 AbbVie Abstract Background and Objective Hepatitis C virus (HCV) infection is of considerable clinical concern in Japan. We modeled the population pharmacokinetics of an oral interferon-free, direct-acting antiviral agent (DAA) regimen (i.e., the 2D regimen) recently approved for the treatment of chronic HCV genotype 1 infection as a new option for affected Japanese patients. Methods Using data from a phase III clinical trial (GIFT-I) that enrolled Japanese patients with HCV genotype 1b infection, population pharmacokinetic models were developed for the drugs that comprise the 2D regimen: paritaprevir, ombitasvir, and ritonavir. Demographic and clinical covariates with potential to influence 2D pharmacokinetics were evaluated for their effects on drug exposures. Proposed models were assessed using goodness-of-fit plots, visual predictive checks, and bootstrap evaluations. Results One-compartment models with first-order absorption and elimination adequately described the population pharmacokinetics of paritaprevir, ombitasvir, and ritonavir. On average, patients with cirrhosis had approximately 95–145 % higher, 19–24 % lower, and 58–68 % higher exposures of paritaprevir, ombitasvir, and ritonavir, respectively. Female patients had 58–81 % higher ombitasvir exposures, whereas patients with mild renal impairment (creatinine clearance 75 mL/min) had 9–14 % higher ombitasvir exposures than did patients with normal renal function (creatinine clearance 105 mL/min). The DAA exposure values were comparable between responders and non-responders. Conclusion Population pharmacokinetic modeling did not reveal any patient-related or clinical parameters that would require dose adjustment of the 2D regimen when used for the treatment of HCV genotype 1b infection in Japanese patients. 2.3+ billion citations Join for free ... This patient did not have hyperbilirubinemia and appears as an outlier in Fig 3a. Gopalakrishnan et al. have shown that the range of paritaprevir exposure was comparable between Japanese and western patients [30] . However, these exposures were normally distributed in westerners. ... ... In contrast, those in the Japanese patients varied widely among subjects. There are large interindividual differences in pharmacokinetic profiles in Japanese people [30] . Tomita et al. indicated that the ethnic variability in the plasma exposure of statins (also substrates for OATP1B1), cannot be explained only by the difference in the allele frequencies of OATP1B1; the intrinsic ethnic variability in the activity of OATP1B1 must be considered [31]. ... Gadoxetic acid–enhanced magnetic resonance imaging to predict paritaprevir-induced hyperbilirubinemia during treatment of hepatitis C Article Full-text available Apr 2018 PLOS ONE Hironao Okubo Hitoshi Ando Yushi Sorin Kenichi Ikejima Background Paritaprevir inhibits organic anion–transporting polypeptide (OATP)1B1 and OATP1B3, which transport bilirubin. Hyperbilirubinemia is an adverse event reported during hepatitis C treatment. Gadoxetic acid is also transported by OATP1B1/1B3. We evaluated whether the enhancement effect in gadoxetic acid–enhanced magnetic resonance (MR) imaging could predict the plasma concentration of paritaprevir and might anticipate the development of hyperbilirubinemia. Methods This prospective study evaluated 27 patients with hepatitis C who underwent gadoxetic acid–enhanced MR imaging prior to treatment with ombitasvir, paritaprevir, and ritonavir. The contrast enhancement index (CEI), a measure of liver enhancement during the hepatobiliary phase, was assessed. Plasma trough concentrations, and concentrations at 2, 4, and 6 h after dosing were determined 7 d after the start of treatment. Results Seven patients (26%) developed hyperbilirubinemia (≥ 1.6 mg/dl). Paritaprevir trough concentration (Ctrough) was significantly higher in patients with hyperbilirubinemia than in those without (p = 0.022). We found an inverse relationship between CEI and Ctrough (r = 0.612, p = 0.001), while there was not a significantly weak inverse relationship between AUC0–6 h and CEI (r = −0.338, p = 0.085). The partial correlation coefficient between CEI and Ctrough was −0.425 (p = 0.034), while excluding the effects of albumin and the FIB-4 index. Receiver operating characteristic (ROC) curve analysis showed that the CEI was relatively accurate in predicting hyperbilirubinemia, with area under the ROC of 0.882. Multivariate analysis showed that the CEI < 1.61 was the only independent predictor related to the development of hyperbilirubinemia, with an odds ratio of 9.08 (95% confidence interval 1.05–78.86, p = 0.046). Conclusions Hepatic enhancement with gadoxetic acid was independently related to paritaprevir concentration and was an independent pretreatment factor in predicting hyperbilirubinemia. Gadoxetic acid–enhanced MR imaging can therefore be useful in determining the risk of paritaprevir-induced hyperbilirubinemia. View ... Table 1 goes here.*** BLQ data are substituted with LLOQ/2, however subsequent, consecutive BLQ observations from the same subject are discarded M6 [1,12,34,35,59,63,117,[225][226][227][228][229][230][231][232][233][234][235][236][237][238][239][240] [241] [242][243] All BLQ data are substituted with 0 M7 [12,31,33,207,244] All BLQ data are substituted with LLOQ [245,246] Using data between LoD and LLOQ [1,32,41,[247][248][249] A comparison of several approaches for treating BLQ data points was conducted by Xu et al. [76]. ... Utilization of data below the analytical limit of quantitation in pharmacokinetic analysis and modeling: Promoting interdisciplinary debate Article Jul 2018 Max Hecht Ruta Hecht Lewis Couchman Karin Kipper Traditionally, bioanalytical laboratories do not report actual concentrations for samples with results below the LOQ (BLQ) in pharmacokinetic studies. BLQ values are outside the method calibration range established during validation and no data are available to support the reliability of these values. However, ignoring BLQ data can contribute to bias and imprecision in model-based pharmacokinetic analyses. From this perspective, routine use of BLQ data would be advantageous. We would like to initiate an interdisciplinary debate on this important topic by summarizing the current concepts and use of BLQ data by regulators, pharmacometricians and bioanalysts. Through introducing the limit of detection and evaluating its variability, BLQ data could be released and utilized appropriately for pharmacokinetic research. Tratamiento de la Hepatitis C crónica en pacientes de edad avanzada con Enfermedad Renal Crónica: Revisión estructurada Article Full-text available Oct 2018 Monica Ledezma Morales Pedro Amariles Hepatitis C (HC) is a public health problem worldwide and has especially high prevalence in patients over 50 years of age. This population is more prone to suffer from chronic kidney disease (CKD) due to HC infections as well as to age and multiple comorbidities. Those with CKD stages 4 or 5 constitute a population of greater pharmacotherapeutic complexity due to pharmacological variability and limited information on the safety and efficacy of the new antivirals for this group of patients. Objective: This article systematizes information about medications and proper dosages for treating chronic HC and is based on studies and reports that include elderly patients with CKD. Materials and method: This is a structured review of studies carried out in humans with access to full text published between 01/08/2012 and 01/08/2017 in English or Spanish found in PubMed/ Medline using the terms: “Hepatitis C”, “Aged”, and “Renal Insufficiency”. Results: Eighty-three articles were identified, fourteen of which were selected. In addition, four manuscripts referenced in those publications were included. A table with antiviral dosing information for treatment of HC in elderly patients with CKD was structured. Discussion: We present information on adjustment of dosages of antiviral drugs used for chronic HC in elderly patients and CKD. This could favor prescription and monitoring thereby contributing to the effectiveness and safety of these drugs in this population. Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Hepatitis C Virus-Infected Cirrhotic and Non-cirrhotic Patients: Analyses Across Nine Phase III Studies Article Mar 2018 Sathej Gopalakrishnan Sven Mensing Rajeev Menon Jiuhong Zha Background The clinical development program of the direct-acting antiviral (DAA) combination therapy of paritaprevir (coadministered with ritonavir) and ombitasvir, with and without dasabuvir (3-DAA [3D] and 2-DAA [2D] regimens, respectively) used in the treatment of chronic hepatitis C infection has generated a robust dataset across various dosing regimens and patient populations. Objective The current analysis aimed to characterize the population pharmacokinetics in patients without cirrhosis (‘non-cirrhotic’) and with compensated cirrhosis (‘cirrhotic’), while accounting for differences across hepatitis C virus (HCV) genotypes (GT) 1, 2, and 4, multiple regimens (3D regimen ± ribavirin for GT1 in global studies, 2D regimen for subgenotype 1b in Japan, 2D regimen + ribavirin for GT2 in Japan, and 2D regimen + ribavirin for GT4), and ethnicities. Methods Pharmacokinetic data from nine clinical studies (~ 1850 patients) were used to model the population pharmacokinetics of each component of the DAA regimens. Model development was performed in stages, starting with an initial base model. Covariate–parameter relationships were then assessed using forward inclusion/backward elimination procedures. Model development was guided by goodness-of-fit plots, likelihood ratio tests, plausibility of parameter estimates, and knowledge of DAA, ritonavir, and ribavirin pharmacokinetics. Paritaprevir, ombitasvir, and ritonavir pharmacokinetics were described by a one-compartment model, while dasabuvir and ribavirin pharmacokinetics were characterized by a two-compartment model. Results The analysis showed generally overlapping exposures between compensated cirrhotic and non-cirrhotic patients or between subgroups of the identified significant covariates. The largest differences were the approximately 30–60% higher dasabuvir and paritaprevir exposures in compensated cirrhotic patients. Conclusion These differences did not warrant dose adjustments for the DAAs when used in HCV-infected patients with compensated cirrhosis. JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders Article Full-text available Jan 2018 William Vainchenker Emilie Leroy Laure Gilles Stefan N Constantinescu JAK inhibitors have been developed following the discovery of the JAK2V617F in 2005 as the driver mutation of the majority of non-BCR-ABL1 myeloproliferative neoplasms (MPNs). Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations (CALR and MPL) also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with different specificities were assessed in clinical trials and exhibited minimal hematologic toxicity. Interestingly, these JAK inhibitors display potent anti-inflammatory activity. Thus, JAK inhibitors targeting preferentially JAK1 and JAK3 have been developed to treat inflammation, autoimmune diseases, and graft-versus-host disease. Ten years after the beginning of clinical trials, only two drugs have been approved by the US Food and Drug Administration: one JAK2/JAK1 inhibitor (ruxolitinib) in intermediate-2 and high-risk myelofibrosis and hydroxyurea-resistant or -intolerant polycythemia vera and one JAK1/JAK3 inhibitor (tofacitinib) in methotrexate-resistant rheumatoid arthritis. The non-approved compounds exhibited many off-target effects leading to neurological and gastrointestinal toxicities, as seen in clinical trials for MPNs. Ruxolitinib is a well-tolerated drug with mostly anti-inflammatory properties. Despite a weak effect on the cause of the disease itself in MPNs, it improves the clinical state of patients and increases survival in myelofibrosis. This limited effect is related to the fact that ruxolitinib, like the other type I JAK2 inhibitors, inhibits equally mutated and wild-type JAK2 (JAK2WT) and also the JAK2 oncogenic activation. Thus, other approaches need to be developed and could be based on either (1) the development of new inhibitors specifically targeting JAK2V617F or (2) the combination of the actual JAK2 inhibitors with other therapies, in particular with molecules targeting pathways downstream of JAK2 activation or the stability of JAK2 molecule. In contrast, the strong anti-inflammatory effects of the JAK inhibitors appear as a very promising therapeutic approach for many inflammatory and auto-immune diseases. Pharmacokinetics, Safety, and Tolerability of Glecaprevir and Pibrentasvir in Healthy White, Chinese, and Japanese Adult Subjects Article Aug 2017 J CLIN PHARMACOL C.-W. Lin Sandeep Dutta Bifeng Ding Wei Liu Glecaprevir and pibrentasvir are direct-acting antiviral agents being developed as combination therapy for the treatment of chronic hepatitis C virus infection. The aim of the present studies was to assess the effect of race and ethnicity (white, Han Chinese, Japanese) on the pharmacokinetics and safety of multiple oral doses of glecaprevir and pibrentasvir given alone and in combination. Two multiple-dose, single-center, phase 1 studies were conducted in healthy adult male and female subjects (n = 170) of respective Asian and white race/ethnicity. Glecaprevir (100, 200, 300, or 700 mg once daily) and pibrentasvir (80, 120, or 160 mg once daily) were administered alone for 7 days followed by the combination of both direct-acting antiviral agents for another 7 days. Intensive blood sampling was performed, and pharmacokinetic parameters were estimated by noncompartmental analyses. ANOVA was employed to evaluate for differences of steady-state glecaprevir and pibrentasvir exposures between Asian (Japanese or Han Chinese) and white subjects. Glecaprevir and pibrentasvir exposures in Han Chinese and Japanese were similar to those in whites across dose levels. The nonlinear dose-exposure relationships for glecaprevir and pibrentasvir were similar across Japanese, Han Chinese, and white subjects, and the safety profiles of the agents were comparable across these groups. The results of these studies demonstrate that race/ethnicity has no clinically meaningful impact on direct-acting antiviral agent exposures, safety, or tolerability of the glecaprevir and pibrentasvir combination. This is supported in part by the large global registration program of the pangenotypic, coformulated fixed-dose glecaprevir/pibrentasvir regimen and allows for inclusion of diverse ethnic populations. Development of glucose-responsive 'smart' insulin systems May 2017 Nischay Rege Nelson B Phillips Michael A Weiss Purpose of review: The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider. The present review describes the relevant historical background to modern GRI technologies and highlights three distinct approaches: coupling of continuous glucose monitoring (CGM) to deliver devices (algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation of insulin, and molecular modification of insulin itself. Recent findings: Recent advances in GRI research utilizing each of the three approaches are illustrated; these include newly developed algorithms for CGM-based insulin delivery systems, glucose-sensitive modifications of existing clinical analogs, newly developed hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived pancreatic β cells. Summary: Although GRI technologies have yet to be perfected, the recent advances across several scientific disciplines that are described in this review have provided a path towards their clinical implementation. Exposure–Response Relationship for Ombitasvir and Paritaprevir/Ritonavir in Hepatitis C Virus Subgenotype 1b-Infected Japanese Patients in the Phase 3 Randomized GIFT-I Study Mar 2016 Sathej Gopalakrishnan Amit Khatri Sven Mensing Jiuhong Zha IntroductionThe all-oral 2 direct-acting antiviral (DAA) regimen of ombitasvir/paritaprevir/ritonavir 25/150/100 mg once a day has been evaluated in hepatitis C virus subgenotype 1b-infected Japanese adults in the GIFT-I study. The aim of this analysis was to evaluate potential relationships between DAA exposures and laboratory abnormalities/adverse events of peripheral edema in patients in GIFT-I. Methods The GIFT-I study consisted of a randomized, double-blind, placebo-controlled substudy in patients without cirrhosis and an open-label substudy in patients with compensated cirrhosis. Patients received ombitasvir/paritaprevir/ritonavir for 12 weeks. Exposure–response relationships between individual components of the ombitasvir/paritaprevir/ritonavir regimen and clinical parameters of interest were explored using pharmacokinetic and clinical data from patients in the study. Graphical analyses were performed. For events that occurred in at least 10 patients (total bilirubin elevation ≥grade 2 and peripheral edema ≥grade 1), multivariate logistic regression analyses were used to identify significant relationships between predictor variables (drug exposures) and response variables (probability of adverse events or laboratory abnormalities), with consideration for the effect of potential covariates and baseline status of response variables. ResultsData from 321 noncirrhotic and 42 compensated cirrhotic patients were analyzed. There were 14 events of peripheral edema (10 at grade 1 and 4 at grade 2) in patients who received concomitant administration of calcium channel blockers and ombitasvir/paritaprevir/ritonavir. There was no apparent relationship between the incidences of peripheral edema and exposures of paritaprevir, ombitasvir, or ritonavir. There was a shallow relationship between total bilirubin elevation and exposures of paritaprevir which is an inhibitor of bilirubin transporter organic anion-transporting polypeptide 1B. Based on graphical analyses, exposures of paritaprevir, ombitasvir, or ritonavir were weakly associated with hemoglobin decrease, but not associated with post baseline alanine aminotransferase or aspartate aminotransferase elevations. Conclusions In Japanese patients, there were no associations or only shallow relationships between DAA exposures and peripheral edema or laboratory abnormalities. Consequently, therapeutic drug monitoring is not expected to be beneficial in managing patients on the 2-DAA regimen. Trial registrationClinicalTrials.gov identifier, NCT02023099. FundingAbbVie Inc. Ombitasvir/Paritaprevir/r, Dasabuvir and Ribavirin for Cirrhotic HCV Patients with Thrombocytopenia and Hypoalbuminemia Article Aug 2015 LIVER INT Xavier Forns Fred Poordad Marcos Pedrosa Gregory T Everson Background & AimsThrombocytopenia and hypoalbuminemia are surrogate markers for portal hypertension and hepatic synthetic dysfunction, respectively. Patients infected with hepatitis C virus (HCV) with these surrogates have reduced likelihood of sustained virologic response and increased risk for hepatic decompensation or death when treated with peginterferon/ribavirin plus either telaprevir or boceprevir.Methods We conducted a post-hoc analysis of the TURQUOISE-II clinical trial in patients with cirrhosis to examine the impact of these surrogates on efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.ResultsOf 380 genotype 1-infected patients in TURQUOISE-II, 104 had either a platelet count <100 x 109/L or albumin <3.5 g/dL. Sustained virologic response rates were 89 and 97% in patients with thrombocytopenia, and 84 and 89% in patients with hypoalbuminemia after 12 and 24 weeks of ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin, respectively. These rates were similar to those observed in the overall study population (92 and 97% for 12 and 24 weeks). HCV genotype 1a-infected patients with thrombocytopenia or hypoalbuminemia had higher response rates when treated for 24 weeks, whereas only 1 of 35 genotype 1b patients did not achieve a sustained virologic response. Adverse event rates and discontinuations due to adverse events were low.Conclusions The findings of these analyses support the use of ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin in these subpopulations with cirrhosis. Genotype 1a-infected patients with indicators of portal hypertension may benefit from a 24-week treatment duration.This article is protected by copyright. All rights reserved. Randomized Phase 3 Trial of Ombitasvir/Paritaprevir/Ritonavir for HCV Genotype 1b-infected Japanese Patients With or Without Cirrhosis Article Jul 2015 HEPATOLOGY Hiromitsu Kumada Kazuaki Chayama Lino Rodrigues-Jr Rebecca Redman GIFT-I is a phase 3 trial evaluating efficacy and safety of a 12-week regimen of co-formulated ombitasvir(OBV)/paritaprevir(PTV)/ritonavir(r) for treatment of Japanese HCV genotype(GT) 1b-infected patients. GIFT-I consists of a double-blind, placebo-controlled substudy of patients without cirrhosis and an open-label substudy of patients with compensated cirrhosis. Patients without cirrhosis were randomized 2:1 to once daily OBV/PTV/r(25mg/150mg/100mg; Group A) or placebo(Group B). Patients with cirrhosis received open-label OBV/PTV/r(Group C). The primary efficacy endpoint was the rate of sustained virologic response 12 weeks post-treatment(SVR12) in interferon-eligible, treatment-naïve patients without cirrhosis and HCV RNA ≥100,000 IU/ml in Group A. A total of 321 patients without cirrhosis were randomized and dosed with double-blind study drug(106 received double-blind placebo and later received open-label OBV/PTV/r) and 42 patients with cirrhosis were enrolled and dosed with open-label OBV/PTV/r. In the primary efficacy population, the SVR12 rate was 94.6%(106/112; 95% confidence interval 90.5-98.8). SVR12 rates were 94.9%(204/215) in Group A, 98.1%(104/106) in Group B(open-label), and 90.5%(38/42) in Group C. Overall, virologic failure occurred in 3.0%(11/363) of patients who received OBV/PTV/r. The rate of discontinuation due to adverse events was 0-2.4% in the three patient groups receiving OBV/PTV/r. The most frequent adverse event in patients in any group was nasopharyngitis. In this broad HCV GT1b-infected Japanese patient population with or without cirrhosis, treatment with OBV/PTV/r for 12 weeks was highly effective and demonstrated a favorable safety profile. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases. Incorporation of concentration data below the limit of quantification in population pharmacokinetic analyses Article Mar 2015 Ron Keizer Robert S Jansen Hilde Rosing Alwin D R Huitema Handling of data below the lower limit of quantification (LLOQ), below the limit of quantification (BLOQ) in population pharmacokinetic (PopPK) analyses is important for reducing bias and imprecision in parameter estimation. We aimed to evaluate whether using the concentration data below the LLOQ has superior performance over several established methods. The performance of this approach (“All data”) was evaluated and compared to other methods: “Discard,” “LLOQ/2,” and “LIKE” (likelihood-based). An analytical and residual error model was constructed on the basis of in-house analytical method validations and analyses from literature, with additional included variability to account for model misspecification. Simulation analyses were performed for various levels of BLOQ, several structural PopPK models, and additional influences. Performance was evaluated by relative root mean squared error (RMSE), and run success for the various BLOQ approaches. Performance was also evaluated for a real PopPK data set. For all PopPK models and levels of censoring, RMSE values were lowest using “All data.” Performance of the “LIKE” method was better than the “LLOQ/2” or “Discard” method. Differences between all methods were small at the lowest level of BLOQ censoring. “LIKE” method resulted in low successful minimization (<50%) and covariance step success (<30%), although estimates were obtained in most runs (~90%). For the real PK data set (7.4% BLOQ), similar parameter estimates were obtained using all methods. Incorporation of BLOQ concentrations showed superior performance in terms of bias and precision over established BLOQ methods, and shown to be feasible in a real PopPK analysis. In Vitro and In Vivo Antiviral Activity and Resistance Profile of Ombitasvir, an Inhibitor of HCV NS5A. Article Dec 2014 Preethi Krishnan Jill Beyer Neeta Mistry Ombitasvir (ABT-267) is an HCV NS5A inhibitor with picomolar (pM) potency and pan-genotypic activity with an EC50 range of 0.82 to 19.3 pM against HCV genotypes 1-5, and 366 pM against genotype 6a. Ombitasvir retained these levels of potency against a panel of 69 genotype 1-6 chimeric replicons containing the NS5A gene derived from HCV-infected patients, despite the existence of natural sequence diversity within NS5A. In vitro resistance selection identified variants that conferred resistance to ombitasvir in the HCV NS5A gene at amino acid positions 28, 30, 31, 58 and 93 in genotypes 1-6. Ombitasvir was evaluated in vivo in a 3-day monotherapy study in 12 HCV genotype 1-infected patients at 5, 25, 50 or 200 mg dosed once daily. All patients in the study were HCV genotype 1a-infected and were without pre-existing resistant variants at baseline by clonal sequencing. Decreases in HCV RNA up to 3.1 log10 IU/mL were observed. Resistance-associated variants at positions 28, 30, or 93 in NS5A were detected in patient samples 48-hours after the first dose. Clonal sequencing analysis indicated that wild-type virus was largely suppressed by ombitasvir during 3-day monotherapy, and at doses higher than 5 mg, resistant variant M28V was also suppressed. Ombitasvir was well tolerated at all doses, and there were no serious or severe adverse events. These data support clinical development of ombitasvir in combination with inhibitors targeting HCV NS3/4A protease (ABT-450 with ritonavir) and HCV NS5B polymerase (ABT-333, dasabuvir) for the treatment of chronic HCV genotype 1. Copyright © 2014, American Society for Microbiology. All Rights Reserved. In Vitro and In Vivo Antiviral Activity and Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor ABT-450 Tami Pilot-Matias The development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. However, rapid emergence of drug resistance can limit efficacy and lead to cross-resistance among members of the same drug class. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, or 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, or 6a, respectively. In vitro, the most common amino acid variants selected by ABT-450 in genotype 1 were located in NS3 at positions 155, 156, and 168, with the D168Y variant conferring the highest level of resistance to ABT-450 in both genotype 1a and 1b replicons (219- and 337-fold, respectively). In a three-day monotherapy study in HCV genotype 1-infected patients, ABT-450 was coadminstered with ritonavir, a cytochrome P450 3A4 inhibitor, shown previously to markedly increase peak, trough, and overall drug exposures of ABT-450. A mean maximum HCV RNA decline of 4.02 log10 was observed at the end of the 3-day dosing period across all doses. The most common variants selected in these patients were R155K and D168V in genotype 1a and D168V in genotype 1b. However, selection of resistant variants was significantly reduced at the highest ABT-450 dose compared to lower doses. These findings were informative for the subsequent evaluation of ABT-450 in combination with additional drug classes in clinical trials in HCV-infected patients. Copyright © 2014, American Society for Microbiology. All Rights Reserved. ABT-450/r-Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis Fred Poordad Background: Interferon-containing regimens for the treatment of hepatitis C virus (HCV) infection are associated with increased toxic effects in patients who also have cirrhosis. We evaluated the interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir (ABT-267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin in an open-label phase 3 trial involving previously untreated and previously treated adults with HCV genotype 1 infection and compensated cirrhosis. Methods: We randomly assigned 380 patients with Child-Pugh class A cirrhosis to receive either 12 or 24 weeks of treatment with ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment. The rate of sustained virologic response in each group was compared with the estimated rate with a telaprevir-based regimen (47%; 95% confidence interval [CI], 41 to 54). A noninferiority margin of 10.5 percentage points established 43% as the noninferiority threshold; the superiority threshold was 54%. Results: A total of 191 of 208 patients who received 12 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 91.8% (97.5% CI, 87.6 to 96.1). A total of 165 of 172 patients who received 24 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 95.9% (97.5% CI, 92.6 to 99.3). These rates were superior to the historical control rate. The three most common adverse events were fatigue (in 32.7% of patients in the 12-week group and 46.5% of patients in the 24-week group), headache (in 27.9% and 30.8%, respectively), and nausea (in 17.8% and 20.3%, respectively). The hemoglobin level was less than 10 g per deciliter in 7.2% and 11.0% of patients in the respective groups. Overall, 2.1% of patients discontinued treatment owing to adverse events. Conclusions: In this phase 3 trial of an oral, interferon-free regimen evaluated exclusively in patients with HCV genotype 1 infection and cirrhosis, multitargeted therapy with the use of three new antiviral agents and ribavirin resulted in high rates of sustained virologic response. Drug discontinuations due to adverse events were infrequent. (Funded by AbbVie; TURQUOISE-II ClinicalTrials.gov number, NCT01704755.). Treatment of chronic hepatitis C virus infection in Japan: Update on therapy and guidelines Hepatitis C virus (HCV) infection is a serious health problem leading to cirrhosis, liver failure and hepatocellular carcinoma. The recent introduction of telaprevir, which was approved in November 2011, in combination with peg-interferon and ribavirin is expected to markedly improve the eradication rate of the virus. However, side effects of triple therapy may be severe. In a phase three III clinical trial, 2250 mg of telaprevir, which is the same dosage used in clinical trials in Western countries, was given to Japanese patients. As this dosage is considered to be relatively high for Japanese patients, who typically have lower weight than patients in Western countries, reduction of telaprevir is recommended in the 2012 revision of the guidelines established by the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis published by the Ministry of Health, Labour and Welfare of Japan. Other protease inhibitors with fewer side effects are now in clinical trials in Japan. Alternatively, treatment of patients with combination of direct acting antivirals without interferon has been reported. In this review we summarize current treatment options in Japan and discuss how we treat patients with chronic HCV infection. Inaugural Article: A comparison of the molecular clock of hepatitis C virus in the United States and Japan predicts that hepatocellular carcinoma incidence in the United States will increase over the next two decades The prevalence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is considerably lower in the U.S. than in Japan. To elucidate this difference, we determined the time origin of the HCV epidemic in each country by using molecularly clocked long-term serial samples obtained from HCV carriers of genotypes 1a and 1b. The molecular clock estimated that HCV genotype 1 first appeared in Japan in around 1882, whereas emergence in the U.S. was delayed until around 1910. In addition, by statistical analysis using coalescent theory, the major spread time for HCV infection in Japan occurred in the 1930s, whereas widespread dissemination of HCV in the U.S. occurred in the 1960s. These estimates of viral spread time are consistent with epidemiologic observations and predict that the burden of HCC in the U.S. will increase in the next two to three decades, possibly to equal that currently experienced in Japan. Pharmacokinetic-Pharmacodynamic Modeling and Simulation The Art of Modeling.- Linear Models and Regression.- Nonlinear Models and Regression.- Variance Models, Weighting, and Transformations.- Case Studies in Linear and Nonlinear Modeling.- Linear Mixed Effects Models.- Nonlinear Mixed Effects Models: Theory.- Nonlinear Mixed Effects Models: Practical Issues.- Nonlinear Mixed Effects Models: Case Studies.- Bayesian Modeling.- Generalized Linear Models and Its Extensions.- Principles of Simulation.- Appendix.- Index Dose- and Formulation-Dependent Non-Linear Pharmacokinetic Model of Paritaprevir, a Protease Inhibitor for the Treatment of Hepatitis C Virus Infection: Combined Analysis from 12 Phase I Studies Amit Khatri Background and objectives: Paritaprevir is a direct-acting antiviral agent that is a component of approved multidrug regimens used in the treatment of hepatitis C virus (HCV) infection. A population pharmacokinetic model for paritaprevir was developed using data from formulation, bioavailability, and drug-drug interaction studies that evaluated the pharmacokinetics of paritaprevir (coadministered with ritonavir to enhance exposure) with or without ombitasvir and/or dasabuvir at different paritaprevir dose levels. Methods: A non-linear mixed-effects modeling approach was applied to data from 12 phase I, single- and multiple-dose studies that enrolled a total of 369 healthy volunteers. Age, sex, race, ethnicity, body weight, body surface area, body mass index, and baseline creatinine clearance were evaluated as covariates during model development. In addition, the influences of dose, formulation, and concomitant medications (e.g. ombitasvir and dasabuvir) on paritaprevir bioavailability were included in the model. Results: A two-compartment model with first-order absorption and elimination optimally described paritaprevir plasma concentration-time data. Paritaprevir bioavailability was formulation- and dose-dependent, and increased supraproportionally. The accumulation of paritaprevir was 1.57-fold on repeated dosing compared with the first dose. Coadministration of dasabuvir increased paritaprevir bioavailability by 59 %; however, ombitasvir coadministration did not affect the pharmacokinetic profile of paritaprevir. No subject-specific covariate influenced the paritaprevir pharmacokinetics. The pharmacokinetic model was robust in bootstrap evaluations and was consistent with observed data based on diagnostic goodness-of-fit plots and visual predictive checks. Conclusion: The complex pharmacokinetics of paritaprevir were well described by the model, which can be used as a basis for clinical trial dosing and further evaluations in patients with HCV. hu Beibei Rajeev Menon Paritaprevir (administered with low-dose ritonavir), ombitasvir, and dasabuvir are direct-acting antiviral agents administered as combination regimens for the treatment of chronic hepatitis C virus infection. Drug-drug interactions between 2D (ombitasvir/paritaprevir/ritonavir) or 3D (ombitasvir/paritaprevir/ritonavir and dasabuvir) regimens and omeprazole, a CYP2C19 substrate and acid-reducing agent, were evaluated in 24 healthy volunteers. Subjects received omeprazole (40 mg once daily) on day 1 and days 20-24 and the 2D or 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily ± dasabuvir 250 mg twice daily) on days 6-24. Compared with omeprazole alone, coadministration with the 2D or 3D regimen decreased omeprazole geometric mean Cmax and AUCt values by 40% to 50%. Ombitasvir, dasabuvir, and ritonavir mean exposures showed <10% change, and paritaprevir mean exposures showed <20% change when the 2D or 3D regimen was administered with omeprazole compared with administration without omeprazole. Although no a priori dose adjustment is needed, a higher omeprazole dose should be considered if clinically indicated when coadministered with the 2D or 3D regimen. No dose adjustment is required for the 2D or 3D regimen when administered with omeprazole, other acid-reducing agents, or CYP2C19 inhibitors. Viekira Pak (Ombitasvir, Paritaprevir, and Ritonavir Tablets; Dasabuvir Tablets): All-Oral Fixed Combination Approved for Genotype 1 Chronic Hepatitis C Infection P0820 : Pharmacokinetics of paritaprevir, ombitasvir, dasabuvir, ritonavir and ribavirin in subjects with HCV genotype 1 infection in phase 3 studies J HEPATOL	https://www.researchgate.net/publication/304065904_Population_Pharmacokinetics_of_Paritaprevir_Ombitasvir_and_Ritonavir_in_Japanese_Patients_with_Hepatitis_C_Virus_Genotype_1b_Infection
SPENCER v. STATE \| 466 S.W.2d 749 \| Tex. Crim. App. \| Judgment \| Law \| CaseMine Get free access to the complete judgment in SPENCER v. STATE on CaseMine. SPENCER v. STATE Court of Criminal Appeals of Texas. Jun 2, 1971 SPENCER v. STATE 466 S.W.2d 749 Case Information CITATION CODES 466 S.W.2d 749 DOCKET NO. No. 43497. ATTORNEY(S) Charles W. Tessmer, Ronald L. Goranson, Dallas, for appellant. Henry Wade, Dist. Atty., John B. Tolle, Harry J. Schulz, Jr., W. T. Westmoreland, Jr., and Edgar A. Mason, Asst. Dist. Attys., Dallas, and Jim D. Vollers, State's Atty., Austin, for the State. ACTS No Acts See more information ... Important Paras Elizondo v. State, 130 Tex.Crim. R., 94 S.W.2d 457, 458 ; Fowler v. State, 171 Tex.Crim. R., 352 S.W.2d 838 ; Chatterfield v. State, Tex.Cr.App., 436 S.W.2d 146 . Go to No objection to the charge was made at the trial court, and no requested charge was submitted. Under Art. 36.14 and 36.15, V.A.C.C.P., no error is shown. Martinez v. State, Tex.Cr.App., 448 S.W.2d 488 ; Burleson v. State, Tex.Cr.App., 449 S.W.2d 252 . Go to The trial court should determine whether the courtroom identification is tainted or is of independent origin. Here, the trial court properly held a hearing to determine the question, but it failed to enter written findings or state into the record the reason for admitting the testimony. See: Martinez v. State, supra. We adhere to the rule that the court should make findings but in the present case there was no request or objection to the failure to do so. The record contains sufficient evidence for the court to conclude as he no doubt did, that the in-court identification was not tainted. Go to In this case, the record indicates that the trial court afforded the appellant a fair hearing on the matter, and after hearing the evidence, held that the identification was admissible. Roberts gave testimony that he could positively identify the appellant based on his observations of July, 1968, and being an experienced agent knew he would be called on at a later date to identify the person from whom he made the purchase. He had seen the appellant on three successive days. There was no abuse of discretion for the court to hold that the in-court identification was not tainted. See: Smith v. State, Tex.Cr.App., 459 S.W.2d 642 ; Lucas v. State, Tex.Cr.App., 444 S.W.2d 638 . Go to At the hearing, the burden is upon the prosecution to establish by 'clear and convincing proof' that the testimony is not the fruit of the earlier identification made in the absence of counsel or intelligent waiver of counsel. By 'clear and convincing' is meant 'so clear as to leave no substantial doubt' and 'sufficiently strong to command the unhesitating assent of every reasonable mind.' Martinez v. State, supra; In re Jost (1953), 117 Cal.App.2d 379, 256 P.2d 71 . Go to Appellant's third ground of error complains of the evidence that the appellant offered to sell Roberts some LSD. The offer to sell both drugs was part of the same transaction, and all of the facts and circumstances of the commission of the offense are admissible. Dillard v. State, Tex.Cr.App., 434 S.W.2d 126 ; Lassere v. State, Tex.Cr.App., 458 S.W.2d 81 . Go to From this testimony, it would not be an abuse of discretion for the trial judge to find that the visits were made solely to seek the appellant's help in apprehending narcotics dealers and not for the purpose of identifying the appellant. Since Roberts, as a State's witness, did view the appellant, his visits to the appellant in jail necessarily constituted a pre-trial identification without counsel as contemplated by Wade, Gilbert, and Martinez, and a determination as to whether the identification was tainted was clearly necessary. Nevertheless, we must keep in mind that the rationale of Wade and Gilbert was that a witness to a crime may be unduly influenced by an identification procedure which unfairly suggests that a particular person is the one the witness is trying to identify. Because it is the suggestiveness that is crucial, it is relevant for the court to consider that the witness is a trained law enforcement officer, experienced in making identifications, and who first comes in contact with the accused for the sole purpose of watching and observing him in order to be able to accurately identify him in court. Under those circumstances, the Wade-Gilbert proscription against undue suggestiveness is more easily satisfied than when the witness is a victim of a crime of violence, or a bystander untrained and inexperienced in making identifications, and who only observes the accused for a short time and under stress. The fact that the improper viewing of the accused was made for a legitimate purpose other than identification is also a factor for the court's consideration where the witness is a law enforcement officer with Roberts' qualifications and who first came in contact with the accused for the sole purpose of later identifying him. Go to The fourth ground refers to these remarks on the State's opening argument: 'Ladies and Gentlemen, The State has proved its case. We are entitled and Dallas County is entitled to a verdict of guilty.' This statement amounts to a plea for a conviction; there was no mention of public opinion or what the people of Dallas County want or expect the jury to do. Cox v. State, 157 Tex.Crim. R., 247 S.W.2d 262 ; and Pennington v. State, 171 Tex.Crim. R., 345 S.W.2d 527 , are clearly distinguishable because of this, and any comparison with those cases is without merit. Go to SPENCER v. STATE OPINION ROBERTS, Judge. This is an appeal from a conviction for sale of marihuana; the jury assessed the punishment at 50 years. Sam J. Roberts, a special agent of the Bureau of Narcotics and Dangerous Drugs, testified outside the presence of the jury, in a hearing to determine the admissibility of his in-court identification of appellant, that on July 3, 1968, he met the appellant, who identified himself to Roberts by the name of 'Chuck.' He further testified that on that date he purchased marihuana from the appellant and that since that date he had seen the appellant in the Dallas County Jail in a one to one confrontation with no attorney present, but that his identification was based solely on having seen the appellant on July 3, 1968, and that he would still be able to identify the appellant had he not seen him in the Dallas County Jail. The sale was made in Lee Park in Dallas. At that time, he described the appellant as having a moustache, a goatee, and long hair which was not long enough to hang down on his shoulders. He saw the appellant in the jail on two different nights in July of 1969. On one of those visits, the appellant signed a waiver of constitutional rights, and Roberts tried to persuade him to become an informer. The appellant moved that Roberts' testimony be suppressed on the grounds that his identification was influenced by the jail visits which did not meet the requirements of United States v. Wade,388 U.S. 218,87 S.Ct. 1926,18 L.Ed.2d 1149. The court then denied the motion to suppress. The jury was then returned to the courtroom and Roberts testified that he had been a narcotics agent for seven years. In response to a prosecution question as to why he was wearing sun glasses, he stated that his left eye had been 'severely injured' in another narcotics raid in February, 1969. On July 2, 1968, he went to Lee Park and saw the appellant, who had longer hair thanhe now had and also had a moustache and a goatee. Roberts testified that the appellant told him that in a few hours he would pick up a pound of marihuana and some LSD. They made an agreement for Roberts to purchase 10 tablets of LSD at $7 a tablet and one or two 'lids' of marihuana. The next day, July 3, Roberts purchased two 'lids' from 'Chuck' for $30, while they drove around the block in a yellow, 1958 Volkswagen. The two bags of marihuana were then introduced into evidence. Prior to June 1, 1969, Roberts had never seen the appellant without the long hair, moustache, and goatee. Roberts further testified that he had made approximately 800 buys of marihuana during the last seven years. Also, he traced the yellow Volkswagen and it was owned by Randy Thornton. A chemist with the Dallas Regional Laboratory of the Bureau of Narcotics and Dangerous Drugs testified that he had analyzed the contents of the two bags given him by Roberts and found that the substance was marihuana. The bags contained 32.7 grams, which could make from 50 to 150 marihuana cigarettes. James Williams, another agent for the Federal Bureau of Narcotics and Dangerous Drugs, observed the incident, saw a person drive up in a yellow Volkswagen, and identified the appellant as that person who had longer hair, a moustache, and a goatee. Williams had never seen the appellant shaven and with short hair until the day of trial, but had seen pictures of him. On re-direct examination, Williams testified, 'I would say he resembles him greatly.' The appellant took the stand in his own behalf and testified that he was 22 years old, was working as a gravedigger in Smithfield, and had quit school in the tenth grade to enlist in the Navy. He denied that he sold or offered to sell either marihuana or LSD to Roberts, denied that he was ever paid $30 for either marihuana or LSD, and denied that he ever saw Roberts. He further testified that he did not know Randy Thornton, had never driven a yellow Volkswagen, and had never been in a Volkswagen with Roberts. He admitted that in July of 1968, he had longer hair, a moustache, and a goatee. He also testified that he had never seen the type of substance contained in the two bags before. Appellant's first ground of error is that Roberts' in-court identification was inadmissible because it was tainted by unlawful pre-trial identification. The cases of United States v. Wade,388 U.S. 218,87 S.Ct. 1926,18 L.Ed.2d 1149, and Gilbert v. California,388 U.S. 263,87 S.Ct. 1951,18 L.Ed.2d 1178, 'were fashioned to deter law enforcement authorities from exhibiting an accused to witnesses prior to trial for identification purposes without notice to and in the absence of counsel absent an intelligent waiver by the accused.' Martinez v. State, Tex.Cr.App.,437 S.W.2d 842. If, as was done in this case, the accused is subjected to a pre-trial identification process in the absence of counsel, 'the in-court identification is not admissible at all unless the prosecution can establish by clear and convincing proof that the testimony is not the fruit of the earlier identification made in the absence of the accused's counsel.' Martinez v. State, supra. Put another way, these cases mean that the in-court identification 'is not to be received into evidence without first determining that it was not tainted by the illegal lineup or pre-trial identification procedure but was of independent origin.' Martinez v. State, supra; Gilbert v. California, supra. The trial court should determine whether the courtroom identification is tainted or is of independent origin. Here, the trial court properly held a hearing to determine the question, but it failed to enter written findings or state into the record the reason for admitting the testimony. See: Martinez v. State, supra. We adhere to the rule that the court should make findings but in the present case there was no request or objectionto the failure to do so. The record contains sufficient evidence for the court to conclude as he no doubt did, that the in-court identification was not tainted. At the hearing, the burden is upon the prosecution to establish by 'clear and convincing proof' that the testimony is not the fruit of the earlier identification made in the absence of counsel or intelligent waiver of counsel. By 'clear and convincing' is meant 'so clear as to leave no substantial doubt' and 'sufficiently strong to command the unhesitating assent of every reasonable mind.' Martinez v. State, supra; In re Jost (1953),117 Cal.App.2d 379,256 P.2d 71. The waiver alluded to is not in the record and therefore not reviewable by this Court. The appellant argues that Roberts' visits to Spencer were made for the purpose of allowing Roberts to identify Spencer, since out of several Federal Narcotics Officers in Dallas County, it was he who went to the jail to question Spencer. Some of the relevant testimony was as follows: "Q I will ask you, at a time after that, that is the date of July the 3rd, 1968, if you had an occasion to see him in the Dallas County Jail? "A Since July the 3rd I have seen him in the County Jail. "Q Had you not seen him in the County Jail, would you be able to identify him in Court today as one and the same person that you observed on July the 3rd of 1968 that sold to you a narcotic drug? "A Yes, sir. "Q And your identification is made solely on having seen him on the date of July the 3rd of 1968 and is not based on having seen him since nor any other reason, is that correct? "A Yes, sir. "A I asked him if he would cooperate with us on trying to get some sources of narcotics. "Q And by cooperation, just what did you mean? "A I meant by his giving us names of people who were buying — dealers that he was aware of and so on so we could take it from there and try and develop cases against them. 'Q * * * Did you or did you not seek to make an informer of my client? "A I sought to get some cooperative information from him. "Q That was in the nature of information, wasn't it? "A Yes, sir. "Q That would make him an informer, wouldn't it? "A Yes, sir. "Q Would you explain to us the duties of an undercover Federal Narcotics Officer? From this testimony, it would not be an abuse of discretion for the trial judge to find that the visits were made solely to seek the appellant's help in apprehending narcotics dealers and not for the purpose of identifying the appellant. Since Roberts, as a State's witness, did view the appellant,his visits to the appellant in jail necessarily constituted a pre-trial identification without counsel as contemplated by Wade, Gilbert, and Martinez, and a determination as to whether the identification was tainted was clearly necessary. Nevertheless, we must keep in mind that the rationale of Wade and Gilbert was that a witness to a crime may be unduly influenced by an identification procedure which unfairly suggests that a particular person is the one the witness is trying to identify. Because it is the suggestiveness that is crucial, it is relevant for the court to consider that the witness is a trained law enforcement officer, experienced in making identifications, and who first comes in contact with the accused for the sole purpose of watching and observing him in order to be able to accurately identify him in court. Under those circumstances, the Wade-Gilbert proscription against undue suggestiveness is more easily satisfied than when the witness is a victim of a crime of violence, or a bystander untrained and inexperienced in making identifications, and who only observes the accused for a short time and under stress. The fact that the improper viewing of the accused was made for a legitimate purpose other than identification is also a factor for the court's consideration where the witness is a law enforcement officer with Roberts' qualifications and who first came in contact with the accused for the sole purpose of later identifying him. The question, then, which is presented before us, is whether the trial court abused its discretion in finding that every reasonable mind must agree that Roberts' courtroom identification was of an independent origin. In this case, the record indicates that the trial court afforded the appellant a fair hearing on the matter, and after hearing the evidence, held that the identification was admissible. Roberts gave testimony that he could positively identify the appellant based on his observations of July, 1968, and being an experienced agent knew he would be called on at a later date to identify the person from whom he made the purchase. He had seen the appellant on three successive days. There was no abuse of discretion for the court to hold that the in-court identification was not tainted. See: Smith v. State, Tex.Cr.App.,459 S.W.2d 642; Lucas v. State, Tex.Cr.App.,444 S.W.2d 638. Appellant's first ground of error is overruled. Appellant's second ground of error complains of the trial court's refusal to grant a mistrial when Roberts stated the cause of the injury to his eye. This testimony was as follows: "Q Mr. Roberts, I notice you're wearing sun glasses there on the witness stand. Would you tell us the reason for that, please? "A Yes, sir. My left eye was severely injured in a narcotics raid in February. "Q That was here in Texas? "A Yes, sir. "MR.GREEN: Your Honor, I'm going to object to this and make a Motion for a new trial — I mean a mistrial at this time. "THE COURT: Sustained. Disregard about the injury. Overruled as to the mistrial.' Appellant cites several casesin which this Court held that irrelevant testimony, the only effect of which was to inflame the minds of the jury, and which linked the defendant to the inflammatory testimony, was prejudicial. In this case, however, there was no connection made between the appellantand the challenged testimony. On the contrary, it was perfectly clear that the appellant had nothing to do with that incident, and the admonition to the jury cured any error presented. The rule, as stated in White v. State, Tex.Cr.App.,444 S.W.2d 921, is: 'An error in asking an improper question or in admitting improper testimony may be generally cured or rendered harmless by a withdrawal of such testimony and an instruction to disregard the same except in extreme cases where it appears that the question or evidence is clearly calculated to inflame the minds of the jury and is of such character as to suggest the impossibility of withdrawing the impression produced on their minds.' The question and answer here is not that type of 'extreme case,' and appellant received adequate relief from the trial court. Elizondo v. State, 130 Tex.Crim. R., 94 S.W.2d 457, 458 ; Fowler v. State, 171 Tex.Crim. R., 352 S.W.2d 838 ; Chatterfield v. State, Tex.Cr.App., 436 S.W.2d 146 . The appellant's second ground of error is overruled. Appellant's third ground of error complains of the evidence that the appellant offered to sell Roberts some LSD. The offer to sell both drugs was part of the same transaction, and all of the facts and circumstances of the commission of the offense are admissible. Dillard v. State, Tex.Cr.App.,434 S.W.2d 126; Lassere v. State, Tex.Cr.App.,458 S.W.2d 81. Appellant's fourth through ninth grounds of error concern the prosecutor's arguments. The fourth ground refers to these remarks on the State's opening argument: 'Ladies and Gentlemen, The State has proved its case. We are entitled and Dallas County is entitled to a verdict of guilty.' This statement amounts to a plea for a conviction; there was no mention of public opinion or what the people of Dallas County want or expect the jury to do. Cox v. State, 157 Tex.Crim. R.,247 S.W.2d 262; and Pennington v. State, 171 Tex.Crim. R.,345 S.W.2d 527, are clearly distinguishable because of this, and any comparison with those cases is without merit. The fifth ground refers to the statement: 'If you want justice done in your county, you can say so by your verdict * * ' This injects no new fact into the case. The seventh ground complains of the following: "MR. GREEN: I object to that remark, 'If you want to do justice for your County.' I believe that's reversible error and ask for a mistrial. "THE COURT: Overrule you on both of them. "MR. ERWIN: Maybe he doesn't want justice done. The remark, though improper, does not present such error as would harm the appellant. The sixth ground refers to the following portion of the State's final argument: "Ladies and gentlemen, when you see a person three days running and that is a person you are going to pinpoint your identification of because you know maybe not the next week because you can't arrest him right then — it might be months before you can clear up enough of it to where you could go ahead and round up all the people involved, but you know that you're going to look at that man close enough to be able to identify him whether he has got a moustache or whether he's got a goatee. Mr. Green tried to make it even better. He wanted to put him in sunglasses. Mr. Green would have had him out there with a sack over his head if he could have. That's not the case.' The appellant's objection was sustained, but the court overruled the motion formistrial. This was not a personal attack on the defense counsel. The court's sustaining of the request to have the jury disregard the statement cured any error. The eighth ground of error concerns the following portion of the State's final argument: " * * Mr. Green isn't satisfied with the way the chemist testified. The man only had what, thirteen years of experience. I'm sure if we could have have brought you a ninety year old chemist with sixty years of experience Mr. Green would have liked it better.' This error, if any, was clearly harmless. The ninth ground of error complains of the following argument: "* * * Now, we talk about probation and whether or not a person deserves it, because the law says it's your discretion. Well, it seems amazing that a man that's been on the earth for twenty-two years and who has lived in a city the size of Dallas, Texas with over a million people, it seems amazing that not one person could mount that witness stand and give you one reason to probate this man. Have you heard from one person to tell you that he's worth it? No. Not family, not friends, not minister or preacher, or whatever have you, because he's not worth it.' Art. 37.07, of the Vernon's Ann. Code of Criminal Procedure provides that at the punishment stage of the trial, 'evidence may be offered by the State and the defendant as to the prior criminal record of the defendant, his general reputation and his character.' The prosecutor's argument, then, was a fair comment on the evidence adduced at the punishment stage of the trial. Appellant's tenth ground of error alleges that it was fundamental error for the court not to submit the appellant's 'defense of mistaken identity' to the jury in the court's charge. No objection to the charge was made at the trial court, and no requested charge was submitted. Under Art. 36.14 and 36.15, V.A.C.C.P., no error is shown. Martinez v. State, Tex.Cr.App.,448 S.W.2d 488; Burleson v. State, Tex.Cr.App.,449 S.W.2d 252. Appellant's tenth ground of error is overruled. There being no reversible error, the judgment is affirmed.	https://www.casemine.com/judgement/us/5914c75fadd7b049347e224b
Materials \| Free Full-Text \| Evaluation of New Hollow Sleeve Composites for Direct Post-Core Construction The preset shape and diameter of a prefabricated FRC post rarely follows the anatomy of the root canal. To solve this problem, a new hollow sleeve composite (HSC) system for post-core construction was developed and characterized. A woven fiber was impregnated with two types of resins: Bis-GMA or PMMA, and rolled into cylinders with outer diameter of 2 mm and two different inner diameters, namely 1.2 or 1.5 mm. The commercial i-TFC system was used as a control. Dual-cure resin composite was injected into these sleeves. Additionally, conventional solid fiber post was used as the inner part of the sleeve. The three-point bending test was used to measure the mechanical properties of the specimens and the fracture surface was examined using an electron microscope (SEM). The HSC (1.5 mm, Bis-GMA) revealed a statistically similar flexural modulus but higher flexural strength (437 MPa) compared to i-TFC (239 MPa; ANOVA, p & lt; 0.05). When a fiber post was added inside, all values had a tendency to increase. After hydrothermal accelerated aging, the majority of specimens showed a significant (p & lt; 0.05) decrease in flexural strength and modulus. SEM fracture analysis confirmed that the delamination occurred at the interface between the outer and inner materials. The HSC system provided flexibility but still high mechanical values compared to the commercial system. Thus, this system might offer an alternative practical option for direct post-core construction. Evaluation of New Hollow Sleeve Composites for Direct Post-Core Construction Chiaki Kitamura 3 , Pekka K. Vallittu 1,4 and Lippo V. Lassila 1 1 Department of Biomaterials Science and Turku Clinical Biomaterial Center—TCBC, Institute of Dentistry, University of Turku, 20500 Turku, Finland 2 Division of Promoting Learning Design Education, Kyushu Dental University, Fukuoka 803-8580, Japan 3 Division of Endodontics and Restorative Dentistry, Kyushu Dental University, Fukuoka 803-8580, Japan 4 City of Turku Welfare Division, Oral Health Care, 20101 Turku, Finland * Author to whom correspondence should be addressed. Materials 2021 , 14 (23), 7397; https://doi.org/10.3390/ma14237397 Received: 22 October 2021 / Revised: 26 November 2021 / Accepted: 29 November 2021 / Published: 2 December 2021 (This article belongs to the Special Issue Advanced Restorative Dental Composite Resins: Research and Development ) Abstract : p < 0.05). When a fiber post was added inside, all values had a tendency to increase. After hydrothermal accelerated aging, the majority of specimens showed a significant ( p < 0.05) decrease in flexural strength and modulus. SEM fracture analysis confirmed that the delamination occurred at the interface between the outer and inner materials. The HSC system provided flexibility but still high mechanical values compared to the commercial system. Thus, this system might offer an alternative practical option for direct post-core construction. Keywords: fiber post ; core construction ; hollow fiber ; flexural properties 1. Introduction Endodontically treated teeth (ETT) with a significant coronal loss of dentin may need additional support to retain coronal restoration. Nowadays, the use of prefabricated fiber-reinforced composite (FRC) posts is recommended mainly in cases of severe loss of remaining coronal tooth structure to promote the retention of the final restoration and to optimize the biomechanical behavior of the remaining tooth structure [ 1 , 2 ]. There is wide variation between FRC posts in respect to fiber types, fiber orientations, fiber surface treatments, and methods of incorporating the fibers into the resin matrix [ 3 ]. Glass FRC posts are the most widely used reinforcing fibers with high tensile strength and good bonding to the resin matrix [ 4 ]. Despite the favorable biomechanical behavior of prefabricated glass FRC posts, there has been discussion about the shortcomings as well [ 2 , 5 , 6 ]. The preset shape and diameter of a prefabricated FRC post rarely follows the anatomy of the root canal. Consequently, when inserting a prefabricated FRC post, a big space will be filled with resin cement coronally and a needless amount of dentin may have to be removed apically. Additionally, the inadequate bonding ability of a cross-linked prefabricated FRC post to resin cements, composite core materials, and root canal dentine is emphasized [ 7 ]. With time, a poor bonding between an FRC post and resin cement may result in marginal breakdown and further secondary caries. Thus, some researchers consider that conventional post-core systems especially for large and flared root canals are an inefficient construction method [ 2 , 5 , 7 , 8 ]. To strengthen large root canals, additional auxiliary fiber posts were used to support the primary fiber post [ 9 , 10 ]. Keeping in mind that the endodontic canal is often a flared form and even if auxiliary posts are used, the problem of resin space in the cervical region cannot be completely solved. However, the best way to restore ETT has long been and still is a subject of debate. The i-TFC system (Sun Medical Co., Ltd., Moriyama, Japan) is one of the newly developed fiber post systems for wide and flared root canal. This system consists of a fiber post and a fiber hollow sleeve [ 11 , 12 , 13 ]. When fiber hollow sleeve composite (HSC) system for post-core construction is developed, fiber orientation and design are needed to be carefully studied. The i-TFC fiber sleeve system uses a 20-degree braided fiber structure. Fiber orientation (direction) influences the mechanical properties and reinforcing efficiency (Krenchel’s factor) of the FRC structure [ 14 , 15 ]. Continuous unidirectional fibers, such as those in most prefabricated posts, provide strength, stiffness, and anisotropic mechanical strength to the composite in the direction of the fibers, thus they are suitable for applications in which the direction of the stresses is known. Furthermore, continuous bidirectional (woven) fibers have reinforcing fibers in two directions, thus they have a reinforcing effect equally in two directions [ 14 , 15 ]. Taking into account the positive effect of woven fiber reinforcement and negative side effects of prefabricated unidirectional FRC posts, the question arises: could we have another fiber reinforcement option for post-core construction to restore ETT teeth? To our best knowledge, very little research exists in this field. Therefore, the goal of the current research study was to develop a novel HSC system using woven fiber sheets, which can be molded into any shape, and to investigate its mechanical performance in comparison with the commercial i-TFC system. Furthermore, the impact of different impregnation monomers, diameters, and hydrothermal accelerated aging and filling/inner materials on the mechanical performance of the experimental HSC was evaluated. 2. Materials and Methods Table 1 lists the materials used as well as information on their manufacturing and composition. 2.1. Preparation of HSC System Very thin glass fiber weaves or cylindrical braided fibers were impregnated with either Bis-GMA/TEGDMA monomers to form the hollow sleeve. Two different diameters (1.2 mm and 1.5 mm) of stainless-steel rods were used as a mold. Glass fibers were wrapped around rods (16 mm in length) to form hollow sleeves with an outer diameter of 2 mm. The resin matrix was light-cured by a hand-light curing device for 20 s (Elipar S10, 3M ESPE, St. Paul, MN, USA) with an irradiance of 1200 mW/cm 2 . After the polymerization of the fiber sleeve, the hollow sleeve was filled with different composites ( Figure 1 ). Gradia Core was injected and cured into the hollow space. The MI post was inserted into the hollow space and bonded with Gradia Core. E-glass was inserted into the hollow space and bonded with Bis-GMA. All prepared bars were additionally polymerized for 20 s using a hand-light curing device. As a control, the commercial i-TFC glass system was used with the same outer diameter of 2 mm. The i-TFC system consisted of a hollow sleeve filled with a 1.5 mm i-TFC fiber post. We inserted the fiber post into the i-TFC sleeve with i-TFC resin cement, followed by light curing for 20 s. A total of 108 specimens were prepared ( n = 12/group) and divided into 9 groups ( Table 2 ). Specimens per each group were then either dry stored in a desiccator (room temperature) for 24 h ( n = 6/group) or aged before testing ( n = 6/group). The specimens were aged in boiling deionized distilled water for 16 h. In order to do this, the specimens were placed in glass bottles of 40 mL distilled water and their caps were tightened. The bottles were then set in a heating oven for 16 h at 100 °C. Table 2 shows all fabricated cylindrical bar groups and study designs. 2.2. Flexural Strength and Modulus of Elasticity The three-point bending test was used to measure the mechanical properties of the specimens adapted to the ISO 10477 standard (span, 10 mm; crosshead speed, 1.0 mm/min; cross-sectional diameter of loading tip, 2 mm) [ 16 ]. All specimens were tested with a material testing machine (modelLRX, Lloyd Instruments Ltd., Fareham, UK) and the stress–strain curves were recorded with a PC-computer program (Nexygen, Lloyd Instruments Ltd., Fareham, UK) using a speed of 1.0 mm/min on a 10 mm span. The outer diameter of each specimen was measured before testing. 2.3. Microscopic Analysis After the mechanical tests, FRC bars were cut with cutting stick at the part of the broken cross-section and embedded into the acrylic resin. It was polished to #1500 and then the cross-sections of the specimens were gold coated (BAL-TEC SCD 050 Sputter Coater, Balzers, Liechtenstein) for examination using a scanning electron microscope (SEM; JSM-5500, JEOL Ltd., Tokyo, Japan). SEM analysis was performed at an operating voltage of 15 kV, spot-size of 37, and working distance of 18 mm. SEM photomicrographs were used for visual analysis of the fiber geometry and layer adaptation. In addition, FRC bars were examined by SEM perpendicular to the sleeve surface for measuring the fiber roving’s angulation to the long axis of the bar. 2.4. Statistical Analysis The resulting data were analyzed statistically using a multi-way ANOVA test, followed by one-way ANOVA and Tukey’s HSD test (α = 0.05) to illustrate the differences between the groups by SPSS version 23 (SPSS, IBM Corp., New York, NY, USA). 3. Results and Discussion We aimed to develop a new fiber system that fits to any root canal. In this study, we made a new hollow sleeve composite system by ourselves with an outer diameter of 2 mm and length of 16 mm to compare to a commercial system with the same dimensions. This method involves rolling up the woven impregnated fiber into cylinders, which can be molded into various shapes. The results of the three-point bending test (flexural strength and modulus) of the tested groups are shown in Figure 2 . Despite the type of inner/core material, when the inner diameter of the hollow sleeve was 1.5 mm and the sleeve material was woven fiber with Bis-GMA (Groups A, E, and F), the flexural strength in dry conditions was significantly higher than the other groups. Furthermore, the control group in dry conditions showed similar flexural modulus values to groups A, E, and F. Different material combinations revealed considerable variations between values. However, the presence/absence of air bubbles or wetting defects during specimen manufacturing explains the large standard variation in some groups. In addition, through observation by SEM, Figure 3 a shows the signs of crushing on the sleeve at the part of the broken cross-section. In fact, all specimens were fractured inside the sleeve or between the sleeve and the internal material. Firstly, materials were compared to specimens of the same inner diameters (Groups A and B, C and D). Fibers impregnated with Bis-GMA resin performed better than those impregnated with PMMA ( Figure 2 ). SEM examination of the cross-sections of FRC sleeves showed that delamination occurred between the outer fiber sleeve and the inner core after the test ( Figure 3 b). In addition, Figure 3 b shows that the sleeve fiber was oriented in two directions. This result suggests that the Bis-GMA resin has better adhesive ability and wettability than PMMA. Surprisingly, the groups with smaller inner diameters (1.2 mm) provided lower mechanical values than the 1.5 mm groups in all measurements (Groups A and C, B and D). One of the reasons for this is the fact that all values depend on the thickness of the inner materials. When the inner diameter was 1.5 mm and the sleeve material was woven fiber with Bis-GMA, the group had a similar flexural modulus but higher strength than i-TFC. Cylindrically braided knitted fiber had the lowest flexural modulus due to the complicated knitting pattern of the fiber net, which prevents the resin from penetrating sufficiently. SEM showed the fiber roving orientation to be 0 degrees at the woven fiber, 18 degrees at the i-TFC, and 24 degrees at the cylindrically knitted fiber ( Figure 4 ) The fiber roving orientation had an effect on these results because the smaller the axis, the larger the value of the flexural modulus and max-bending stress [ 17 ]. In the other series of experiments, where the inner materials were compared, both the E-glass or MI post groups had higher flexural strength values than i-TFC and similar flexural moduli (Groups A, E, F, and I). This result suggests that the bending strength can be changed freely by changing the inner material without changing the elastic modulus. The contemporary fiber posts available in the market are effective for the treatment of teeth in normal conditions and for most cases. However, in cases where flared root canals exist, conventional fiber post treatment may not be the optimal choice [ 12 , 18 ]. Therefore, there is room for improvement in the construction methods involving fiber posts. We proposed a new hollow sleeve composite system that follows these concepts. In addition, it is possible to adapt these systems to various shapes and sizes. In this study, we were able to create a system with various physical properties by changing the inner diameter and internal material. They are easy to create and can be used not only for the anterior teeth but also for molars where the available materials may not always be suitable. In contrast, as specimens were hand-impregnated, occasionally, bubbles were observed in the SEM images of all the specimens at the interface joining the outer and inner materials, i.e., the resin and the rolled up woven fiber sheet ( Figure 3 ). A non-polymerized layer remained around the bubbled parts, making the materials mechanically weak and acting as an initiation point for crack. The next step to improve these systems would be to consider a pressurized method to fabricate specimens without air bubbles. In the current research study, FRC specimens were submitted to artificial hydrothermal accelerated aging by boiling the specimens in water. The length of boiling time was according to previous studies, which reported a decrease in the dental composite strength after the first 16 h of immersing specimens in boiling water [ 19 , 20 ]. As a result, the flexural strength and modulus were significantly decreased after hydrothermal accelerated aging ( p < 0.05), except for groups D, G, and H which showed no differences in the flexural modulus. It is important to highlight that in this research study, only a portion of the mechanical performance of hollow sleeve composites were investigated; other clinically important parameters, such as bonding at interfaces, adaptability, crown loading, light transmission, and radiopacity, were not evaluated. Further evaluation is needed to confirm the optimal clinical application. 4. Conclusions In this study, we developed a new HSC system that can be modified for various post cavities. Within the limitations of this study, the following conclusions can be drawn for HSC systems: Sleeve impregnated with Bis-GMA resin mechanically performed better than those impregnated with PMMA; The flexural strength of the HSC system depends on the type of inner material; The mechanical properties of the HSC system can be modified by changing the inner diameter of the sleeve composite; Hydrothermal accelerated aging decreased the flexural properties compared to the control condition for the majority of the tested HSC groups; and Fiber orientation has an essential effect on the mechanical performance of the HSC system. Author Contributions Conceptualization, S.Y., S.G. and L.V.L.; methodology, L.V.L. and S.Y.; software, S.Y. and S.G.; validation, L.V.L., C.K. and P.K.V.; formal analysis, S.Y. and S.G.; investigation, S.Y.; data curation, L.V.L.; writing—original draft preparation, S.Y.; writing—review and editing, S.G., C.K. and P.K.V.; visualization, P.K.V.; supervision, L.V.L.; project administration, L.V.L.; funding acquisition, P.K.V. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement The data presented in this study are available on request from the corresponding author. Conflicts of Interest There are no conflicts of interest declared by the authors. References Garoushi, S.; Tanner, J.; Keulemans, F.; Le Bell-Rönnlöf, A.-M.; Lassila, L.; Vallittu, P.K. 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Effect of Accelerated Aging on Some Mechanical Properties and Wear of Different Commercial Dental Resin Composites. Materials 2021 , 14 , 2769. [ Google Scholar ] [ CrossRef ] [ PubMed ] Figure 1. Schematic drawing of hollow sleeve composite. Figure 1. Schematic drawing of hollow sleeve composite. Figure 2. Bar graph showing mean flexural strength (MPa) and flexural modulus (GPa) with the standard deviations (SD) of the tested groups. Figure 2. Bar graph showing mean flexural strength (MPa) and flexural modulus (GPa) with the standard deviations (SD) of the tested groups. Figure 3. ( a ) SEM images (×50) of the cross-sections of fracture surfaces for various specimens. The alphabet on the upper left of each figure indicates the code of Table 2 . W: woven, G: Gradia core, M: MI post, E: E-glass, S: sleeve fiber net, i: i-TFC sleeve, and P: i-TFC post. Arrowheads indicate the crush point, while arrows indicate the void. ( b ) SEM images (×500) of the cross-sections of fracture surfaces for various specimens. Each figure is an enlarged view of the same alphabet in Figure 3 a. W: woven and G: Gradia core. Arrows indicate the delamination part between the outer fiber sleeve and the inner core. Figure 3. ( a ) SEM images (×50) of the cross-sections of fracture surfaces for various specimens. The alphabet on the upper left of each figure indicates the code of Table 2 . W: woven, G: Gradia core, M: MI post, E: E-glass, S: sleeve fiber net, i: i-TFC sleeve, and P: i-TFC post. Arrowheads indicate the crush point, while arrows indicate the void. ( b ) SEM images (×500) of the cross-sections of fracture surfaces for various specimens. Each figure is an enlarged view of the same alphabet in Figure 3 a. W: woven and G: Gradia core. Arrows indicate the delamination part between the outer fiber sleeve and the inner core. Figure 4. SEM images of the cross-sections of fracture surfaces for various specimens. Figure 4. SEM images of the cross-sections of fracture surfaces for various specimens. Table 1. Materials used in this study. Table 1. Materials used in this study. Material Manufacturer Lot. Composition Woven fiber sheet HEXCEL, Stamford, CT, USA 85M208171309z E-glass Cylindrically knitted fiber Siltex, Julbach, Germany 582 E-glass i-TFC sleeve Sun Medical Co., Ltd., Moriyama, Japan SK1 E-glass and UDMA-based matrix resin i-TFC sleeve Sun Medical Co., Ltd., Moriyama, Japan SK1 E-glass and UDMA-based matrix resin Gradia Core GC Europe, Leuven, Belgium 1804161 Alumino-silicate glass and silicon dioxide (70 wt%); UDMA and other dimethacrylate (30 wt%) MI Core Fiber Post GC Corp, Tokyo, Japan 20170728 UDMA, PMMA, and glass fibers E-glass fiber raw Owens Cornig, Houston, TX, USA 160805 E-glass UDMA, urethane dimethacrylate; PMMA, polymethylmethacrylate; wt%, weight percentage. Table 2. Designed groups for the three-point bending test (n = 6/group). Table 2. Designed groups for the three-point bending test (n = 6/group). Code Sleeve Material Resin Matrix Inner Diameter (mm) Outer Diameter (mm) Inner Material Storage A Woven BisGMA 1.5 2 Gradia Dry or aged B PMMA C BisGMA 1.2 D PMMA E BisGMA 1.5 MI-post F E-glass G Sleeve fiber net BisGMA 1.5 Gradia H PMMA I (control) i-TFC sleeve i-TFC post	https://www.mdpi.com/1996-1944/14/23/7397/htm
FIRST DIVISION [ G.R. No. 210032, April 25, 2017 ] DUTCH MOVERS, INC. CESAR LEE AND YOLANDA LEE, PETITIONERS, VS. EDILBERTO [1] LEQUIN, CHRISTOPHER R. SALVADOR, REYNALDO [2] L. SINGSING, AND RAFFY B. MASCARDO, RESPONDENTS. D E C I S I O N DEL CASTILLO, J.: Before the Court is a Petition for Review on Certiorari assailing the July 1, 2013 Decision [3] of the Court of Appeals in CA-G.R. SP No. 113774. The CA reversed and set aside the October 29, 2009 [4] and January 29, 2010 [5] Resolutions of the National Labor Relations Commission (NLRC), which in turn reversed and set aside the Order [6] dated September 4, 2009 of Labor Arbiter Lilia S. Savari (LA Savari). Also challenged is the November 13, 2013 CA Resolution. [7] which denied the Motion for Reconsideration on the assailed Decision. Factual Antecedents This case is an offshoot of the illegal dismissal Complaint [8] filed by Edilberto Lequin (Lequin), Christopher Salvador, Reynaldo Singsing, and Raffy Mascardo (respondents) against Dutch Movers, Inc. (DMI), and/or spouses Cesar Lee and Yolanda Lee (petitioners), its alleged President/Owner, and Manager respectively. In their Amended Complaint and Position Paper, [9] respondents stated that DMI, a domestic corporation engaged in hauling liquefied petroleum gas, employed Lequin as truck driver and the rest of respondents as helpers; on December 28, 2004, Cesar Lee, through the Supervisor Nazario Furio, informed them that DMI would cease its hauling operation for no reason; as such, they requested DMI to issue a formal notice regarding the matter but to no avail. Later, upon respondents' request, the DOLE NCR [10] issued a certification [11] revealing that DMI did not file any notice of business closure. Thus, respondents argued that they were illegally dismissed as their termination was without cause and only on the pretext of closure. On October 28, 2005, LA Aliman D. Mangandog dismissed [12] the case for lack of cause of action. On November 23, 2007, the NLRC reversed and set aside the LA Decision. It ruled that respondents were illegally dismissed because DMI simply placed them on standby, and no longer provide them with work. The dispositive portion of the NLRC Decision [13] reads: WHEREFORE, the Decision dated October 28, 2005 is hereby REVERSED and SET ASIDE and a new judgment is hereby rendered ordering respondent Dutch Movers, Inc. to reinstate complainants to their former positions without loss of seniority rights and other privileges. Respondent corporation is also hereby ordered to pay complainants their full backwages from the time they were illegally dismissed up to the date of their actual reinstatement and ten (10%) percent of the monetary award as for attorney's fees. SO ORDERED. [14] The NLRC Decision became final and executory on December 30, 2007. [15] And, on February 14, 2008, the NLRC issued an Entry of Judgment [16] on the case. Consequently, respondents filed a Motion for Writ of Execution. [17] Later, they submitted a Reiterating Motion for Writ of Execution with Updated Computation of Full Backwages. [18] Pending resolution of these motions, respondents filed a Manifestation and Motion to Implead [19] stating that upon investigation, they discovered that DMI no longer operates. They, nonetheless, insisted that petitioners - who managed and operated DMI, and consistently represented to respondents that they were the owners of DMI - continue to work at Toyota Alabang, which they (petitioners) also own and operate. They further averred that the Articles of Incorporation (AOI) of DMI ironically did not include petitioners as its directors or officers; and those named directors and officers were persons unknown to them. They likewise claimed that per inquiry with the SEC [20] and the DOLE, they learned that DMI did not tile any notice of business closure; and the creation and operation of DMI was attended with fraud making it convenient for petitioners to evade their legal obligations to them. Given these developments, respondents prayed that petitioners, and the officers named in DMI's AOI, which included Edgar N. Smith and Millicent C. Smith (spouses Smith), be impleaded, and be held solidarity liable with DMI in paying the judgment awards. In their Opposition to Motion to Implead, [21] spouses Smith alleged that as part of their services as lawyers, they lent their names to petitioners to assist them in incorporating DMI. Allegedly, after such undertaking, spouses Smith promptly transferred their supposed rights in DMI in favor of petitioners. Spouses Smith stressed that they never participated in the management and operations of DMI, and they were not its stockholders, directors, officers or managers at the time respondents were terminated. They further insisted that they were not afforded due process as they were not impleaded from the inception of the illegal dismissal case; and hence, thy cannot be held liable for the liabilities of DMI. On April 1, 2009, LA Savari issued an Order [22] holding petitioners liable for the judgment awards. LA Savari decreed that petitioners represented themselves to respondents as the owners of DMI; and were the ones who managed the same. She further noted that petitioners were afforded due process as they were impleaded from the beginning of this case. Later, respondents filed anew a Reiterating Motion for Writ of Execution and Approve[d) Updated Computation of Full Backwages. [23] On July 31, 2009, LA Savari issued a Writ of Execution, the pertinent portion of which reads: [24] Petitioners moved [25] to quash the Writ of Execution contending that the April 1, 2009 LA Order was void because the LA has no jurisdiction to modify the final and executory NLRC Decision and the same cannot anymore be altered or modified since there was no finding of bad faith against them. Ruling of the Labor Arbiter On September 4, 2009, LA Savari denied petitioners' Motion to Quash because it did not contain any ground that must be set forth in such motion. Thus, petitioners appealed to the NLRC. Ruling of the National Labor Relations Commission On October 29, 2009, the NLRC quashed the Writ of Execution insofar as it held petitioners liable to pay the judgment awards. The decretal portion of the NLRC Resolution reads: WHEREFORE, in view of the foregoing, the assailed Order dated September 4, 2009 denying respondents' Motion to Quash Writ is hereby REVERSED and SET ASIDE. The Writ of Execution dated July 13, [26] 2009 is hereby QUASHED insofar as it holds individual respondents Cesar Lee and Yolanda Lee liable for the judgment award against the complainants. Let the entire record of the case be forwarded to the Labor Arbiter of origin for appropriate proceedings. SO ORDERED. [27] The NLRC ruled that the Writ of Execution should only pertain to DMI since petitioners were not held liable to pay the awards under the final and executory NLRC Decision. It added that petitioners could not be sued personally for the acts of DMI because the latter had a separate and distinct personality from the persons comprising it; and, there was no showing that petitioners were stockholders or officers of DMI; or even granting that they were, they were not shown to have acted in bad faith against respondents. On January 29, 2010, the NLRC denied respondents' Motion for Reconsideration. Undaunted, respondents filed a Petition for Certiorari with the CA ascribing grave abuse of discretion against the NLRC in quashing the Writ of Execution insofar as it held petitioners liable to pay the judgment awards. Ruling of the Court of Appeals On July 1, 2013, the CA reversed and set aside the NLRC Resolutions, and accordingly affirmed the Writ of Execution impleading petitioners as party-respondents liable to answer for the judgment awards. On November 13, 2013, the CA denied the Motion for Reconsideration on the assailed Decision. Thus, petitioners filed this Petition raising the following grounds: THE HONORABLE COURT OF APPEALS COMMITTED A REVERSIBLE ERROR IN RULING THAT RESPONDENTS SHOULD BE LIABLE FOR THE JUDGMENT AWARD TO RESPONDENTS BASED ON THE FOLLOWING: I THE VALDERAMA VS. NLRC AND DAVID VS. CA ARE NOT APPLICABLE IN THE INSTANT CASE. II THERE IS NO LEGAL BASIS TO PIERCE THE VEIL OF CORPORATE FICTION OF DUTCH MOVERS, INC. [28] Petitioners argue that the circumstances in Valderrama v. National Labor Relations Commission [29] differ with those of the instant case. They explain that in Valderrama , the LA therein granted a motion for clarification. In this case, however, the LA made petitioners liable through a mere manifestation and motion to implead filed by respondents. They further stated that in Valderrama , the body of the decision pointed out the liability of the individual respondents therein while here, there was no mention in the November 23, 2007 NLRC Decision regarding petitioners' liability. As such they posit that they cannot be held liable under said NLRC Decision. In addition, petitioners claim that there is no basis to pierce the veil of corporate fiction because DMI had a separate and distinct personality from the officers comprising it. They also insist that there was no showing that the termination of respondents was attended by bad faith. In fine, petitioners argue that despite the allegation that they operated and managed the affairs of DMI, they cannot be held accountable for its liability in the absence of any showing of bad faith on their part. Respondents, on their end, counter that petitioners were identified as the ones who owned and managed DMI and therefore, they should be held liable to pay the judgment awards. They also stress that petitioners were consistently impleaded since the filing of the complaint and thus, they were given the opportunity to be heard. Issue Whether petitioners are personally liable to pay the judgment awards in favor of respondents Our Ruling The Court denies the Petition. To begin with, the Court is not a trier of facts and only questions of law may be raised in a petition under Rule 45 of the Rules of Court. This rule, nevertheless, allows certain exceptions, which include such instance where the factual findings of the CA are contrary to those of the lower court or tribunal. Considering the divergent factual findings of the CA and the NLRC in this case, the Court deems it necessary to examine, review and evaluate anew the evidence on record. [30] Moreover, after a thorough review of the records, the Court finds that contrary to petitioners' claim, Valderrama v. National Labor Relations Commission , [31] and David v. Court of Appeals [32] are applicable here. In said cases, the Court held that the principle of immutability of judgment, or the rule that once a judgment has become final and executory, the same can no longer be altered or modified and the court's duty is only to order its execution, is not absolute. One of its exceptions is when there is a supervening event occurring after the judgment becomes final and executory, which renders the decision unenforceable. [33] To note, a supervening event refers to facts that transpired after a judgment has become final and executory, or to new situation that developed after the same attained finality. Supervening events include matters that the parties were unaware of before or during trial as they were not yet existing during that time. [34] In Valderrama , the supervening event was the closure of Commodex, the company therein, after the decision became final and executory, and without any showing that it filed any proceeding for bankruptcy. The Court held that therein petitioner, the owner of Commodex, was personally liable for the judgment awards because she controlled the company. Similarly, supervening events transpired in this case after the NLRC Decision became final and executory, which rendered its execution impossible and unjust. Like in Valderrama , during the execution stage, DMI ceased its operation, and the same did not file any formal notice regarding it. Added to this, in their Opposition to the Motion to Implead, spouses Smith revealed that they only lent their names to petitioners, and they were included as incorporators just to assist the latter in forming DMI; after such undertaking, spouses Smith immediately transferred their rights in DMI to petitioners, which proved that petitioners were the ones in control of DMI, and used the same in furthering their business interests. In considering the foregoing events, the Court is not unmindful of the basic tenet that a corporation has a separate and distinct personality from its stockholders, and from other corporations it may be connected with. However, such personality may be disregarded, or the veil of corporate fiction may be pierced attaching personal liability against responsible person if the corporation's personality "is used to defeat public convenience, justify wrong, protect fraud or defend crime, or is used as a device to defeat the labor laws x x x." [35] By responsible person, we refer to an individual or entity responsible for, and who acted in bad faith in committing illegal dismissal or in violation of the Labor Code; or one who actively participated in the management of the corporation. Also, piercing the veil of corporate fiction is allowed where a corporation is a mere alter ego or a conduit of a person, or another corporation. [36] Here, the veil of corporate fiction must be pierced and accordingly, petitioners should be held personally liable for judgment awards because the peculiarity of the situation shows that they controlled DMI; they actively participated in its operation such that DMI existed not as a separate entity but only as business conduit of petitioners. As will be shown be shown below, petitioners controlled DMI by making it appear to have no mind of its own, [37] and used DMI as shield in evading legal liabilities, including payment of the judgment awards in favor of respondents. [38] First, petitioners and DMI jointly filed their Position Paper, [39] Reply, [40] and Rejoinder [41] in contesting respondents' illegal dismissal. Perplexingly, petitioners argued that they were not part of DMI and were not privy to its dealings; [42] yet, petitioners, along with DMI, collectively raised arguments on the illegal dismissal case against them. Stated differently, petitioners denied having any participation in the management and operation of DMI; however, they were aware of and disclosed the circumstances surrounding respondents' employment, and propounded arguments refuting that respondents were illegally dismissed. To note, petitioners revealed the annual compensation of respondents and their length of service; they also set up the defense that respondents were merely project employees, and were not terminated but that DMI's contract with its client was discontinued resulting in the absence of hauling projects for respondents. If only to prove that they were not part of DMI, petitioners could have revealed who operated it, and from whom they derived the information embodied in their pleadings. Such failure to reveal thus gives the Court reasons to give credence to respondents' firm stand that petitioners are no strangers to DMI, and that they were the ones who managed and operated it. Second, the declarations made by spouses Smith further bolster that petitioners and no other controlled DMI, to wit: [43] Spouses Smith categorically identified petitioners as the owners and managers of DMI. In their Motion to Quash, however, petitioners neither denied the allegation of spouses Smith nor adduced evidence to establish that they were not the owners and managers of DMI. They simply insisted that they could not be held personally liable because of the immutability of the final and executory NLRC Decision, and of the separate and distinct personality of DMI. Furthermore, the assailed CA Decision heavily relied on the declarations of spouses Smith but still petitioners did not address the matters raised by spouses Smith in the instant Petition with the Court. Indeed, despite sufficient opportunity to clarify matters and/or to refute them, petitioners simply brushed aside the allegations of spouses Smith that petitioners owned and managed DMI. Petitioners just maintain that they did not act in bad faith; that the NLRC Decision is final and executory; and that DMI has a distinct and separate personality. Hence, for failure to address, clarify, or deny the declarations of spouses Smith, the Court finds respondents' position that petitioners owned, and operated DMI with merit. Third, piercing the veil of corporate fiction is allowed, and responsible persons may be impleaded, and be held solidarily liable even after final judgment and on execution, provided that such persons deliberately used the corporate vehicle to unjustly evade the judgment obligation, or resorted to fraud, bad faith, or malice in evading their obligation. [44] In this case, petitioners were impleaded from the inception of this case. They had ample opportunity to debunk the claim that they illegally dismissed respondents, and that they should be held personally liable for having controlled DMI and actively participated in its management, and for having used it to evade legal obligations to respondents. While it is true that one's control does not by itself result in the disregard of corporate fiction; however, considering the irregularity in the incorporation of DMI, then there is sufficient basis to hold that such corporation was used for an illegal purpose, including evasion of legal duties to its employees, and as such, the piercing of the corporate veil is warranted. The act of hiding behind the cloak of corporate fiction will not be allowed in such situation where it is used to evade one's obligations, which "equitable piercing doctrine was formulated to address and prevent." [45] Clearly, petitioners should be held liable for the judgment awards as they resorted to such scheme to countermand labor laws by causing the incorporation of DMI but without any indication that they were part thereof. While such device to defeat labor laws may be deemed ingenious and imaginative, the Court will not hesitate to draw the line, and protect the right of workers to security of tenure, including ensuring that they will receive the benefits they deserve when they fall victims of illegal dismissal. [46] Finally, it appearing that respondents' reinstatement is no longer feasible by reason of the closure of DMI, then separation pay should be awarded to respondents instead. [47] WHEREFORE , the Petition is DENIED . The July 1, 2013 Decision and November 13, 2013 Resolution of the Court of Appeals in CA-G.R. SP 113774 are AFFIRMED with MODIFICATION that instead of reinstatement, Dutch Movers, Inc. and spouses Cesar Lee and Yolanda Lee are solidarily liable to pay respondents' separation pay for every year of service. SO ORDERED. Sereno, C. J., (Chairperson), Leonardo-De Castro, Perlas-Bernabe , and Caguioa, JJ. , concur. [1] Spelled in some parts of the records as Ediblerto. [2] Spelled in some parts of the records as Reynalddo. [3] CA rollo , pp. 406-422; penned by Associate Justice Leoncia Real-Dimagiba and concurred in by Associate Justices Rosmari D. Carandang and Ricardo R. Rosario. [4] Id at 51-59; penned by Commissioner Angelita A. Gacutan and concurred in by Presiding Commissioner Raul T. Aquino and Commissioner Teresita D. Castillon-Lora. [5] Id. at 33-35; penned by Presiding Commissioner Raul T. Aquino and concurred in by Commissioner Teresita D. Castillon-Lora. Commissioner Napoleon M. Menese took no part. [6] Id. at 75-76. [7] Id. at 452-453. [8] Id. at 223-224. [9] Id. at 214-221. [10] Department of Labor and Employment - National Capital Region. [11] CA rollo , p. 226. [12] Id. at 157-165. [13] Id. at 130-136; penned by Commissioner Angelita A. Gacutan and concurred in by Presiding Commissioner Raul T. Aquino and Commissioner Victoriano R. Calaycay. [14] Id. at 135-136. [15] As culled from the Writ of Execution dated July 31, 2009; id. at 84. [16] Id. at 91. [17] Id. at 127-128. [18] Id. at 124-126. [19] Id. at 105-111. [20] Securities and Exchange Commission. [21] CA rollo , pp. 98-104. [22] Id. at 95-97. [23] Id. at 87-90. [24] Id. at 85. [25] Id. at 77-82. [26] The Writ of Execution is dated July 31, 2009, not July 13, 2009; id. at 86. [27] Id. at 58-59. [28] Rollo , p. 40. [29] 326 Phil. 477 (1996). [30] Co v. Vargas , 676 Phil. 463, 470-471 (2011). [31] Supra note 29. [32] 375 Phil. 177 (1999). [33] Valderrama v. National Labor Relations Commission , supra note 29 at 483-484; David v. Court of Appeals , supra at 186-187. [34] Bani Rural Bank, Inc. v. De Guzman , 721 Phil. 84, 97 (2013). [35] Concept Builders. Inc. v. National Labor Relations Commission , 326 Phil. 955, 965 (1996). [36] Guillermo v. Uson , G.R. No. 198967, March 7, 2016. [37] Concept Builders, Inc. v. National Labor Relations Commission , supra at 965-966. [38] Guillermo v. Uson , supra. [39] CA rollo , pp. 199-205. [40] Id. at 188-193. [41] Id. at 174-178. [42] Id. at 192, 204. [43] Id. at 99-100. [44] Guillermo v. Uson , supra note 36. [45] See Sarona v. National Labor Relations Commission , 679 Phil. 394, 418-419 (2012). [46] See San Miguel Corporation v. National Labor Relations Commission , 539 Phil. 236, 249-250 (2006). [47] Caliguia v. National Labor Relations Commission , 332 Phil. 128, 142-143 (1996).	https://lawyerly.ph/juris/view/cf62b?printable=1&tryFree=1&user=fbGU2WFpmaitMVEVGZ2lBVW5xZ2RVdz09
Weak Link: Fossil Darwinius Has Its 15 Minutes - Scientific American Scientific American is the essential guide to the most awe-inspiring advances in science and technology, explaining how they change our understanding of the world and shape our lives. Evolution Weak Link: Fossil Darwinius Has Its 15 Minutes Skepticism about a fossil cast as a missing link in human ancestry On May 19 the world met a most unlikely celebrity: the fossilized carcass of a housecat-size primate that lived 47 million years ago in a rain forest in what is now Germany. The specimen, a juvenile female, represents a genus and species new to science, Darwinius masillae, although the media-savvy researchers who unveiled her were quick to give her a user-friendly nickname, Ida. And in an elaborate public-relations campaign, in which the release of a Web site, a book and a documentary on the History Channel were timed to coincide with the publication of the scientific paper describing her in PLoS ONE, Ida’s significance was described in no uncertain terms as the missing link between us humans and our primate kin. In news reports, team members called her “the eighth wonder of the world,” “the Holy Grail,” and “a Rosetta Stone.” The orchestration paid off, as Ida graced the front page of countless newspapers and made appearances on the morning (and evening) news programs. Gossip outlets, such as Peopleand Gawker, took note of her, too. And Google incorporated her image into its logo on the main search page for a day. But a number of outside experts have criticized these claims. Not only is Ida too old to reveal anything about the evolution of humans in particular (the earliest putative human ancestors are a mere seven million years old), but she may not even be particularly closely related to the so-called anthropoid branch of the primate family tree that includes monkeys, apes and us. Scientists have long debated the origin of the anthropoids, also known as the higher primates. The predominant view holds that a group of tarsierlike creatures known as the omomyiforms spawned the anthropoids. Some authorities, however, believe that anthropoids instead arose from a group of extinct primates called the adapiforms. Enter Ida. University of Oslo paleontologist Jørn H. Hurum and his team classify Ida as an adapiform and contend that she also exhibits a number of anthropoidlike characteristics, such as the spatulate shape of her incisor teeth, the absence of a so-called grooming claw on her second toe, and a partially fused lower jaw. They believe that Ida could be on the line leading to anthropoids, thus linking that group and the adapiforms. Critics concur that Ida is an adapiform, but they dispute the alleged ties to anthropoids. Robert Martin of the Field Museum in Chicago charges that some of the traits used to align Ida with the anthropoids do not in fact support such a relationship. Fusion of the lower jaw, for instance, is not present in the earliest unequivocal anthropoids, suggesting that it was not an ancestral feature of this group. Moreover, the trait has arisen independently in several lineages of mammals—including some lemurs—through convergent evolution. Martin further notes that Ida also lacks a defining feature of the anthropoids: a bony wall at the back of the eye socket. “I am utterly convinced that Darwiniushas nothing whatsoever to do with the origin of higher primates,” he declares. Adapiforms “are related to the strepsirrhine group of living primates that include lemurs from Madagascar and galagos [bush babies] and lorises from Africa and Asia,” insists paleontologist Richard F. Kay of Duke University. Claims by the authors to the contrary notwithstanding, he adds, “they are decidedly not in the direct line leading to living monkeys, apes and humans.” Kay and others believe that a primitive primate from China called Eosimiasis a better candidate ancestor of anthropoids than is Darwinius. If the detractors are right, Ida is irrelevant to the question of anthropoid—and thus, human—origins. That does not mean she is without value, though. Unlike Eosimias, which is known only from its fossilized teeth and jaws, Ida is spectacularly complete. Her entire skeleton is preserved, as well as traces of her last meal and impressions of her body contour and fur. Already Hurum’s team has deduced that Ida was good at running and leaping in the trees of her rain forest home, that she grew up relatively quickly, that she dined on leaves and fruits, and that she may have been nocturnal. Further analyses of the fossil will no doubt reveal even more about the life and times of this ancient primate. Perhaps they will also clarify her position in the family tree. Note: This article was originally printed with the title, "Weak Link."	https://www.scientificamerican.com/article/weak-link-fossil-darwinius/?error=cookies_not_supported
Small incision lenticule extraction (SMILE) history, fundamentals of a new refractive surgery technique and clinical outcomes – ScienceOpen This review summarizes the current status of the small incision lenticule extraction (SMILE) procedure. Following the early work by Sekundo et al. and Shah et al., SMILE has become increasingly popular. The accuracy of the creation of the lenticule with the VisuMax femtosecond laser (Carl Zeiss Meditec) has been verified using very high-frequency (VHF) digital ultrasound and optical coherence tomography (OCT). Visual and refractive outcomes have been shown to be similar to those achieved with laser in situ keratomileusis (LASIK), notably in a large population reported by Hjortdal, Vestergaard et al. Safety in terms of the change in corrected distance visual acuity (CDVA) has also been shown to be similar to LASIK. It was expected that there would be less postoperative dry eye after SMILE compared to LASIK because the anterior stroma is disturbed only by the small incision, meaning that the anterior corneal nerves should be less affected. A number of studies have demonstrated a lower reduction and faster recovery of corneal sensation after SMILE than LASIK. Some studies have also used confocal microscopy to demonstrate a lower decrease in subbasal nerve fiber density after SMILE than LASIK. The potential biomechanical advantages of SMILE have been modeled by Reinstein et al. based on the non-linearity of tensile strength through the stroma. Studies have reported a similar change in Ocular Response Analyzer (Reichert) parameters after SMILE and LASIK, however, these have previously been shown to be unreliable as a representation of corneal biomechanics. Retreatment options after SMILE are discussed. Tissue addition applications of the SMILE procedure are also discussed including the potential for cryo-preservation of the lenticule for later reimplantation (Mohamed-Noriega, Angunawela, Lim et al.), and a new procedure referred to as endokeratophakia in which a myopic SMILE lenticule is implanted into a hyperopic patient (Pradhan et al.). Finally, studies reporting microdistortions in Bowman’s layer and corneal wound healing responses are also described. Small incision lenticule extraction (SMILE) history, fundamentals of a new refractive surgery technique and clinical outcomes Author(s): Dan Z Reinstein , Timothy J Archer , Marine Gobbe Publication date (Electronic): 16 October 2014 Journal: Eye and Vision Publisher: BioMed Central Keywords: Small incision lenticule extraction (SMILE) , Laser in situ keratomileusis (LASIK) , Lenticule , Cap , Dry eye , Corneal sensation , Corneal innervation , Corneal biomechanics , Endokeratophakia AbstractThis review summarizes the current status of the small incision lenticule extraction (SMILE) procedure. Following the early work by Sekundo et al. and Shah et al., SMILE has become increasingly popular. The accuracy of the creation of the lenticule with the VisuMax femtosecond laser (Carl Zeiss Meditec) has been verified using very high-frequency (VHF) digital ultrasound and optical coherence tomography (OCT). Visual and refractive outcomes have been shown to be similar to those achieved with laser in situ keratomileusis (LASIK), notably in a large population reported by Hjortdal, Vestergaard et al. Safety in terms of the change in corrected distance visual acuity (CDVA) has also been shown to be similar to LASIK. It was expected that there would be less postoperative dry eye after SMILE compared to LASIK because the anterior stroma is disturbed only by the small incision, meaning that the anterior corneal nerves should be less affected. A number of studies have demonstrated a lower reduction and faster recovery of corneal sensation after SMILE than LASIK. Some studies have also used confocal microscopy to demonstrate a lower decrease in subbasal nerve fiber density after SMILE than LASIK. The potential biomechanical advantages of SMILE have been modeled by Reinstein et al. based on the non-linearity of tensile strength through the stroma. Studies have reported a similar change in Ocular Response Analyzer (Reichert) parameters after SMILE and LASIK, however, these have previously been shown to be unreliable as a representation of corneal biomechanics. Retreatment options after SMILE are discussed. Tissue addition applications of the SMILE procedure are also discussed including the potential for cryo-preservation of the lenticule for later reimplantation (Mohamed-Noriega, Angunawela, Lim et al.), and a new procedure referred to as endokeratophakia in which a myopic SMILE lenticule is implanted into a hyperopic patient (Pradhan et al.). Finally, studies reporting microdistortions in Bowman’s layer and corneal wound healing responses are also described. Additional non-English abstract (French, Francais)Cette revue résume les connaissances actuelles sur la procedure SMILE (small incision lenticule extraction). Apres les travaux préliminaires des groupes de Sekundo et al. et de Shah et al., la procedure SMILE est désormais devenue courante. Le laser femtosecond VisuMax (Carl Zeiss Meditec) permet une découpe précise du lenticule, comme cela a été vérifié par ultrasound numérique à tres haute fréquence (Artemis) et par OCT. Il a été démontré, entre autres par Hjortdal, Vestergaard, et al. dans leur etude sur une population large, que les résultats visuels et refractifs sont comparables à ceux du LASIK, et que le risque de perte de lignes d’acuité corrigée est aussi semblable à celui du LASIK. Avec SMILE, contrairement au LASIK, la partie antérieure du stroma étant seulement découpée par une incision de petite taille, les nerfs cornéens antérieurs sont moins touchés et par consequent, le taux d’yeux secs en phase post-opératoire devrait etre plus faible après SMILE qu’apres LASIK. Quelques études ont effectivement démontré que la sensation cornéenne était moins réduite après SMILE qu’après LASIK et que la récupération de la sensation cornéenne était plus rapide. Quelques études ont aussi utilisé la microscopie confocale pour prouver qu’il y avait une diminution plus faible de la densité des fibres nerveuses de la couche sub-basale après SMILE qu’apres LASIK. Au niveau biomécanique, Reinstein et al. ont proposé un modèle basé sur la non-linéarité de la force de tension du stroma, mettant en avant les avantages potentiels de SMILE. Certaines études ont comparé les paramètres mesurés par l’Ocular Response Analayzer (Reichert) et rapporté un changement similaire après SMILE ou LASIK; cependant, on sait que ces paramètres ne peuvent pas etre pris en compte pour représenter la biomécanique cornéenne. Les options de re-traitement après SMILE sont présentées, ainsi que la possibilité d’ajouter du tisuu cornéen: par example, le potential de cryo-preservation du lenticule pour une ré-implantation ultérieure (Mohamed-Noriega, Angunawela, Lim et al.), et une nouvelle procedure nommée endokératophakie dans laquelle un lenticule SMILE est implanté dans la cornée d’un oeil hypermétrope (Pradhan et al.). Pour finir, des études rapportant des micro-distortions dans la couche de Bowmans et des études sur le processus de reparation de la cornée sont décrites. Contributors Dan Z Reinstein: [email protected] Timothy J Archer: [email protected] Marine Gobbe: [email protected] Journal Journal ID (nlm-ta): Eye Vis (Lond) Journal ID (iso-abbrev): Eye Vis (Lond) Title: Eye and Vision Publisher: BioMed Central ( London ) ISSN (Electronic): 2326-0254 Publication date (Electronic): 16 October 2014 Publication date PMC-release: 16 October 2014 Publication date Collection: 2014 Volume : 1 Affiliations [ ] London Vision Clinic, 138 Harley Street, London, W1G 7LA UK [ ] Department of Ophthalmology, Columbia University Medical Center, New York, NY USA [ ] Centre Hospitalier National d’Ophtalmologie, Paris, France Article Publisher ID: 3 DOI: 10.1186/s40662-014-0003-1 PubMed ID: 26605350 SO-VID: c05f4dba-5762-4ea4-a33d-28fbaf05124e Copyright statement: © Reinstein et al.; licensee BioMed Central 2014 Categories Subject: Review Custom metadata issue-copyright-statement © The Author(s) 2014 Keywords: small incision lenticule extraction (smile) , laser in situ keratomileusis (lasik) , lenticule , cap , dry eye , corneal sensation , corneal innervation , corneal biomechanics , endokeratophakia Data availability: Keywords: small incision lenticule extraction (smile) , laser in situ keratomileusis (lasik) , lenticule , cap , dry eye , corneal sensation , corneal innervation , corneal biomechanics , endokeratophakia	https://www.scienceopen.com/document?vid=c05f4dba-5762-4ea4-a33d-28fbaf05124e
ANNEX 3 (JECFA Food Additives Series 48) SAFETY EVALUATION OF CERTAIN FOOD ADDITIVES AND CONTAMINANTS ANNEX 3 Joint FAO/WHO Expert Committee on Food AdditivesRome, 5–14 June 2001Members Dr J. Alexander, Department of Environmental Medicine, National Institute of Public Health, Torshov, Oslo, Norway Ms J. Baines, Senior Nutritionist, Australia–New Zealand Food Authority, Barton, ACT, Australia Professor J.R. Bend, Chairman, Department of Pharmacology & Toxicology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada ( Joint Rapporteur ) Dr S. M. Dagher, Professor, American University of Beirut, Beirut, Lebanon Dr D.G. Hattan, Director, Division of Health Effects Evaluation, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington DC, USA Dr Y. Kawamura, Section Chief, Division of Food Additives, National Institute of Health Sciences, Tokyo, Japan Dr A.G.A.C. Knaap, Centre for Substances and Risk Assessment, National Institute of Public Health and the Environment, Bilthoven, Netherlands Dr P.M. Kuznesof, Leader, Chemistry and Exposure Assessment Team, Division of Product Manufacture and Use, Office of Pre-market Approval, CFSAN, Food and Drug Administration, Washington DC, USA ( Joint Rapporteur ) Dr J.C. Larsen, Head, Division of Biochemical and Molecular Toxicology, Institute of Food Safety and Toxicology, Danish Veterinary and Food Administration, Søborg, Denmark Mrs I. Meyland, Senior Scientific Adviser, Institute of Food Research and Nutrition, Danish Veterinary and Food Administration, Ministry of Food, Agriculture and Fisheries, Søborg, Denmark ( Chairman ) Dr G. Pascal, Scientific Director, Human Nutrition and Food Safety, National Institute for Agricultural Research, Paris, France Dr M.V. Rao, Head of Chemistry Unit, Food & Environment Laboratory, Dubai, United Arab Emirates Dr P. Sinhaseni, Deputy Director for Research, Institute of Health Research, Chulalongkorn University, Bangkok, Thailand Professor R. Walker, Emeritus Professor of Food Science, School of Biological Sciences, University of Surrey, Guildford, Surrey, United Kingdom ( Vice-Chairman ) Mrs H. Wallin, Senior Food Control Officer, National Food Agency, Helsinki, Finland Dr B. Whitehouse, Food Regulatory Affairs, Bowdon, Cheshire, United Kingdom Secretariat Dr P.J. Abbott, Australia New Zealand Food Authority, Canberra, ACT, Australia ( WHO Temporary Adviser ) Dr A.J. Baars, National Institute of Public Health and the Environment, Bilthoven, Netherlands ( WHO Temporary Adviser ) Dr D. Benford, Food Standards Agency, London, United Kingdom ( WHO Temporary Adviser ) Dr R.A. Canady, Toxicologist, Office of Plant & Dairy Foods and Beverages, Center for Food Safety & Applied Nutrition, Food and Drug Administration, Washington, DC, USA ( WHO Temporary Adviser ) Dr C.E. Cerniglia, Director, Division of Microbiology and Chemistry, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA ( WHO Temporary Adviser ) Ms M.L. Costarrica, Senior Nutrition Officer, Food Quality Liaison Group, Food Quality and Standards Service, Food and Nutrition Division, FAO, Rome, Italy Dr K. Crump, Ruston, LA, USA ( WHO Temporary Adviser ) Dr M. DiNovi, Office of Pre-market Approval, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC, USA ( WHO Temporary Adviser ) Ms J. Eastwood, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada ( WHO Temporary Adviser ) Dr C.E. Fisher, Food Quality Liaison Group, Food Quality and Standards Service, Food and Nutrition Division, FAO, Rome, Italy ( FAO Consultant ) Dr J. Freijer, National Institute of Public Health and the Environment, Bilthoven, Netherlands ( WHO Temporary Adviser ) Dr J. Gry, Institute of Toxicology, National Food Agency of Denmark, Ministry of Food, Agriculture and Fisheries, Søborg, Denmark ( WHO Temporary Adviser ) Mr E.F.F. Hecker, Chairman, Codex Committee on Food Additives and Contaminants, Deputy Director of the Department of Veterinary and Food Policy and Environmental Affairs, Ministry of Agriculture, Nature Management and Fisheries The Hague, Netherlands ( WHO Temporary Adviser ) Dr J.L. Herrman, Scientist, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland ( WHO Joint Secretary ) Mrs E. Heseltine, Communication in Science, Lajarthe, Saint-Léon-sur-Vézère, France ( Editor ) Dr F. Kayama, Division of Environmental Immunology & Toxicology, Department of Health Science, Jichi Medical School, Tochigi, Japan ( WHO Temporary Adviser ) Dr M. Kogevinas, Associate Professor, Respiratory and Environmental Health Research Unit, Municipal Institute of Medical Research, Barcelona, Spain ( WHO Temporary Adviser ) Dr C.A. Lawrie, Food Standards Agency, London, England ( FAO Expert ) Dr R. Lorentzen, Office of Science, Center for Food Safety and Applied Nutrition, Food and Drug Administration Washington DC, USA ( WHO Temporary Adviser ) Dr M. Luetzow, Nutrition Officer, Food Quality and Standards Service, Food and Nutrition Division, FAO, Rome, Italy ( FAO Joint Secretary ) Dr R. Malisch, Chemisches und Veterinäruntersuchungsamt, Freiburg, Germany ( FAO Consultant ) Dr A. Mattia, Division of Product Policy, Office of Pre-market Approval, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington DC, USA ( WHO Temporary Adviser ) Dr G. Moy, Food Safety Programme, World Health Organization, Geneva, Switzerland Dr I.C. Munro, President, CanTox Health Sciences International, Mississauga, Ontario, Canada ( WHO Temporary Adviser ) Dr A. Nishikawa, Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan ( WHO Temporary Adviser ) Dr S.W. Page, Joint Institute of Food Safety and Applied Nutrition, Food and Drug Administration, Washington DC, USA ( WHO Temporary Adviser ) Dr J. Park, President, LabFrontier Co. Ltd, Seoul, Republic of Korea ( WHO Temporary Adviser ) Professor A.G. Renwick, Clinical Pharmacology Group, University of Southampton, Southampton, United Kingdom ( WHO Temporary Adviser ) Dr J. Rice, Chief, Unit of Carcinogen Identification and Evaluation, International Agency for Research on Cancer, Lyon, France Dr J. Schlatter, Swiss Federal Office of Public Health, Institute of Veterinary Pharmacology and Toxicology, Zürich, Switzerland ( WHO Temporary Adviser ) Professor P. Shubik, Senior Research Fellow, Green College, Oxford, England ( WHO Temporary Adviser ) Professor I.G Sipes, Department of Pharmacology & Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, USA ( WHO Temporary Adviser ) Dr G.J.A. Speijers, Head, Section on Public Health, Centre for Substances & Risk Assessment, National Institute of Public Health and Environmental Protection, Bilthoven, Netherlands ( WHO Temporary Adviser ) Dr P.J.P. Verger, Scientific Directorate on Human Nutrition and Food Safety, National Institute for Agricultural Research, Paris, France ( FAO Expert ) Dr J.D. Wilson, Senior Fellow, Center for Risk Management, Resources for the Future, Washington DC, USA (WHO Temporary Adviser) Dr M. Zeilmaker, Centre for Substances and Risk Assessment, National Institute of Public Health and the Environment, Bilthoven, Netherlands ( WHO Temporary Adviser ) Dr N.W. Zeman, Triangle Biotechnology Consulting, Chapel Hill, NC, USA ( FAO Consultant) See Also: Toxicological Abbreviations	https://inchem.org/documents/jecfa/jecmono/v48je23.htm
Legal Document: Jules, Josue Vs Jules, Tercilia \| Trellis.Law Access this legal document in Doe, Jane et al vs U.S.Bank National Association As Trustee, Sucessor In Interest To Bank Of America National Association As Succcessor By Merger To Lasalla Bank, N.A. As Trustee For Washington Mutual Mortgage on Trellis.Law. Review the document, case details, and relevant case updates to stay informed on this notable legal proceeding. Document for Jules, Josue Vs Jules, Tercilia On August 29, 2008 a Cover Letter was filed involving a dispute between U.S.Bank National Association As Trustee, Sucessor In Interest To Bank Of America National Association As Succcessor By Merger To Lasalla Bank, N.A. As Trustee For Washington Mutual Mortgage, and Doe, Jane, Doe, John, Jules, Tercilia, Jules, Josue, for Homestead Residential Foreclosure $250,000 or more in the District Court of Collier County. Preview LAW OFFICES 2 OF MARSHALL C. WATSON, PA. LAW Zid 1800 NORTH WEST 49TH STREET, SUITE #120 FORT LAUDERDALE, FLORIDA 33309 Telephone (954) 453-0365 i Facsimile (954) 771-6052 } Toll Free (800) 441-2438 50 :€l dd August S202 Honorable Presiding Judge (Collier County) Circuit Civil Judge 3315 Tamiami Trail East, Suite 204 Naples, FL 34112 RE: LASALLE BANK NA AS TRUSTEE FOR WASHINGTON MUTUAL MORTGAGE PASS-THROUGH CERTIFICATES WMALT SERIES 2006-ARS TRUST vs. JOSUE JULES AND TERCILIA JULES Case Nuiber: 08-06574 MCW File Number: 08-43570 Dear Judge: Plaintiff's Motion for Substitution of Party Plaintiff has been set for hearing on September 20, 2012 at 9:30 AM. In that connection, 1 enclose the following: X A copy of the Notice of Hearing, Motion for Substitution of Party Plaintiff and Order of Referral along, with envelopes to be mailed out to the respective parties. The original has been filed with the Clerk. Should you have any questions, or require additional information, please do not hesitate to contact this office. Resp lly, uth Je: Enclosures CC: ALL PARTIES 08-43570LASALLE BANK NA AS TRUSTEE FOR IN THE CIRCUIT COURT OF THE WASHINGTON MUTUAL MORTGAGE PASS- 20TH JUDICIAL CIRCUIT, IN AND FOR THROUGH CERTIFICATES WMALT SERIES COLLIER COUNTY, FLORIDA 2006-AR5 TRUST, CIVIL DIVISION: Plaintiff, CASE NO.: 08-06574 vs. JOSUE JULES AND TERCILIA JULES, et al, Defendants. NOTICE OF HEARING (PLAINTIFF WILL APPEAR BY TELEPHONE) PLEASE TAKE NOTICE that the above style action will be heard by the Magistrate David Friedman (Collier County) in Chambers at 3301 Tamiami Trail East, Naples FL 34112 of the Collier County Courthouse, on September 20, 2012, at 9:30 AM or as soon thereafter as counsel may be heard, upon the follgwing: “< i MOTION FOR SUBSTITUTION OF PARTY PLAINTIFF { PLEASE GOVERN YOURSELF ACCORDINGLY If you are a person with a disability who needs any accommodation in order to participgite in thi proeseding you are entitled, at no cost to you, to the provision of certain assistance. Please contact John Carter, & Administrative Services Manager, whose office is located at 3315 East Tamiami Trail, Suite 501, Naples, Florida 34112, and whose telephone number is (239) 252-8800, at least 7 days before your scheduled court appearance, or immediately upon receiving this notification if the time before the scheduled appearance is less than 7 days; if you are hearing or voice impaired, call 711. iH! CERT, that_a trye cppy of foregoing was delivered to the parties on the attached mailing list by mail this day 01 2012. Law Offices of Marshall C. Watson, P.A. Attorneys for Plaintiff 1800 NW 49th Street, Suite 120 Fort Lauderdale, Florida 33309 Telephone: (954) 453-0365 Fa il 954 <6052 y <00-44 j-2438 FL) Dd, lan Jean, Eso Florida Barfidmber: 30866 08-43570MAILING LIST Case No: 08-06574 ANTHONY P. LISTROM, ESQ. ATTORNEY FOR DEFENDANTS 877 915" AVENUE NORTH, SUITE 2 NAPLES, FL 34108 UNKNOWN TENANT(S) 3561 31ST AVENUE SW NAPLES, FL 34117 08-43570IN THE CIRCUIT COURT OF THE 20TH JUDICIAL CIRCUIT, IN AND FOR COLLIER COUNTY, FLORIDA LASALLE BANK NA AS TRUSTEE FOR WASHINGTON MUTUAL MORTGAGE PASS- THROUGH CERTIFICATES WMALT SERIES 2006-AR5 TRUST, CIVIL DIVISION Plaintiff, CASE NO.: 08-06574 vs. JOSUE JULES AND TERCILIA JULES, et al, Defendants. MOTION FOR SUBSTITUTION OF PARTY PLAINTIFF Plaintiff, by and through the undersigned counsel, respectfully requests that this Court enter an Order Substituting Party Plaintiff pursuant to Florida Rules of Civil Procedures 1.260(c), and as grounds therefore states that: On or about August 26, 2008, Plaintiff filed a complaint for foreclosure of real property in Collier County naming LASALLE BANK NA AS TRUSTEE FOR WASHINGTON MUTUAL MORTGAGE, PASS-THROUGH CERTIFICATES WMALT SERIES 2006-ARS TRUST as the party plaintiff. Bank of America National Assoication was the successor by merger to Lasalle Bank and as a result of 1. 2. the merger replaced Lasalle Bank as Trustee. 3. Bank of America National Association has resigned as Trustee and U.S. Bank National Association has been appointed to act as successor Trustee. See Notice Documents attached as Exhibip“A”. 3° 2 s 4. U.S. BANK NATIONAL ASSOCIATION AS TRUSTEE, SUCCESSOR IN INTEREST TOBAMG & OF AMERICA NATIONAL ASSOCIATION AS SUCCESSOR BY MERGER TO: LASALEE BANK NA AS TRUSTEE FOR WASHINGTON MUTUAL MORTGAGE PASS-THROUGH ae CERTIFICATES WMALT SERIES 2006-AR5 TRUST should be substituted for UASALL NRE NA AS TRUSTEE FOR WASHINGTON MUTUAL MORTGAGE PASS-THRO! = S CERTIFICATES WMALT SERIES 2006-AR5 TRUST as party plaintiff. ° ° Rg 5. No prejudice will result from the granting of this Motion. WHEREFORE, Plaintiff requests the Court for the entry of an Order substituting Plaintiff for LASALLE. BANK NA AS TRUSTEE FOR WASHINGTON MUTUAL MORTGAGE PASS-THROUGH CERTIFICATES WMALT SERIES 2006-ARS TRUST. I HEREBY CERTIFY that a true cop; foregoi as delivered to the parties on the attached mailing list by mail this _¢ 3 day of, Us 2012. f the 4 Gg Law Offices of Marshall C. Watson, P.A 1800 NW 49th Street, Suite 120 Fort Lauderdale, Florida 33309 Telephone:(954) 453-0365 Facsimile: (954) 771-6052 Toll Free: 1-800-441-2438 08-43570MAILING LIST Case No: 08-06574 ANTHONY P. LISTROM, ESQ. ATTORNEY FOR DEFENDANTS 8779157 AVENUE NORTH, SUITE 2 NAPLES, FL 34108 UNKNOWN TENANT(S) 3561 31ST AVENUE SW NAPLES, FL 34117LaSalle Global Trust Services January 2, 2009 NOTICE OF RESIGNATION To: — The parties listed on Schedule A Re: Washington Mutual Mortgage Pass-Through Certificates, WMALT. Séties “2006-ARS Trust oT - Reference is hereby made to the Pooling and Servicing Agreement, dated as of June 1, 2006 (the “Agreement”), by and among WaMu Asset Acceptance Corp., as depositor, JPMorgan Chase Bank, National Association, successor-in-interest to Washington Mutual Bank, as servicer, Christiana Bank & Trust Company, as Delaware trustee and Bank of America, N.A., successor by merger to LaSalle Bank National Association (“Bank of America”), as trustee for the Washington Mutual Mortgage Pass-Through Certificates, WMALT Series 2006-AR5. Capitalized terms used but not defined herein shall have the respective meanings assigned thereto in the Agreement. In connection with the acquisition of Countrywide Financial Corporation, by Bank of America Corporation on July 1, 2008, Bank of America hereby resigns as Trustee under the Agreement pursuant to Section 8.07 thereof, effective as of the date hereof. Further, Bank of America hereby resigns as (i) Certificate Registrar under the Agreement, (ii) Authenticating Agent pursuant to Section 8.11 of the Agreement, and (iii) Paying Agent pursuant to Section 8.12 of the Agreement, in each case, effective as of the date hereof. As Tequired by the Agreement, Bank of America will continue to perform its obligations as Trustee, Certificate Registrar, Authenticating Agent and Paying Agent under the Agreement until a successor trustee has been appointed by the Servicer. If no successor trustee shall have been appointed and shall have accepted such appointment within 30 days after the date hereof, be advised that Bank of America, as Trustee, has the right under Section 8.07 of the Agreement to petition any court of competent jurisdiction for the appointment of a successor trustee. As required by the Agreement, Bank of America will cooperate with the Servicer and any successor trustee to deliver to the successor trustee all Mortgage Files, related documents, statements and all other property held by it under the Agreement and execute and deliver such instruments and do such other things as may reasonably be required for more fully and certainly vesting and confirming in the successor trustee all of the rights, powers, duties and obligations of Bank of America as predecessor trustee. Please be advised that effective October 17, 2008 the charter of LaSalle Bank National Association was collapsed into the charter of Bank of America, N.A., with the result that LaSalle CMBS \| 114-135-16-25 135 $. LaSalie St. j Chicaga, IL 60603 Ey fLaSalle Global Trust Services Bank National Association no longer has separate legal existence, but is now part of, and known as, Bank of America, N.A. BANK OF AMERICA, N.A., successor by merger to LaSalle Bank National Association ‘. By: . Name:_Kathryn Hawkinson Title:_Vice PresidentLaSalle Global Trust Services SCHEDULE A WaMu Asset Acceptance Corp. 1301 Second Avenue, WMC 3501A Seattle, Washington 98101 Attn: WMALT 2006-AR5 JPMorgan Chase Bank, National Association (successor-in-interest to Washington Mutual Bank) 2210 Enterprise Drive Florence, South Carolina 29501 Attn: Vice President, Investor Reporting WMALT 2006-ARS Washington Mutual Bank Legal Department 1301 Second Avenue, WMC 3501 Seattle, Washington 98101 Attn: WaMu -- WMALT 2006-ARS5 Washington Mutual Mortgage Securities Corp. 1301 Second Avenue, WMC 1401 Seattle, Washington 98101 Attn: Bond Administration -- WMALT 2006-AR5 Christiana Bank & Trust Company 1314 King Street Wilmington, Delaware 19801 Attn: WMALT 2006-ARS Standard & Poor’s Ratings Services, a division of the McGraw-Hill companies, Inc. 55 Water Street New York, New York, 10041 Attn: Residential Mortgage Surveillance Group ~ WMALT 2006-AR5 Moody’s Investors Service, Inc. 7 World Trade Center 250 Greenwich Street New York, New York 10007 Attn: Monitoringme bank. - Five Star Service Guaranteed (473) Corporate Trust Services EP-MN-WS3D 60 Livingston Avenue Sl. Paul, MN $5107-2092 February 10, 2009 NOTICE To: The parties listed on Schedule A Re: Washington Mutual Mortgage Pass-Through Certificates WMALT Series 2006- ARS Trust Reference is hereby made to the Pooling and Servicing Agreement, dated as of January 1, 2006 (the “Agreement”), by and among WaMu Asset Acceptance Corp., as depositor, JPMorgan Chase Bank, National Association, acquirer, of certain assets of Washington Mutual Bank, as servicer (the “Servicer”), Christiana Bank & Trust Company, as Delaware trustee, and Bank of America, N.A., successor by merger to LaSalle Bank National Association (“Bank of America”), as trustee for the Washington Mutual Mortgage Pass-Through Certificates, WMALT Series 2006-ARS Trust. Capitalized terms used but not defined herein shall have the respective meanings assigned thereto in the Agreement. ~ Pursuant to Section 8.08 of the Agreement, notice is hereby provided that Bank of America has resigned as Trustee and the Servicer has appointed U.S. Bank National Association (“U.S. Bank”) to act as successor Trustee, pursuant to Section 8.07 of the Agreement. As successor Tnustee, U.S. Bank will make available each month the Distribution Date statement on its website, located at www.usbank.com/mbs. The address of the corporate trust office for U.S. Bank, and the new location of the Certificate Account, is: U.S. Bank National Association Corporate Trust Services One Federal Street, 3" Floor Boston, Massachusetts 02110 EX-MA-FED Telephone: (617) 603-6401 Facsimile: (617) 603-6637 Attention: WMALT 2006-AR5S ce PES TUL aly-, (Sbank “ PEF wert Five Star Service Guaranteed (635) Corporate Trust Services EP-MN-WS3D_ 60 Livingston Avenue St Paul, MN 55107-2292 Pursuant to Sections 8.11 and 8.12 of the Agreement, notice is also hereby provided that U.S. Bank, as successor Trustee, shall act as Authenticating Agent and Paying Agent, respectively, under the Agreement. This notice shal! satisfy the notice obligations of the Servicer under Sections 8.08 and 10.11(b) of the Agreement. U.S. BANK NATIONAL ASSOCIATION as Trustee By: u Who Name: Michelle Moeller Title: istant Vice Prest Assistant SOE Assi @bank. - Five Star Service Guaranteed (¢"2) Corporate Trust Services EP-MN-WS3D 60 Livingston Avenue St. Paul, MN 55107-2292 SCHEDULE A PES UL arti) Moody’s Investors Services 7 World Trade Center 250 Greenwich Street New York, New York 10007 Attn: Monitoring Standard & Poor’s, a division of The McGraw-Hill Companies, Inc. 55 Water Street New York, New York 10041 Attn: Residential Mortgage Surveillance Group — WMALT 2006-ARS JPMorgan Chase Bank, National Association 3415 Vision Drive Columbus, Ohio 43219 Attn: Diane Bentz Certificateholders SP Case Info Judge Hayes, Hugh D Track Judge’s New Case Case No. Document Filed Date August 17, 2012 Case Filing Date August 29, 2008 County Category Homestead Residential Foreclosure $250,000 or more Status Disposed Parties Sun Cny Properties Llc3rd Party Bidder U.S.Bank National Association As Trustee, Sucessor In Interest To Bank Of America National Association As Succcessor By Merger To Lasalla Bank, N.A. As Trustee For Washington Mutual MortgagePlaintiff Doe, JaneDefendant Doe, JohnDefendant Jules, TerciliaDefendant Jules, JosueDefendant Tenia Chimere HunterAttorney Anthony Peter ListromAttorneys for Plaintiffs Molly Ann HageAttorney Bruce K FayAttorney	https://trellis.law/doc/19251539/coverage/california/losangeles
SAE MOBILUS Multi Disc Wet Clutch with Oil Spatter Cooling System in Main Manual Shift Transmission for Tractors Technical Paper 2012-01-2004 ISSN: 0148-7191 , e-ISSN: 2688-3627 DOI: https://doi.org/10.4271/2012-01-2004 Published September 24, 2012 by SAE International View list of content related to the publisher(s) in United States Sector: Commercial Vehicle Content related to Commercial Vehicle Event: SAE 2012 Commercial Vehicle Engineering Congress Technical Paper presented at SAE 2012 Commercial Vehicle Engineering Congress Language: English Abstract The scope of tractor usages are widely expanding to various non-agricultural and construction/earthmoving applications like loaders, dozers etc. The tractors with manual transmission driveline subjected to such heavy duty cycles are having conventional dry type clutches in general. These types of dry clutch when operated in such heavy application generate large amount of heat within shorter period of time on the surfaces of friction discs. This increase in disc surface temperature determines not only the level of the friction but also the rate of wear and durability. Number of clutch operation per minute for this application is also increasing to meet the improved productivity requirements. Analysis shows that the rate of heat removal from the friction disc through oil flow system is higher compared to oil immersion type. In this work, an oil spatter concept is designed to provide active circulation of oil to the multi disc clutch during engaged conditions. The system is designed in such a way to cut-off the oil flow in to the clutch unit while clutch disengagement. This arrangement provides improved heat removal rate and significantly reduces the drag torque which in turn will increases the clutch life by 6 to 7 times more than that of the conventional dry clutch. A mathematical model is developed to predict the interfacial surface temperature on the friction discs during the engagement. A complimentary numerical model is also made to determine the cooling oil flow rate based on the clutch slip relation and interface temperature. The effects of drag torque and thermal properties on the performance behavior of the clutch system are investigated to facilitate the conceptual design of oil spatter wet clutch system. An experimental setup is built. The result of analytical model is validated with that of experimental setup. Authors Suresh Kumar N Works by Suresh Kumar N - Tractors and Farm Equipments Ltd. Content by authors affiliated with Tractors and Farm Equipments Ltd. S Sriraman Works by S Sriraman - Tractors and Farm Equipments Ltd. Content by authors affiliated with Tractors and Farm Equipments Ltd. Rakesh Verma Works by Rakesh Verma - Tractors and Farm Equipments Ltd. Content by authors affiliated with Tractors and Farm Equipments Ltd. Topic Manual transmissions Content related to Manual transmissions Clutches Content related to Clutches Mathematical models Content related to Mathematical models Citation N, S., Sriraman, S., and Verma, R., "Multi Disc Wet Clutch with Oil Spatter Cooling System in Main Manual Shift Transmission for Tractors," SAE Technical Paper 2012-01-2004, 2012, https://doi.org/10.4271/2012-01-2004 . Also In References Anderson, A. “Friction and Wear of Paper Type Wet Friction Elements,” SAE Technical Paper 720521 1972 10.4271/720521 Ting, L.L “Engagement behavior of Lubricated porous annular disks. Part I: Squeeze film phase-surface roughness and elastic deformation effects Wear 1975 34 2 159 172 Jen, Tien-Chen Nemecek, Daniel James “Thermal analysis of a wet-disk clutch subjected to a constant energy engagement” International journal of Heat and Mass transfer 51 2008 1757 1769 Rowson, D.M. “The Interfacial surface temperature of disc brake” The Higher petroleum Institute, tobruk (Libiya) Wear 47 1978 323 328 Kitabayashi, H. Li, C. Hiraki, H. “Analysis of the Various Factors Affecting Drag Torque in Multiple-Plate Wet Clutches,” SAE Technical Paper 2003-01-1973 2003 10.4271/2003-01-1973 Yuan, Shihua Guo, Kai Hu, Jibin Peng, Zengxiong “Study on aeration for disengaged wet clutches using a two-phase flow model” National key laboratory of vehicular transmission Beijing institute of technology Beijing, China Yuen, W.Y.D. “Heat conduction in sliding solids” International journal of heat and mass transfer 31 3 637 1988 Shaver, F.R. “Manual Transmission Clutch Systems,” SAE International Warrendale, PA 978-1-56091-984-1 1997 10.4271/AE-17 “Handbook of Reliability prediction procedures for Mechanical Equipment” Carderdockdiv January 10 2006 Product Code Document Title File Type Download 2012-01-2004 Multi Disc Wet Clutch with Oil Spatter Cooling System in Main Manual Shift Transmission for Tractors Download File Type Download File Format: .xlsx .csv Text Number of Results: Selected 25 50 100 All(upto 1000) Select Fields to Export Item Number Content Type Title Author(s) Affiliation(s) Publisher Publish Date Abstract/scope Citation DOI Submit	https://saemobilus.sae.org/content/2012-01-2004/
The fast and effective isolation of nanocellulose from selected cellulosic feedstocks \| Request PDF Request PDF \| On Apr 1, 2016, Matjaž Kunaver and others published The fast and effective isolation of nanocellulose from selected cellulosic feedstocks \| Find, read and cite all the research you need on ResearchGate April 2016 Carbohydrate Polymers 148 DOI: 10.1016/j.carbpol.2016.04.076 Authors: Matjaz Kunaver National Institute of Chemistry Alojz Anzlovar National Institute of Chemistry Ema Žagar Ema Žagar This person is not on ResearchGate, or hasn't claimed this research yet. Request full-text Download citation Copy link Link copied Request full-text Download citation Copy link Link copied To read the full-text of this research, you can request a copy directly from the authors. Citations (68) References (50) Discover the world's research 25+ million members 160+ million publication pages 2.3+ billion citations Join for free No full-text available To read the full-text of this research, you can request a copy directly from the authors. Request full-text PDF Citations (68) References (50) ... These exceptional features are attributed to the uniaxial molecular orientation of cellulose molecules in the microfibrils and their high crystallinity [40]. The crystallinity index (CI) of a material is defined as the mass ratio of the crystalline substance in the total dry sample on the basis of the crystallographic two-phase model [41][42] [43] . CNCs which are mainly produced through acid hydrolysis generally have higher crystallinity than the CNFs due to the removal of most of the amorphous cellulose fraction. Figure 3 depicts the amorphous and crystalline domains of nanocellulose in the cellulose fiber. ... ... Crystallinity is also greatly influenced by the source of lignocellulosic biomass. Kunaver et al. (2016) [43] reported that the crystallinity of nanocellulose produced from cotton liner using the glycolysis method is 80%; whereas spruce wood, Chinese silver grass, and Eucalyptus wood nanocelluloses had a lower crystallinity (62.8 to 66%). ... ... Crystallinity is also greatly influenced by the source of lignocellulosic biomass. Kunaver et al. (2016) [43] reported that the crystallinity of nanocellulose produced from cotton liner using the glycolysis method is 80%; whereas spruce wood, Chinese silver grass, and Eucalyptus wood nanocelluloses had a lower crystallinity (62.8 to 66%). ... Recent Development and Environmental Applications of Nanocellulose-Based Membranes Article Full-text available Mar 2022 Syafiqah Syazwani Jaffar Suryani Saallah Mailin Misson Wuled Lenggoro Extensive research and development in the production of nanocellulose production, a green, bio-based, and renewable biomaterial has paved the way for the development of advanced functional materials for a multitude of applications. From a membrane technology perspective, the exceptional mechanical strength, high crystallinity, tunable surface chemistry, and anti-fouling behavior of nanocellulose, manifested from its structural and nanodimensional properties are particularly attractive. Thus, an opportunity has emerged to exploit these features to develop nanocellulose-based membranes for environmental applications. This review provides insights into the prospect of nanocellulose as a matrix or as an additive to enhance membrane performance in water filtration, environmental remediation, and the development of pollutant sensors and energy devices, focusing on the most recent progress from 2017 to 2022. A brief overview of the strategies to tailor the nanocellulose surface chemistry for the effective removal of specific pollutants and nanocellulose-based membrane fabrication approaches are also presented. The major challenges and future directions associated with the environmental applications of nanocellulose-based membranes are put into perspective, with primary emphasis on advanced multifunctional membranes. View Show abstract ... There have been several examples of cellulosebased hydrogels for drug delivery reported in scientific literature (Basu et al. 2018;Hai et al. 2019;Ilkar Erdagi et al. 2020;Loh et al. 2020;Ning et al. 2020). To the best of our knowledge this is the first time that nanocellulose isolated from the Eucalyptus wood chips by fast and effective method reported by Kunaver et al. (2016) , is used for the preparation of PMAA hydrogels with NC (PM/NC hydrogels). ... ... Nanocellulose was isolated from the Eucalyptus wood chips as described in details by Kunaver et al. (2016) . Briefly, nanocellulose was isolated by the process of liquefaction of lignocellulosic biomass using propylene glycol as main solvent and low concentration of acid catalyst (methane sulfonic acid). ... ... It is also presented in FTIR spectra of all PM/ NC-MN hydrogels (Figs. 2, 3). This peak is attributed to the glycosidic C-O-C deformation of the bglycosidic link in cellulose (Kunaver et al. 2016 ) and presents the evidence of the presence of NC in the PM/ NC-MN hydrogels. The addition of NC did not affect neither the position nor the intensity of the peaks presented in the FTIR spectrum of the PM/0.5NC, ... Green pH- and magnetic-responsive hybrid hydrogels based on poly(methacrylic acid) and Eucalyptus wood nanocellulose for controlled release of ibuprofen Article Full-text available Nov 2021 CELLULOSE Maja Markovic Sanja Seslija Vukašin Ugrinović Pavle Spasojevic pH- and magnetic-sensitive hybrid hydrogels based on poly(methacrylic acid) (PMAA), nanocellulose (NC), carboxymethyl cellulose (CMC) and magnetite particles (MN) were prepared as ibuprofen delivery system. NC was isolated from wood waste material and added to highly hydrophilic PMAA in order to improve the mechanical properties of PMAA and enable the encapsulation of poorly water-soluble ibuprofen. CMC was added in order to stabilize magnetite particles. The pH- and magnetic-sensitivity of the obtained hybrid hydrogels (originated from PMAA and MN, respectively) provided targeted delivery and controlled release of ibuprofen. Hybrid hydrogels were characterized by various technics: FTIR, SEM, XRD, VSM, the modified Faraday method, photon correlation spectroscopy and by using single compression tests. The swelling behavior of hybrid hydrogels and cumulative ibuprofen release were investigated depending on wt% of NC and MN in two media which were simulating pH environments in human stomach and intestines. The swelling degree of hybrid hydrogels and the percent of cumulative ibuprofen release decreased with the increase in wt% of NC. The same was found for increasing wt% of MN. Ibuprofen release kinetics was investigated with Korsmeyer–Peppas model. The obtained results showed that the prepared green dual responsive hybrid hydrogels were excellent candidates for the controlled release of ibuprofen, showing that the release kinetic can be easily tuned by changing only one hydrogel component. Graphic abstract View Show abstract ... Cellulose nanocrystals (CNCs) are highly promising nanostructures isolated by a selective acid hydrolysis of amorphous domains of cellulose fibrils using mostly mineral acids, predominantly sulfuric acid, thereby leaving the crystalline domains mostly intact (Klemm et al. 2011;Kos et al. 2014; Kunaver et al. 2016; Anžlovar et al. 2016). Due to excellent mechanical properties (specific Young's modulus even higher than steel) CNCs are increasingly attractive potential nanofillers in various polymer matrices (Dufresne 2013). ... ... CNCs were isolated by the 'polyol method' (Kunaver et al. 2016) from cotton linters in a mixture of diethylene glycol and glycerol (w/w = 70/30) in a 4 h reaction time at 150°C using 3 wt.% of methanesulfonic acid as a catalyst. CNCs were washed 5 9 with dioxane, 3 9 with acetone, and finally with DI H 2 O. ... ... Cellulose nanocrystals were isolated by the polyol method and lyophilized. They have average particle length of 300 nm and diameter from 20 to 50 nm ( Fig. 1) (Kunaver et al. 2016; Anžlovar et al. 2018). When conventionally dried, CNCs form highly stable aggregates due to strong interparticle hydrogen bonding between the surface hydroxyl groups. ... Silane modified cellulose nanocrystals and nanocomposites with LLDPE prepared by melt processing Article Full-text available Jul 2020 CELLULOSE Alojz Anzlovar Andraž Krajnc Ema Žagar Cellulose nanocrystals (CNCs) were surface modified with 3-isocyanatopropyl triethoxysilane (ICPTS) in tetrahydrofuran at 62–63 °C using triethylamine as a catalyst. ICPTS modified CNCs were further studied as a nanofiller in nanocomposites with linear low-density poly(ethylene) (LLDPE) prepared by melt processing. The modification of CNCs was confirmed by FTIR, solid state NMR, and thermogravimetric analysis. Compared to unmodified CNCs, the ICPTS modified CNCs show enhanced compatibility with LLDPE as shown by SEM. Nanocomposites processed at 70 °C reveal slightly enhanced mechanical properties and this effect was further intensified by increasing the molding temperature up to 120 °C. Under such conditions, a 20% increase in Young’s modulus and 30% increase in tensile strength are achieved compared to neat LLDPE. Differential scanning calorimetry confirms the degree of LLDPE crystallinity, beside the CNC reinforcing network formation, as an important decisive factor in defining the final mechanical properties of LLDPE/CNC nanocomposites. The maximal enhancement of mechanical properties was observed at rather low amount of added ICPTS modified CNC (1–2 wt.%), which is important for practical application as CNCs are still rather expensive nanofiller. By modification of CNC with ICPTS the CNC polarity is reduced, which result in their improved compatibility with LLDPE, while on the other hand they function as a plasticizer and thus reduce the LLDPE crystallization degree, especially at high CNC concentrations. Graphic abstract View Show abstract ... The DTF sample experienced a decrease in T max of the RTF from 377.64 to 363.37 °C, which was a result of the release of the outer wax and impurity components, thereby making the DTF particles become larger. In turn, the surface area being exposed to heat was also wide [60] . At stage 1 of degradation, the weight loss showed a decreasing trend with the treatment of TF from 10.1 to 8.02%. ... ... The same reason applies to charcoal residue. Larger amount of charcoal is produced when linters with a larger proportion of carbon are in highly crystalline samples [60] . ... The effectiveness of isolation and characterization nanocelullose from Timoho fiber for sustainable materials Article Full-text available Dec 2022 Femiana Gapsari Andoko Doko Kuncoro Diharjo Suchart Siengchin Timoho fiber (TF) has proven to be a potential reinforcement for composites due to its high cellulose content. Various efforts have been made to improve the TF performance in the composite fabrication, one of which is by making nanocellulose from the fiber. The structure can be the basic material for nanocomposites. Nanocellulose forms of fibers have good mechanical properties and lower density. Therefore, TF was prepared into nanocellulose by using effective methods of isolation and extraction. Fabrication process was done in three main stages namely extraction which was performed in three processes: dewaxing, mercerization, and delignification. Next, the cellulose was characterized using FTIR, XRD, FE-SEM. TEM, and TGA. Density and crystallinity index of TF nanocellulose were 0.52 g/cm3 and 88.47%. The TF morphology described the random structure which was adequate as nanocellulose method was effective to extract nanocellulose and is recommended as a sustainable cellulose bionanocomposite material. View Show abstract ... β is expressed in radians, while 2θ is in degrees. 31 The amount of surface chains (R) proportional to total amount of chains was calculated using lattice plane d-spacings of the cellulose I monoclinic unit cell. 28 The freeze-dried samples were measured with FT-IR Spectrum Two (PerkinElmer, Waltham, USA) instrument in a range of wavelengths of 4000−400 cm −1 with 64 scans with increments (resolution) of 4 cm −1 . ... ... The CNCs are in the form of rod-shaped particles that tend to aggregate, as visible in Figure 1a, with an average length of 294 ± 84 nm and width 11 nm ±5 nm (Figure 1b), which is in agreement with the literature. 31 On the other hand, CNFs are shaped as a long, fibrilous network with an average diameter of a single fibril being 17 nm ± 6 nm and length of more than 100 μm (Figure 1c,d). Additional TEM images with lower magnification can be found in the Supporting Information ( Figure S2). ... Multiscale Study of Functional Acetylation of Cellulose Nanomaterials by Design: Ab Initio Mechanisms and Chemical Reaction Microkinetics Article Full-text available Nov 2022 Matej Huš Ana Oberlintner Blaz Likozar Uroš Novak Cellulose nanomaterials, namely cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs), present a class of multipurpose, renewable, biodegradable, and nontoxic materials, paving the way into the future of biobased materials. The abundance of hydroxyl groups on the surface allows modification of the materials properties according to application; however, to fully exploit their potential, better compatibility on the molecular level with the hydrophobic matrixes has to be explored beyond lab scale. One of the main missing pieces in functionalization of nanomaterials is a lack of studies focusing on mechanisms and kinetics, which are prerequisite for further optimization of conditions leading to optimal process in terms of both sustainable processing and optimal performance. In this study, the “by design” based approach to tailor biomaterial properties has been simulated multiscale-wise, thus providing a greatly needed input for commercialization. The microkinetic parameters of the elementary reaction steps for acetylation of two distinct types of cellulose nanomaterials were determined and refined by regression analysis. Ab initio part utilizes the density functional theory (DFT) for cellotriose as a model, which suggested that products were obtained through a mechanism consisting of active intermediate formation/subsequent competing one- or two-step (through binding/decomposition of complex) reactions. Quantum chemical simulations were used to pinpoint the most probable sequence through calculated activation barriers that served as a foundation for the development of a thorough regression analysis on experimental data sets. The yield of reaction, through formed acetyl groups was determined through Fourier transform infrared spectroscopy, leading to acquisition of critical elementary characteristics. View Show abstract ... Cellulose nanocrystals (CNCs) extracted from non-wood cellulosic sources have attracted significant attention due to their numerous advantages, including non-toxicity, excellent mechanical properties and high surface areas. [6] [7] [8][9][10][11][12] In recent years, there have been increased efforts to scale up the processing and economy of CNCs isolation. For example, CNCs isolation in large scale production has been reported in Canada and the United States for potential utilization as reinforcement or functional additive in commercial products. ... ... Interestingly, various acids utilized for the hydrolysis are commercially readily available. 1, 7, 32 Acid hydrolysis generally yields needle-like morphologies, with diameters of 10-20 nm and lengths of several hundred nanometres. On the other hand, TEMPO-mediated oxidation, enzymatic hydrolysis and mechanical methods extract long flexible networks of fibrils, with the diameter in the nanoscale (5-110 nm) and length of a few micrometres. ... EFFECTS OF ACID HYDROLYSIS ON THE EXTRACTION OF CELLULOSE NANOCRYSTALS (CNCs): A REVIEW Article Sep 2022 CELL CHEM TECHNOL Samson MASULUBANYE Mohomane Setumo Motloung Lehlohonolo Koao Motaung Tshwafo "The potential utilization of cellulose nanocrystals (CNCs) as reinforcing materials has lately attracted significant research attention. This is mainly due to their versatility and suitability for various applications in fields such as food packaging, cosmetics, biomaterials and pharmaceuticals. Several methods have been reported in the literature for isolating CNCs from plant sources, including acid hydrolysis, mechanical treatment and enzymatic hydrolysis, resulting in CNCs with different dimensions, crystallinities and thermal stabilities. However, acid hydrolysis using sulphuric acid (H2SO4) remains the favourite, as it requires shorter time and produces a stable suspension, with high crystallinity, compared to other methods. Sulphuric acid hydrolysis is generally performed with 64% acid concentration, with varying acid to fibre ratios, at temperatures around 45-50 °C, for 30-75 min duration under vigorous stirring. It typically produces needle-like structures, with the diameter and length in the range of 4–25 nm and 100–300 nm, respectively. This review analyses the results reported in the literature regarding the influence of hydrolysis parameters on the extraction of CNCs from various cellulosic materials. The study examines various hydrolysis parameters, specifically extraction time, temperature and acid concentration, to isolate CNCs with controlled morphology, crystallinity and thermal stability." View Show abstract ... Nanocellulose was extracted from the Eucalyptus wood chips using approach which is described in details by M. Kunaver et al. [14] . Briefly, propylene glycol and low concentration of acid catalyst (methane sulfonic acid) were used for liquefaction of ligninocellulose biomass. ... ... By comparing the FTIR spectra of neat PMAA and PMNC sample ( Fig. 1. a)) it can be notices the presence of a new peak at 1116 cm−1 in FTIR spectrum of PMNC sample. This peak is attributed to the glycosidic C-O-C deformation of the β-glycosidic link in cellulose and is present in FTIR spectra of all PMNC/MN-L samples [14] . This peak confirmed the presence of NC in PMNC/MN-L samples. ... Dual responsive hybrid hydrogels for controlled release of local anesthetic Article Full-text available Jan 2022 Vesna Panic Maja Markovic Sanja Seslija Pavle Spasojevic Inteligent hydrogels, such as pH sensitive hydrogels based on poly(methacrylic acid) (PMAA) are widely used for targeted drug delivery. Still, PMAA lack of good mechanical properties often limits its application. In order to overcome this limitation nano-cellulose (NC) was extracted from wood waste material and then added to PMAA because NC is biocompatible, non-toxic and has excellent mechanical properties. Further, carboxymethyl cellulose (CMC) (cellulose derivate widely used for controlled release of drugs) was added. CMC can stabilize magnetite nanoparticles (MN) which is then also added. MN can significantly improve mechanical properties of hydrogels and also possess magnetic properties due to which MN can be used for targeted drug delivery. The as-prepared material can protect drug, deliver it to the site of action, control its release rate and enable in that way its efficient application with reduced side effects. Local anesthetic-lidocaine hydrochloride (LH) is often administrated by injection which can induce severe side effects. This problem is solved in present study by encapsulating LH into hydrogels based on PMAA, NC, CMC and MN (PMNC/MN-L). PMNC/MN-L hydrogels were characterized by FTIR and SEM spectroscopies and single compressive tests and then their swelling behavior and LH release were analyzed. Present study offers unique approach for green synthesis of dual responsive hydrogels with improves properties and their application for controlled release of local anesthetic with reduced side effects. View Show abstract ... NC was extracted from the Eucalyptus wood chips according to the procedure which is described in details by M. Kunaver et al. (Kunaver et al., 2016) . Briefly, lignocellulosic biomass was liquefied by the propilen glycol and with low concentration of acid catalyst -methane sulfonic acid. ... ... Characteristic peaks of PMAA are presented in FTIR spectra of all PM/NC-Lid samples ( Fig. 1. a) When FTIR spectra of neat PMAA and PM/1NC ( Fig. 1. a)) are compared a new peak at 1115 cm −1 in FTIR spectrum of PM/1NC sample is noticed. This peak is present in FTIR spectra of all PM/NC-Lid samples and is attributed to the glycosidic C-O-C deformation of the β-glycosidic link in cellulose (Kunaver et al., 2016) . This is the evidence of the presence of NC in PM/NC-Lid samples. ... Hydrogels based on poly(methacrylic acid) and nanocellulose with potential application in dental treatments Conference Paper Full-text available Mar 2021 Julijana D. Tadić Maja Markovic Sanja Seslija Pavle Spasojevic pH sensitive hydrogels, such as hydrogels based on poly(methacrylic acid) (PMAA), are tremendous materials with great properties due to which they have application in many fields, such as: targeted drug delivery, tissue engineering, as contact lenses etc. Hydrogels based on PMAA are non-toxic, biocompatible and able to absorb and retain huge amount of water. These hydrogels are widely used for targeted drug delivery due to their specific pH swelling behavior which enable drug release in environments with pH values higher than pKa(PMAA). However, poor mechanical properties of hydrogels based on PMAA often limit their application. In order to overcome this limitation, green approach is used in present study. Namely, nanocellulose (NC) extracted from wood waste material is added to PMAA due to NC non-toxicity, biocompatibility, biodegradability and great mechanical properties (which is used for improvement of hydrogels mechanical characteristics). Further improvement of hydrogels based on PMAA and NC is achieved by adding carboxymethyl cellulose (CMC). CMC is non-toxic, biocompatible, biodegradable, pH-sensitive derivate of cellulose widely used in drug delivery systems. Drug delivery system prepared in that way can enable controlled release of drug (such as lidocaine hydrochloride (Lid)) for prolonged period of time and therefore, reduce the number of acquired drug dosages which further lead to safe and efficient drug application. Therefore, Lid is encapsulated in hydrogels based on PMAA, NC and CMC (PM/NC-Lid). Lid is local anesthetic often used in dental treatment and it is usually administrated by injection, which is painful, unpleasant and treatment is often required several dosages. These limitations can be overcome by applying PM/NC-Lid hydrogels as buccal patches for controlled release of lidocaine hydrochloride. Present study describes green synthesis and characterization of PM/NC-Lid hydrogels (using the Fourier Transform Infrared spectroscopy (FT-IR), the Scanning Electron Microscopy (SEM) and the single compression tests). Also, PM/NC-Lid swelling behavior and Lid controlled release from PM/NC-Lid hydrogels is investigated depending on the variable synthesis parameter (NC wt%) in simulated buccal environment. Results presented in this study show that PM/NC-Lid hydrogels are promising materials for controlled release of anesthetic drugs and for potential application as buccal patches in dental treatments. View Show abstract ... Benzoic acid anhydride-BzAnh, 98%, Fluka, Buchs; N,N-dimethylaminopyridine-DMAP, 99%, Sigma-Aldrich, Saint Louis, Missouri, USA; freeze-dried CNCs (length 200-500 nm; isolated by the previously published method) (Kunaver et al. 2016 ); PS-Supreme SC 201 LV, atactic, SPL, India; tetrahydrofuran-THF, p.a., Merck, Germany, dried with molecular sieves; acetone, 99.5%, Riedel-de-Haen, Seelze, Germany. CNCs were washed according to the isolation procedure described in the literature (Anžlovar et al. 2018). ... ... SEM micrograph in Fig. 1a shows the morphology of CNCs isolated from cotton linters (estimated CNC length and width of 200-500 nm and 10-30 nm, respectively) (Kunaver et al. 2016) . TEM micrograph (Fig. 1b) shows the crystalline CNC structure with a light-colored layer on the surface, presumably consisted of amorphous cellulose. ... Composites of polystyrene and surface modified cellulose nanocrystals prepared by melt processing Article Full-text available Aug 2021 CELLULOSE Iztok Švab Alojz Anzlovar Andraž Krajnc Ema Žagar Cellulose nanocrystals (CNCs) were surface modified with benzoic acid anhydride (BzAnh) at room temperature in 48-h reaction time. FTIR spectroscopy confirmed the high degree of modification of the CNCs with BzAnh, while ¹³C CP MAS NMR showed that the total degree of modification was 16%, indicating that the degree of surface modification of the CNCs was very high (estimated to be 50% or even higher). 2D ¹H-¹³C CP-HETCOR MAS NMR and ¹³C-detected proton spin-diffusion (PSD) experiments confirmed that BzAnh reacted mainly with –CH2–OH groups in the amorphous regions of CNC nanocrystals. The crystallinity indices of unmodified and BzAnh-modified CNCs showed little difference, indicating that the modification did not destroy crystalline domains, thus confirming NMR results that the esterification reaction occurred mainly in the amorphous cellulose regions. Unmodified and BzAnh-modified CNCs were used to produce nanocomposites with polystyrene (PS) by melt processing at 200 °C. SEM microscopy confirmed the improved compatibility of BzAnh-modified CNCs with PS matrix compared to PS nanocomposites prepared with unmodified CNCs. The results of tensile tests showed that the addition of BzAnh-modified CNCs increased the Young’s modulus and tensile strength of the composites, while unmodified CNCs showed deterioration in mechanical properties. The addition of 5 wt% CNCs to the PS matrix resulted in a 30% improvement in tensile strength and a 23% increase in Young’s modulus. The increased compatibility and improved mechanical properties of BzAnh-modified CNCs were attributed to the intense entanglement of PS chains and BzAnh-modified CNCs due to π–π interactions between benzene rings. Graphic abstract View Show abstract ... The yield of ASN was 41.53%, which suggested maximum removal of amorphous fractions, indicating an efficient time, temperature, and acid concentration combination for cellulose hydrolysis. The yield was higher than previously reports on nanocrystalline cellulose extracted from coconut husk (12.0%), soy hull (20.0%), pinewood (2.3%) and corn cob (6.0%) [12,46,47] and lower than those extracted from cotton linters (74.5%), spruce wood (61%), Chinese silver grass (55.6%), eucalyptus wood (63%) and sugarcane bagasse (50-58%) [48, 49]. ... ... Another band at 1734 cm -1 of AS is associated with the C=O stretching of acetyl and uronic ester groups of hemicellulose and xylans or carboxylic group ester linkages of ferulic and p-coumaric acids in lignin [40,53]. The absence of all these bands and increased prominence of the band at 2921 cm -1 (C-H stretching vibration of cellulose) for ASC and ASN depicted successful removal of non-cellulosic components during delignification [14, 48] . In holocellulose matrix, these components inhibit inter-cellulose H-bonding. ... Extraction and Characterization of Cellulose and Cellulose Nanowhiskers from Almond Shell Biomass, Metal Removal and Toxicity Analysis Article Full-text available Apr 2022 Sumira Rashid Ankush Kumar Shahi Himjyoti Dutta Jatindra Kumar Almond shell is a major agro-industry waste. Cellulose is the major crystalline component of naturally porous almond shell biomass. In this study, cellulose (ASC) was isolated from almond shell (AS) by the dewaxing-alkali treatment-bleaching method, and nanocrystalline cellulose (ASN) was obtained by sulphuric acid hydrolysis of the obtained ASC. Separation efficiency was confirmed by X-ray diffraction and IR absorption studies. ASC exhibited predominantly microporous monolithic structures under a scanning electron microscope. Its porosity resulted in significant absorption of Cu(II) and Pb(II) ions when applied as an absorbent in their solutions. Transmission electron microscopy and atomic force microscopy revealed the formation of ASN nanowhiskers with an average length and diameter of 170 nm and 20 nm, respectively. Zeta potential of-32.4 mV suggested good colloidal dispersibility of the nanowhiskers. No hemolytic toxicity to erythrocyte cells was recorded, which suggested the potential applicability of the obtained nanomaterial in foods and pharmaceuticals. Remarkably high crystallinity and thermal resistance observed from calorimetry and thermogravimetry studies indicated enhanced density of the crystalline moiety during synthesis. ASC and ASN can be developed as effective metal absorption substrates and reinforcement agents in heat-resistant composite materials. View Show abstract ... Fig. 4 shows the NCs average size and particle size distribution measured with DLS. The value given by this technique is the hydrodynamic radius of a sphere having the same diffusion coefficient as the rod-like nanocellulose particles [53] . The ball mill transforms cellulose microstructures into nanoparticles by cellulosic structures breakage of and exposure of -OH groups [54]. ... ... In longer milling times (9 and 12 h), the surfactant decreased particle sizes (Fig. 4b and c), indicating that there was a conversion of kinetic energy to friction and shear forces, sufficient for the cellulose to be transformed into nanocellulose and to adsorb the surfactant in the NCs superficially. Particle sizes above 500 nm may be associated with aggregates [53] . ... Innovative process for obtaining modified nanocellulose from soybean straw Article Oct 2020 David Fernando dos Santos Alana Gabrieli de Souza Rafaela Reis Ferreira D. S. Rosa In the present research, soybean straw was used to prepare nanocellulose (NC) via a ball mill, in different milling times (6, 9, and 12 h) and in-situ modified with an anionic surfactant. NCs were characterized for their chemical structure, surface composition, dimension and stability, morphology, crystalline structure, and thermal stability. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy results indicated a cellulosic structure for NCs and a physical interaction due to the electronic attractions between nanocellulose hydroxyls and surfactant end chain groups. The dynamic light scattering, Zeta potential, and transmission electron microscopy indicated that the in situ modified samples showed smaller sizes and good electrostatic stability. Besides, while ball mill resulted in nanofibers, the in situ modified-NC showed a nanocrystal shape, indicating that the surfactant alters the milling process and cellulose scale reduction. The modified-NC showed lower crystallinity and crystal size than unmodified nanocelluloses due to the surfactant chains' addition and influence during the milling process. The modified-NC showed slightly superior thermal stability. The NC-12S showed smaller particle sizes, high electrostatic, and thermal stability and indicated that 12 h is adequate to prepare modified nanocellulose via in situ modification. The prepared samples could be potentially used as coatings, emulsifiers, and nanocomposites reinforcing agents. View Show abstract ... Cellulose grabs more researchers' interest for its notable excellent mechanical properties (a high Young's Modulus of 138 GPa), high aspect ratio, a very low coefficient of thermal expansion (10 -7 K -1 in longitudinal direction), large active surface area, a highly porous mesh, low cost and eco-friendly (Hubbe et al., 2008;Medeiros et al., 2008) which makes it a promising candidate for reinforcement in composites. Cellulose fibers can be obtained from various sources such as kenaf and wheat straw (Nuruddin et al., 2015), posidonia oceanica (Bettaieb et al., 2015), Bagasse (Sofla et al., 2016), wood fibers (Abe et al., 2007;Zhang et al., 2015), spruce wood, eucalyptus wood and Chinese silver grass (Kunaver et al. 2016) , soybean Ferrer et al., 2016), elephant grass, lemon grass (Nascimento, & Rezende, 2018;Mishra et al., 2018), maize (Maepa et al., 2015), hempfiber , sisal (Moran et al., 2008; Page 2 of 20 AUTHOR SUBMITTED MANUSCRIPT -MRX-118693. R1 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 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 A c c e p t e d M a n u s c r i p t 3 Johari et al., 2016), rice straw, wheat straw, barley straw and soy hulls (Alemdar& Sain, 2008a;Oun & Rhim, 2016), arecanut husk (Chandra et al., 2016), sugar beet (Hietala et al., 2017;Yang et al., 2018), banana rachis (Zuluaga et al., 2009;Khawas and Deka 2016), cotton (Soni et al., 2015;Kunaver et al., 2016), coconut husk fibers (Rosa et al., 2010), potato (Ralet et al., 2016), pineapple leaf fibres (Cherian et al., 2010), bamboo (Xie et al., 2016), corncob residue (Liu et al., 2016), Oil palm trunk (Lamaming et al., 2017), hard wood kraft (Masruchin et al., 2015). ... ... Cellulose fibers can be obtained from various sources such as kenaf and wheat straw (Nuruddin et al., 2015), posidonia oceanica (Bettaieb et al., 2015), Bagasse (Sofla et al., 2016), wood fibers (Abe et al., 2007;Zhang et al., 2015), spruce wood, eucalyptus wood and Chinese silver grass (Kunaver et al. 2016), soybean Ferrer et al., 2016), elephant grass, lemon grass (Nascimento, & Rezende, 2018;Mishra et al., 2018), maize (Maepa et al., 2015), hempfiber , sisal (Moran et al., 2008; Page 2 of 20 AUTHOR SUBMITTED MANUSCRIPT -MRX-118693. R1 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 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 A c c e p t e d M a n u s c r i p t 3 Johari et al., 2016), rice straw, wheat straw, barley straw and soy hulls (Alemdar& Sain, 2008a;Oun & Rhim, 2016), arecanut husk (Chandra et al., 2016), sugar beet (Hietala et al., 2017;Yang et al., 2018), banana rachis (Zuluaga et al., 2009;Khawas and Deka 2016), cotton (Soni et al., 2015; Kunaver et al., 2016) , coconut husk fibers (Rosa et al., 2010), potato (Ralet et al., 2016), pineapple leaf fibres (Cherian et al., 2010), bamboo (Xie et al., 2016), corncob residue (Liu et al., 2016), Oil palm trunk (Lamaming et al., 2017), hard wood kraft (Masruchin et al., 2015). ... Cellulose microfibrils from banana fibers: Characterization at different chemical processes Article Full-text available Dec 2019 Vignesh Prakasam Mallikarjuna Reddy D Gopalan Venkatachalam The objective of this paper is to investigate the morphological, chemical and thermal behaviors of cellulose microfibrils isolated from banana stem fibers by different chemical processes. The structural properties of cellulose microfibrils are analyzed by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), Powdered X-Ray Diffraction (PXRD), and Thermogravimetric analysis (TGA). Results reveal that cellulose microfibrils of diameter 1-2μm can be isolated at the end of chemical treatment. Chemical characterization confirms that the α-cellulose content is increased from 68% to 82% by acid-alkali treatment. FT-IR spectroscopy shows the partial removal of hemicellulose and lignin content. PXRD results show improved crystallinity after acid-alkali treatment. TGA results show that the cellulose microfibrils are trusted candidate for reinforcement with polymers having degradation temperature reaches beyond 380C. View Show abstract ... Several top-down approaches are available for NC isolation, such as chemical, biological, mechanical, and combination of chemical and mechanical [7] [8] [9]. However, an environmentally-friendly combination method that does not employ strong acids or toxic reagents has not been widely explored. ... ... The DLS measures the translational diffusion coefficient of particles in water, which undergo Brownian motion. The value given by this technique is the hydrodynamic radius (R H ) of a sphere having the same diffusion coefficient as the rod-like cellulose nanoparticles [8, 43,44]. Fig. 3S shows the curves of the size distribution and information about the maximum, minimum, and average sizes of the milled samples. ... Use of ball mill to prepare nanocellulose from eucalyptus biomass: Challenges and process optimization by combined method Article Nov 2019 Rafaela Reis Ferreira Lucas L. Nunes Alana Gabrieli de Souza D. S. Rosa A combination of mechanical methods was developed to obtain a suspension of nanocellulose (NC) from Eucalyptus sawdust. In this two-step process, the ball milling (1–4 h) was followed by a high-intensity ultrasound (10–30 min) irradiation. The prepared samples were characterized using Fourier-transform infrared spectroscopy, Raman, dynamic and static light scattering, Zeta potential, X-ray diffraction, X-ray photoelectron spectroscopy, Thermogravimetric analysis, Field-emission scanning electron microscopy, and Transmission electron microscopy. The crystallinity was calculated using different methods and compared. The mechanical grinding results in a random and irregular break of the fibers. In a combined method, the ultrasound waves generate more defibrillation and separation of the nanofibers and, consequently, the reduction of fiber diameters. The high-intensity ultrasound promoted an increase in the homogeneity, crystallinity, and electrostatic and thermal stability of the NC suspension. The samples milled for 2 h and 20 min ultrasound irradiation presented the high-efficiency in obtaining NC. View Show abstract ... The paper industry is one of the most important in the world, with significant annual paper production. Brazilian is the second biggest producer of cellulose in the world, and paper production in 2016 totaled 10 .3 million tons [4]. However, this industry presents the high generation of waste during the processes. ... ... This interest is related to the intrinsic properties of CNSs, such as high mechanical strength and surface area, renewability, it is a non-toxic and biodegradable material. In addition, there is the possibility of producing CNSs from a multitude of sustainable, widely available and lowcost resources such as forest residues (wood saw-dust -pine and eucalyptus), agricultural (wheat straw, sugar cane) and industrial (cotton waste, paper waste, and tobacco industry) [2,[8][9] [10] [11][12]. CNSs can be applied in a variety of areas, such as electronic displays, paints, packaging, membranes, implants, polymer composites and others [13]. ... Variation of the milling conditions in the obtaining of nanocellulose from the paper sludge Article Full-text available Jan 2019 Fabiany Kano Alana Gabrieli de Souza D. S. Rosa This work aimed to evaluate three different milling conditions, seeking the optimization of CNS isolation process. The paper sludge was chemically treated with detergent and H2O2, by two steps, to remove the noncellulosic contents (hemicellulose and lignin). After these treatments, the sample was milled with the variation of a liquid medium. The three liquids milling medium were: i) dry medium (CNS-D); ii) moist with water and (CNS-W) iii) moist with ethanol (CNS-E). The CNSs were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), zeta potential and dynamic light scattering (DLS). The milled samples presented different behavior, depending on the medium applied. The CNS-W presented low efficiency due to the formation of agglomerates around the ceramic ball, resulting in larger fiber sizes (microsizes). Although, the samples CNS-D and CNS-E presented similar behavior of sizes distribution, with average size 340 nm and 373 nm, respectively, determined by DLS. The CNS-E sample presented higher yield and electrostatic stability in solution, besides not presenting loss of crystallinity, as occurred with CNS-D, observed by FTIR analysis. Thus, the isolation with ethanol showed more efficient process among the three processes studied. This work achieved the isolation of CNS; besides, it proposed an environmentally friendly isolation method, and this may add value in the paper sludge. View Show abstract ... Some authors used the DLS hydrodynamic diameter combining with TEM or SEM microscopies to estimate the nanofibril lengths (Gamelas et al. 2015; Kunaver et al. 2016; Mao et al. 2017). However, it must be noted that DLS is a technique based on the Brownian motion of macromolecules in solution and relates this motion to the particle size. ... Innovative system based on natural polyelectrolyte complex and cellulose micro/nanofibers to improve drainability and properties of recycled paper Article Full-text available May 2023 CELLULOSE Gabriela Bastida Miguel Zanuttini Quim Tarrés María Verónica Galván In this work, the efficiency of a polyelectrolyte complex (PEC) to retain different cellulose micro/nanofibers (CMNFs) during paper formation and to improve the physical properties of recycled unbleached fiber paper was analyzed. CMNFs were obtained from a commercial bleached eucalyptus pulp (BEP) using a PFI refiner followed by a chemical treatment with oxalic acid at two different concentrations. Finally, the pulp was fibrillated using a high-pressure homogenizer at three different intensities. The PEC was formed by addition of the xylan (Xyl) solution on chitosan (CH) solution with a Xyl/CH mass ratio of 80/20. The required dosages of PEC solution to neutralize the charges of different nanocellulose fractions were determined by ζ-potential measurements, and the CMNF retentions on recycled unbleached fibers were evaluated in a Britt Dynamic Drainage Jar. The results showed that the maximum retention was obtained when the neutral PEC-CMNF system was added to pulp. Besides, a significant decrease on °SR was observed when PEC and PEC-CMNF systems were added to the untreated pulp, limiting the negative effects of nanocellulose addition on pulp drainability. The incorporation of PEC-CMNF systems to the handsheets increased the tensile index (up to 28%), Mullen index (up to 40%) and internal bonding (up to 255%). Finally, the compressive strength of the handsheets, namely SCT and CMT, increased up to 30 and 70%, respectively. These simultaneous improvement on drainability and mechanical properties makes the proposed PEC-CMNF system a promising solution for the production of packaging paper. View Show abstract ... There are large number of studies carried out to the production of nanocellulose from agricultural waste (Boerjan et al. 2003;Gibson et al. 2010;Song et al. 2009;An et al. 2020;Bongao et al. 2020;Israel et al. 2008;Udonne et al. 2006) of the plants growing in Kazakhstan land, special attention is paid to hemp weed, where the content of cellulose in the plant stems exceeds 50-70% (Ibrayeva et al. 2020;Jean et al. 2010), rice straw and husks (Boerjan et al. 2003;Gibson et al. 2010;Lwako et al. 2013;Sumira et al. 2020), the residue of coniferous logging (wood chips, pine branches and needles) with a target product yield of more than 13% (Moriana et al. 2016; Kunaver et al. 2016) . Analysis of literature sources shows that there are few studies related to the processing of SFH into nanocellulose. ... Highly-efficient Isolation of Microcrystalline Cellulose and Nanocellulose From Sun Flower Seeds Waste via Environmentally Benign “soft” Method Preprint Full-text available Aug 2021 Kydyrmolla Akatan Sana Kabdrakhmanova Tilek Kuanyshbekov Sabu Thomas The main focus of this study was to introduce a natural microcrystalline cellulosic raw material source from the residue of sunflower seeds, after oil extraction. For this purpose, the conventional method of organosolvent oxidation was changed to a "soft" method where microcrystalline cellulose (MCC) was extracted from sunflower seed husk (SFH) and the characterization of MCC and cellulose nanocrystals (CNCs) were carefully carried out. In this method, the concentration of acetic acid and hydrogen peroxide required for the preparation of peroxyacetic acid (PAA) was reduced by two times. The physico-chemical characterization, particle size, optical properties, chemical and crystal structure, surface morphology, and thermal stability of MCC and CNC were studied. The FTIR analysis, revealed the structural similarity of all derivatives of cellulose. Surface morphology was monitored with SEM, and the surface of MCC fibers was rough, and the morphology of cellulose nanocrystal (CNC) was fine, smooth and rod-like (overlapping each other) appearance, CNC film surface was found to be brown was filled with nano fibrils. The XRD analysis and determination of average particle size revealed that the MCC had a CI of 72.9%, a coherent scattering length (CSL) of 2.9 nm, and an average particle size of 1971 nm along the fibers, and a width of 266 nm. The acid hydrolysis resulted in the reduction of length of CNCs by 4 times and the width was reduced about 5 times. At the same time there observed an increase in the crystallinity index (CI) value. It was found that cellulose materials were destroyed at temperatures between 200 ₒ С and 358 ₒ С. Overall, it was concluded that sunflower seed husk was considered as a potential source for CNCs and the method employed for the extraction of cellulose from agricultural biomass waste was cost effective and environmentally benign. View Show abstract ... Journal of Nanomaterials It has shown that in ultrastructural morphological analysis, the average particulate diameter is 36 nm. Furthermore, they investigate four distinct types of lignocelluloses: feedstocks, a rapid and effective grinding method, liquefaction, centrifugation, and washing for nanocrystalline cellulose isolation [77] . Liquefaction of glycol and methane sulfonic acid shows efficacy during isolation. ... Study of Progress on Nanocrystalline Cellulose and Natural Fiber Reinforcement Biocomposites Article Full-text available Oct 2022 J NANOMATER T. Aravind Mohd Shaikhul Ashraf A.S. Rajesh SisayKetema Sida Cellulosic biomass hydrolysis yields a nanoscale substance known as nanocrystalline cellulose (NCC). Gel, liquid, or powder is adaptable to a variety of uses. Nanocrystalline cellulose has unique renewability, biodegradability, and mechanical and physicochemical qualities, and abundance boosts the material’s mechanical strength by many orders of magnitude when introduced into the material matrix (polymer, ceramic, or metal). Nanocrystalline cellulose is not related with any serious environmental issues because it is a natural substance. The progress of this biomaterial as a green and renewable biomaterial for the fabrication of lightweight and biodegradable composite materials gives further impetus. The current aim of nanocrystalline cellulose research is to optimise nanocrystalline cellulose characteristics for dispersion in hydrophilic and hydrophilic media. To assess the nanocrystalline cellulose reinforcing, antibacterial, stability, hydrophilicity, and biodegradability, imaging methods and protocols in complicated matrices will need to be developed. This review includes a discussion on nanocrystalline cellulose biocomposites. View Show abstract ... Other authors have also identified CNC as having a rodlike structure; however, they discovered that the DLS technique is appropriate. 90 Many other authors 35,76,91 have used the DLS technique for CNC particle size distribution. The average hydrodynamic diameter of CNC in this study is Polydispersity occurred due to the sample's size dispersion or agglomeration during isolation. ... Isolation and Characterization of Cellulose Nanocrystals from Date Palm Waste Article Full-text available Jul 2022 Fawzi Banat Ali H. Al-Marzouqi Mohsin Raza Basim Abu-Jdayil This study presents the isolation, characterization, and kinetic analyses of cellulose nanocrystals (CNCs) from date palm waste in the United Arab Emirates. After bleaching date palm stem waste with acidified NaClO2 and delignification via NaOH treatments, cellulose was extracted. Mineral acid hydrolysis (62 wt % H2SO4) was performed at 45 °C for 45 min to produce crystalline nanocellulose. Fourier transform infrared (FTIR) and chemical composition analysis confirmed the removal of noncellulosic constituents. The crystallinity index increased gradually with chemical treatments, according to the obtained X-ray diffraction (XRD) results. Thermogravimetric analysis and differential scanning calorimetry results revealed that the CNC has high thermal stability. The Coats-Redfern method was used to determine the kinetic parameters. The kinetic analysis confirmed that CNC has more activation energy than cellulose and thus confirms its compact and resistive crystalline structure. This has been attributable to the stronger hydrogen bonding in CNC crystalline domains than that in cellulose crystalline domains. Scanning electron microscopy revealed that lignin and hemicellulose were eliminated after chemical pretreatments, and CNC with a rodlike shape was obtained after hydrolysis. Moreover, transmission electron microscopy confirmed the nanoscale of crystalline cellulose. ζ potential analysis indicated that the CNC afforded a stable suspension (-29.27 mV), which is less prone to flocculation. Kinetic analyses of cellulose and cellulose nanocrystals isolated from date palm waste are useful for making composites and designing selective pyrolysis reactors. View Show abstract ... Renewable bio-based polymers and a large part of the composites derived from natural resources are producing a great interest due to the new way of managing fossil fuel resources and the negative effect in environmental impact of fuel-based plastic products [1][2] [3] [4]. Therefore, the use of biopolymers from renewable natural resources is one of the potential ways to reduce the dependence on fossil fuels due to its sustainable nature [5][6][7][8] Another advantage of the development of biobased polymers is the reduction of the carbon footprint with the reduction of CO 2 emissions into the environment. ... Alternative modification by grafting in bamboo cellulose nanofibrils: A potential option to improve compatibility and tunable surface energy in bionanocomposites Article May 2022 INT J BIOL MACROMOL Carlos Alejandro Rodríguez Ramírez Alain Dufresne Norma D'Accorso Nancy Lis Garcia Chemical modification in surface of cellulose nanofibrils CNFs (20 nm) from an endemic and non-significant value-added, Argentine bamboo, was developed. The modification in the CNFs was carried out with three simple routes using a low molecular weight polylactic acid synthesized in our laboratory (PLA1). The first step comprises of protection of the hydroxyl groups of PLA1 through a benzoylation (PLA1Bz). The next step consisted of the activation of carboxyl groups using thionyl chloride and the last reaction was the grafting of the modified PLA onto the CNFs (PLA1Bz-g-CNF). The covalently functionalization is confirmed by spectroscopically techniques as well as PLA1Bz-g-CNFs were characterized by thermal analyses. The PLA1Bz-g-CNFs were taken up such as nanocharges to improve properties of compatibilization and changing surface properties in films based on PLA. The comparison between the films with PLA1Bz-g-CNFs with respect to the physic mixture of the components (PLA1Bz/g/CNF), shows an improvement in the thermal, mechanical, and surface properties of the material, particularly when 5% of PLA1Bz-g-CNFs was added. The dispersive (γS D) component of film is increased in 36.1 mN/m respect to 29.3 mN/m from the films obtained with the physic mixture nanofibrils without modification and a plasticizing effect was noticed in the final material. View Show abstract ... The chemical composition of pineapple residues contains approximately 38% to 50 % of cellulose, 23 % to 32 % of hemicellulose, and 13% to 30 % of lignin (Sierra et al. 2008). Therefore, hemi-cellulosic resources, including agricultural and industrial residues, offer a suitable alternative for the extraction of high-value renewable products (Kunaver et al. 2016) . Lignocellulosic waste has become an alternative natural resource for the extraction of a valuable sugar, xylose. ... Effects of ultrasonic-assisted alkaline pretreatment on xylose production from pineapple peel waste Article Full-text available May 2022 Choosit Hongkulsup Panchalee Pathanibul The pineapple industry generates large amounts of unusable waste (peel and core) with adverse environmental impacts. This experimental study aims to systemize the potential of ultrasonic-assisted alkaline pretreatment for xylose production from pineapple peel waste. The best condition for single alkaline pretreatment (1 % NaOH w/v, 100 °C, 60 min) has obtained hemicellulose, cellulose, and lignin composition at 34.80 %, 32.16 %, and 8.66 %, respectively, retained in the biomass. Meanwhile, a combination of alkaline (1 % NaOH, w/v) and ultrasonic (frequency 40 kHz, 45 min) pretreatment has obtained the percentage yield of hemicellulose and lignin at 51.15 % and 7.15 %, respectively. Both single alkaline and ultrasonic-assisted alkaline pretreated samples were subsequently hydrolyzed with 2 % H2SO4 (w/v). After acid hydrolysis for 30 min, the maximum xylose concentration of 48.85 g.L-1 was achieved by using ultrasonic-assisted alkaline pretreatment, while single alkaline pretreatment contributed to the lowest yield of xylose (37.11 g.L-1). It is shown that the ultrasonic-assisted alkaline treatment is more favorable than single alkaline pretreatment as it can produce high xylose concentration after the subsequent hydrolysis. These results indicated that ultrasonic-assisted alkaline pretreatment and its subsequent acid hydrolysis were appropriate for producing xylose from pineapple peel waste. View Show abstract ... The entire spectra, also for the samples aged in darkness, are shown in Additional file 1: Fig. S2. There are higher peaks at 1605 cm −1 , 1430 cm −1 , 1372 cm −1 and 1313 cm −1 for some samples, but these are generic bands for any cellulosic material, including isolated nanocellulose from cotton linters [44] . Since they show no trend under the applied aging conditions, we cannot draw a conclusion as to specific oxidations or other features of any constituent of papyri. ... Shine a light on papyrus: monitoring the aging process Article Full-text available Apr 2022 Florian Bausch Dickson D. Owusu Jörg Graf Antje Potthast The aging behavior of ancient papyri is not entirely understood, although such understanding is crucial for tailored conservation concepts to preserve these precious historical documents for the millennia to come. In a study on accelerated aging, the effect of light on papyrus sheets was studied, and the consequences were monitored by a combination of non-invasive and invasive techniques. Papyrus sheets were aged for two months at 90 °C and 50% relative humidity, with and without the influence of light. Changes at the optical, mechanical, and molecular levels were monitored using CIELAB color measurements, tensile tests, Fourier transform-infrared spectroscopy (FTIR), and size exclusion chromatography—multi angle light scattering (SEC-MALS). Light exposure has severe consequences for the optical and mechanical properties of papyri, reflected by a strong decrease in cellulose chain length and tensile strength. SEC-MALS proved to be the best method to assess the conservation status of papyri due to its clear results and low sample demand. This publication seeks to highlight the effects of light-induced degradation of papyri and to facilitate an understanding of the underlying aging mechanisms, to support in future conservation measures. Graphical Abstract View Show abstract ... There are a number of studies that have been carried out on the production of nanocellulose from agricultural waste (Boerjan et al. 2003;Gibson et al. 2010;Song et al. 2009;An et al. 2020;Bongao et al. 2020;Israel et al. 2008;Yandan et al. 2015). In addition to rice, straw and the aforementioned husks (Boerjan et al. 2003;Gibson et al. 2010;Lwako et al. 2013;Sumira et al. 2020), attention has been paid to the residue of coniferous wood, inclusive of wood chips, pine branches and needles, with a target production yield of more than 13% (Rosana et al. 2016; Kunaver et al. 2016) . Furthermore, among the plants that could be cultivated in Kazakhstan, special consideration should be given to hemp, with a cellulose content in the plant stems that exceeds 50-70% (Jean et al. 2010). ... Highly-efficient isolation of microcrystalline cellulose and nanocellulose from sunflower seed waste via environmentally benign method Article Full-text available May 2022 CELLULOSE Kydyrmolla Akatan Sana Kabdrakhmanova Tilek Kuanyshbekov Sabu Thomas The main focus of the study was to create natural microcrystalline cellulose obtained from a raw material source, the residue of sunflower seeds following oil extraction. For this purpose, organosolvent oxidation was chosen instead of the conventional method, whereby microcrystalline cellulose (MCC) was extracted from sunflower seed husks (SFHs), after which the refining of cellulose nanocrystals (CNCs) was carefully conducted. The organosolvent method of obtaining MCC involves the use of peroxyacetic acid (PAA), which provides a high yield of cellulose and eliminates the need to use chlorine-containing compounds in the process of bleaching. The environmentally benign method of obtaining MCC using the organosolvent method consisted of halving the concentration of acetic acid and hydrogen peroxide, to 58% and 15%, respectively, so as to obtain PAA, which yields an MCC of 47.8%. Physico-chemical characterization of particle sizes, optical properties, chemical and crystal structure, surface morphology, and thermal stability of MCC and CNCs was performed. FTIR analysis revealed the structural similarity of all the materialsof the extracted cellulose. Surface morphology was observed using SEM, showing that the surface of MCC fibers appeared rough, whereas that of CNCs was smooth with overlapping rod-like structures. The surface of CNC film was found to be colorless and composed of nanofibrils. XRD analysis and determination of average particle size revealed that the MCC had a crystallinity index (CI) of 72.9 ± 4%, a coherent scattering length (CSL) of 2.9 ± 0.1 nm, and an average particle length of 1971 ± 100 nm and width of 266 ± 35 nm. Acid hydrolysis resulted in the reduction of the length of CNCs by 4 times and the width by around 5 times, accompanied by an increase in the CI value. Cellulose was found to break down in the temperature range of 200–358 °C. Overall, SFHs are considered to be an effective potential source for CNCs, while the method employed herein for the extraction of cellulose from agricultural biomass waste is both cost-effective and environmentally benign. Graphical abstract View Show abstract ... The succinylation reaction, followed by the conjugation with lipase, did not change the morphology and particle size distribution of nanocellulose as shown in Figure 5. NCB and NCB-suc has average diameters of 30 -40 nm and average lengths of 300 -400 nm giving an aspect ratio of ~13. This results in shape, size and aspect ratio agree with what was found by other authors [33] [34] [35] . ... Covalent Immobilization of Lipase on Bacterial Cellulose Membrane and Nanocellulose Article Full-text available Feb 2022 Juliano Brisola Gabriel Jonathan Sousa Andrade Sabrina Alves de Oliveira Cesar Tischer Abstract The cellulose from Komagataeibacter hansenii is synthesized as a thin film at the surface of glucose based media. Strong acid hydrolysis release sections of crystalline cellulose chains in nanometric scale that leads to persistent suspensions in water. The cellulose anhydro-glucose hydroxyls are suitable to receive functional groups as enzymes, and lipases have great economic value being a valuable model for protein immobilization. In this work both, the membrane of bacterial cellulose as well the nanocellulose produced trough acid hydrolysis, was functionalized with a lipase. The bacterial cellulose membranes were produced by Hestrin-Schramm medium, and nanocelluloses produced from the pristine material was characterized using techniques as 13C solid state NMR and transmission electron microscopy (TEM). The pristine membranes and nanocellulose were functionalized with succinic acid as linker, then lipase was conjugated using EDC (N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride), and NHS (N-Hydroxysuccinimide). The effectiveness of the chemical process was characterized, and the lipase activity were measured. The presence of the succinic acid and amide linkage, as well physical-chemical changes on the functionalized polysaccharide. Hence, we inferred that after immobilization the enzyme maintained its activity in both cellulose and the cellulose membrane. View Show abstract ... The latter synthesis method was used in present work since it is the least energy and financially expensive. Synthetic cellulose is obtained from many cellulose-containing materials [17] [18] [19][20][21]. In this work the stalks of plant material promising for cellulose production [22] were used for the synthesis of nanocellulose. ... Influence of cellulose particles on chemical resistance, mechanical and thermal properties of epoxy composites Article Full-text available Jan 2020 Nadiia Sigareva Dmitro Starokadomsky Sergey V. Shulga Borys Gorelov Background: The technological developments for nanocellulose production from cheaper plant materials compared to wood, in particular, agricultural waste is an urgent task of nanobiophysics. The discovery of possibility of expanding the functional characteristics of materials in compositions with modified cellulose particles essentially stimulated the interest of researchers in cellulose composites. Surface modification of cellulose particles by functional materials, such as dyes, metal oxides, silicon, allows applying composites with modified cellulose in various areas of modern industry. A significant improvement in the operational performances of functionalized cellulose particles can be achieved by using them as filler in polymers. Epoxy resin compositions with modified and unmodified cellulose particles, studied in present work, are an example of hybrid biosystem. The interfacial interaction of filler particles with the epoxy matrix, their concentration and dispersion can change the physical and chemical properties of the biopolymer and the functional parameters of biocomposites. Studying the influence of external fields on the physical and chemical properties of epoxy resin-based biosystems and their influence on operational parameters seems to be an urgent problem of advanced and sustained materials science. Objectives: The purpose of this work was to develop an effective nanocellulose synthesis from plant materials and surface functionalization of micro- and nanocellulose particles with clathrochelate iron (ΙΙ) dye as well obtaining biocompositions of epoxy resin with functionalized and non-functionalized micro- and nanocellulose, and to explore of the morphology, chemical resistance, mechanical and thermal properties of epoxy composites with cellulose micro and nanoparticles. Materials and methods: The studying objects were the composites of epoxy resin Eposir-7120 with a polyethylene polyamine “PEPA” hardener in a ratio of 6.2:1 and 10% cellulose micro and nanoparticles. The microcellulose obtained from wood has been a commercial product. Nanocellulose has been synthesized from organosolv cellulose obtained from Miscanthus x giganteus stalks. Surface modification of micro- and nanocellulose was performed using the clathrochelate iron (ΙΙ) dye. The specific surface area of cellulose particles was determined using low-temperature nitrogen adsorption-desorption according to the Brunauer-Emmett-Teller method. Mechanical parameters were determined using universal Shopper and UMM-10 machines. Thermal analysis was performed using Q1500 analyzer. Swelling was determined by the gravimetric method. Results: Elastic modulus E, compressive strength σ and thermogravimetric parameters were determined. It was shown that in composites with micro and nanocellulose the E rises in 7.0–12.2% while the σ increases in 9.1% for composites with cellulose micro particles. The loading resin with nanocellulose and modified cellulose microparticles no affects the σ value of composites. The thermal stability of epoxy polymer (310°C) reduces after loading with micro and nanocellulose to 290 and 300°C, respectively. Chemical resistance of composites with both celluloses to 20% nitric acid reduces. In neutral medium swelling characterizes by rapid sorption to saturation of 15–20% acetone in 36 hours. Conclusions: Thus, the synthesis method of nanocellulose from plant materials and functionalization of its surface with clathrochelate iron (ΙΙ) were developed. Light response of dye was detected in visible spectral range. Epoxy resin composites with 10% micro and nanocellulose were obtained. The filling effect with micro- and nanocellulose at elastic modulus, compressive strength, and thermal stability of epoxycomposites was studied. The swelling processes run similarly in composites with cellulose micro and nanoparticles. View Show abstract ... CNC was prepared in accordance with the procedure described by Kunaver, Anžlovar, and Žagar in 2016 [28] . The liquefaction reaction, using glycols and mild acid catalysis (methane sulphonic acid), was applied to eucalyptus wood. ... Functional Nanocellulose, Alginate and Chitosan Nanocomposites Designed as Active Film Packaging Materials Article Full-text available Jul 2021 Gregor Lavrič Inese Filipova Urška Vrabič-Brodnjak Ana Oberlintner The aim of the study was to characterize and compare films made of cellulose nanocrystals (CNC), nano-fibrils (CNF), and bacterial nanocellulose (BNC) in combination with chitosan and alginate in terms of applicability for potential food packaging applications. In total, 25 different formulations were made and evaluated, and seven biopolymer films with the best mechanical performance (tensile strength, strain)—alginate, alginate with 5% CNC, chitosan, chitosan with 3% CNC, BNC with and without glycerol, and CNF with glycerol—were selected and investigated regarding morphology (SEM), density, contact angle, surface energy, water absorption, and oxygen and water barrier properties. Studies revealed that polysaccharide-based films with added CNC are the most suitable for packaging purposes, and better dispersing of nanocellulose in chitosan than in alginate was observed. Results showed an increase in hydrophobicity (increase of contact angle and reduced moisture absorption) of chitosan and alginate films with the addition of CNC, and chitosan with 3% CNC had the highest contact angle, 108 ± 2, and 15% lower moisture absorption compared to pure chitosan. Overall, the ability of nanocellulose additives to preserve the structure and function of chitosan and alginate materials in a humid environment was convincingly demonstrated. Barrier properties were improved by combining the biopolymers, and water vapor transmission rate (WVTR) was reduced by 15–45% and oxygen permeability (OTR) up to 45% by adding nanocellulose compared to single biopolymer formulations. It was concluded that with a good oxygen barrier, a water barrier that is comparable to PLA, and good mechanical properties, biopolymer films would be a good alternative to conventional plastic packaging used for ready-to-eat foods with short storage time. View Show abstract ... Various methods are employed for extracting relatively pure CNCs from the cell wall [23,53]. Other methods such as high-intensity ultrasonication of microcrystalline celluloses (MCCs), microwave-assisted hydrolysis, acid hydrolysis, steam explosion, chemical pulping, and mechanical pulping (of wood) are also used to produce CNCs [54, 55]. Sulfuric acid hydrolysis or heat-controlled approaches present extraction processes, which are widely used for producing CNC [56,57]. ... Application of nanocellulose composites in the environmental engineering as a catalyst, flocculants, and energy storages: a review Article Full-text available Jul 2021 JCC Mario Pagliaro Rosaria Ciriminna Mohammad Yusuf Zahra Rezaei Nezhad Nanocellulose, the most promising bionanomaterial, is obtained either from the degradation of natural polymers or by the activity of bacteria and microorganisms. These biomaterials present various advantages, including full recyclability, biodegradability, and lack of harmful effects on the human body and environment. Furthermore, nanocelluloses are candidates to fabricate thin transparent layers, fibers, hydrogels, and aerogels due to their remarkable optical, thermal, and mechanical behaviors, including high crystallinity, Young’s modulus, and porosity content. These exceptional properties present the superb potential of these materials for the device of environmentally engineered tenable products. This paper presents an outline of the contemporary nanocellulose research works as well as details and information on the nanocellulose materials, especially the synthesis process of composites, along with the areas in which these materials can be utilized, such as energy, flocculant, pollution sensors, and catalysts, to respond to the rising requests of these materials. View Show abstract ... Renewable bio-based polymers and composites derived from natural resources are generating a great interest due to the depletion of fossil fuel resources and the negative environmental impact of fossil fuel-based plastic products (Kunaver et al. 2016 Among the most promising biodegradable polymers stands out polylactic acid (PLA), because it has been known for several decades and has attracted much attention in both the academic and industrial sectors. The advantages of this polymer are due to the fact that it is an environmentally friendly plastic, commercially available, making it the most representative biodegradable and bio-based polymer (Scaffaro et al. 2017;Mao et al. 2019). ... Graft modification in bamboo cellulose nanofibrils: An effective option to improve compatibility and tunable surface energy Preprint Full-text available Jan 2021 Carlos Alejandro Rodríguez-Ramírez Alain Dufresne Norma D'Accorso Nancy Lis Garcia In this work, from an endemic and non-significant value-added bamboo argentine, nanofibrils (CNFs) of 20 nm in width were obtained. These nanofibrils were chemical modified in surface with three simple steps using a noncommercial low molecular weight polylactic acid. The success of modification was confirmed by FTIR, TGA, DSC and XRD analysis. The modified nanofibrils were taken up for changing surface properties in films based on commercial PLA. The results show that dispersive (γ D/S) component of films increase of 34.7 mN/m to 36.1 mN/m after the addition of modified nanofibrils from 2 to 5% in formulation of the films, comparing with a physical blend. Interesting others result in physical, mechanical, and thermal properties of the nanocomposites, were reported. View Show abstract ... It can be observed that the aspect ratio of the nanocellulose from Gelidium elegans algae (L/d)= 25) was similar to Eucalyptus wood (L/d=24) [35], using a similar hydrolysis process. However, the aspect ratio of yielded algae nanocellulose was larger than nanocelluloses isolated from sugar palm fibre (L/d = 13-14) [13], cotton linter (L/d = 5) [36], C=curaua (L/d = 13-17) [37], chinese silver grass (L/d = 15) [38] , and mengkuang leaves (L/d = 10-20) [32] via H2SO4 hydrolysis under similar hydrolysis conditions. It has been reported by Ilyas et al. [8] that nanocellulose could have an aspect ratio of up to 100, depending on the preparation method of NCCs and the source of NCCs used. ... Production of nanocellulose from sustainable algae marine biomass Conference Paper Full-text available Jan 2021 Ilyas R.A. Atikah Mahamud The global algae product market is projected to grow from USD 3.20 Billion in 2017 to USD 5.38 Billion by 2025 at a compound annual growth rate (CAGR) of 6.7% during the forecast period of 2018-2025. Typically, the exploitation of algae biomass in the main commercial agar production and the food industry would lead to a massive amount of solid residues that are normally discharged into the environment. These solid residues have vast potential as feedstocks for nanocellulose. Currently, nanocellulose possesses huge potential in many ranges of applications, from plastic packaging to flexible optoelectronics. This is due to its intrinsic properties, such as high specific surface area with abundant surface hydroxyl groups, high tensile strength and stiffness, high crystallinity, lightweight, high strength and modulus, high aspect ratio, high thermal resistance, abundant in nature, cost-effectiveness, and environmental benefits due to its biodegradability and recyclability. We discuss the potential production of nanocellulose from sustainable algae marine biomass with a special focus on cellulose content of algae biomass and methods of nanocellulose isolation from algae biomass, presenting our opinion regarding important recent advances in algae nanocellulose researches and the directions driving current technologies and future outlooks. We look forward to bringing to our readers some of the excitement that currently surrounds algae nanocellulose research, which is obtained from the renewable and sustainable green nature of particles, their interesting chemical, physical, properties, and the variety of applications this material can influence. View Show abstract ... After centrifuging, waste liquor is obtained which is recycled through the process several times in place of a fresh multifunctional alcohol mixture. The process route is presented in Figure 2, and further details are described by Kunaver et al. (2016) . The key difference to liquefied wood is the use of cellulose-rich feedstock (waste textiles, residual cotton linters, etc.) which yields little to no cyclic hydrocarbon content in waste liquor. ... Comparative Analysis of Bio-Intermediates and Waste-Derived Fuels in Experimental Gas Turbine Article Full-text available Sep 2020 Žiga Rosec Véronique Dias Francesco Contino Tine Seljak The paper presents a first comparative analysis of emission formation phenomena of three different bioliquids, derived from low-cost waste streams while utilizing the same gas turbine-based experimental setup. A consistent and unbiased comparison is ensured by the application of the same experimental test rig featuring only those minor fuel-based adaptations, which are required to ensure the most favorable operation of each of the analyzed fuels. This provides the direct comparative data between combustion performance of liquefied wood, obtained through solvolysis process, glycerol, and waste liquor from nanocellulose production which were previously tested in various combustion systems, hence making a direct evaluation of fuel's suitability difficult. The study focuses on the analysis of all key thermodynamic parameters and significant emission species covering CO, NO x , HC particulate matter, and soot as well as identification of underlying phenomena for observed emission trends. These indicate that for NO x emissions, a good correlation exists to the stoichiometric ratio of the fuels, where a low stoichiometric ratio results in lower NO x emissions, provided that oxygen content is the main diluent and fuel-bound nitrogen is low. As all tested fuels feature oxygen content above 43%, this enables a large improvement in NO x-CO trade off, as CO emissions are reduced with higher peak combustion temperatures while minimally increasing NO x emissions. Similar observations are made for particulate matter-NO x trade off; however, the ash content significantly impacts the particulate matter emission, hence reducing the potential for clean combustion of waste liquor. In the case of glycerol with no ash content, soot emissions are minimal and for an order of magnitude lower than for benchmark diesel fuel, as there are numerous phenomena effectively reducing their formation and increasing their oxidation. The presented research confirms that utilization of bio-intermediates and waste-derived fuels in appropriate combustion setups can, beside a low CO 2 footprint, feature also very low emissions of other pollutant species, providing that fuels feature high oxygen content, low ash content, and low nitrogen content. With such approach, it is possible to achieve clean combustion that is fully in line with circular economy guidelines. View Show abstract ... The same liquefaction process was used for the isolation of the nanocrystalline cellulose from biomass (Kunaver, 2016) . The method is a novelty and a model procedure for NCC isolation from different natural cellulosic sources with high yields and with high crystallinity index. ... BIOMASS UTILIZATION IN POLYMER SYNTHESIS AND NANOCELLULOSE PRODUCTION Article Full-text available Jun 2018 Matjaz Kunaver Ema Žagar Raša Urbas Biobased platform chemicals can be provided through lignocellulosic conversion in biorefineries. Acid catalyzed glycolysis of biomass wastes is such example. The liquefaction reaction was the basic platform for production of polymers, adhesives, energy and nanocellulose. We used the liquefied wood as a polyol in the polyester synthesis, which was applied in polyurethane foam production. Liquefied biomass reacts with thermosetting systems containing melamine–urea–formaldehyde resin and it was found that a 50% addition of liquefied wood met the European standard quality demands for particle boards. Two fuels, namely liquefied cotton fibres and liquefied biomass, were used in gas turbine. Stable combustion was achieved and experimental results indicate successful utilization of these biofuels in professional gas turbines. The same liquefaction process was used for isolation of nanocrystalline cellulose (NCC) from biomass. This method represents a novelty and is a model procedure for NCC isolation from different natural cellulosic sources with high yields and with high crystallinity index. View Show abstract ... Agricultural, forest, and industrial wastes may be used to prepare cellulose and isolating their nanostructures (CNSs) due to its availability and low cost. Eucalyptus waste is an attractive raw material due to its high content of cellulose (~ 35 wt%) and good mechanical and thermal properties [1] [2][3]. The revalorization of these forest byproducts is a way to make the production of sustainable and renewable materials more commercially attractive. ... A New Proposal of Preparation of Different Polymorphs of Nanocellulose from Eucalyptus citriodora Article Full-text available Apr 2020 Mariana T. Junqueira Giovanni Lima Alana Gabrieli de Souza D. S. Rosa Cellulose is a renewable, sustainable, and high available biopolymer; their common form is the type-I polymorph. However, polymorphic changes are associated with different properties and a wide range of applications. In this study, we proposed a new method to prepare polymorphic cellulose nanostructures (CNSs): first, the CNS were isolated, and then the polymorphs were converted. CNS-I (type-I), CNS-II (type-II), and CNS-III (type-III) were successfully obtained, and the structure, crystallinity, superficial characteristic, morphology, and thermal stability were evaluated. The results showed that CNS-II and CNS-III are more amorphous than CNS-I due to the strong reagents used for the polymorphic conversion, which results in a swelling, increased chain spacing, and structural disorganization. This effectively changed the morphology of the CNS, from cellulose nanocrystals from irregular quasi-spherical nanoparticles. The proposed method allows a wide range of applications, from package and nanocomposites with CNS-I due to its high crystallinity and crystal morphology, to drug carrier, food thickener and biomedical products for CNS-II and CNS-III due to its quasi-spherical shape and more amorphous structure. Graphic Abstract View Show abstract ... All diffractograms showed peaks around 16⁰, 22.5⁰, and 34⁰, which were associated with the diffraction planes of (101), (002), and (040), respectively. This indicated the crystal lattice of cellulose type I (Kunaver et al. 2016) . Similar curves and peaks of diffractograms of CNC exhibited that the acid hydrolysis did not interrupt the structure of the cellulose. ... An Alkaline Deep Eutectic Solvent Based on Potassium Carbonate and Glycerol as Pretreatment for the Isolation of Cellulose Nanocrystals from Empty Fruit Bunch Article Full-text available Jan 2020 BIORESOURCES Peigie Gan S.T. Sam Muhammad Faiq Abdullah Lian See Tan Cellulose nanocrystals (CNC) were successfully isolated from oil palm empty fruit bunch (EFB) using sulphuric acid hydrolysis preceded by alkaline deep eutectic solvent (DES) pretreatment and bleaching. In this study, an alkaline DES consisting of potassium carbonate and glycerol (molar ratio of 1:7) was used as the pretreatment solvent to promote the dissolution of lignin and hemicellulose. The processing parameters of acid hydrolysis were optimized using Box-Behnken Design. The results showed that the yield of CNC was 37.1%, under the optimal conditions of 60.0 wt% acid concentration at 46.1 °C for 58.5 min. The field emission scanning electron microscopy (FESEM), chemical composition analysis, and Fourier transform infrared (FTIR) results indicated that unwanted impurities, such as hemicellulose and lignin, were efficiently eliminated from the raw EFB fibers by DES pretreatment and bleaching. The average diameter of CNC was less than 10 nm. The raw EFB fiber, treated cellulose, and CNC showed crystallinities of 38.7%, 51.2%, and 65.3%, respectively. The CNC had lower thermal stability, which was ascribed to the sulphate group present on the CNC surface. View Show abstract ... Since world timber resources steadily decrease, the production of pulp from non-wood plant materials, which includes cereal stalks (wheat, rye, rice, corn) and technical fibers (cotton, flax, kenaf, hemp), is an urgent problem (Sánchez et al. 2016;Morais et al. 2013;Kamoga et al. 2013). The literature describes the technologies for obtaining nanocellulose from different cellulose-containing materials (Kim et al. 2016;Travalini et al. 2016;Bansal et al. 2016; Kunaver et al. 2016) . During the processing of grain and industrial crops, fibrous waste is formed, which can be used as an alternative to wood in pulp production. ... Preparation and application of nanocellulose from non-wood plants to improve the quality of paper and cardboard Article Full-text available Jan 2020 Valerii Barbash Olha V. Yashchenko The study describes the preparation of pulp and nanocellulose from non-wood plant materials, as well as an improved properties of paper and cardboard for mass production. The pulps from wheat straw, kenaf and flax fibers were prepared by the environmentally friendly organosolv method—cooking in a solution of isobutanol or peracetic acid. The organosolv pulps used to prepare nanocellulose had traces of lignin and mineral substances. The process of hydrolysis of the investigated organosolv pulps was optimal when carried out under the following conditions: 43% sulfuric acid, temperature 60 °C, hydrolysis time 90 min and ultrasonic treatment 60 min. Using the methods of SEM, XRD, TEM, AFM and TGA, the structure and properties of organosolv pulps and nanocellulose were studied. The use of nanocellulose in bulk and on the surface of mass types of paper and cardboard—paper for corrugation, offset paper, recycled containerboard and cardboard for flat layers of corrugated cardboard were investigated. We established the positive effect of nanocellulose application on the physical and mechanical properties of paper and cardboard. Low consumption of nanocellulose allows production of the paper and cardboard with properties that meet the requirements to appropriate standards and replacement of synthetic reinforcing materials. View Show abstract ... Optimization of lignocellulosic delignification. Typically, lignocellulosic delignification -which produces cellulose to nanocellulose -entails the disruption of cellulose, hemicellulose, and lignin using a combination of mechanical and chemical pulping, steam explosion, hydrolysis, as well as alkaline and bleaching processes 40, 41 . A similar technique has been reported in our previous study, whereby alkaline-bleaching was performed repetitively up to six times until the desired purity of cellulose was obtained 17 (see Fig. 1a). ... Telescopic synthesis of cellulose nanofibrils with a stable dispersion of Fe(0) nanoparticles for synergistic removal of 5-fluorouracil Article Full-text available Aug 2019 Mohd Shaiful Sajab Denesh Mohan Jude Santanaraj Nur Hidayatul Nazirah Kamarudin The recognition of cellulose nanofibrils (CNF) in the past years as a high prospect material has been prominent, but the impractical cellulose extraction method from biomass remained as a technological barrier for industrial practice. In this study, the telescopic approach on the fractionation of lignin and cellulose was performed by organosolv extraction and catalytic oxidation from oil palm empty fruit bunch fibers. The integration of these techniques managed to synthesize CNF in a short time. Aside from the size, the zeta potential of CNF was measured at −41.9 mV, which allow higher stability of the cellulose in water suspension. The stability of CNF facilitated a better dispersion of Fe(0) nanoparticles with the average diameter size of 52.3–73.24 nm through the formulation of CNF/Fe(0). The total uptake capacity of CNF towards 5-fluorouracil was calculated at 0.123 mg/g. While the synergistic reactions of adsorption-oxidation were significantly improved the removal efficacy three to four times greater even at a high concentration of 5-fluorouracil. Alternatively, the sludge generation after the oxidation reaction was completely managed by the encapsulation of Fe(0) nanoparticles in regenerated cellulose. View Show abstract ... In the context of industrial application, woody biomass is a renewable, carbon-neutral source of lignocellulosic materials for construction, pulp, bioenergy and, increasingly, for advanced biomaterials such as nanocellulose (Kunaver et al., 2016; Thomas et al., 2018). These and other biorefinery products, including novel biopolymers and biochemicals, are key to the emerging plant-based bio (Vanholme et al., 2013a;Van de Wouwer et al., 2018). ... Systems and Synthetic Biology of Forest Trees: A Bioengineering Paradigm for Woody Biomass Feedstocks Article Full-text available Jun 2019 Alexander A Myburg Steven Hussey Jack P. Wang Eshchar Mizrachi Fast-growing forest plantations are sustainable feedstocks of plant biomass that can serve as alternatives to fossil carbon resources for materials, chemicals, and energy. Their ability to efficiently harvest light energy and carbon from the atmosphere and sequester this into metabolic precursors for lignocellulosic biopolymers and a wide range of plant specialized metabolites make them excellent biochemical production platforms and living biorefineries. Their large sizes have facilitated multi-omics analyses and systems modeling of key biological processes such as lignin biosynthesis in trees. High-throughput ‘omics’ approaches have also been applied in segregating tree populations where genetic variation creates abundant genetic perturbations of system components allowing construction of systems genetics models linking genes and pathways to complex trait variation. With this information in hand, it is now possible to start using synthetic biology and genome editing techniques in a bioengineering approach based on a deeper understanding and rational design of biological parts, devices, and integrated systems. However, the complexity of the biology and interacting components will require investment in big data informatics, machine learning, and intuitive visualization to fully explore multi-dimensional patterns and identify emergent properties of biological systems. Predictive systems models could be tested rapidly through high-throughput synthetic biology approaches and multigene editing. Such a bioengineering paradigm, together with accelerated genomic breeding, will be crucial for the development of a new generation of woody biorefinery crops. View Show abstract Quantification of Hydrolytic Sugars from Eucalyptus globulus Bio-Oil Aqueous Solution after Thermochemical Liquefaction Article Full-text available Apr 2023 Luciana Silva Sofia Moreira Fernandes Diogo Gonçalves Rui Galhano dos Santos Eucalyptus globulus sawdust is a residue from the pulp and paper industry which has been underutilised and undervalued. The thermochemical liquefaction of sawdust can be considered an alternative for recycling this residue, as it results in the production of a bio-oil that, when extracted in water, allows the obtention of an aqueous solution composed of carbohydrates. The sugars resulting from the aqueous fraction of bio-oil can be valued by and applied in the industry to produce sustainable materials. For the first time, the sugar composition of the aqueous extract of bio-oil was disclosed, identified, and quantified by a high-pressure liquid chromatograph (HPLC) coupled to a refractive index (RID) detector containing fructose (36.58%) and glucose (33.33%) as the main components, sucrose (15.14%), trehalose (4.82%) and xylose (10.13%). The presence of these sugars was further confirmed by two-dimensional (2D) 1H-13C heteronuclear single-quantum correlation–nuclear magnetic resonance (HSQC–NMR) spectroscopy. Fourier-transform infrared (FTIR-ATR) and elemental analyses were also used. In addition, the pathway leading to the identified sugars is also suggested. View Show abstract EFFECT OF ACID HYDROLYSES ON PROPERTIES OF CELLULOSE/POLY FURFURAL ALCOHOL (PFA) COMPOSITES FROM MAIZE STALK Article Feb 2023 WOOD RES-SLOVAKIA Nduduzo Khumalo MASULUBANYE S. MOHOMANE Linda Zikhona Linganiso Motaung Tshwafo The study investigated morphology and thermal properties of cellulose/poly furfural alcohol (PFA) composites prepared from maize stalk through acid mixtures. The cellulose nanocrystals (CNCs) were extracted from maize stalk via acid hydrolysis using mixtures of various acids.The prepared CNCs were encapsulated in a PFA matrix via in situpolymerization process using p-toluene sulfonic acid as catalyst. The properties of untreated maize stalk, cellulose and their nanocomposites were analysed by scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transmission infrared (FTIR) and thermogravimetric analysis (TGA). The crystallinity of maize stalk was generally increased after an acid hydrolysis dominated by H2SO4/HNO3 and H2SO4/HCl. The same trend was observed from TGA, except that H2SO4/H3PO4and H2SO4/HClO4dominated thermal stability trailed by H2SO4hydrolysed CNC nanocomposite. The surface breakage of fibers observed in SEM images was depended on the strength of acids used tohydrolysed the CNC. There was also evidence of aggregation and cracked PFA surface with addition of acid hydrolysed CNCs, dependent on the acids strength. The H2SO4/HClO4hydrolysed CNC/PFA displayed afairly good dispersion of CNCs in the PFA matrix with no surface breakage. View Show abstract Environmentally Benign Pulping Processes Chapter Feb 2023 Pratima Bajpai The pulp and paper industry has been severely impacted by economic conditions and environmental pressures, and it is under intense pressure to improve performance in relation to the release of pollutantsPollutants. Pressure to adopt new, environmentally friendly technologies is growing due to growing environmental concerns. The general steps of pulpingPulping, bleachingBleaching, and paper production are all included in an integrated pulp and paper process. Over the past two decades, new environmental laws and consumer activism have drastically changed how chemical pulps are produced. The pulping processes that can address the environmental challenges of the pulp and paper industry are presented in this chapter. These include Steam explosion pulpingSteam Explosion Pulping; High yield pulpingHigh Yield Pulping; OzoneOzonefor high yield pulpingHigh Yield Pulping; Oxygen delignificationOxygen delignification (ODL); Ozone delignificationOzone delignification; Organosolv PulpingOrganosolv pulping; Ionic liquidsIonic liquid; Deep eutectic solventsDeep eutectic solventsand BiopulpingBiopulping. View Show abstract Preparation and Properties of Cellulosic Nanomaterials Article Full-text available Jan 2022 Alain Dufresne What are the reasons for the effervescence and explosion of the scientific literature during the last decade in the field of cellulosic and other polysaccharide nanomaterials? First, the raw materials are abundant, available in a variety of forms, renewable, non-toxic, low density, and biodegradable. In addition, it is well known that unexpected and attractive properties can be observed when decreasing the size of a material down to the nanoscale. Different forms of cellulose nanomaterials, resulting from a top-down deconstructing strategy (cellulose nanocrystals – CNCs, cellulose nanofibrils – CNFs) or bottom-up strategy (bacterial cellulose – BC), can be prepared. Multiple mechanical shearing actions applied to cellulosic fibers release more or less individually the nanofibrils. A controlled strong acid hydrolysis treatment can be applied to cellulosic fibers allowing the selective dissolution of non-crystalline domains and disengagement of nanocrystalline cellulose regions. The mechanical modulus of crystalline cellulose is the basis of many potential applications. With a Young's modulus of the order of 100–130 GPa and a specific surface of several hundred m2·g–1, these cellulosic nanomaterials have a significant capacity of reinforcement at low filler content. Several properties reviewed in this article are impacted by the nanoscaling process View Show abstract Preparation and Applications of Cellulose Nanomaterials Article Dec 2022 Alain Dufresne The interest in materials from biological resources has grown tremendously in recent years as a result of their high potential to manufacture high value products with low impact on the environment. Cellulose is the most abundant natural biopolymer. It constitutes 50% of biomass. Its exploitation dates back to the beginning of civilization, but it has received considerable attention in recent decades in view of the transformations of properties generated at the nanometric scale. Unexpected properties can be obtained by reducing the size of a material to the nanoscale, and cellulose in not an exception. In this article, we review the preparation of nanomaterials from different cellulosic sources, along with wood. By transforming cellulose at a nanoscale, new properties are accessible and many new industrial applications can be expected in different fields. A quick overview of the promising markets where cellulose nanomaterials can find an application is provided. View Show abstract Contemporary nanocellulose-composites: A new paradigm for sensing applications Article Aug 2022 CARBOHYD POLYM Sanjay Kumar Mr Ngasainao Deepa Sharma Pratibha Kumari Nanocellulose (NC) is the biological polymeric nanomaterial booming in the international market. The burgeoning demand for cellulose materials and advancements in nanotechnology have intensified the researches on the development of cellulose-based nanomaterials. Substantial research on nanocellulose-based composites in energy, electronics, biomedical, health, and the environment has been carried out in the last few decades. NC offers a plethora of outstanding properties such as biodegradability, renewability, and excellent fibrous structure. The recent advancement in the synthetic methodologies for various types of nanocellulose materials and their applications in a myriad of fields such as biosensing, chemical sensing, gas sensing, and strain sensing have been explored. The surface modification ability and robust nature of NC offer various possibilities for hybrid materials in the sensing field. Many sensors developed on plastic, paper, and glass platforms will be replaced with NC to modify the conventional sensing probes in the near future. View Show abstract Cellulose Structures as a Support or Template for Inorganic Nanostructures and Their Assemblies Article Full-text available May 2022 Alojz Anzlovar Ema Žagar Cellulose is the most abundant natural polymer and deserves the special attention of the scientific community because it represents a sustainable source of carbon and plays an important role as a sustainable energent for replacing crude oil, coal, and natural gas in the future. Intense research and studies over the past few decades on cellulose structures have mainly focused on cellulose as a biomass for exploitation as an alternative energent or as a reinforcing material in polymer matrices. However, studies on cellulose structures have revealed more diverse potential applications by exploiting the functionalities of cellulose such as biomedical materials, biomimetic optical materials, bio-inspired mechanically adaptive materials, selective nanostructured membranes, and as a growth template for inorganic nanostructures. This article comprehensively reviews the potential of cellulose structures as a support, biotemplate, and growing vector in the formation of various complex hybrid hierarchical inorganic nanostructures with a wide scope of applications. We focus on the preparation of inorganic nanostructures by exploiting the unique properties and performances of cellulose structures. The advantages, physicochemical properties, and chemical modifications of the cellulose structures are comparatively discussed from the aspect of materials development and processing. Finally, the perspective and potential applications of cellulose-based bioinspired hierarchical functional nanomaterials in the future are outlined. View Show abstract Effects of Bacterial Cellulose Whisker Melting Composite on Crystallization and Mechanical Properties of PHBV Composites Article May 2022 MACROMOL RES Zhou Xin Ting Liu Jin Yan Acetylation of bacterial cellulose whisker (BCW) with acetic anhydride can effectively improve the thermal stability of BCW and the dispersion of interface compatibility with PHBV. The influence of the modified cellulose whiskers on the crystallization and mechanical properties of the PHBV matrix was studied using differential scanning calorimetry (DSC), polarization optical microscopy (POM), and XRD. The results show that ABCW has heterogeneous nucleation and hindrance effect on the PHBV matrix simultaneously. With the increase of ABCW content, PHBV gradually decreases from large spherulite and then increases, and the crystallinity decreases. When the content of ABCs is 1.2%, ABCW has the best strengthening effect on PHBV, and the bending strength and bending modulus are 44.7% and 34.5% higher than PHBV. View Show abstract Luminescence turn-off detection of metal ions and explosives using graphene quantum dots Article Feb 2022 Shubhra Jyotsna Subha Sadhu Vinay Sharma Pankaj Poddar Green luminescent graphene quantum dots (GQDs) obtained from combustion of white printing paper were used for detection of fourteen different metal ions and six different explosives in an aqueous medium. These were obtained using a microwave-assisted synthesis process. After optimizing the experimental conditions (pH 6; quantum yield (QY) ~ 38.2%), a sensitive sensing system was developed to detect explosives and free residual metal ions in the environment based on fluorescence quenching of GQDs. The as-synthesized GQDs, as a sensing system, is most sensitive for Cu2+ ion and 2,4-DNP with a detection limit of 0.62 µM and 0.50 µM, respectively.Graphical abstract View Show abstract Kinetic and thermodynamic analyses of date palm surface fibers pyrolysis using Coats-Redfern method Article Oct 2021 RENEW ENERG Mohsin Raza Basim Abu-Jdayil Ali H. Al-Marzouqi Abrar Inayat This study presents the thermo-kinetics and thermodynamic analyses of date palm surface fibers (DPSFs) using thermogravimetric analysis. DPSFs were heated non-isothermally from 20 to 800 OC at a ramp rate of 10 OC/min in nitrogen atmosphere. Thermogravimetric analysis indicated that there have been two stages for pyrolysis of DPSFs. Kinetic and thermodynamic parameters have been calculated for the second stage which is further subdivided into two mass-loss regions. The low-temperature stable components were decomposed in a temperature range of 270–390 OC and high-temperature stable components were degraded in a temperature range of 390–600 OC. The Coats–Redfern integral method was employed with 21 different kinetic models from four major solid-state reaction mechanisms. Among all models, the two diffusion models: Ginstling–Brounshtein and Ginstling diffusion were the best fitted models with highest regression coefficient values (R² > 0.99) in both mass-loss regions. For mass-loss regions: I (270–390 OC) and II (390–600 OC), the activation energy values were found to be 96–98 and 113–114 kJ/mol, respectively. Thermodynamic parameters (ΔH, ΔG, ΔS) were calculated using kinetic data. The findings reported herein are helpful in characterizing date palm fibers as a source of energy, designing reactors, producing chemicals, and understanding the properties of surface fibers for making composites. View Show abstract Extraction of cellulose to progress in cellulosic nanocomposites for their potential applications in supercapacitors and energy storage devices Article Full-text available Jun 2021 J MATER SCI Muhammad Wasim Fei Shi Jingxiao Liu Xinran Zhao Nanocellulose products derived from different forms of biomass have significant importance in the modern era. This is due to its extraordinary physical characteristics, wide surface area as well as its biodegradability, which lead to being promising reinforcements as a nanomaterial. The nanomaterials which represent the cellulosic structures comprise nanocellulose reinforcements with biodegradable characteristics and tremendous ability to be used in eco-friendly applications to supplant fossil-based products. Meanwhile, the syntheses approach of such nanoscale structures still possesses challenging tasks at nanoscales. In addition, the virtuous distribution of nanocellulose in the hydrophobic polymer matrix has still difficulties to produce high-performance nanomaterials. Consequently, this study concludes many approaches and techniques to structural alteration of cellulosic materials to improve the distribution of nanocellulose to enhance the characteristics and features of nanocomposites. The macroscale and nanoscale cellulosic structures get popularity because of their high strength, stiffness, biodegradability, renewability, and use in the preparation of nanocomposites. Application of cellulose nanofibres for the production of nanocomposites is a relatively recent research field. Cellulose macro- and nanofibres can be used as insulation nanocomposite materials because of the improved mechanical, thermal, and biodegradation properties of nanocomposites. Cellulose fibres are hydrophilic, so it became important to improve their surface roughness for the production of nanocomposites with improved properties. This article includes the surface modifications of cellulose fibres by different methods as well as production processes, properties, and various applications of nanocellulose and cellulosic nanocomposites. A high thermal conductivity of cellulosic nanocomposite material for electronic devices can be obtained by combining cellulose nanofibrils (CNF) as the framework material with carbon nanotubes, graphene, and inorganic nitrides. Additionally, the research developments in this field with prospective applications of CNF-based materials for supercapacitors, lithium-ion batteries, and solar cells are emphasized. Moreover, the emerging challenges of different cellulosic nanofibrils-based energy storage devices have been discussed in this review paper. Graphical abstract View Show abstract Cellulose Nanocrystal Based Composites: A Review Article May 2021 Jamileh Shojaeiarani Dilpreet S Bajwa Saptaparni Chanda Cellulose nanocrystals (CNC) have received much attention as renewable, biodegradable, nontoxic, and low-cost nanomaterials with some remarkable properties. Desirable engineering properties of CNC include large surface to volume ratio, high tensile strength (∼10 GPa), high stiffness (∼110-130 GPa), and high flexibility. They can be chemically modified to tailor their properties for high-end engineering and biomedical applications. Despite their outstanding properties, the wide-scale application is lacking due to their surface characteristics and processing challenges. To achieve their full potential safer extraction methods, improved surface modification and functionalization methods and processing techniques are being researched. This review attempts to access methods for characterizing CNC, and CNC composites as well as their emerging new applications as smart materials. The review is a valuable resource for researchers and scientists working in industry or academia to provide an update on the use of CNC materials and their composites in packaging, biomedical, and high-efficiency energy systems. View Show abstract Hybrid Nanocelluloses Isolated through Electron-Beam Irradiation in the Wet State: Redispersibility in Water and Superstability for Pickering Emulsions Article Feb 2021 Min Haeng Heo Hyunho Lee Jin San Jeong Shin Jihoon View Hydrophobic Functionalization Reactions of Structured Cellulose Nanomaterials: Mechanisms, Kinetics and in silico Multi-scale Models Article Feb 2021 CARBOHYD POLYM Ana Oberlintner Blaz Likozar Uroš Novak Nanoscale-interfaced cellulose nanomaterials are extracted from polysaccharides, which are widely available in nature, biocompatible and biodegradable. Moreover, the latter have a potential to be recycled, upcycled, and formulate therefore a great theoretical predisposition to be used in a number of applications. Nanocrystals, nano-fibrils and nanofibers possess reactive functional groups that enable hydrophobic surface modifications. Analysed literature data, concerning mechanisms, pathways and kinetics, was screened, compared and assessed with regard to the demand of a catalyst, different measurement conditions and added molecule reactions. There is presently only a scarce technique description for carbon–OH bond functionalization, considering the elementary chemical steps, sequences and intermediates of these (non)catalytic transformations. The overview of the prevailing basic research together with in silico modelling approach methodology gives us a deeper physical understanding of processes. Finally, to further highlight the applicability of such raw materials, the review of the development in several multidisciplinary fields was presented. View Show abstract Micro and nanocrystalline cellulose derivatives of lignocellulosic biomass: A review on synthesis, applications and advancements Article Aug 2020 CARBOHYD POLYM Dibyajyoti Haldar Mihir Kumar Purkait The present review article is focused on the progress in different aspects of synthesis, modification and advanced applications of both of microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC). First of all, the potential of lignocellulosic biomass towards the formation of MCC and NCC was discussed. Further, different routes for the extraction of the derivatives are individually explained based on the mechanism involved in the formation of MCC and NCC. Moreover, the phenomenon of surface modification was highlighted in order to improve the functionality of the materials. Thereafter, the emerging and advanced applications of both of MCC and NCC are explored in different fields. Finally, the paper is concluded with the challenges that are frequently encountered during the process of commercial production of MCC and NCC. This paper will be beneficial to the readers for acquiring all the important aspects of both of MCC and NCC together in a single article. View Show abstract Show more Modification of nanocrystalline cellulose for application as a reinforcing nanofiller in PMMA composites Article Full-text available Feb 2016 CELLULOSE Miroslav Huskić Alojz Anzlovar Ema Žagar Nanocrystalline cellulose (NCC) with particle length of 100–500 nm was prepared from microcrystalline cellulose and modified with a reversible addition–fragmentation chain transfer (RAFT) agent, i.e., 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPADB). From the surface of CPADB-modified NCC, methyl methacrylate (MMA) was grafted to produce poly(methyl methacrylate) (PMMA)-modified NCC. Unmodified NCC, CPADB-modified NCC, and PMMA-modified NCC were further used as reinforcing nanofillers in PMMA composite plates prepared by bulk polymerization of MMA. Regardless of NCC type, the PMMA plates were transparent to visible light at low NCC concentrations but became translucent with increasing NCC concentration. At given NCC concentration, the visible-light transparency of the PMMA/NCC composites decreased in the order PMMA-modified NCC, CPADB-modified NCC, unmodified NCC. PMMA-modified NCC and CPADB-modified NCC showed moderate potential for reinforcing the PMMA matrix, while unmodified NCC detrimentally affected the mechanical properties of the PMMA composites due to more pronounced particle aggregation. View Show abstract Liquefied Wood as Inexpensive Precursor-Feedstock for Bio-Mediated Incorporation of (R)-3-Hydroxyvalerate into Polyhydroxyalkanoates Article Full-text available Sep 2015 Martin Koller Miguel Miranda De Sousa Dias Rodríguez-Contreras Alejandra Gerhart Braunegg Liquefied wood (LW) prepared in a microwave process was applied as a novel; inexpensive precursor feedstock for incorporation of (R)-3-hydroxyvalerate (3HV) into polyhydroxyalkanoate (PHA) biopolyesters in order to improve the biopolyester’s material quality; Cupriavidus necator was applied as microbial production strain. For proof of concept, pre-experiments were carried out on a shake flask scale using different mixtures of glucose and LW as carbon source. The results indicate that LW definitely acts as a 3HV precursor, but, at the same time, displays toxic effects on C. necator at concentrations exceeding 10 g/L. Based on these findings, PHA biosynthesis under controlled conditions was performed using a fed-batch feeding regime on a bioreactor scale. As major outcome, a poly(3HB-co-0.8%-3HV) copolyester was obtained displaying a desired high molar mass of Mw = 5.39 × 105 g/mol at low molar-mass dispersity (ĐM of 1.53), a degree of crystallinity (Xc) of 62.1%, and melting temperature Tm (176.3 °C) slightly lower than values reported for poly([R]-3-hydroxybutyrate) (PHB) homopolyester produced by C. necator; thus, the produced biopolyester is expected to be more suitable for polymer processing purposes. View Show abstract A review on delignification of lignocellulosic biomass for enhancement of ethanol production potential Article Full-text available Apr 2014 RENEW SUST ENERG REV Renu Singh Ashish Shukla Sapna Tiwari Monika Srivastava View Fast preparation of nanocrystalline cellulose by microwave-assisted hydrolysis Article Full-text available Aug 2014 Tomaž Kos Alojz Anzlovar Ema Žagar Matjaz Kunaver In this work we report on the procedure for fast and controlled preparation of nanocrystalline cellulose (NCC) from commercially available microcrystalline cellulose using microwave-assisted hydrolysis. By varying the sulfuric acid concentration and hydrolysis temperature, an average hydrodynamic diameter of NCC between 126 and 1,310 nm with corresponding yields between 16 and 82 %, respectively, was obtained in a very short reaction time of 10 min. An additional advantage of the described procedure is its high reproducibility and ability to fine-tune the average NCC particle size by adjusting the reaction conditions, i.e., the sulfuric acid concentration and/or reaction temperature. View Show abstract Overview on native cellulose and microcrystalline cellulose I structure studied by X-ray diffraction (WAXD): Comparison between measurement techniques Article Full-text available Jan 2011 Nicoleta Terinte Roger Ibbett Kurt Christian Schuster The crystalline structure of cellulose has been studied for a long time. It is well known that crystallinity of cellulose can be measured using quite a number of methods, X-ray diffraction, solid state 13 C CP-MAS NMR, Fourier transform-infrared (FT-IR) spectroscopy and Raman spectroscopy. The solid state 13 C CP-MAS NMR and FT-IR spectroscopy considers contributions from both crystalline and non-crystalline cellulose regions resulting in relative values, while the alternative X-ray diffraction approach gives more detailed data on features of crystalline and less on the non-crystalline fraction of cellulose. Raman spectroscopy is also used to study cellulose crystallinity. This paper gives an overview on the crystallinity of three cellulose samples, cotton linters, microcrystalline cellulose (cotton linters) and Avicel powder cellulose (Avicel PH-101) determined by wide angle X-ray diffraction (WAXD). The study compares literature data with our data for the apparent crystallinity (%) of the mentioned samples from different sources to demonstrate the dissimilarities that can be obtained using different X-ray methods. For the crystallinity analysis, assumption had to be made that all cotton linters and Avicel PH-101 used in the literature were of the same quality, even though it has been reported that the quality of both samples can vary between batches and production locations. The reported crystallinity values of cotton linters were between 56-78 %, for microcrystalline cellulose (MCC), crystallinity varied within the range 65-83 % and Avicel PH-101 powder gave crystallinity values between 37-93 % dependent on the X-ray methods and experimental mode used. View Show abstract Influence of cellulose polymerization degree and crystallinity on kinetics of cellulose degradation Article Full-text available Aug 2012 BIORESOURCES Edita Jasiukaitytė Ida Poljanšek Matjaz Kunaver Cellulose was treated in ethylene glycol with p-toluene sulfonic acid monohydrate as a catalyst at different temperatures. At the highest treatment temperature (150 °C) liquefaction of wood pulp cellulose was achieved and was dependant on cellulose polymerization degree (DP). Furthermore, the rate of amorphous cellulose weight loss was found to increase with cellulose degree of polymerization, while the rate of crystalline cellulose weight loss was reciprocal to the size of the crystallites. The cellulose degradation was studied by monitoring of the molecular mass decrease by size-exclusion chromatography. It was revealed that microcrystalline cellulose degrades via a 'quantum mode' mechanism, while the degradation of Whatman filter paper no 1. and cotton linters proceeded randomly and were partly dependent on the starting polymerization degree, crystallinity, and treatment temperature. The kinetics of cellulose degradation in heterogeneous media was described by means of a one-stage model, characterised by the consumption of glycosidic bonds in amorphous and crystalline cellulose regions until the levelling-off degree of polymerization is reached. View Show abstract Wood, liquefied in polyhydroxy alcohols as fuel for gas turbines Article Full-text available Nov 2012 APPL ENERG Tine Seljak Samuel Rodman Opresnik Tomaž Katrašnik Matjaz Kunaver The paper reports foremost the results of a successful combustion of an innovative lignocellulosic biofuel in a gas turbine. The fuel was processed through liquefaction of lignocellulosic materials with polyhydroxy alcohols in an acid catalyzed reaction. The liquefaction process features: high efficiency, high liquid yields and inexpensive, easily available process equipment. For the purpose of this analysis the following were developed: an experimental gas turbine with internal combustion chamber, a preheated pressurized fuel supply system with swirl-air fuel injector and a heat exchanger to obtain high primary air temperatures. The paper gives results on the emissions of CO, THC, NOx and soot. For the purpose of benchmarking the turbine was also run on diesel fuel. The paper presents analyses of the underlying phenomena with which it aims to provide guidelines for improvements in the fuel processing and in the experimental equipment. It has been shown that direct utilization of this innovative lignocellulosic biofuel gives promising results. Although the CO and THC emissions are higher compared to the benchmark diesel results it has been shown that both emissions decrease with increased turbine inlet temperature and with the increased fuel preheat temperature, due to a very high viscosity of the fuel. It is additionally shown that NOx emissions are low and comparable to those of the diesel fuel, whereas soot emissions are very low for both fuels. View Show abstract Facile extraction of thermally stable cellulose nanocrystals with a high yield of 93% through hydrochloric acid hydrolysis under hydrothermal conditions Article Full-text available Feb 2013 Houyong Yu Zongyi Qin Banglei Liang Long Chen A facile approach for extracting cellulose nanocrystals (CNCs) was presented through hydrochloric acid hydrolysis of cellulose raw materials under hydrothermal conditions. The influences of preparation parameters, such as reaction time, reaction temperature, and acid-to-cellulose raw material ratio, and different neutralization methods on the yield, microstructure and properties were studied. A high yield of up to 93.7%, crystallinity of 88.6%, and a maximum degradation temperature (Tmax) of 363.9 °C can be achieved by combining hydrochloric acid hydrolysis under hydrothermal conditions and neutralization with ammonia, compared with only 30.2%, 84.3% and 253.2 °C for sulfuric acid hydrolysis, respectively. More importantly, good stability of aqueous CNC suspensions can also be obtained due to the existence of ammonium groups, which can easily be removed through simple heat treatment before using the CNCs. View Show abstract Production of cellulose nanocrystals using hydrobromic acid and click reactions on their surface Article Full-text available Nov 2011 Hasan Sadeghifar Ilari Filpponen Sarah Clarke Dimitris S Argyropoulos Cellulose nanocrystals (CNCs) were prepared by acidic hydrolysis of cotton fibers (Whatman #1 filter paper). In our efforts to select conditions in which the hydrolysis media does not install labile protons on the cellulose crystals, a mineral acid other than sulfuric acid (H2SO4) was used. Furthermore, in our attempts to increase the yields of nanocrystals ultrasonic energy was applied during the hydrolysis reaction. The primary objective was to develop hydrolysis reaction conditions for the optimum and reproducible CNC production. As such, the use of hydrobromic acid (HBr) with the application of sonication as a function of concentration (1.5–4.0M), temperature (80–100°C), and time (1–4h) was examined. Applying sonic energy during the reaction was found to have significant positive effects as far as reproducible high yields are concerned. Overall, the combination of 2.5M HBr, 100°C, and 3h associated with the sonication during the reaction generated the highest nanocrystal yields. In addition to the optimization study three types of surface modifications including TEMPO-mediated oxidation, alkynation, and azidation were used to prepare surface-activated, reactive CNCs. Subsequently, click chemistry was employed for bringing together the modified nanocrystalline materials in a unique regularly packed arrangement demonstrating a degree of molecular control for creating these structures at the nano level. View Show abstract Cellulose nanofibers from white and naturally colored cotton fibers Article Full-text available Jun 2010 Eliangela Teixeira Ana Carolina Corrêa Alexandra Manzoli Luiz Henrique Capparelli Mattoso Suspensions of white and colored nanofibers were obtained by the acid hydrolysis of white and naturally colored cotton fibers. Possible differences among them in morphology and other characteristics were investigated. The original fibers were subjected to chemical analysis (cellulose, lignin and hemicellulose content), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). The nanofibers were analyzed with respect to yield, elemental composition (to assess the presence of sulfur), zeta potential, morphology (by scanning transmission electron microscopy (STEM)) and atomic force microscopy (AFM), crystallinity (XRD) and thermal stability by thermogravimetric analysis in air under dynamic and isothermal temperature conditions. Morphological study of several cotton nanofibers showed a length of 85–225 nm and diameter of 6–18 nm. The micrographs also indicated that there were no significant morphological differences among the nanostructures from different cotton fibers. The main differences found were the slightly higher yield, sulfonation effectiveness and thermal stability under dynamic temperature conditions of the white nanofiber. On the other hand, in isothermal conditions at 180 °C, the colored nanofibers showed a better thermal stability than the white. View Show abstract A Hepatic Protein, Fetuin-A, Occupies a Protective Role in Lethal Systemic Inflammation Article Full-text available Feb 2011 PLOS ONE Wei Li Shu Zhu Jianhua Li Haichao Wang A liver-derived protein, fetuin-A, was first purified from calf fetal serum in 1944, but its potential role in lethal systemic inflammation was previously unknown. This study aims to delineate the molecular mechanisms underlying the regulation of hepatic fetuin-A expression during lethal systemic inflammation (LSI), and investigated whether alterations of fetuin-A levels affect animal survival, and influence systemic accumulation of a late mediator, HMGB1. LSI was induced by endotoxemia or cecal ligation and puncture (CLP) in fetuin-A knock-out or wild-type mice, and animal survival rates were compared. Murine peritoneal macrophages were challenged with exogenous (endotoxin) or endogenous (IFN-γ) stimuli in the absence or presence of fetuin-A, and HMGB1 expression and release was assessed. Circulating fetuin-A levels were decreased in a time-dependent manner, starting between 26 h, reaching a nadir around 24-48 h, and returning towards base-line approximately 72 h post onset of endotoxemia or sepsis. These dynamic changes were mirrored by an early cytokine IFN-γ-mediated inhibition (up to 50-70%) of hepatic fetuin-A expression. Disruption of fetuin-A expression rendered animals more susceptible to LSI, whereas supplementation of fetuin-A (20-100 mg/kg) dose-dependently increased animal survival rates. The protection was associated with a significant reduction in systemic HMGB1 accumulation in vivo, and parallel inhibition of IFN-γ- or LPS-induced HMGB1 release in vitro. These experimental data suggest that fetuin-A is protective against lethal systemic inflammation partly by inhibiting active HMGB1 release. View Show abstract Cellulose crystallinity index: measurement techniques and their impact on interpreting cellulase performance. Biotech Biofuels 3:10 Article Full-text available May 2010 BIOTECHNOL BIOFUELS Sunkyu Park John O. Baker Michael E. Himmel David K Johnson Although measurements of crystallinity index (CI) have a long history, it has been found that CI varies significantly depending on the choice of measurement method. In this study, four different techniques incorporating X-ray diffraction and solid-state 13C nuclear magnetic resonance (NMR) were compared using eight different cellulose preparations. We found that the simplest method, which is also the most widely used, and which involves measurement of just two heights in the X-ray diffractogram, produced significantly higher crystallinity values than did the other methods. Data in the literature for the cellulose preparation used (Avicel PH-101) support this observation. We believe that the alternative X-ray diffraction (XRD) and NMR methods presented here, which consider the contributions from amorphous and crystalline cellulose to the entire XRD and NMR spectra, provide a more accurate measure of the crystallinity of cellulose. Although celluloses having a high amorphous content are usually more easily digested by enzymes, it is unclear, based on studies published in the literature, whether CI actually provides a clear indication of the digestibility of a cellulose sample. Cellulose accessibility should be affected by crystallinity, but is also likely to be affected by several other parameters, such as lignin/hemicellulose contents and distribution, porosity, and particle size. Given the methodological dependency of cellulose CI values and the complex nature of cellulase interactions with amorphous and crystalline celluloses, we caution against trying to correlate relatively small changes in CI with changes in cellulose digestibility. In addition, the prediction of cellulase performance based on low levels of cellulose conversion may not include sufficient digestion of the crystalline component to be meaningful. View Show abstract Scherrer grain-size analysis adapted to grazing-incidence scattering with area detectors. Erratum Article Full-text available Dec 2009 D.-M. Smilgies Ever since its formulation, the Scherrer formula has been the workhorse for quantifying finite size effects in X-ray scattering. Various aspects of Scherrer-type grain-size analysis are discussed with regard to the characterization of thin films with grazing-incidence scattering methods utilizing area detectors. After a brief review of the basic features of Scherrer analysis, a description of resolution-limiting factors in grazing-incidence scattering geometry is provided. As an application, the CHESS D1 beamline is characterized for typical scattering modes covering length scales from the molecular scale to the nanoscale. View Show abstract Wood, Chemistry, Ultrastucture, Reactions Article Jan 1984 D. Fengel G. Wegener View Nanocrystalline cellulose prepared from softwood kraft pulp via ultrasonic-assisted acid hydrolysis Article Sep 2011 BIORESOURCES Wei Li Rui Wang Shouxin Liu Nanocrystalline cellulose (NCC) with small particle size and high crystallinity was prepared via the combined method of ultrasonication and acid hydrolysis from bleached softwood kraft pulp (BSKP). Scanning electron microscopy, transmission electron microscopy, X-ray diffraction (XRD), and Fourier transform infrared spectroscopy were used for determination of morphology, crystal structure, and surface chemical groups. Thermal behavior was analyzed by thermogravimetric analysis. The analyses revealed that rod-shaped NCC particles with diameter of 10 to 20 nm can be obtained. Ultrasonication can induce cellulose folding, surface erosion, and external fibrillation of BSKP, together with the shorter average length of NCC (96 nm) than that prepared without ultrasonication (150 nm). Due to the smaller size and larger number of free ends of chains, the thermal stability of NCC was lower than BSKP. The degradation of BSKP exhibited one significant pyrolysis stage within the range of 300 to 420 °C. In contrast, UH-NCC exhibited three pyrolysis stages within the range of 210 to 450 °C. NCC prepared with ultrasonication decomposed at lower temperature and over a wider temperature range, together with higher char yield of 43% (compared with 27% for that without ultrasonication). The obtained NCC had similar surface chemical structures but higher crystallinity (82%) compared with that of the starting BSKP (74%). View Show abstract Hours of Service and Truck Crash Risk Article Dec 2010 TRANSPORT RES REC Sang-Woo Park Paul P Jovanis A case-control study of 231 truck crashes (and 462 controls) was completed with data from three trucking companies from 2004, when new hours-of-service (HOS) regulations went into effect in the United States. Analysis using time-dependent logistic regression indicates that increased crash risk is associated with hours of driving, with risk increases of 50% to 260% compared with the first hour of driving. These findings help to provide a baseline estimate of crash risk relationships for this HOS policy. A series of models indicates that the pattern of crash risk is different for nonsleeper operations and for sleeper schedules. Models of nonsleeper operations indicate that crash risk is strongly associated with multiday driving somewhat more than with hours of driving. Models of sleeper operations indicate strong association of crash risk with hours driving. These findings, though consistent with many results from similar modeling conducted with 1980s data, are subject to important limitations. The small sample size in many cases likely contributed to the relatively high estimates of crash odds (e.g., often in the range of 100% to 200% increases) and to an inability to identify clear trends in some variables. Ideally, this study should be repeated with additional firms over a longer time period. In particular, collecting driver data that cover at least 2 weeks of driving should allow for a much better understanding of the effect of any restart policy. The effects of extended driving, however, strongly suggest that a change back to the 10-h maximum should be considered in any future HOS adjustments. View Show abstract A novel green approach for the preparation of cellulose nanowhiskers from white coir Article Sep 2014 CARBOHYD POLYM Diego Magalhães do Nascimento Jessica S. Almeida Amanda Ferreira Dias Morsyleide De Freitas Rosa The aim of this work was to optimize the extraction of cellulose nanowhiskers (CNW) from unripe coconut husk fibers (CHF). The CHF was delignified using organosolv process, followed by alkaline bleaching (5% (w/w) H2O2+4% (w/w) NaOH; 50°C, 90min). The CHF was subsequently hydrolyzed with 30% (v/v) sulfuric acid (60°C, 360min). The process yielded a partially delignified acetosolv cellulose pulp and acetic black liquor, from which the lignin was recovered. The CNW from the acetosolv pulp exhibited an average length of 172±88nm and a diameter of 8±3nm, (aspect ratio of 22±8). The surface charge of the CNW was -33mV, indicating a stable aqueous colloidal suspension. The nanocrystals presented physical characteristics close to those extracted from cellulose pulp made by CHF chlorine-pulping. This approach offers the additional advantage of extracting the lignin as an alternative to eradication. View Show abstract A roadmap for conversion of lignocellulosic biomass to chemicals and fuels Article Aug 2012 Elif I Gürbüz Stephanie G. Wettstein David Martin Alonso James A. Dumesic Graphical abstract Roadmap for conversion of sugars to platform chemicals.Figure optionsView in workspace Highlights ► Fractionation of lignocellulosic biomass increases process flexibility. ► Integrated processing of C5 and C6 sugars advances biorefinery development. ► Management of mineral acids used in pretreatment steps is a significant challenge. ► Biphasic reactors allow for recovery and recycle of mineral acids during lignocellulose conversion. ► Biphasic reactors increase process yields for conversion of lignocellulose to platform chemicals. View Show abstract Constructing NFC-pigment composite surface treatment for enhanced paper stiffness and surface properties Article Apr 2011 Cathy J Ridgway Patrick Gane The use of nano- or microfibrillar cellulose (NFC or MFC) in papermaking is generally hampered by high cost and potentially wasteful use in typical wet end applications. The solubility and fines nature of the material makes it inefficient to retain, and when retained it is generally inefficiently applied within the spatial distribution of the paper fibre matrix. To illustrate the benefits of capturing the important NFC in a layer structure to enhance surface and stiffness properties of paper and board, we present a study whereby NFC is entrapped at the surface of a fibrous web by forming an in situ composite using a porous coating layer, consisting in the exemplified case of modified calcium carbonate. It is shown that NFC can integrate itself within the porous structure providing excellent holdout and thin layer continuity essential in developing an efficient concentration of the NFC at the surface of the substrate. The effect is likened to the well-known I-beam construction. An additional feature is the potential for recycling the remaining fibrous content in the NFC or, more particularly, MFC product after the nanocrystalline cellulose (NCC) gel fraction has been absorbed, allowing for further efficient processing if needed and hence providing a potential cost reduction in the overall NFC/MFC production. The increased smoothness and uniformity obtained is illustrated by confocal laser profilometry and electron microscopy. The effect on permeability is also illustrated. View Show abstract Fabrication of nanocelluloses from hemp fibers and their application for the reinforcement of hemp fibers Article Jan 2013 IND CROP PROD Dasong Dai Mizi Fan Philip E.F. Collins A novel fabrication has been employed to produce nanocelluloses from natural fibers (hemp) and the developed nanocellulose was then used as “coupling agent” to modify hemp fibers themselves.The size distribution of nano-particles (nanocellulose) was measured by nanoparticle tracking analysis (NTA). Results showed that the oxidation–sonication developed nanocellulose had wider size range (29–281 nm) and the average size (100–112 nm). Morphologies of nanocellulose displayed a slight difference under field emission gun-scanning electron microscopy (FEG-SEM) and atomic force microscopy (AFM). Mechanical testing showed that the nanocellulose modification could improve the mechanical properties of natural fibers significantly. The modulus, tensile stress and tensile strain of nanocellulose modified hemp fibers were increased by 36.13%, 72.80% and 67.89%, respectively. FEG-SEM and X-ray diffractogram (XRD) were used to reveal the mechanism of nanocellulose reinforcement on natural fibers. FEG-SEM illustrated that the nanocellulose treatment had resulted in an effective distribution of nanocellulose along the stria on the surface of fibers, giving rise to a significant increase in the tensile strength of the treated hemp fibers. The XRD analysis also showed that the crystallinity index of the treated fibers had increased from 55.17% to 76.39%. X-ray photoelectron spectroscopy (XPS) has been used to characterize the surface of fibers and attenuated total reflectance-fourier transform infrared (ATR-FTIR) was carried out to determine the surface chemical reaction in order to elucidate the interface properties and self-modification mechanisms of the hemp fibers. View Show abstract Extraction, preparation and characterization of cellulose fibres and nanocrystals from rice husk Article May 2012 IND CROP PROD Nurain Johar Ishak Ahmad Alain Dufresne Cellulose fibres and cellulose nanocrystals were extracted from rice husk. Fibres were obtained by submitting the industrial rice crop to alkali (NaOH) and bleaching treatments. Nanocrystals were extracted from these fibres using sulphuric acid (H2SO4) hydrolysis treatment. The material obtained after each stage of the treatments was carefully characterized and its chemical composition was determined. Morphological investigation was performed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fourier transform infrared (FTIR) spectroscopy showed the progressive removal of non-cellulosic constituents. X-ray diffraction (XRD) analysis revealed that the crystallinity increased with successive treatments. The thermal stability of the rice husk fibres and cellulose nanocrystals was also investigated using thermogravimetric analysis (TGA). View Show abstract Maximizing the yield of nanocrystalline cellulose from cotton pulp fiber Article May 2012 CARBOHYD POLYM Jin-shi Fan Yan-hao Li Nanocrystalline cellulose (NCC) has attracted a significant interest in recent years as it is made from renewable resources and has many unique characteristics. In this paper, we prepared NCC from cotton pulp fiber by the method of sulfuric acid hydrolysis, with the objective of achieving a maximum yield. The yield and the particle size of NCC were measured as a function of sulfuric acid concentration, reaction temperature and hydrolysis time, and optimized by an orthogonal test. A high NCC yield of more than 60% was found when the sulfuric acid concentration is 64%, reaction temperature is 50 °C and the hydrolysis time is 5 h. The morphology and the size of NCC were characterized by scanning electron microscope (SEM) and particle size analyzer. The finding from this study should provide guidance in maximizing the yield of NCC from cotton pulps using acid hydrolysis. View Show abstract Isolation of nanocellulose from waste sugarcane bagasse (SCB) and its characterization Article Aug 2011 CARBOHYD POLYM Arup Mandal Debabrata Chakrabarty Nanocellulose obtained by acid hydrolysis of sugarcane bagasse (SCB) has been characterized by Fourier transformed infrared (FTIR) spectra, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscopy (SEM) and atomic force microscopy (AFM) and transmission electron microscopy (TEM) studies. Nanocellulose and cellulose exhibited identical FTIR spectra quite different from SCB. TG analysis shows that the bagasse starts to degrade earlier than cellulose and the nanocellulose shows an even earlier onset of degradation compared to SCB but leaves the maximum residue within the range of temperatures studied. DSC studies revealed that SCB, cellulose and the nanocellulose differ in their loosely bound moisture content. The nanocellulose exhibits an intermediate behavior between SCB and cellulose. The XRD shows enrichment in the proportion of crystalline cellulose in nanocellulose, which manifests significant conversion of cellulose I to cellulose II. DLS studies show particle size distribution in the nanorange which has been substantiated by SEM, AFM and TEM. View Show abstract Cellulose microfibrils: A novel method of preparation using high shear refining and cryocrushing Article Jan 2005 HOLZFORSCHUNG Ayan Chakraborty Mohini Sain Mark T. Kortschot This paper describes a novel technique to produce cellulose microfibrils through mechanical methods. The technique involved a combination of severe shearing in a refiner, followed by high-impact crushing under liquid nitrogen. Fibers treated in this way were subsequently either freeze-dried or suspended in water. The fibers were characterized using SEM, TEM, AFM, and high-resolution optical microscopy. In the freeze-dried batch, 75% of the fibrils had diameters of 1 μm and below, whereas in the water dispersed batch, 89% of the fibrils had diameters in this range. The aspect ratio of the microfibrils ranged between 15 and 55 for the freeze-dried fibrils, and from 20 to 85 for the fibrils dispersed in water. These measurements suggest that the microfibrils have the potential to produce composites with high strength and stiffness for high-performance applications. The microfibrils in water were compounded with polylactic acid polymer to form a biocomposite. Laser confocal microscopy showed that the microfibrils were well dispersed in the polymer matrix. View Show abstract An Empirical Method for Estimating the Degree of Crystallinity of Native Cellulose Using the X-Ray Diffractometer Article Oct 1959 TEXT RES J L. C. Segal J.; Jr Creely A.E.J. Martin Carl M. Conrad An empirical method for determining the crystallinity of native cellulose was studied with an x-ray diffractometer using the focusing and transmission techniques. The influence of fluctuations in the primary radiation and in the counting and recording processes have been determined. The intensity of the 002 interference and the amor phous scatter at 2θ = 18° was measured. The percent crystalline material in the total cellulose was expressed by an x-ray "crystallinity index." This was done for cotton cellulose decrystallized with aqueous solutions containing from 70% to nominally 100% ethylamine. The x-ray "crystallinity index" was correlated with acid hydrolysis crys tallinity, moisture regain, density, leveling-off degree of polymerization values, and infrared absorbance values for each sample. The results indicate that the crystallinity index is a time-saving empirical measure of relative crystallinity. The precision of the crystallinity index in terms of the several crystallinity criteria is given. Based on over 40 samples for which acid hydrolysis crystallinity values were available, the standard error was 6.5%. View Show abstract Microfibrillated cellulose, a new cellulose product: Properties, uses and commercial potential Conference Paper Jan 1983 A.F. Turbak F.W. Snyder Karen Sandberg A new form of cellulose, which is expanded to a smooth gel when dispersed in polar liquids, is produced by a unique, rapid, physical treatment of wood cellulose pulps. A 2% suspension of microfibrillated cellulose (MFC) in water has thixotropic viscosity properties and is a stable gel on storage, or when subjected to freeze-thaw cycles. At this concentration, MFC is an excellent suspending medium for other solids and an emulsifying base for organic liquids. In laboratory tests, microfibrillated cellulose has been demonstrated to have wide utility in the preparation of foods such as low-calorie whipped toppings, cake frostings, salad dressings, gravies, and sauces. At 0.3% cellulose concentration in ground meats, MFC helps retain juices during cooking. Tests were also conducted in formulating paints, emulsions, and cosmetics and in the use of MFC as a binder for nonwoven textiles and as a mineral suspending agent. From economic studies, it is estimated that a 2% MFC dispersion can be produced for about 1.5 cents/lb, total cost. 6 references, 9 figures, 2 tables. View Show abstract Chemically and mechanically isolated nanocellulose and their self-assembled structures Article Jun 2013 Feng Jiang You-Lo Hsieh View Isolation of Thermally Stable Cellulose Nanocrystals by Phosphoric Acid Hydrolysis Article Mar 2013 BIOMACROMOLECULES Sandra Camarero Espinosa Tobias Kuhnt E. Johan Foster Christoph Weder On account of their intriguing mechanical properties, low cost, and renewable nature, high-aspect-ratio cellulose nanocrystals (CNCs) are an attractive component for many nano¬materials. Due to hydrogen bonding between their surface hydroxyl groups, un¬modi¬fied CNCs (H-CNCs) aggregate easily and are often difficult to disperse. It is shown here that on account of ionic repulsion be¬tween charged surface groups, slightly phosphorylated CNCs (P-CNCs, average dimensions 31 ± 14 x 316 ± 127 nm, surface charge density = 10.8 ± 2.7 mmol/kg cellulose), prepared by controlled hydrolysis of cotton with phosphoric acid, are readily dispersable and form stable dispersions in polar solvents such as water, dimethyl sulfoxide, and dimethyl-formamide. Thermogravimetric analyses reveal that these P-CNCs exhibit a much higher thermal stability than parti¬ally sulfated CNCs (S-CNCs), which are frequently employed, but suffer from limited thermal stability. Nanocomposites of an ethylene oxide-epichlorohydrin copolymer and unmodified CNCs (H-CNCs), S-CNCs, and P-CNCs were prepared, and their mechanical properties were studied by dynamic mechanical thermal analysis. The results show that P-CNCs offer a reinforcing capability that is comparable to that of H-CNCs or S-CNCs. View Show abstract Production of nanocrystalline cellulose from lignocellulosic biomass: Technology and applications Article Apr 2013 CARBOHYD POLYM Lucia Brinchi F. Cotana Elena Fortunati Jose M. Kenny View Extraction and characterization of nanocellulose structures from raw cotton linter Article Jan 2013 João Paulo Saraiva Morais Morsyleide De Freitas Rosa Men de Sá Moreira de Souza Filho Ana Ribeiro Cassales This study aimed to characterize nanocellulose extracted from cotton (Gossypium hirsutum) linters. The nanocellulose was subjected to electronic microscopy, thermal analysis, X-ray diffractometry, light scattering, and contact angle. The properties of the nanocellulose are considerably different from the linter. The acidic hydrolyses applied to extract the nanocrystals increased the crystallinity index and the hydrophilicity and decreased the thermal stability. On average, the nanocrystals were 177nm long and 12nm wide, with an aspect ratio of 19 when measured by microscopy. The light scattering results were coherent with the crystal dimensions. Cotton linter is a potential source of nanocellulose crystals, particularly to be used in the production of hydrophilic nanocomposites. Extraction of nanocellulose from raw cotton linter does not require pulping. View Show abstract Gas-chromatographic determination of polyhydric alcohols in oils and alkyd resins by formation of trimethylsilyl derivatives Article Jul 1969 George G. Esposito Melvin H. Swann View Liquefaction of Wood, Synthesis and Characterization of Liquefied Wood Polyester Derivatives Article Sep 2009 J APPL POLYM SCI James T. Guthrie Matjaz Kunaver Edita Jasiukaitytė Nataša Čuk Liquefaction of Central-European softwoods meal was performed using a mixture of diethylene glycol and glycerol and a minor addition of p-toluenesulfonic acid as a catalyst. The liquefied wood was used as a replacement of a certain amount of the polyhydroxy alcohol in the polyester synthesis, enabled by the large number of hydroxyl groups that were available in the liquefied wood. Three different polyesters were synthesized by using adipic acid and phthalic acid anhydride as reagents. The products were characterized using FTIR, GPC/SEC, and viscosity measurements. The polyesters have hydroxyl values that were reduced due to esterification, from 1043 mg KOH/g of the liquefied wood to 400–800 mg KOH/g. Polyhydroxyl alcohols (22–23%) in the polyester formulations were replaced by wood derivatives. Such saturated polyesters are suitable for further use in polyurethane foam production. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 View Show abstract Liquefaction of wood in the presence of phenol using phosphoric acid as a catalyst and the flow properties of the liquefied wood Article Jun 1994 J APPL POLYM SCI Lianzhen Lin Mariko Yoshioka Yaoguang Yao Nobuo Shiraishi The liquefaction of wood in the presence of phenol using phosphoric acid as a catalyst and the flow properties of the obtained liquefied wood were investigated. It was found that phosphoric acid is a satisfactory catalyst for liquefying wood. The amount of phenol that reacts with the liquefied wood components (i.e., combined phenol) increases with an increase in liquefaction temperature, liquefaction time, catalyst content, or liquid ratio. By removing the free phenol, the resulting liquefied woods become novolaclike resins. The measurements of the flow properties of these liquefied woods reveal that the melts of liquefied woods behave as pseudoplastics and their flows obey the Ostwald de Waele power law equation. The amount of combined phenol within the liquefied wood and the presence of filler in the liquefied wood have great influence on their flow properties. The flowing temperature, activation energy, and zero shear viscosity of the liquefied woods show tendencies to increase with an increase in combined phenol. © 1994 John Wiley & Sons, Inc. View Show abstract Liquefaction of wheat straw and preparation of rigid polyurethane foam from the liquefaction products Article Jan 2009 J APPL POLYM SCI Fangeng Chen Zhuomin Lu Wheat straw was liquefied in the mixture of polyethylene glycol (PEG 400) and glycerin in the presence of acid at the temperature 130–160°C. The final liquefaction products having the hydroxyl number of 250–430 mg KOH/g and the of about 1050 can be used as the polyol component to manufacture polyurethane. A kind of polyurethane foam was prepared from liquefied wheat straw, commercial polyol, and diisocyanates in the presence of organotin catalysts and foaming agents. The polyurethane foam presented better compressive strength and thermal stability than that manufactured from diisocyanate and polyol alone. The thermal stability of PU foam was improved with the increase of [NCO]/[OH] ratio and the addition of liquefied wheat straw. The polyurethane foam presented faster biodegradation at ambient temperature than normal polyurethane foam did. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009 View Show abstract Relation of certain infrared bands to cellulose crystallinity and crystal lattice type. Part II. A new infrared ratio for estimation of crystallinity in celluloses I and II Article May 1964 J APPL POLYM SCI Mary L. Nelson Robert T. O'Connor A new infrared ratio, α1372 cm.−1/α2900 cm.−1, is proposed for measuring crystallinity in cellulosic materials. The advantage of this ratio over others which have been used is that it can be applied to both celluloses I and II and, therefore, to samples containing a mixed lattice. Two series of samples, encompassing a wide range of crystallinity, were prepared from highly crystalline celluloses I and II. The infrared ratios of these samples were compared with crystallinity values from x-ray diffractograms and density measurements, and with accessibility data from moisture sorption. It was shown that the new infrared ratio ranks samples of both lattice types, as well as partly mercerized cottons, in the same order as do x-ray, density, and moisture sorption data. The correlation of the new infrared ratio with accessibility, derived from moisture regain, is better than with crystallinities from either x-ray or density measurements. Reasons for this are suggested. View Show abstract Polyhydric alcohol liquefaction of some lignocellulosic agricultural residues Article Jan 2008 IND CROP PROD El Barbary Hassan N. Shukry Liquefaction of bagasse and cotton stalks was conducted by using polyhydric alcohols (polyethylene glycol PEG#400 and glycerin) in the presence of sulfuric acid (SA) as a catalyst. The effects of different liquefaction conditions, such as ratio raw material/liquefying solvent, effect of PEG#400/glycerin, acid concentration, liquefaction temperature and time on the liquefaction yield have been investigated. The hydroxyl and acid numbers for some liquefied samples were also determined. The results showed that the minimum residue content was obtained at 1/5 raw material to liquefying solvent. PEG#400 alone is not favoured as liquefying solvent as it gives ∼19% residual content for bagasse and ∼22% for cotton stalks at the optimum studied reaction conditions. Replacing 10% of PEG#400 with glycerin as well as increasing the SA concentration, liquefaction temperature or time, decreased the amount of residue for both bagasse and cotton stalks to less than 10%. The hydroxyl number of the produced polyols slowly decreased from 253 to 223 mg KOH/g on extending the reaction time till 120 min and the residual polyols prevented re-condensation of the liquefied components. It seems that this system can be applied on various types of lignocellulosic agricultural residues. View Show abstract Characterization of the products resulting from ethylene glycol liquefaction of cellulose Article Jan 2001 Tatsuhiko Yamada Hirokuni Ono The composition of liquefied cellulose in the presence of ethylene glycol (EG) was studied. The liquefied products were fractionated and analyzed with highperformance liquid chromatography and nuclear magnetic resonance. EG-glucosides were detected as the only saccharides and 2-hydroxyethyl levulinate as the highly decomposed compound derived from cellulose. Quantitative analysis of the EG-glucosides and levulinic acid that comes from the levulinate shows the presence of the following mechanism in the EG-liquefaction of cellulose. First, cellulose is degraded and produces considerable amounts of EG-glucosides during the early stage of liquefaction. Then, when liquefaction is prolonged, the glucosides are decomposed, leading to a large quantity of levulinates. View Show abstract On the determination of crystallinity and cellulose content in plant fibres Article Dec 2005 Anders Thygesen Jette Oddershede Hans Lilholt Kenny Ståhl A comparative study of cellulose crystallinity based on the sample crystallinity and the cellulose content in plant fibres was performed for samples of different origin. Strong acid hydrolysis was found superior to agricultural fibre analysis and comprehensive plant fibre analysis for a consistent determination of the cellulose content. Crystallinity determinations were based on X-ray powder diffraction methods using side-loaded samples in reflection (Bragg-Brentano) mode. Rietveld refinements based on the recently published crystal structure of cellulose Iβ followed by integration of the crystalline and amorphous (background) parts were performed. This was shown to be straightforward to use and in many ways advantageous to traditional crystallinity determinations using the Segal or the Ruland–Vonk methods. The determined cellulose crystallinities were 90–100g/100g cellulose in plant-based fibres and 60–70g/100g cellulose in wood based fibres. These findings are significant in relation to strong fibre composites and bio-ethanol production. View Show abstract Applications of functionalized and nanoparticle-modified nanocrystalline cellulose Article Mar 2012 Edmond Lam Keith B Male Jonathan H Chong John H. T. Luong Nanocrystalline cellulose (NCC), a rod-shaped nanoscale material with exceptional strength and physicochemical properties, can be prepared from inexpensive renewable biomass. Besides its potential use as a reinforcing agent for industrial biocomposites, pristine NCC exhibits low toxicity and poses no serious environmental concerns, providing impetus for its use in bioapplications. Here, we review recent developments in the use of modified NCC for emerging bioapplications, specifically enzyme immobilization, antimicrobial and medical materials, green catalysis, biosensing and controlled drug delivery. We focus on the modification of NCC with chemical functionalities and inorganic nanoparticles, reviewing practical considerations such as reusability, toxicity and scale-up capability. View Show abstract Green Composites from Sustainable Cellulose Nanofibrils: A review Article Jan 2011 CARBOHYD POLYM Abdul Khalil H.P.S Aamir H. Bhat A.F. Ireana Yusra View Polymer Nanocomposites Reinforced by Cellulose Whiskers Article Aug 1995 V. Favier H. Chanzy J.-Y. Cavaillé There are many examples where animals or plants synthesize extracellular high-performance skeletal biocomposites consisting of a matrix reinforced by fibrous biopolymers. Cellulose is one, which occur as whiskerlike microfibrils that are biosynthesized and deposited in a continuous fashion. Mostly, this mode of biogenesis leads to crystalline microfibrils that are almost defect-free. In this study, attempts to imitate biocomposites are made by blending cellulose whiskers from the mantles of tunicates with synthetic polymer lattices. The films cast from such mixtures have a nanocomposite organization whose structure and mechanical properties are described in this paper. View Show abstract Extraction of nanocellulose fibrils from lignocellulosic fibres: A novel approach Article Oct 2011 CARBOHYD POLYM Eldho Abraham Deepa B Laly A Pothan Uroš Cvelbar View Ultrasonically assisted liquefaction of lignocellulosic materials Article Jan 2012 Edita Jasiukaitytė Nataša Čuk Matjaz Kunaver In our research, we have utilized high energy ultrasound for the liquefaction of different lignocellulosic materials, wood wastes in particular. We developed a highly efficient way of transforming this biomass waste into valuable chemicals. It was found, that the reaction yield in all experiments was high and that the reaction times were shortened up to nine times when using the ultrasound process with smaller residual particles and with no influence on the hydroxyl number of the final products. The use of the ultrasound process inhibits the formation of the large molecular structures during the liquefaction from the degradation products, by keeping the reactive segments apart and due to such a short reaction time being used. The short reaction time and subsequent low energy consumption for the liquefaction reaction leads to the creation of the new method for the transformation of the wood waste materials into valuable chemicals. View Show abstract Production of Biofuels from Cellulose and Corn Stover Using Alkylphenol Solvents Article Aug 2011 CHEMSUSCHEM David Martin Alonso Stephanie G. Wettstein Jesse Q. Bond James A. Dumesic Alkylphenol solvents allow a more effective production of biofuels from corn stover by enabling selective extraction and hydrogenation of levulinic acid to γ-valerolactone, and by increasing the final concentration of GVL through successive extraction/hydrogenation steps. The versatility of alkylphenol solvents may lead to their use in other biomass conversion processes utilizing mineral acids for biomass deconstruction. View Show abstract Cellulose Nanocrystals: Chemistry, Self-Assembly, and Applications Article Mar 2010 CHEM REV Youssef Habibi Lucian Amerigo Lucia Orlando J Rojas The hydrogen-bonding network and molecular orientation in cellulose vary widely that gives rise to cellulose polymorphs or allomorphs, depending on the respective source, method of extraction, or treatment. Microcrystalline cellulose (MCC) offers a significant opportunity for multiple uses in pharmaceutical industry as a tablet binder, in food applications as a texturizing agent and fat replacer, and also, as an additive in paper and composites applications. The main process for the isolation of cellulose nanocrystal (CN) from cellulose fibers is based on acid hydrolysis. The sulfuric and hydrochloric acids have been extensively used for CN preparation, but phosphoric and hydrobromic acids have also been employed for such purposes. The cellulose nanocrystal generated from hydrochloric acid hydrolysis and then treated with sulfuric acid solution has the same particle size as those directly obtained from sulfuric acid hydrolysis. View Show abstract Application of liquefied wood as a new particle board adhesive system Article Feb 2010 Matjaz Kunaver Sergej Medved Natasa Cuk Tatjana Strnad Different types of southern European hardwoods and softwoods were subjected to a liquefaction process with glycerol/diethylene glycol. The liquefied spruce wood was reacted in a condensation reaction in the hot press with different melamine-formaldehyde and melamine-urea-formaldehyde resin precursors and used as adhesives for wood particle boards. The mechanical properties of these particle boards and the determination of formaldehyde release, proved that addition of 50% of the liquefied wood to such resin precursors caused the product to meet the European standard quality demands for particle boards. Up to 40% reduction of the formaldehyde emission was achieved. The temperature of the press unit was lowered from 180 degrees C to 160 degrees C with no significant influence on the mechanical properties. On the basis of the presented results it was possible to conclude that liquefied wood can be used as substitute for synthetic resin precursors in adhesives that are used for the particle board production. View Show abstract Liquefaction of kenaf (Hibiscus cannabinus L.) core for wood laminating adhesive Article Feb 2010 M.F. Juhaida Paridah M. Tahir M. Mohd. Hilmi A. R. Mohamad Zaki A study was carried out to produce polyurethane (PU) as a wood laminating adhesive from liquefied kenaf core (LKC) polyols by reacting it with toluene-2,4-diisocyanate (TDI) and 1,4-butanediol (BDO). The LKC polyurethane (LKCPU) adhesive has a molecular weight (MW) of 2666, viscosity of 5370 mPa s, and solids content of 86.9%. The average shear strength of the rubberwood (RW) bonded with LKCPU adhesive was 2.9 MPa. Most of the sheared specimens experienced a total adhesive failure. The formation of air bubbles through the liberation of carbon dioxide was observed to reduce the adhesive penetration and bonding strength which was obviously seen on the sheared specimens. The percentage of catalyst used can be varied based on the usage and working time needed. Nonetheless, the physical properties of LKCPU produced in this work had shown good potential as edge-bonding adhesive. View Show abstract Cellulose: Fascinating Biopolymer and Sustainable Raw Material Article Sep 2005 Dieter Klemm Brigitte Heublein H.-P. Fink Andreas Bohn As the most important skeletal component in plants, the polysaccharide cellulose is an almost inexhaustible polymeric raw material with fascinating structure and properties. Formed by the repeated connection of D-glucose building blocks, the highly functionalized, linear stiff-chain homopolymer is characterized by its hydrophilicity, chirality, biodegradability, broad chemical modifying capacity, and its formation of versatile semicrystalline fiber morphologies. In view of the considerable increase in interdisciplinary cellulose research and product development over the past decade worldwide, this paper assembles the current knowledge in the structure and chemistry of cellulose, and in the development of innovative cellulose esters and ethers for coatings, films, membranes, building materials, drilling techniques, pharmaceuticals, and foodstuffs. New frontiers, including environmentally friendly cellulose fiber technologies, bacterial cellulose biomaterials, and in-vitro syntheses of cellulose are highlighted together with future aims, strategies, and perspectives of cellulose research and its applications. View Show abstract Cellulose crystallinity of woods, wood pulps, and agricultural fibers by FT-Raman spectroscopy Jan 2011 U P Agarval R R Reiner S A Ralph Agarval, U. P., Reiner, R. R., & Ralph, S. A. (2011). Cellulose crystallinity of woods, wood pulps, and agricultural fibers by FT-Raman spectroscopy. In Proceedings of the 16th ISWFPC Mass Spectral Data 7th Ed Jan 1999 Wiley Wiley Registry of Mass Spectral Data 7th Ed., (1999). Agilent Technologies, Palo Alto, CA 94306 U.S.A. Show more Recommendations Discover more Article Comparative study on two-step concentrated acid hydrolysis for the extraction of sugars from lignoce... May 2014 · Bioresource Technology Yanuar Philip Wijaya Robertus Dhewangga Vania Tanda Widyaya [...] Chang Soo Kim Read more Looking for the full-text? You can request the full-text of this article directly from the authors on ResearchGate. Request full-text Already a member? Log in ResearchGate iOS App Get it from the App Store now. Install Keep up with your stats and more Access scientific knowledge from anywhere or Discover by subject area Recruit researchers Join for free Login Email Tip: Most researchers use their institutional email address as their ResearchGate login Password Forgot password? Keep me logged in Log in or Continue with Google Welcome back! 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Improving initial estimates of the Chained Consumer Price Index : Monthly Labor Review: U.S. Bureau of Labor Statistics An examination of the reasoning underlying the most recent update to the formula used to produce the preliminary Chained Consumer Price Index. Improving initial estimates of the Chained Consumer Price Index Effective with the release of the January 2015 Consumer Price Index for All Urban Consumers, the U.S. Bureau of Labor Statistics improved the preliminary Chained Consumer Price Index. This article examines the theoretical framework of the Chained Consumer Price Index for All Urban Consumers (C-CPI-U), discusses why the Geometric Young formula was originally chosen over the constant elasticity of substitution (CES) formula, and explains the rationale behind the move to improve the C-CPI-U formula. Further, it presents analysis of the preliminary C-CPI-U to show why the CES formula is a better estimate of the final C-CPI-U than the Geometric Young formula. In January 2015, the U.S. Bureau of Labor Statistics (BLS) implemented two improvements to the Chained Consumer Price Index for All Urban Consumers (C-CPI-U). First, the revision schedule of the index series was changed from an annual revision to a quarterly revision. As a result of the more frequent revisions, the lag between the initial and final publication of each monthly index was reduced by an average of 11 months. 1Second, and the focus of this article, the index formula used to calculate the initial version of the index was changed from an adjusted Geometric Young formula to a constant elasticity of substitution (CES) formula. The new formula was implemented to more closely approximate the final indexes than the previous Geometric Young formula. C-CPI-U theoretical framework The objective of the BLS Consumer Price Index (CPI) is to approximate a cost-of-living index (COLI). This is accomplished by addressing the following question: What is the cost, at the current month’s market prices, of achieving the standard of living attained in the base period? 2Within the context of consumer utility-maximization behavior, this cost represents the change in spending needed to attain a constant level of consumer satisfaction when faced with prices in future periods that differ from those in the base period. The headline Consumer Price Index for All Urban Consumers (CPI-U) assumes that consumers respond to price change by purchasing the same quantities as in the past and does not reflect consumer substitution in response to relative price change for a defined biennial period. The CPI-U, therefore, is an overstatement of a COLI if, within a biennial period, consumers change their consumption patterns in response to changing relative prices, like buying fewer goods at relatively higher prices and substituting with comparable goods at relatively lower prices. In contrast to the CPI-U, the C-CPI-U, first introduced with the release of July 2002 CPI data, employs a formula that reflects the effect of substitution that consumers make across item categories in response to changes in relative prices. 3The final C-CPI-U is a superlative index 4and is a second-order approximation of a COLI. 5The final C-CPI-U better approximates a COLI for several reasons, not the least of which is due to the weights. The weights used are derived from the current period and base period, the periods over which price change is measured. A first-order approximation like the CPI-U uses weights from only one of the periods. The monthly weights for the C-CPI-U formula directly reflect substitutions that consumers make when facing relative price change. Prior to the release of the January 2015 CPI-U, three upper-level aggregation formulas were calculated for BLS CPI products: Lowe (used for the CPI-U and the Consumer Price Index for Urban Wage Earners and Clerical Workers), Tornqvist (used for the final C-CPI-U), and Geometric Young (used for preliminary versions of the C-CPI-U). 6Starting with the release of the January 2015 CPI-U, the Lloyd–Moulton CES formula (referred to as CES for the remainder of this article) replaced the Geometric Young formula for preliminaryversions of the C-CPI-U. 7Each of these formulas use the same measure of elementary item-area price change as an input: (IX t/IX t -1). However, the expenditure weight input varies on the basis of assumption of the overall consumers’ substitution elasticity (σ). The four formulas are summarized in table 1. The CPI-U is calculated with a Lowe fixed quantity formula, in which quantities are represented by price-updated expenditures. 8This formula assumes that substitution elasticity is zero within a biennial period, meaning consumers do not substitute across items in response to relative price change. The difference between price change estimated using fixed quantity weights and the actual quantities purchased is referred to as upper-level substitution bias in the CPI-U. A Tornqvist formula, which includes consumer substitution using the current and previous month weights, is used to calculate final C-CPI-U. BLS is currently unable to produce the final C-CPI-U in real time because the monthly expenditure weights lags the current index period by about four quarters. This time lag is necessary to conduct and process the Consumer Expenditure Survey household data, the source of the monthly weight estimates. BLS publishes preliminary C-CPI-U indexes, designed to approximate the final C-CPI-U index, to address the time gap. Up to the January 2015 CPI-U release, preliminary C-CPI-U indexes were estimated with a Geometric Young formula that assumes substitution elasticity to be unitary within a biennial period. The underlying assumption of this estimator implied consumers always substitute to items whose prices are falling relative to items whose prices are increasing. Since the release of the January 2015 CPI-U, the preliminary versions of the C-CPI-U have been estimated with a CES index formula, which assumes consumer substitution is constant within a biennial time period and the level of substitution is estimated by prior period behavior. The remainder of this article describes the process behind making this formula change to the preliminary C-CPI-U, and the resulting improvement. Table 1 shows the price index formula relationships among different CPI products. Figure 1 displays a comparison of index levels from these formulas with December 1999 = 100. Level Figure 1. Comparison of index formulas: final Chained Consumer Price Index for All Urban Consumers (C-CPI-U) , Consumer Price Index for All Urban Consumers (CPI-U), Geometric Young formula, and constant elasticity of substitution (CES) formula with sigmas 0 to 0.999, 2000–12 Final C-CPI-U CPI-U Geometric Young CES = 0.0 CES = 0.1 CES = 0.2 CES = 0.3 CES = 0.4 CES = 0.5 CES = 0.6 CES = 0.7 CES = 0.8 CES = 0.9 CES = 0.999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 80 100 120 140 Source: U.S. Bureau of Labor Statistics. Summary of original selection of preliminary C-CPI-U index formula When the C-CPI-U was introduced in 2002, the Geometric Young formula was selected over the CES formula as a, “plausible, simpler approximate of the Tornqvist in real time.” 9At that time, CES was characterized as a possible alternative. However, many issues related to the substitution elasticity estimate could not be resolved, including a variable estimate of substitution elasticity, an unstable value across months, and a lagged estimate not representative of the current index period. A variable substitution elasticity estimate would, in principal, be linked to the CPI elementary level of indexes to construct an entire demand system. The CPI elementary structure consists of more than 200 consumption items and 38 geographic areas. This structure would theoretically be based on over 20,000 substitution pairs of items ((211 * 210)/2) in each of the 38 areas. Creating a representative measure of substitution across the requisite elementary cells is not feasible for index estimation; therefore, research shifted to establishing a single “constant” estimate of substitution elasticity. Robert Cage, John Greenlees, and Patrick Jackman attempted to determine which substitution parameter most consistently produced a CES index that came closest to the final Tornqvist index, based on data from 1987 to 2000. To do this, they calculated monthly CES indexes using the substitution parameter values 0.1, 0.5, and 0.9. Then, the optimal parameter value was selected in which the resulting CES index was closest to the final Tornqvist index. For the original analysis of a constant estimate of substitution elasticity, the stability of the estimator was cited as a major weakness of CES and research showed monthly substitution values that ranged from 0.06 to 2.78. 10 Reexamination of the preliminary C-CPI-U Why the CES formula is an improvement Research by John Greenlees in 2010 demonstrated that many of the earlier cited weaknesses could be effectively addressed. 11First, as indicated above, a constant estimate of substitution elasticity could replace a variable estimator. Second, using a model to pool data over longer periods created a more stable estimator by minimizing the impact of monthly price changes. Finally, fixed biennial expenditure shares could be replaced by weights that are updated to an index month comparable to the CPI-U aggregation weights. Furthermore, Greenlees showed the CES formula could outperform the Geometric Young formula using empirical CPI data, resulting in smaller C-CPI-U revisions and smaller estimates of prediction error. Subsequent research focused on evaluating which preliminary C-CPI-U formula is the best estimate of the final C-CPI-U. The following sections explain why CES formula performed better than the Geometric Young formula for estimation of the preliminary C-CPI-U. Components of the CES formula Sigma Sigma is the measure of elasticity of substitution in the CES formula. To estimate sigma, Greenlees used a regression model developed by Robert Feenstra and Marshall Reinsdorf. 12The model estimates consumer elasticity of substitution as a function of the relationship between the relative change in expenditure shares and the relative change in prices. Greenlees calculated sigma values that ranged from 0.56 to 0.64 and effectively addressed the weakness of an unstable sigma by using the Feenstra–Reinsdorf model and pooling data over annual periods. The limitations of using a constant elasticity-of-substitution measure for all items and areas remain. The level of consumer substitution between two items such as gasoline and public transportation may be much different from the level of substitution between a different pair, such as coffee and tea. The Feenstra–Reinsdorf pooled regression model, however, measures the average level of consumer substitution across all elementary items and areas to produce a constant sigma value. So the assumption that consumer substitution across all pairs of elementary items is constant remains. The Feenstra–Reinsdorf model, shown in equation (1), is summarized as the change in expenditures because of a change in price. Sigma is measured as 1 minus the resulting beta (β) of the Feenstra–Reinsdorf pooled regression. The annual expenditure shares are calculated using elementary level annual expenditure weights. The annual average index relatives are calculated using elementary level 12-month average price index relatives. The Feenstra–Reinsdorf pooled regression over annual periods is expressed as follows: , (1) where is the natural log annual expenditure weight share at the item area stratum level, is the natural log annual index relative at the item area stratum level, is the annual reference period of expenditure weights and indexes, and is the previous annual reference year of expenditure weights and indexes. The Feenstra–Reinsdorf formula, equation (1), is weighted as follows: , (2) where AEWS is the annual expenditure weight share at the item area stratum level. Greenlees used annual expenditure weight and price index data from 1999 to 2008, and recommended excluding items with large decreasing index relatives. He calculated a relatively stable sigma value that ranged from 0.58 to 0.64, pooled across annual periods. The results from the Greenlees article are based on an analysis of annual data; however, estimating an optimal sigma using annualized data from biennial expenditure reference periods would procedurally coincide with the weight updates of the CPI-U as demonstrated in equation (3). The Feenstra–Reinsdorf pooled regression over biennial periods is expressed as follows: , (3) where is the natural log biennial expenditure weight share at the item area stratum level, is the natural log biennial index relative at the item area stratum level, is the biennial reference period of expenditure weights and indexes, and is the previous annual reference year of expenditure weights and indexes. The above Feenstra–Reinsdorf formula, equation (3), is weighted as follows: , (4) where BEWS is the biennial expenditure weight share at the item area stratum level. Sigma results based on a biennial time frame are summarized in table 2. For the biennial relative years 2003–04:2001–02, the biennial expenditure weight share is equal to the natural log expenditure share and the 24-month average price indexes are based on natural log average price indexes from 2003–04 relative to 2001–02 time frame. The pooled results summarize the Beta values across biennial time periods, and then the sigma pooled is equal to 1 minus beta pooled. Table 2. Estimates of beta, beta pooled, and sigma results for biennial periods Biennial period Relative period Beta Pooled biennial periods from 2003-04 Beta pooled Sigma pooled Constant elasticity of substitution index period2003–04 2001–02 0.398 to 2003–04 0.398 0.602 ―2004–05 2003–04 0.479 to 2005–06 0.438 0.562 ―2007–08 2005–06 0.324 to 2007–08 0.403 0.597 ―2009–10 2007–08 0.493 to 2009–10 0.417 0.583 ―2011–12 2009–10 0.522 to 2011–12 0.438 0.562 2014–152013–14 2011–12 0.229 to 2013–14 0.421 0.579 2016–17Source: U.S. Bureau of Labor Statistics. Biennial period Relative period Beta Pooled biennial periods from 2003-04 Beta pooled Sigma pooled Constant elasticity of substitution index period Beta values range from 0.229 to 0.522 over the 6 biennial periods. Beta averaged across the 6 biennial periods is equal to 0.408, comparable to the 2003–04 to 2013–14 beta pooled result of 0.421. Sigma pooled values range from 0.562 to 0.602 across the pooled biennial periods. The CPI has elected to use a sigma value of 0.6, which equals the rounded sigma pooled value for the current period, as well as the previous 5 pooled biennial periods. 13 Revisions to the value of sigma will be considered in conjunction with biennial weight revisions, which occur in January of even years. The criteria for making a revision to the sigma value will be based on evaluating the size of changes to the pooled estimate of sigma, and evaluating potential index direction bias. Small changes to sigma have a limited impact on the resulting CES index. Therefore, sigma will only be updated if its optimal value changes by greater than 0.1. Updated CES weights The Geometric Young formula uses biennial expenditure weights from 12 to 24 months before the index month. For instance, the initial indexes in 2012 used weights that reflect expenditures made by consumers in 2009 and 2010. The CES formula uses biennial expenditure weights that are more current because the price portion is updated to the current index pivot month by using index relatives, as shown in equation (5). For example, 2009–10 biennial weights are updated by index relatives to represent expenditures in December 2011. Equation (5) displays how the CES expenditure weights are updated to the pivot period. This weight update process is comparable to the last step of aggregation weight calculation. There, elementary level expenditure weights are adjusted by the corresponding elementary level index in order to calculate an expenditure weight value with an implicit price in the pivot month and an implicit quantity of the weight reference period. 14 The CES pivoted expenditure weight for biennial reference periods is expressed as follows: , (5) where is the elementary level annualized expenditure weight from the biennial reference period, is the elementary level 24 month average index from the biennial reference period, is the sigma for the biennial reference weight period, and is the elementary level annualized expenditure weight from a biennial reference period in which prices are from a pivot period adjusted for consumer substitution. CES index relatives The CPI preliminary estimate of 1-month price change, calculated using the CES formula, is derived from the ratio of CES current and previous month indexes, relative to the pivot month, as shown in equation (6). The pivot-month index is updated every 24 months in conjunction with the biennial weight revisions. The CES functional form also contains the substitution parameters as exponents applied at the elementary-level index relatives, and then at the aggregate level. To create a constant level of substitution across elementary level cells, the same sigma must be applied to the elementary level index relative and the resulting aggregate level index relative. The CES index for relative biennial periods is expressed as follows: (6) Analysis of sigma Distributional analysis of optimal sigma The following analysis extends the distributional analysis of sigma prepared by Cage, Greenlees, and Jackman by evaluating biennial, annual, and monthly weights to create a real time CES that uses previous period weights. The optimal sigma for each period is the value yielding the closest CES estimate of the final C-CPI-U index. Sigmas ranging from 0 to 1, incremented by 0.01, were tested, as shown in equations (7) and (8). Analysis of the optimal sigma was capped at 1 because in theory, sigma of 1 will result in unitary substitution preferences and therefore will be equal to the Geometric Young formula. CES index relatives are trimmed values in which elementary-level (item/area) relatives greater than 10 are set equal to a value of 10 and relatives less than a value of 0.1 are set equal to a value of 0.1. A histogram of the optimal values is shown in figure 1. , (7) (8) where is the weight periodicity (biennial, annual, monthly) from the previous period; is the sigma for component index period, and aggregate index period ranging from .01 to .99, incremented by .01; and is the final aggregate index relative. Optimal sigmas are relatively similar across weight periodicity as shown in figure 2, which displays a count of months with optimal sigmas from 2000–12. The largest difference of absolute values across weight periodicities was 7 months for bins 0.1, 0.3, 0.7, and 0.9. The overall average across weight periods is approximately 0.7, which indicates that the weight periodicity potentially has a minimal impact when optimal sigma is evaluated for this type of analysis. Months Figure 2. Months with optimal elasticity of substitution, 2000–12 Previous biennial period Previous year Previous month 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0 25 50 75 100 Click legend items to change data display. Hover over chart to view data. Source: U.S. Bureau of Labor Statistics. Bin Index analysis of optimal sigma The optimal sigma producing the best CES estimate relative to the final C-CPI-U index varies across index months. The index months can roughly be divided into three optimal sigma periods, as displayed by the periods to the left, center, and right of the gray highlight in figure 3. From January 2000 to December 2003, the optimal sigma is 0.999, indicating unitary substitution preferences. From January 2004 to December 2007, the optimal sigma is 0.8, and from January 2008 to December 2012, the optimal sigma is 0.7. Level Figure 3. Comparison of final Chained Consumer Price Index for All Urban Consumers (C-CPI-U) less Consumer Price Index for All Urban Consumers (CPI-U), Geometric Young formula, and constant elasticity of substitution (CES) indexes with sigma equal to 0.0, 0.6, 0.7, 0.8, and 0.999, 2000–12 CPI-U Geometric Young CES = 0.0 CES = 0.6 CES = 0.7 CES = 0.8 CES = 0.999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 -6 -4 -2 0 2 4 Source: U.S. Bureau of Labor Statistics. Analysis of CES and Geometric Young indexes relative to the Tornqvist index The following analysis compares revision sizes of the final C-CPI-U less the CES and Geometric Young formulas to evaluate how predictive these preliminary formulas are of the final C-CPI-U. This analysis excludes revision chaining to isolate the impact of the preliminary formula. 15 For a 1-month change, the revision size of CES is smaller than Geometric Young for 101 out of 156 months (65 percent), as displayed in figure 4. The size of revision associated with each formula is summarized in absolute terms in table 3. For a sum of absolute revision size, CES is 77 percent of Geometric Young. For a mean of absolute errors, CES is 78 percent of Geometric Young. For the root mean squared error revision size, CES is 66 percent of Geometric Young. Each of these measures of revision size of a 1-month change from the CES formula is lower than the Geometric Young formula, indicating the CES formula more closely predicted the final C-CPI-U than the Geometric Young formula. 16 Level Figure 4. One-month change based on final Chained Consumer Price Index for All Urban Consumers (C-CPI-U) less preliminary C-CPI-U, excludes revision chaining, 2000–12 Geometric Young Constant elasticity of substitution 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 -0.004 -0.002 0.000 0.002 0.004 Source: U.S. Bureau of Labor Statistics. Table 3. Summary of 1-month percent change based on final Chained Consumer Price Index for All Urban Consumers (C-CPI-U) less preliminary C-CPI-U, excludes revision chaining, 2000–12 Values Geometric Young formula Constant elasticity of substitution (CES) formula CES/Geometric YoungSum absolute 8.46 6.55 77Mean absolute 0.055 0.043 78Root mean square error absolute 0.050 0.033 66Source: U.S. Bureau of Labor Statistics. Values Geometric Young formula Constant elasticity of substitution (CES) formula CES/Geometric Young For 12-month change, the revision size of CES is smaller than Geometric Young for 83 out of 132 months (63 percent) as displayed in figure 5. The size of revision is summarized in absolute terms in table 4. For a sum of absolute revision size, CES is 65 percent of Geometric Young. For a mean of absolute revision size, CES is 65 percent of Geometric Young. For the root mean square error of revision size, CES is 57 percent of Geometric Young. Each of these measures of revision size of 12-month change is lower for CES than the Geometric Young formula, indicating the CES formula more closely predicts the final C-CPI-U than the Geometric Young formula. Level Figure 5. Twelve-month change based on final Chained Consumer Price Index for All Urban Consumers (C-CPI-U) less preliminary C-CPI-U, excludes revision chaining, 2002–12 Geometric Young Constant elasticity of substitution 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 -0.005 0.000 0.005 0.010 Source: U.S. Bureau of Labor Statistics. Table 4. Summary of 12-month percent change based on final Chained Consumer Price Index for All Urban Consumers (C-CPI-U) less preliminary C-CPI-U, excludes revision chaining, 2002–12 Values Geometric Young formula Constant elasticity of substitution (CES) formula CES/Geometric YoungSum absolute 26.43 17.09 65Mean absolute 0.200 0.129 65Root mean square error absolute 0.168 0.095 57Source: U.S. Bureau of Labor Statistics. Values Geometric Young formula Constant elasticity of substitution (CES) formula CES/Geometric Young Conclusion For the 2002 introduction of the C-CPI-U, the CPI opted to implement the Geometric Young formula for the preliminary version. This formula was, in large part, chosen over the CES formula because of problems with the CES formula identified by Cage et al., such as the instability of a monthly sigma. In 2010, Greenlees effectively resolved the instability of sigma with a Feenstra–Reinsdorf regression model that pooled data across biennial periods. The CPI has also identified another improvement in the CES formula: the incorporation of weights updated to a more current pivot period, comparable to the aggregation weights of the CPI-U. This implementation of the CES formula produces a better estimate of the final C-CPI-U than the Geometric Young formula because, for most months, the revisions are smaller and the corresponding absolute revision sizes and root mean square errors are smaller. The updated CES formula allows for a defined level substitution within a biennial time frame that is more flexible than the unitary substitution preferences of the Geometric Young formula, in which substitution across items occurs in response to price change, and more flexible than the substitution preferences of the Lowe formula, in which substitution across items does not occur in response to price change. The CPI implemented the CES formula with the release of the January 2015 CPI-U for the preliminary version of the C-CPI-U. This analysis supports the Greenlees 2010 analysis that the CES formula with a sigma equal to 0.6 approximates the final C-CPI-U better than the Geometric Young formula. Suggested citation: Joshua Klick, "Improving initial estimates of the Chained Consumer Price Index," Monthly Labor Review,U.S. Bureau of Labor Statistics, February 2018,https://doi.org/10.21916/mlr.2018.6 Notes 1See Consumer Price Index: October 2014, USDL-14-2106 (U.S. Bureau of Labor Statistics, November 20, 2014),https://www.bls.gov/news.release/archives/cpi_11202014.pdf. 2 BLS handbook of methods, chapter 17, “The Consumer Price Index” (U.S. Bureau of Labor Statistics, June 2015), p. 2,https://www.bls.gov/opub/hom/pdf/homch17.pdf. 3Seehttps://www.bls.gov/cpi/additional-resources/chained-cpi.htm. 4Robert Cage, John Greenlees, and Patrick Jackman, “Introducing the chained Consumer Price Index” (paper presented at the Seventh Meeting of the International Working Group on Price Indices, Paris, France, 2003), p. 213,http://www.ottawagroup.org/Ottawa/ottawagroup.nsf/home/Meeting+7/$file/2003+7th+Meeting+-+Cage+&+Greenlees+&+Jackman+-+Introducing+the+Chained+Consumer+Price+Index.pdf. 5W. E. Diewert, “Exact and superlative index numbers,” Journal of Econometrics 4, 1976, p. 117; Practical guide to producing consumer price indices(International Labour Organization, 2009), p. 3,http://www.ilo.org/public/english/bureau/stat/download/cpi/guide1.pdf. 6Upper-level estimation uses these price index formulas to aggregate elementary indexes and elementary weights into a final product such as the all-items U.S. city average, the default aggregation level used throughout this article. 7See P.J. Lloyd, “Substitution effects and bias in nontrue price indexes,” American Economic Review, 1975, vol. 65, issue 3, pp. 301–13; Brent Moulton, “Constant elasticity cost of living index in share relative form,” unpublished manuscript (U.S. Bureau of Labor Statistics, 1996). 8 Consumer price index manual: theory and practice(International Labour Organization, 2004), pg. 6, par. 1.48,http://www.ilo.org/wcmsp5/groups/public/---dgreports/---stat/documents/presentation/wcms_331153.pdf. 9Cage, et al., “Introducing the chained Consumer Price Index,” p. 228. 10Ibid. 11John Greenlees, “Improving preliminary values of the chained CPI-U,” Business and Economic Statistics Section—JSM, 2010,https://www.bls.gov/osmr/research-papers/2010/pdf/st100060.pdf . 12Robert C. Feenstra and Marshall B. Reinsdorf, “Should exact index numbers have standard errors?Theory and application to Asian growth” (paper presented at the CRIW Conference, September 2003),http://cid.econ.ucdavis.edu/Papers/pdf/Feenstra-Reinsdorf.pdf. 13Note that this model is sensitive to outlier values, particularly large decreases, because of natural logged index relatives. To mitigate the impact of outliers for the sigma analysis below, index relatives less than 0.25 were set at 0.25. Six cells were trimmed over the 2001–02 to 2013–14 biennial periods: two cells during 2001–02, one cell during 2005–06, and three cells during 2009–10. 14 BLS handbook of methods,chapter 17, p. 33. 15The published initial C-CPI-U CES formula is revised for 3 quarters in succession by chaining to the terminal month final C-CPI-U. In contrast, the discontinued published C-CPI-U Geometric Young formula is revised annually by chaining to the terminal month final C-CPI-U. For more information, see BLS handbook of methods, chapter 17, p. 34https://www.bls.gov/opub/hom/pdf/homch17.pdf; BLS News Release, Consumer Price Index- January 2015, p. 5,https://www.bls.gov/news.release/archives/cpi_02262015.pdf. 16Results support Statistical Canada CPI analysis of price index formulas to reduce substitution bias that results from an asymmetric formula such as Lowe. For more information, see Ning Huang, Waruna Wimalaratne, and Brent Pollard, “Choice of index number formula and the upper-level substitution bias in the Canadian CPI” (paper presented at the 14th Ottawa Group Meeting, May 2015),http://www.stat.go.jp/english/info/meetings/og2015/pdf/t1s4p13_pap.pdf.	https://www.bls.gov/opub/mlr/2018/article/improving-initial-estimates-of-the-chained-consumer-price-index.htm
Evaluating the Effect of Carbon Nanotube on Low Temperature Property of Asphalt Binder through Dissipated Energy–Based Approach \| Request PDF Request PDF \| Evaluating the Effect of Carbon Nanotube on Low Temperature Property of Asphalt Binder through Dissipated Energy–Based Approach \| Although many research works are available on evaluating the effect of carbon nanotube (CNT) on intermediate and high temperature performance of... \| Find, read and cite all the research you need on ResearchGate Article Evaluating the Effect of Carbon Nanotube on Low Temperature Property of Asphalt Binder through Dissipated Energy–Based Approach March 2020 Journal of Materials in Civil Engineering32(3):04019376 DOI: 10.1061/(ASCE)MT.1943-5533.0003056 Authors: <here is a image 6ea57d4f532b96be-9c31a3820cc916ba> Prabin Ashish Indian Institute of Technology Kanpur <here is a image 4049eb07db110d94-e0090fc7ec7fcfb6> Dharamveer Singh Indian Institute of Technology Bombay <here is a image f2f62089ad6ff61c-d19572ff1996375a> Rahul Jain Rahul Jain Abstract Although many research works are available on evaluating the effect of carbon nanotube (CNT) on intermediate and high temperature performance of asphalt binder, limited studies have been reported for its effect on low temperature properties. Moreover, reported research work showed inconsistent conclusive remarks about its influence on the low temperature properties of asphalt binder. Therefore, along with the conventionally adopted technique, this study aimed at investigating the effect of CNT on low temperature properties of asphalt binder using the dissipated energy-based approach to make an appropriate conclusive remark. CNT content was varied as 0%, 0.75%, 1.5%, and 2.25% by the weight of asphalt binder. Initially, creep stiffness and creep rate corresponding to 60 s creep period were evaluated. Although CNT addition changed the creep stiffness and creep rate, the impact was not statistically significant at 0.75% CNT. However, a subsequently higher dose of 1.5% CNT significantly increased the creep stiffness and decreased the creep rate. A master curve for creep stiffness, relaxation modulus, creep stiffness rate, and creep relaxation rate was drawn to understand the effect of prolonged creep period on low temperature properties. The detrimental effect of CNT on low temperature properties of asphalt binder was found to be apparent, especially in a higher creep period zone. Subsequently, viscoelastic modeling of creep compliance data obtained from a bending beam rheometer (BBR) test was carried out using the Burgers model. Different energy components (stored and dissipative) were subsequently evaluated based on model parameters. Stored, as well as dissipated energy components, were found to be decreasing with an increase in CNT content to 1.5%. However, the degree of decrease in the dissipated energy component was found to be relatively higher compared to the corresponding decrease in the stored energy component. As a result, the dissipated energy ratio (DER), which is expected to be higher for better low temperature performance, was found to be decreasing with the incremental dosages of CNT. Although CNT addition decreased the DER value, the impact was not statistically significant at 0.75% CNT. However, a subsequently higher dose of 1.5% CNT showed a significant decrease in DER value. Such a response further reinforced that CNT addition may have a negative impact on low temperature properties of asphalt binder. ... In their study, Liang et al. [28] observed that CNTs/polymer composite improved the rheological properties including cracking resistance, better resistance to moisture damage, and enhanced workability. Ashish et al. [29] investigated the effects of CNTs on the low temperature properties of the asphalt-binder. From the study [29] results, it was found that the dissipated energy ratio, which was theoretically expected to be higher for better low temperature performance, decreased with an increase in the CNTs dosage. ... ... Ashish et al. [29] investigated the effects of CNTs on the low temperature properties of the asphalt-binder. From the study [29] results, it was found that the dissipated energy ratio, which was theoretically expected to be higher for better low temperature performance, decreased with an increase in the CNTs dosage. ... Characterizing the mechanical properties of Multi-Layered CNTs reinforced SBS modified Asphalt-Binder Article May 2021 CONSTR BUILD MATER <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Xiaorui Zhang <here is a image 3ead86047aca7e66-737fc9b3f61fbc4f> Xinxing Zhou Wei Ji <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Frédéric Otto Due to their superior characteristic properties, multi-layered carbon nanotubes (MCNTs) make ideal candidates for use as reinforcing materials, modifiers, or enhancers in asphalt-binders. With this background, this study was conducted to improve the mechanical properties of styrene–butadienestyrene (SBS) modified asphalt-binder (denoted as SBSMA) through injection of various MCNTs dosages into the SBSMA matrix. In the study, molecular dynamic simulations were used to model and quantify the elastic properties (i.e., bulk, shear modulus, etc.) of SBSMA as a function of MCNTs content. The mechanical response curves of the MCNTs reinforced SBSMA, denoted as MSBSMA, were evaluated using the atomic force microscope (AFM) device. The MSBSMA’s rheological properties (i.e., complex modulus and phase angle) were measured using the dynamic shear rheometer (DSR) test device. The corresponding results indicated that MCNTs had a profound impact on enhancing both the rheological properties and mechanical response-behavior of MSBSMA. Furthermore, the molecular simulations were found to be satisfactorily comparable to the laboratory experimentation results. Overall, the study findings substantiated that MCNTs can potentially be used to reinforce and enhance SBSMA. ... Samples. Many studies have reported the self-aggregation of CNT in asphalt matrix, 12, 50 which weakens the properties of CNT−asphalt nanocomposites. To suppress the self-aggregation phenomenon of CNT, the high-speed shear (HSM-100L) method was used, which is widely accepted to obtain uniformly dispersed CNT−asphalt nanocomposites. ... Multiscale Interfacial Interactions in Carbon Nanotube–Asphalt Nanocomposites: Implications for Asphalt Pavement Materials Article May 2023 <here is a image e7e6ad9de61ec514-25f28dd4b2cf5b64> Caihua Yu <here is a image cae16dc2550ea77a-33d591b1de3d19eb> Qilin Yang Carbon nanotube (CNT)−asphalt nanocomposites are considered to be the next generation of pavement materials; however, the interaction between CNT and asphalt at the interface and the mechanisms of property enhancement are not well understood, which limits the application of CNT−asphalt nanocomposites. In this study, CNT is used as a representative of onedimensional nanomaterials, and the interfacial multiscale interaction mechanism between CNT and asphalt molecules is investigated by density functional theory (DFT), molecular dynamics simulation, atomic force microscopy (AFM), gelation permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), and performance evaluation. It has been shown that CNT and asphalt substrates are very compatible at the atomic scale, mainly due to π−π stacking, mechanical entanglement, and van der Waals forces. The interfacial energy barrier is −2.63 (kcal/mol)/Å2 and the shear barriers are 52.70 MPa, with asphaltene and aromatic making the greatest contribution to interfacial stress transfer. This research provides a theoretical basis for the targeted tuning of properties and establishes the basis for CNT−asphalt nanocomposites for highway applications. ... Low-temperature cracking is one of the major distresses found in asphalt pavement built under low-temperature climatic conditions. A significant increase in thermal stress accumulation ultimately results in the generation of transverse cracks extending at the surface of the pavement when the temperature drops below a certain limit value known as the critical temperature [1, 2]. Asphalt binder plays a dominant role in the low-temperature performance of asphalt mixture, contributing up to 80% according to the Strategic Highway Research Program (SHRP) [3]. ... Cracking Resistance of Recycled Rubber Asphalt Binder Composed of Warm-Mix Additives Article Full-text available Jun 2022 Wanmei Gui Li Liang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Lan Wang Fei Zhang Warm-mix asphalt technology has been applied to recycled rubber asphalt binder (RAB), which forms warm-mixed crumb rubber-modified asphalt binder (W-RAB) as a "green" material for environmental conservation and to enhance road performance. Furthermore, low-temperature cracking is one of the major distresses for asphalt pavement, which drastically restricts ride quality and service level. Therefore, the main objective of this study is to comparatively analyze the low-temperature properties of W-RABs based on thermal stress and the simple fractional model. W-RABs were obtained by mixing 60 mesh recycled rubber (CR) and two different types of warm-mix additives, namely viscosity reducer (1, 2, and 3%) and surfactant (0.4, 0.6, and 0.8%). First, Hopkins and Hamming's numerical algorithm and the Boltzmann superposition principle were used for obtaining thermal stress σT. Subsequently, critical cracking temperature Tcr was derived using the single asymptote procedure (SAP) theory. Second, the simple fractional viscoelasticity model was used to calculate the creep compliance, damping ratio, and dissipation energy ratio, and the results were compared with the Superpave protocol results obtained with bending beam rheometer (BBR) tests. The results showed that a combination of CR and warm-mix additives could slightly improve the thermal crack resistance of the asphalt binder. The addition of 0.6% surfactant yielded the optimum performance, while only a high dosage (3%) of viscosity reducer provided a marked improvement in efficiency, which decreased with a decrease in temperature. This study recommends the use of RAB composited with 0.6% surfactant for areas with extremely low temperature. ... Therefore, to overcome such limitations, post hoc analysis is suggested by several researchers, which helps make a pairwise comparison between different datasets. Among different post hoc approaches (Newman-Keul test, Fisher's least significant difference, Tukey's honestly significant difference test, Holm-Bonferroni procedure, etc.), Tukey's honestly significant difference test has been popularly adopted by several researchers for pairwise comparison in pavement materials related research works [25][26][27][28][29] [30] . Therefore, this research work considered Tukey's honestly significant difference test for statistical analysis. ... Potential application of over-burnt brick and fly ash for sustainable inverted pavement structure Aug 2022 CONSTR BUILD MATER <here is a image a08d8160c6eb5f38-ffa938694caeae96> Shahbaz Khan <here is a image 6ea57d4f532b96be-9c31a3820cc916ba> Prabin Ashish Venkatasrinivas Kannelli <here is a image d614553749469b44-c694f53aca0ff1fd> Devesh Tiwari The scarcity of natural aggregate required for infrastructural development (including road construction) is a global problem. Therefore, researchers have constantly been exploring the possibility of different kinds of non-conventional aggregate for sustainable road construction. In this context, over-burnt brick is one among the most common wastes from the construction industry in India, which can be utilized as non-conventional aggregates in the granular layer of pavement structure with the help of a stabilization technique. Pavement structure containing stabilized/cementitious underlying base/sub-base layer is termed as inverted pavement (asphalt layer supported by a relatively stiffer stabilized layer). Attempts have been made in the past to utilize over-burnt brick as an alternative aggregate in different types of pavement structures. However, whether such over-burnt aggregate can be utilized in the stabilized layer of the inverted pavement structure is still unknown. Therefore, this research aimed to explore the potential application of over-burnt brick with the help of stabilization using a cement-fly ash mixture for the base layer of inverted pavement. Likewise, the mixture of fly ash and cement mixture was investigated for their potential application in the subbase layer of the inverted pavement structure. The optimal quantity of cement in both layers for stabilization was initially determined based on strength and durability criteria. Finally, the inverted pavement was analyzed based on the design of experiment approach using the response surface methodology. The analysis of strength and durability components indicated that cement content equal to 6% for brick-fly ash mixture is suitable for the base layer of the inverted pavement. Likewise, cement content equal to 7% with fly ash was found to be suitable for its application in the sub-base layer. It is expected that this research work will help improve the sustainability quotient associated with an inverted pavement structure. ... Furthermore, various studies have demonstrated that AgNPs affect soil microorganisms that support plant growth and nutrient cycling, such as rhizobacteria, Pseudomonas fluorescence, Pseudomonas putida, and others. A major source of worry is the inhibition of denitrifying bacteria, with studies showing that at concentrations of 100 mg of AgNPs/kg of soil, there is a complete loss of these communities with no recovery signals, resulting in reduced nitrate to nitrogen conversion [60] . Meier et al. expressed concern that anthropogenic activities could affect soil ecosystems, causing microbial health to decline [61]. ... Biogenic Silver Nanoparticles as a Stress Alleviator in Plants: A Mechanistic Overview Article Full-text available May 2022 MOLECULES <here is a image 162adcb321dc1269-3826b7b6a8b527a2> Fozia Abasi <here is a image 8414bc3a741c3765-9cced26276a7fde8> Naveed Iqbal Raja Zia Ur <here is a image acc4f20e78025410-fd590b9c4eb44839> Jaroslaw Prockow Currently, the growth and yield of crops are restrained due to an increase in the occurrence of ecological stresses globally. Biogenic generation of nanomaterials is an important step in the development of environmentally friendly procedures in the nanotechnology field. Silver-based nanomaterials are significant because of their physical, chemical, and biological features along with their plentiful applications. In addition to useful microbes, the green synthesized Ag nanomaterials are considered to be an ecologically friendly and environmentally biocompatible method for the enhancement of crop yield by easing stresses. In the recent decade, due to regular droughts, infrequent precipitation, salinity, and increased temperature, the climate alternation has changed certain ecological systems. As a result of these environmental changes, crop yield has decreased worldwide. The role of biogenic Ag nanomaterials in enhancing methylglyoxal detoxification, antioxidant defense mechanisms, and generating tolerance to stresses-induced ROS injury has been methodically explained in plants over the past ten years. However, certain studies regarding stress tolerance and metal-based nanomaterials have been directed, but the particulars of silver nanomaterials arbitrated stresses tolerance have not been well-reviewed. Henceforth, there is a need to have a good understanding of plant responses during stressful conditions and to practice the combined literature to enhance tolerance for crops by utilization of Ag nanoparticles. This review article illustrates the mechanistic approach that biogenic Ag nanomaterials in plants adopt to alleviate stresses. Moreover , we have appraised the most significant activities by exogenous use of Ag nanomaterials for improving plant tolerance to salt, low and high temperature, and drought stresses. ... Hassan et al. [14] found that the addition of 1% CNT into asphalt increased asphalt viscosity by 1.5 times and proved that CNT-modified asphalt mixtures had higher resistance to rutting at high temperatures and thermal cracking. Ashish et al. [15] investigated CNT-modified asphalt properties at low temperatures and found that CNT addition presented an adverse effect on the low temperature properties of asphalt. Joao et al. [16] developed new nanocomposites (MWCNTs-modified asphalt) and found that the addition of MWCNT to asphalt improved its viscosity and fatigue resistance and declined its penetration. ... Study on the interfacial contact behavior of carbon nanotubes and asphalt binders and adhesion energy of modified asphalt on aggregate surface by using molecular dynamics simulation Article Jan 2022 CONSTR BUILD MATER Wentian Cui <here is a image 7211f315e1665161-11e2bc04f8290647> Wenke Huang <here is a image a5e436722b9d611b-9670462045b1ec2b> Hafiz Muhammad Zahid Hassan Kuanghuai Wu In this work, a comprehensive study has been conducted on the interfacial contact behavior of carbon nanotubes (CNTs) and asphalt binders as well as the influence of multi-walled carbon nanotubes (MWCNTs) embedded into asphalt on the adhesion ability of asphalt on aggregate surface at atomic scale. CNT/asphalt composite and asphalt-aggregate interface models were investigated by molecular dynamics (MD) simulations to evaluate the molecular interactions of materials. The interfacial adhesion characteristics of functionalized single-walled carbon nanotubes (SWCNTs) and MWCNTs with asphalt binders were investigated by performing pull-out simulations and the interactions of SWCNTs and asphalt components were analyzed. The obtained results showed that asphalt components with low molecular weight were more easily adsorbed by SWCNTs than higher weight components. For CNTs/asphalt composite model, Van der Waals (VdW) energy is much higher than electrostatic energy accounting for a great portion of interaction energy. Although functional groups on the surface of CNTs can increase interfacial interaction, this increase is far less than the enhancement of interaction energy and interfacial shear stress between MWCNTs and asphalt binders. Therefore, MWCNTs are regarded as a better additive to be inserted into asphalt binders to enhance the interfacial adhesion of CNTs/asphalt composites. In addition, the results of adhesion energy change of asphalt-aggregate interface models indicated that MWCNT addition into asphalt significantly increased the adhesion ability of asphalt on aggregate surface (especially for alkaline aggregates). ... On the one hand, Carbon nanotubes are recognized to strengthen the rutting performance of asphalt binders [1]. However, On the other hand, carbon nanotube has an adverse effect on the low-temperature cracking resistance of binders [3] . It should be noted that the more abundant and cheaper the nanoparticles, the more they are expected to be used. ... Rheological behavior of asphalt binders and fatigue resistance of SMA mixtures modified with nano-silica containing RAP materials under the effect of mixture conditioning Article Full-text available Oct 2021 CONSTR BUILD MATER <here is a image 039baddd37828897-5dbcf6de1aa24d77> Neda Kamboozia <here is a image d16cd1da0948b387-e38f96d1a56662a4> Seyed Ataollah Saed <here is a image 340a4328540f41fa-2f3b731217e1b7b6> Sina Mousavi Rad Due to the environmentally associated issues regarding the construction or rehabilitation of asphalt pavements with merely virgin materials, researchers have proposed the re-utilization of the reclaimed asphalt pavement (RAP) materials. However, their adoption in asphalt pavements is detrimental to the fatigue performance of asphalt pavements. For this, modifying asphalt binders with nanoparticles has been one of the successful choices among researchers. In this study, different compounds of asphalt binders and stone matrix asphalt (SMA) mixtures containing 20%, 30%, 40%, and 50% RAP materials modified with 2%, 4%, and 6% nano-silica were prepared. Moreover, the rheological behavior of each mix was evaluated using several tests, including rotational viscosity (RV) considering the flow activation energy (FAE) method, frequency sweep, Multiple Stress Creep Recovery (MSCR), Linear Amplitude Sweep (LAS), and Bending Beam Rheometer (BBR). Besides, the fatigue performance of aged SMA mixtures was investigated using the four-point beam fatigue (4 PB) test. The results indicated that the temperature susceptibility of binders was decreased by the addition of nano-silica and RAP binder. Also, according to the MSCR and frequency sweep tests results, the rutting resistance of modified binders with the RAP binder was superior to that of the base binder. Besides, due to the establishment of a network by nano-silica within the structure of the asphalt binder in which the functional groups of asphalt binder interact with nanoparticles, the modified binders with RAP binder outperformed their unmodified counterparts regarding the fatigue life. Also, aging had a less detrimental impact on the fatigue life of the RAP contained SMA mixtures. However, the low-temperature performance of binders was degraded by the addition of nano-silica. Selection of Optimal Warm-Mix Additive for Recycled Crumb-Rubber Modified Asphalt Binder Based on Rheological Tests and Viscoelastic Models Article May 2023 J MATER CIVIL ENG Wanmei Gui Li Liang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Lan Wang Multiscale Enhancement Mechanism of Carbon Nanotube-Modified Asphalt at High Temperature by Oxidative Aging: A Molecular Dynamics Simulation Investigation Article Nov 2022 <here is a image cae16dc2550ea77a-33d591b1de3d19eb> Qilin Yang <here is a image e7e6ad9de61ec514-25f28dd4b2cf5b64> Caihua Yu Low-temperature rheological properties and micro-mechanism of DIBCH plasticizer modified bitumen Article Nov 2021 Zhen Fu Songran Liu Feng Ma Menglei Lin In this study, a diisobutyl cyclohexane dicarboxylate (DIBCH) plasticizer was used to modify bitumen for preventing cracking and improving the performance of bitumen pavements. The low-temperature rheological properties of the DIBCH plasticizer–incorporated bitumen were studied via bending beam rheometer (BBR) and dynamic shear rheometer (DSR) tests. Fourier transform infrared spectroscopy (FTIR) and saturate, aromatic, resin, and asphaltene (SARA) fraction tests were performed to investigate the mechanism of the modification of bitumen by the DIBCH plasticizer. The results indicated that the incorporation of DIBCH could enhance the low-temperature deformation ability and stress-relaxation ability of bitumen, and the higher the DIBCH content, the greater the improvement in the low-temperature performance of the bitumen. Furthermore, a microscopic analysis revealed that the modification mechanism of bitumen by the DIBCH plasticizer was that of physical blending, and they did not react chemically. Moreover, the incorporation of DIBCH increased the proportion of light components in the bitumen, thereby improving its low-temperature properties. Low-Temperature Crack Resistance of Wood Tar-Based Rejuvenated Asphalt Based on Viscoelastic Rheological Method Article Aug 2021 Chonglin Liu Jiaying Du Chaofan Wu Kang Jiang The low-temperature crack resistance of recycled asphalt has an important influence on the road performance of its mixture, and the existing study and evaluation of low-temperature performance of rejuvenated asphalt mostly adopt the method of laboratory test. To avoid the one-sided evaluation of the low-temperature performance of rejuvenated asphalt by bending beam creep stiffness test (BBR), based on the viscoelastic rheological method, Burgers model was built. The rheological indexes, including creep stiffness, creep rate, relaxation time, dissipated energy ratio and creep compliance derivative, were used to compare and analyze the low-temperature crack resistance of the original asphalt, wood tar-based rejuvenated asphalt and RA-102 rejuvenated asphalt under different low-temperature conditions. Combined with the results of component analysis, the correlation between rheological parameters and test results was established by gray correlation analysis, and the rejuvenation mechanism of low-temperature performance of wood tar-based rejuvenated asphalt was expounded. The results show that wood tar-based rejuvenator can significantly improve the low-temperature crack resistance of aged asphalt, and Burgers model can better reflect the low-temperature creep and stress relaxation characteristics of rejuvenated asphalt. Wood tar-based rejuvenator can obviously improve the relaxation property and dissipation energy ratio of aged asphalt, 10 and 12 wt% wood tar-based rejuvenated asphalt has good creep deformation ability at low temperature, which can relax the deformation caused by temperature stress in time, avoid the low-temperature cracking caused by stress concentration, thus has good low-temperature crack resistance. Investigating Low-Temperature Properties of Nano Clay–Modified Asphalt through an Energy-Based Approach Article Feb 2020 <here is a image 6ea57d4f532b96be-9c31a3820cc916ba> Prabin Ashish <here is a image 4049eb07db110d94-e0090fc7ec7fcfb6> Dharamveer Singh Nanotechnology has the potential to create many new materials and devices with wide-ranging purposes. Nano-sized particles have been used in numerous applications to improve the properties of various materials. The utilization of nanotechnology in civil engineering is expected to increase and may become an attractive alternative for asphalt binder modification. The objective of this study was to investigate and evaluate the rheological properties of binders containing various percentages of carbon nanoparticles after a short-term aging process. The experimental design for this study included five binder sources (three grades including PG 64-22, PG 64-16, and PG 52-28), three nano percentages (0.5, 1.0, and 1.5% by weight of the virgin binder), and control binders. The rheological characteristics of the rolling thin film oven (RTFO) binders, including failure temperature, performance grade, creep and creep recovery, viscous flow, and frequency and amplitude sweep, were tested. The results of the experiments indicated that the addition of nanoparticles was helpful in increasing the failure temperature, complex modulus, and elastic modulus values and in improving rutting resistance of the RTFO binder. The phase angle of the binders generally decreased with an increase in nano content and RTFO aging procedure. In addition, statistical analysis indicated that the asphalt binder source plays a key role in determining the rheological properties because of significant evaluations. Evaluation of High Temperature Rheological Characteristics of Asphalt Binder with Carbon Nano Particles J TEST EVAL In recent years, nano technology, a relatively new field in science dealing with structures that are on the nano scale, have been used in numerous applications to improve properties of various materials. However, the use of this technology has not been explored in detail in the area of asphalt binder materials. The objective of this study was to investigate and evaluate the high temperature rheological properties of the binders containing various percentages of carbon nano particles. The experimental design for this study included the utilization of five binder sources, three binder grades (PG 64-22, PG 64-16, and PG 52-28), one type of nano particle, and four percentages of nano particles (0.0 %, 0.5 %, 1.0 %, and 1.5 % by weight of the virgin binder). Some of the rheological characteristics of these binders were obtained, including rotational viscometer (four testing temperatures of 120, 135, 150 , and 165°C) and dynamic shear rheometer. The results of the experiments indicated that the addition of nano particles was helpful in increasing the viscosity, failure temperature, phase angle, and viscous and elastic modulus values and in improving the rutting resistance of the binders. On the other hand, the binder sources and grades generally influenced their rheological properties as the nano particles were added to the asphalt binder. Characterization of Unaged Asphalt Binder with Carbon Nano Particle In recent years, nanotechnology has been utilized in many engineering applications. In this technology, nano-sized particles a reused in improving the properties of various materials. The construction industry, in general, has not embraced this technology; however, these particles could be used to enhance the physical and chemical properties of the materials such as asphalt binders. The objective of this study was to investigate and evaluate the rheological properties of three asphalt binder sources containing various percentages of carbon nano particles. The experimental design for this study included the utilization of three binder sources (PG 64-22), one type of nano particle, and four nano dosage percentages (0.2%, 0.5%, 1.0%, and 1.5% by weight of the binder). The following rheological properties were tested and evaluated: viscosity, performance grade, creep and creep recovery, and frequency sweep. The results of the experiments indicated that the addition of nano particles was helpful in increasing the viscosity, failure temperature, complex modulus, and elastic modulus values as well as in improving rutting resistance of the binder. On the other hand, the content analysis of nano particles showed that a relatively low percentage (<0.2%) of nano particles did not have a significant effect on improving the binder properties while a relative high percentage (>1.0%) of nano particles is recommended for the modification of an asphalt binder Interconversion between viscoelastic functions using the Tikhonov regularisation method and its comparison with approximate techniques Article ROAD MATER PAVEMENT <here is a image 27ba08bf39453de6-318a7beb89e2e21b> Milad Ebrahimi <here is a image fac03fb38c59cd56-1924bac872ce1df4> M.F. Saleh <here is a image 2c1f02f0b5a3bdc4-6a71e772d39c764a> Miguel Moyers-Gonzalez Asphalt concrete behaves as a viscoelastic material under normal traffic loading and field conditions. The stress–strain behaviour depends on the rate of loading as well as the actual pavement temperature. In order to model the viscoelastic behaviour of the asphalt materials, viscoelastic functions need to be determined. In this study, a uniaxial static creep test was carried out for AC 20 and AC 14 asphalt mixtures. Several asphalt specimens were tested at different temperatures subjected to various deviator stresses in order to verify the proposed approach. Prony series for the creep compliance were determined for raw and smoothed data. Various optimisation techniques were utilised to ensure a monotonic increase in the Prony coefficient. A number of approximate interconversion techniques were evaluated in determining relaxation modulus resulted from the creep compliance interconversion. It was clear that Prony series constants affect the interconverted relaxation modulus. It was also obvious that using the discretisation of the slope of n value (slope of log creep compliance with log t) over the time domain instead of using one single constant value of the slope provides a better solution of the interconverted relaxation modulus. Finally, the exact interconversion method was applied to check the accuracy of approximate techniques. Tikhonov regularisation with the L-curve method was considered to solve the convolution integral. The exact solution was recommended as a result of investigating the extracted data. The approximate solution showed around 7.0% error comparing different approaches. Application of bitumen rheological parameters to predict thermal cracking behavior of polymer modified asphalt mixture Article Full-text available CONSTR BUILD MATER Amir Hossein Sheikhmotevali <here is a image 8e6c9e2497566e60-61af73b0219e118e> Mahmoud Ameri Effects of bitumen rheology on low temperature properties of polymer modified asphalt mixtures were studied. The rheology of the bitumens were characterized using SHRP bending beam rheometer (BBR), and the low temperature properties of the mixtures were evaluated by indirect tensile strength test and creep compliance test at different polymer contents. The results indicate that, in most cases, polymer modification do not show significant low temperature performance grade improvements as compared to the corresponding base bitumen. The mixture fracture temperature does not match as well bitumen cracking temperature. Based on the results obtained, it was concluded that not all of the bitumens with same low temperature performance grade may perform the same. The results indicate that it would be very difficult to establish general relationships between properties of polymer modified bitumen and the performance of pavement at low temperatures leading to the conclusion that the most sensible would be to evaluate the performance on the polymer modified asphalt mixture. A Study on Mechanical Properties of CNT-Reinforced Carbon/Carbon Composites Article Full-text available Yi-Luen Li <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ming-Yuan Shen <here is a image c14306ae003680a5-62a1c53b7208acca> Huang-Suo Su <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ming-Chuen Yip Carbon/carbon composites (C/C composites) possess superior characteristics of low density, high strength, extremely low coefficient of thermal expansion, and high fatigue resistance. In carbonization process, the high-temperature pyrolysis made of carbon, hydrogen, oxygen, and other elements results in a lot of voids and cavities generated in the interior of C/C composites. Therefore, the C/C composites are densified to fill the voids by using repeated impregnation. But densification is a time-wasting and complex process, which increases production costs in the manufacturing process. In this study, the multiwall carbon nanotubes (MWNTs) were adopted as a reinforcement material for C/C composites to reduce the existence of voids or cavities and enhance the mechanical properties of C/C composites. According to the experimental results, the CNT-added C/C composite containing 1.2 wt% CNT possesses the greatest flexure strength, flexure modulus, and interlaminar shearing strength. Plus, the above-mentioned strength and modulus are increased by 23%, 19.2%, and 30%, respectively. Comparing Effects of Biobinder with Other Asphalt Modifiers on Low-Temperature Characteristics of Asphalt Article J MATER CIVIL ENG <here is a image 77da002e85349f34-2255d5cc02cb687b> Sassan Aflaki Pouria Hajikarimi Ellie H. Fini Boubacar Zada This paper examines effects of a new biobased modifier, "biobinder," on low-temperature properties of asphalt binder and compares the results with those of conventional modifiers: crumb rubber, Gilsonite, styrene-butadiene-styrene (SBS), and polyphosphoric acid (PPA). Low-temperature characteristics of modified and nonmodified asphalts were studied using experimental and modeling approaches. A three-point bending beam rheometer was used to measure the stress-strain response of each specimen. A theoretical approach was used to determine stiffness and stress release rate; in addition, the Burgers model was implemented to predict the stored and dissipated energy ratio and quantity of derivation of creep compliance in each of modified and nonmodified asphalt specimens. Effects of various modifications were compared based on both the calculated stored and dissipated energy ratio and quantity of derivation of creep compliance. The proposed biobinder is produced from the thermochemical conversion of biomass (including animal waste, switch grass, and woody biomass). Biobinder is then blended with virgin binder to produce biomodified binder (BMB). This paper argues that the improved low-temperature rheological properties in biomodified binder is reflected in the enhancement in energy dissipation ratio and quantity of derivation of creep compliance. Laboratory Evaluation of Environmental Performance of Photocatalytic Titanium Dioxide Warm-Mix Asphalt Pavements Data Full-text available J MATER CIVIL ENG <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Marwa M. Hassan M Asce Heather Dylla <here is a image c7a091215f63efc1-bb3738ec9db5167b> Samuel Cooper The use of titanium dioxide (TiO 2) coating for pavements has received considerable attention in recent years to improve air quality near large metropolitan areas. However, the proper method of applying TiO2 to asphalt pavements is still unclear. This study evaluated the benefits of incorporating TiO 2 in the preparation of warm-mix asphalt (WMA). Two application methods to integrate TiO 2 were evaluated, a water-based TiO 2 solution applied as a thin coating and using TiO 2 as a modifier to asphalt binder in the preparation of WMA. On the basis of the results of the experimental program, it was determined that the photocatalytic compound was not effective in degrading NO x in the air stream when used as a modifier to the binder in the preparation of WMA. This could be attributed to the fact that only a small amount of TiO 2 is present at the surface. When used as part of a surface spray coating, TiO 2 was effective in removing nitrogen oxide (NO xÀ) pollutants from the air stream with an efficiency ranging from 31 to 55%. The maximum NO x removal efficiency was achieved at a coverage rate of 0:05 L∕m 2 . However, durability of the surface spray coating requires further evaluation. In addition, the increase in flow rate and relative humidity negatively impacted the effectiveness of NO x reduction efficiency. In contrast, the increase in ultraviolet (UV) light intensity improved the NO x removal efficiency of the surface coating. DOI: 10.1061/(ASCE)MT.1943-5533.0000408. © 2012 American Society of Civil Engineers. Use of nanomaterial for asphalt binder and mixtures: a comprehensive review on development, prospect, and challenges Article ROAD MATER PAVEMENT <here is a image 6ea57d4f532b96be-9c31a3820cc916ba> Prabin Ashish <here is a image 4049eb07db110d94-e0090fc7ec7fcfb6> Dharamveer Singh This article aimed at providing comprehensive information on the use of nanomaterial in asphalt binder and mixes based on an exhaustive review of the literature. The complete literature review can broadly be perceived into three different segments. The first segment of this review discusses (a) the need of nanomaterial, and (b) different types of nanomaterials with their respective characteristics. The second segment of this review work discusses about the various functional aspects which have been reported to have an important role on or before construction of asphaltic layer, i.e. (a) mixing of nanomaterials with asphalt binder, (b) nanomaterial dispersion into asphalt binder matrix, and (c) high-temperature storage stability of binary composite (asphalt binder and nanomaterial) and triple composite (asphalt binder, polymer additive and nanomaterial) under high-temperature condition. Among different types of mixing approach, use of a high shear mixer and ultra-sonication individually or in combination has been reported in the literature for an efficient way for dispersion of nanomaterial in an asphalt binder matrix. To evaluate mixing of nanomaterial in asphalt binder matrix, different microscopic approach such as X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Atomic Force Microscopy (AFM) has been recommended in the literature. The third segment emphasises on the effect of nanomaterial addition on performance-based parameters for (a) aging resistivity potential, (b) moisture damage resistivity potential, (c) intermediate, (d) high, and (e) low-temperature performance. The review of the literature showed that the addition of nanomaterial to asphalt binder not only improves the aging resistivity potential of asphalt binder but also improves the moisture damage resistivity potential, high, and intermediate temperature performance of asphalt binder and mixes. However, the mixed response was observed from the review of literature for the corresponding effect of nanomaterial on low-temperature performance parameters. Effect of Carbon Nano Tube on performance of asphalt binder under creep-recovery and sustained loading conditions Article CONSTR BUILD MATER Dharamveer Singh <here is a image 6ea57d4f532b96be-9c31a3820cc916ba> Prabin Ashish The present study aimed at evaluating the rutting performance of Carbon Nano Tube (CNT) modified asphalt binder under different loading conditions. CNT content was varied as 0%, 0.4%, 0.75%, 1.5% and 2.25% by the weight of control binder. Superpave rutting parameter (G/Sinδ) and Shenoy parameter (G/(1-(1/TanδSinδ))) were initially evaluated using temperature sweep test. Though both parameters showed a similar trend, the later one found to have more sensitivity towards evaluating unrecoverable strain value. Creep-recovery test was further conducted at four different stress levels (100 Pa, 3200 Pa, 5000 Pa, and 10000 Pa) to understand the effect of CNT under cyclic loading-unloading condition. Improvement in recovery value and a corresponding decrease in non-recoverable creep compliance value was observed with the addition of CNT. Further attempt was made to model the strain response from creep-recovery test using the Burgers model and Power model. Based upon the variation of viscous component of steady flow obtained from the Burgers model, CNT addition found to improve the rutting performance. Further, the power model also showed an excellent prediction of strain response under creep period, however, deviation from the experimentally observed response was observed in the recovery period. Modification to the power law model was done which significantly improved the strain prediction in the recovery period. Likewise, the effects of CNT under sustained loading condition was evaluated using a creep test at two different stress levels (100 Pa and 3200 Pa). Incremental dosages of CNT shifted the binder response from linear to nonlinear viscoelastic region at comparatively lower creep period. Significant decrease in deformation rate was also observed with CNT addition. Rheological and micro-structural characterization of bitumen modified with carbon nanomaterials Article CONSTR BUILD MATER <here is a image cae16dc2550ea77a-33d591b1de3d19eb> Qilin Yang <here is a image 877a6d24f66a5fb3-d62516be03ad2162> Quan Liu Jing Zhong Markus Oeser Study on understanding functional characteristics of multi-wall CNT modified asphalt binder Article <here is a image 6ea57d4f532b96be-9c31a3820cc916ba> Prabin Ashish <here is a image 4049eb07db110d94-e0090fc7ec7fcfb6> Dharamveer Singh This study evaluates important functional characteristics such as dispersion, aging resistivity potential, temperature susceptibility, and high temperature storage stability of Carbon Nano Tube (CNT) modified asphalt binders. CNT content was varied as 0%, 0.4%, 0.75%, 1.5% and 2.25% by weight of control binder (AC-10). Scanning Electron Microscopic (SEM) images was captured to get direct observation of CNT dispersion. Viscosity was further measured to understand the workability and dispersion characteristics. Further, viscosity temperature susceptibility parameters (A and VTS), activation energy and Penetration Index (PI) values were estimated to evaluate temperature susceptibility. SEM images and viscosity data showed that CNT content up to 1.5% may be recommended without potential problem of entanglement/clustering. Similarly, analysis of softening point, complex modulus and phase angle data showed positive effect of CNT on aging resistivity potential. Such improvement in functional characteristics can be attributed to high specific surface area (190 m²/gm), higher aspect ratio (length/diameter = 645) and excellent mechanical properties of CNT. Likewise, high temperature storage stability was evaluated using softening point and Multiple Stress Creep Recovery (MSCR) tests. Though softening point test method showed sufficiently stable nature of CNT under high temperature storage condition, settling of CNT (unstable nature) was observed from MSCR testing approach. Effects of Regular and Nano Sized Hydrated Lime Fillers on Fatigue and Bond Strength Behavior of Asphalt Mastic Article TRANSPORT RES REC <here is a image db7ad1dcffe94dd4-0446fd3a83547d5b> Aditya Kumar Das <here is a image 4049eb07db110d94-e0090fc7ec7fcfb6> Dharamveer Singh The present study evaluates effects of regular sized hydrated lime (RHL) and nano sized hydrated lime (NHL) on fatigue and bond strength of asphalt mastic. The asphalt mastics were produced in the laboratory using AC-30 binder with different combinations of basalt–RHL, and basalt–NHL fillers. The dosages of RHL and NHL were selected as 0%, 5%, 10%, 15%, and 20% by weight of asphalt binder, and the percentage of basalt filler was adjusted accordingly. Filler to binder (F/B) ratio was selected as 0.8 (by mass ratio) for all mastic sample preparation. The fatigue damage behavior (number of cycles to fatigue damage/failure) of asphalt mastic was evaluated using a linear amplitude sweep (LAS) test. Further, the interfacial bond strengths of asphalt mastic and aggregate samples were evaluated using the bitumen bond strength (BBS) test. Overall test results indicate that mineralogy, surface area, and interaction properties of RHL and NHL fillers have a significant effect on fatigue, bond strength, and moisture damage performance of asphalt mastic. The results from the LAS test showed that NHL filler predominantly enhanced the fatigue life of asphalt mastic as compared with RHL filler. BBS test results imply that the contribution of NHL filler is significant over RHL filler in improving the bond strength and moisture damage resistance of asphalt mastic. Overall asphalt mastic with 20% NHL filler had better fatigue life, bond strength, and moisture damage performance over mastic with other percentages of RHL or NHL fillers. Low-temperature properties of bituminous nanocomposites for road applications Article CONSTR BUILD MATER <here is a image 52b97b756c66beb6-3461e806127ed1a3> Lucia Tsantilis <here is a image e6d086bd8cd25be5-cfd0ac0e324aba9f> Orazio Baglieri <here is a image d26b9526b53912c0-fe5ba0a6d4729516> Ezio Santagata This paper focuses on low-temperature performance of bituminous nanocomposites for road paving applications. In the experimental investigation, one type of carbon nanotubes and two types of nanoclays were combined with three base bitumens at various dosages by following a protocol based on the use of shear mixing and sonication. All rheological measurements were carried out by means of a Bending Beam Rheometer at temperatures comprised between −6 and −24 °C. Results, which were interpreted by combining different analysis models, showed that the effectiveness of nano-modification is strictly influenced by the combination of base binder, additive type and dosage. Development of empirical model for predicting G ∗ /Sinδ and viscosity value for nanoclay and Carbon Nano Tube modified asphalt binder Article CONSTR BUILD MATER <here is a image 6ea57d4f532b96be-9c31a3820cc916ba> Prabin Ashish <here is a image 4049eb07db110d94-e0090fc7ec7fcfb6> Dharamveer Singh The present research work was undertaken to develop a simple empirical model to evaluate superpave rutting factor (G∗/Sinδ) and viscosity value for Nano Clay (NC) and Carbon Nano Tube (CNT) modified asphalt binders. The amount of NC was varied as 0%, 2%, 4% and 6%, while CNT was varied as 0%, 0.4%, 0.75%, 1.5% and 2.25% by the weight of control binder. Nanomaterial factors (NCf for NC modified and CNTf for CNT modified asphalt binder) and temperature factors were evaluated to develop the final empirical model for G∗/Sinδ and viscosity. NC factor (NCf) as well as CNT factor (CNTf) were found to have exponential variation for viscosity model. In case of G∗/Sinδ model, CNTf found to have quadratic variation due to reduction in stiffness value at higher CNT doses, whereas, NCf showed exponential variation. Development of empirical model for evaluating G∗/Sinδ and viscosity value for NC and CNT modified asphalt binders has been successfully demonstrated in the present paper. Overall, it is expected that the proposed models may be helpful to practicing engineers for making judicious decision on selection of amount of NC or CNT to improve rutting and workability requirement of asphalt binder. High- and Intermediate-Temperature Performance of Asphalt Binder Containing Carbon Nanotube Using Different Rheological Approaches Article J MATER CIVIL ENG <here is a image 6ea57d4f532b96be-9c31a3820cc916ba> Prabin Ashish <here is a image 4049eb07db110d94-e0090fc7ec7fcfb6> Dharamveer Singh The present research work was undertaken to evaluate the rutting performance of carbon nanotube (CNT)–modified asphalt binders. Additionally, intermediate-temperature performance, aging resistivity potential, and high-temperature storage stability were also evaluated. Reported literature on rutting performance of CNT-modified asphalt binders is mainly based on the Superpave rutting parameter (G/sinδ), which does not account for the recovery aspect of binder. The paper first highlights the importance of the elastic response of CNT-modified asphalt binders for better understanding about its rutting performance. Further, different approaches such as the evaluation of zero shear viscosity (ZSV), creep test, and multiple stress creep recovery (MSCR) were utilized to reach appropriate conclusions. A recently developed approach, linear amplitude sweep (LAS), was used for evaluating intermediate-temperature performance. The CNT was varied as 0, 0.4, 0.75, 1.5, and 2.25% by the weight of control binder. The G/sinδ value was found to increase until 1.5% CNT content; however, the addition of 2.25% CNT resulted in decreased G/sinδ, indicating reduced rutting performance at higher CNT content. Contrary to the G/sinδ trend, significant improvement in recovery value was observed for all CNT percentages. Further, based on detailed analysis carried out for different rheological parameters such as ZSV value (evaluated using the steady shear approach), deformation resistivity potential from creep test, recovery (R), and nonrecoverable creep compliance (Jnr) from the MSCR test, CNT addition to the control binder showed significant improvement in rutting resistivity potential for all CNT percentages. Although ZSV value significantly improved with the addition of CNT, the increase in CNT content showed an early transition from Newtonian to non-Newtonian behavior. Further, analysis for stress sensitivity was carried based on the R and Jnr values obtained from the MSCR test, which showed an increase in stress sensitivity with the addition of CNT to the control binder. The need for improvement in the current protocol used for evaluating stress sensitivity of asphalt binder (based on the MSCR test) has also been discussed. Improvement in intermediate-temperature performance evaluated through LAS test was also observed. Also, CNT addition to asphalt binder was found to be stable under high-temperature storage conditions. Overall, improvement in high- and intermediate-temperature performance can be expected with the addition of CNT to the control binder. Investigating the performance, chemical, and microstructure properties of carbon nanotube-modified asphalt binder Article ROAD MATER PAVEMENT <here is a image e60ef54fb0d5486c-78296e57af9fc6f3> Minghui Gong <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jun Yang Hongmiao Yao <here is a image 8fa1b842c1752896-a0b1ef26107f041f> John E. Haddock Carbon nanotubes (CNT) hold the potential to enhance the performance of construction materials such as asphalt binders and mixtures. With the goal of designing long-life asphalt pavements, this research report investigates the laboratory performance of CNT-modified asphalt. Mixing combination conditions including shearing time and shearing rate are studied in the first step. Then modified asphalts with different CNT contents are evaluated by penetration, softening point, and ductility indexes. Storage stability of modified asphalt is accessed using the separation test. After that, aged asphalts are obtained by using the thin film oven test (TFOT). Samples of base and CNT-modified asphalts before and after ageing are characterised by running the rotational viscosity (RV) test, dynamic shear rheometer (DSR) test, and bending beam rheometer (BBR) test. Furthermore, Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM) are employed to characterise the functional groups and microstructures of base and modified asphalt binders before and after ageing. It is shown that shearing rate and shearing rate*shearing time interaction have a profound influence on the property of modified asphalt whereas shearing time does not. Conventional test results indicate that increasing CNT content would decrease penetration and ductility while increasing the softening point. The separation test shows that CNT may settle down during the storage process. Rheological test results show that the addition of CNT can improve the high temperature performance and ageing resistance while decreasing the low temperature performance. The functional groups in base and modified asphalt are found to be similar which indicates that there are no chemical reactions during modification. It demonstrates that CNT-modified asphalt has better anti-ageing property with a lower increase in sulphoxide index after ageing. AFM characterisation provides details of the CNT modification mechanism. This research provides useful guidance and potential problems on the use of CNT as a high performance modifier. Evaluation of properties and fatigue life estimation of asphalt mixture modified by organophilic nanoclay Article CONSTR BUILD MATER <here is a image 311f2bdac923ea67-b4b0e6a8092aa663> João Victor Staub de Melo <here is a image 7d99cccfc7b589b4-613d9dad9890d75f> Glicério Trichês This paper presents the results for the influence of an organophilic nanoclay on the properties of an asphalt mixture. The main mechanical and rheological properties of a nanomodified mixture were evaluated, including moisture-induced damage, resistance to permanent deformation, complex modulus and fatigue resistance. The results obtained show gains in the properties of the asphalt mixture modified by nanoclay. The beneficial effect of the nanoclay was also verified in the numerical simulation of a pavement structure, since the lifespan of the nanomodified asphalt surface increased with regard to the fatigue fracture, when compared to a conventional asphalt surface. The main conclusion of this study is that the addition of an organophilic nanoclay to an asphalt mixture can improve its resistance in relation to the main mechanisms involved in the deterioration of pavements. A statistical analysis on the mechanical properties of nanocomposite modified asphalt mixtures Article <here is a image ed8dbdc60d988a22-8a1a99e5dc125504> Mahdi Delaviz Bayekolaei <here is a image 7daed06a2ba01911-eee94f119a868b28> Koorosh Naderi <here is a image 72f4d73f84773df5-277e3cd9372d530c> Fereidoon Moghadas Nejad This study aimed to characterize the rate of change that takes place in the mechanical properties of polymer-nanocomposite asphalt (PNMA) mixtures due to altering asphalt binder grade and styrene-butadiene-styrene (SBS) type. Laboratory testing program included Marshall stability, resilient modulus, and wheel-tracking tests. Test results were compared and analyzed statistically by means of two-way analysis of variance and Tukey test. Variance analysis indicated the significant effect of both binder type and SBS grade on mechanical properties of asphalt mixtures. Interaction between binder type and SBS grade is also meaningful in all the experiments. The results also show that the binder type is the primary affecting factor, followed by the SBS grade. Effect of multi-walled carbon nanotubes on the performance of styrene–butadiene–styrene copolymer modified asphalt Effect of filler on low temperature physical hardening of bitumen Article CONSTR BUILD MATER Lars S Johansson Ulf Isacsson Laboratory investigations of low temperature physical hardening of bitumen using a Bending Beam Rheometer (BBR) are described. The study encompasses five bitumens, three conditions with regard to additives and three testing temperatures (−15, −25 and −30°C). As additives, two fillers, hydrated lime and calcium carbonate, were used. The effect of the fillers on the isothermal low temperature hardening was evaluated with the aid of a physical hardening index. The viscoelastic nature of the bitumens and bitumen/filler mixtures was investigated utilising the Burger model, and the Burger parameters were used to calculate dissipation energy ratios (dissipated energy over stored energy) in each BBR test. The results obtained did not indicate any significant effect of the fillers on low temperature physical hardening. Analyses of the dissipation energy ratio showed a considerable capacity for energy dissipation, even at a temperature as low as −30°C. With few exceptions, more energy was dissipated than stored during a BBR test. It appears that the dissipation energy ratio is not necessarily related to the stiffness of the binder. Polyethylene multiwalled carbon nanotube composites Article POLYMER Tony McNally <here is a image a12fe782de6c7c82-c49a41f26f1191d9> Peter J. Halley John Paul Quinn Polyethylene (PE) multiwalled carbon nanotubes (MWCNTs) with weight fractions ranging from 0.1 to 10 wt% were prepared by melt blending using a mini-twin screw extruder. The morphology and degree of dispersion of the MWCNTs in the PE matrix at different length scales was investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM) and wide-angle X-ray diffraction (WAXD). Both individual and agglomerations of MWCNTs were evident. An up-shift of 17 cm−1 for the G band and the evolution of a shoulder to this peak were obtained in the Raman spectra of the nanocomposites, probably due to compressive forces exerted on the MWCNTs by PE chains and indicating intercalation of PE into the MWCNT bundles. The electrical conductivity and linear viscoelastic behaviour of these nanocomposites were investigated. A percolation threshold of about 7.5 wt% was obtained and the electrical conductivity of PE was increased significantly, by 16 orders of magnitude, from 10−20 to 10−4 S/cm. The storage modulus (G′) versus frequency curves approached a plateau above the percolation threshold with the formation of an interconnected nanotube structure, indicative of ‘pseudo-solid-like’ behaviour. The ultimate tensile strength and elongation at break of the nanocomposites decreased with addition of MWCNTs. The diminution of mechanical properties of the nanocomposites, though concomitant with a significant increase in electrical conductivity, implies the mechanism for mechanical reinforcement for PE/MWCNT composites is filler-matrix interfacial interactions and not filler percolation. The temperature of crystallisation (Tc) and fraction of PE that was crystalline (Fc) were modified by incorporating MWCNTs. The thermal decomposition temperature of PE was enhanced by 20 K on addition of 10 wt% MWCNT. Effect of CNT Decoration With Silver Nanoparticles on Electrical Conductivity of CNT-Polymer Composites CARBON Jang-Kyo Kim A simple approach to decorate carbon nanotube (CNT) with silver nanoparticles (Ag-NPs) was developed to enhance the electrical conductivity of CNT. CNTs were functionalized using ball milling in the presence of ammonium bicarbonate, followed by reduction of silver ions in N, N-dimethylformamide, producing silver decorated CNTs (Ag@CNTs). The Ag@CNTs were employed as conducting filler in epoxy resin to fabricate electrically conducting polymer composites. The electrical, thermal and mechanical properties of the composites were measured and compared with those containing pristine and functionalized CNTs. It was found that when pH was about six, highly dispersed Ag-NPs can be decorated on functionalized CNTs. The electrical conductivity of composites containing 0.10 wt% of Ag@CNTs was more than four orders of magnitude higher than those containing same content of pristine and functionalized CNTs, confirming the advantage of the Ag@CNTs as effective conducting filler. The ameliorating effect of improved electrical conductivity was not at the expense of thermal or mechanical properties. Effects of silane functionalization on the properties of carbon nanotube/epoxy nanocomposites COMPOS SCI TECHNOL <here is a image c98f8b58401ba658-ca23679580ebdb72> Peng-Cheng Ma Jang-Kyo Kim The effects of silane functionalization of multi-wall carbon nanotubes (CNTs) on properties of CNT/epoxy nanocomposites are investigated in this work. Epoxy-based nanocomposites reinforced with CNTs with and without functionalization were prepared. The properties of nanocomposites were characterized extensively using the scanning electronic microscopy (SEM), electrical conductivity measurement, thermo-gravimetric analysis (TGA), dynamic mechanical analysis (DMA), three-point bending test and fracture toughness measurement. The results showed that grafting silane molecules onto the CNT surface improved the dispersion of CNTs in epoxy along with much enhanced mechanical and thermal properties as well as fracture resistance of nanocomposites compared to those containing CNTs without functionalization. The electrical conductivity of nanocomposites decreased due to the wrapping of CNTs with non-conductive silane molecules. These findings confirmed the improved interfacial interactions arising from covalent bonds between the functionalized CNTs and epoxy resin. Mihai O. Marasteanu <here is a image a2aae4ae3deb5759-5f1340696142d382> Jean-Claude Carret <here is a image b05a9d4d7fc6b71a-8a6212b08d4a23d8> Augusto Cannone Falchetto <here is a image 98df31d0315f6c30-86787cd3be064d31> Cédric Sauzéat <here is a image 41f72f6e1debf31a-4c0a09206044038f> Saad Ahmad Abo-Qudais	https://www.researchgate.net/publication/339606232_Evaluating_the_Effect_of_Carbon_Nanotube_on_Low_Temperature_Property_of_Asphalt_Binder_through_Dissipated_Energy-Based_Approach
Lew, Daniel Julio \| Duke Cancer Institute Our research interests focus on the control of cell polarity. Cell polarity is a nearly universal feature of eukaryotic cells. A polarized cell usually has a single, clear axis of asymmetry: a “front” and a “back”. In the past several years it has become apparent that the highly conserved Rho-family GTPase Cdc42, first discovered in yeast, is a component of a master pathway, employed time and again to promote polarity in different contexts. Most cells know which way to polarize. Concentration gradients of attractants, repellents, nutrients, or pheromones reveal the optimal directions for successful attack, escape, feeding, or mating. However, cells can and do polarize even when deprived of directional cues, choosing a random axis and committing to it as if they knew where they were going. This process, called " symmetry breaking" , reflects the presence of a core internal polarity program. Our work has uncovered the biochemical basis for this core program, which uses positive feedback loops to reinforce inequalities in the local concentrations of polarity factors, so that stochastic fluctuations are amplified into a single dominating asymmetry. We use the tractable budding yeast as a model system. Because the genes and processes we study are highly conserved, we anticipate that learning the answers to fundamental questions in yeast will be relevant and informative for a wide range of organisms. Our work combines molecular genetics, cell biology, and mathematical modeling, and addresses questions including: Why is there one and only one “front”? How is polarity turned on and off? How does Cdc42 organize the cytoskeleton? How is polarity guided by pheromone gradients? Daniel Lew Overview: Our research interests focus on the control of cell polarity. Cell polarity is a nearly universal feature of eukaryotic cells. A polarized cell usually has a single, clear axis of asymmetry: a “front” and a “back”. In the past several years it has become apparent that the highly conserved Rho-family GTPase Cdc42, first discovered in yeast, is a component of a master pathway, employed time and again to promote polarity in different contexts. Most cells know which way to polarize. Concentration gradients of attractants, repellents, nutrients, or pheromones reveal the optimal directions for successful attack, escape, feeding, or mating. However, cells can and do polarize even when deprived of directional cues, choosing a random axis and committing to it as if they knew where they were going. This process, called "symmetry breaking", reflects the presence of a core internal polarity program. Our work has uncovered the biochemical basis for this core program, which uses positive feedback loops to reinforce inequalities in the local concentrations of polarity factors, so that stochastic fluctuations are amplified into a single dominating asymmetry. We use the tractable budding yeast as a model system. Because the genes and processes we study are highly conserved, we anticipate that learning the answers to fundamental questions in yeast will be relevant and informative for a wide range of organisms. Our work combines molecular genetics, cell biology, and mathematical modeling, and addresses questions including: Why is there one and only one “front”? How is polarity turned on and off? How does Cdc42 organize the cytoskeleton? How is polarity guided by pheromone gradients? Positions: James B. Duke Distinguished Professor of Pharmacology and Cancer Biology Pharmacology & Cancer Biology School of Medicine Professor of Pharmacology and Cancer Biology Pharmacology & Cancer Biology School of Medicine Professor in Molecular Genetics and Microbiology Molecular Genetics and Microbiology School of Medicine Professor of Cell Biology Cell Biology School of Medicine Member of the Duke Cancer Institute Duke Cancer Institute School of Medicine Education: Ph.D. 1990 Rockefeller University Grants: Studies of cell polarity, chemotropism, and cell-cycle control Administered By Pharmacology & Cancer Biology Awarded By National Institutes of Health Role Principal Investigator Start Date July 01, 2017 End Date June 30, 2027 Publications: A Novel Stochastic Simulation Approach Enables Exploration of Mechanisms to Regulate Polarization Dynamics Authors Ramirez, SA; Pablo, M; Burk, S; Lew, DJ ; Elston, TC MLA Citation Ramirez, Samuel A., et al. “ A Novel Stochastic Simulation Approach Enables Exploration of Mechanisms to Regulate Polarization Dynamics .” Biophysical Journal , vol. 118, no. 3, CELL PRESS, 2020, pp. 135A-135A. URI https://scholars.duke.edu/individual/pub1434697 Source wos Published In Biophysical Journal Volume 118 Published Date 2020 Start Page 135A End Page 135A Exploratory polarization facilitates mating partner selection in Saccharomyces cerevisiae. Yeast decode pheromone gradients to locate mating partners, providing a model for chemotropism. How yeast polarize toward a single partner in crowded environments is unclear. Initially, cells often polarize in unproductive directions, but then they relocate the polarity site until two partners' polarity sites align, whereupon the cells "commit" to each other by stabilizing polarity to promote fusion. Here we address the role of the early mobile polarity sites. We found that commitment by either partner failed if just one partner was defective in generating, orienting, or stabilizing its mobile polarity sites. Mobile polarity sites were enriched for pheromone receptors and G proteins, and we suggest that such sites engage in an exploratory search of the local pheromone landscape, stabilizing only when they detect elevated pheromone levels. Mobile polarity sites were also enriched for pheromone secretion factors, and simulations suggest that only focal secretion at polarity sites would produce high pheromone concentrations at the partner's polarity site, triggering commitment. Authors Clark-Cotton, MR; Henderson, NT; Pablo, M; Ghose, D; Elston, TC; Lew, DJ MLA Citation Clark-Cotton, Manuella R., et al. “ Exploratory polarization facilitates mating partner selection in Saccharomyces cerevisiae. ” Mol Biol Cell , vol. 32, no. 10, May 2021, pp. 1048–63. Pubmed , doi:10.1091/mbc.E21-02-0068. URI https://scholars.duke.edu/individual/pub1475825 PMID 33689470 Source pubmed Published In Molecular Biology of the Cell Volume 32 Published Date 2021 Start Page 1048 End Page 1063 DOI 10.1091/mbc.E21-02-0068 Mechanistic insights into actin-driven polarity site movement in yeast. Directed cell growth or migration are critical for the development and function of many eukaryotic cells. These cells develop a dynamic "front" (also called "polarity site") that can change direction. Polarity establishment involves autocatalytic accumulation of polarity regulators, including the conserved Rho-family GTPase Cdc42, but the mechanisms underlying polarity reorientation remain poorly understood. The tractable model yeast, Saccharomyces cerevisiae, relocates its polarity site when searching for mating partners. Relocation requires polymerized actin, and is thought to involve actin-mediated vesicle traffic to the polarity site. In this study, we provide a quantitative characterization of spontaneous polarity site movement as a search process and use a mechanistic computational model that combines polarity protein biochemical interactions with vesicle trafficking to probe how various processes might affect polarity site movement. Our findings identify two previously documented features of yeast vesicle traffic as being particularly relevant to such movement: tight spatial focusing of exocytosis enhances the directional persistence of movement, and association of Cdc42-directed GTPase-Activating Proteins with secretory vesicles increases the distance moved. Furthermore, we suggest that variation in the rate of exocytosis beyond simple Poisson dynamics may be needed to fully account for the characteristics of polarity site movement in vivo. Authors Ghose, D; Lew, D MLA Citation Ghose, Debraj, and Daniel Lew. “ Mechanistic insights into actin-driven polarity site movement in yeast. ” Mol Biol Cell , vol. 31, no. 10, May 2020, pp. 1085–102. Pubmed , doi:10.1091/mbc.E20-01-0040. URI https://scholars.duke.edu/individual/pub1451399 PMID 32186970 Source pubmed Published In Molecular Biology of the Cell Volume 31 Published Date 2020 Start Page 1085 End Page 1102 DOI 10.1091/mbc.E20-01-0040 How Diffusion Impacts Cortical Protein Distribution in Yeasts. Proteins associated with the yeast plasma membrane often accumulate asymmetrically within the plane of the membrane. Asymmetric accumulation is thought to underlie diverse processes, including polarized growth, stress sensing, and aging. Here, we review our evolving understanding of how cells achieve asymmetric distributions of membrane proteins despite the anticipated dissipative effects of diffusion, and highlight recent findings suggesting that differential diffusion is exploited to create, rather than dissipate, asymmetry. We also highlight open questions about diffusion in yeast plasma membranes that remain unsolved. Authors Moran, KD; Lew, DJ MLA Citation Moran, Kyle D., and Daniel J. Lew. “ How Diffusion Impacts Cortical Protein Distribution in Yeasts. ” Cells , vol. 9, no. 5, Apr. 2020. Pubmed , doi:10.3390/cells9051113. URI https://scholars.duke.edu/individual/pub1439943 PMID 32365827 Source pubmed Published In Cells Volume 9 Published Date 2020 DOI 10.3390/cells9051113 A budding yeast's polarity site biases its movement up pheromone gradients. Authors Ghose, D; Elston, TC; Lew, DJ MLA Citation Ghose, D., et al. “ A budding yeast's polarity site biases its movement up pheromone gradients. ” Molecular Biology of the Cell , vol. 29, no. 26, AMER SOC CELL BIOLOGY, 2018. URI https://scholars.duke.edu/individual/pub1428902 Source wos Published In Molecular Biology of the Cell Volume 29 Published Date 2018 Show More Research Areas: Actin Cytoskeleton Adaptor Proteins, Signal Transducing CDC28 Protein Kinase, S cerevisiae Cell Cycle Cell Division Cell Polarity Cell Shape Cell Wall Chemotaxis Computer Simulation Cyclin B Cyclin-Dependent Kinases Cyclins Cytokinesis Cytoskeleton Feedback, Physiological Fluorescence Recovery After Photobleaching GTP-Binding Proteins GTPase-Activating Proteins Guanine Nucleotide Exchange Factors MAP Kinase Signaling System Microscopy, Confocal Mitogen-Activated Protein Kinases Morphogenesis Phosphothreonine Polarity Protein Kinases Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Septins Signal Transduction Systems Biology Time-Lapse Imaging Yeast cdc42 GTP-Binding Protein cdc42 GTP-Binding Protein, Saccharomyces cerevisiae p21-Activated Kinases James B. Duke Distinguished Professor of Pharmacology and Cancer Biology Contact: Profile https://scholars.duke.edu/person/daniel.lew Email [email protected] C359 Lev Sci Res Ctr, Durham, NC 27708	http://dukecancerinstitute.org/member/lew-daniel?page=%2C2
People v. Galvin, s. 90CA0321 - Colorado - Case Law - VLEX 892139933 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object] People v. Galvin, s. 90CA0321 Docket Nº Nos. 90CA0321 Citation 835 P.2d 603 Case Date July 02, 1992 Court Court of Appeals of Colorado Page 603 835 P.2d 603 The PEOPLE of the State of Colorado, Plaintiff-Appellee, v. James R. GALVIN, Jr., Defendant-Appellant. Nos. 90CA0321, 91CA1280. Colorado Court of Appeals, Div. A. Gale A. Norton, Atty. Gen., Raymond T. Slaughter, Chief Deputy Atty. Gen., Timothy M. Tymkovich, Sol. Gen., Robert M. Petrusak and Roger G. Billotte, Asst. Attys. Gen., Denver, for plaintiff-appellee. David F. Vela, State Public Defender, Nancy J. Lichtenstein, Deputy State Public Defender, Denver, for defendant-appellant. Opinion by Chief Judge STERNBERG. Defendant, James R. Galvin, Jr., appeals the trial court's order denying his Crim.P. 35(c) motion for post-sentence confinement credit and for good-time credit. We reverse the order. In case 87CR618, defendant pled guilty to criminal attempt second degree burglary and, on March 9, 1988, was sentenced to two years probation. In case 88CR1012, defendant pled guilty to criminal attempt second degree burglary and, on January 27, 1989, was sentenced to community corrections for four years. On February 1, 1989, defendant's probation in 87CR618 was revoked, and he was sentenced to community corrections for one year, to run consecutive to the sentence imposed in 88CR1012. On June 15, 1989, defendant's initial sentence to community corrections was revoked, and he was again resentenced to community corrections for four years in 88CR1012 and for one year in 87CR618. These sentences were ordered to run consecutively. No credit for time served or for good time was awarded to the defendant. On May 15, 1991, defendant's community corrections sentence was again revoked, and he was resentenced to a four-year term in the Department of Corrections. Defendant was awarded credit for the time served from June 15, 1989, to May 15, 1991. Thereafter, the defendant filed the Crim.P. 35(c) motion here at issue requesting credit for the time served from January 27, 1989, to June 15, 1989, and also good-time credit for the entire period of his confinement in residential community corrections. Relying on § 16-11-306, C.R.S. (1991 Cum.Supp.) and Castro v. District Court, 656 P.2d 1283 (Colo.1982), the trial court found that the community corrections facility here is operated by a private organization and is governed by a board appointed by the county commissioners. Therefore, the trial court held that defendant was not entitled to credit for the time served from January 27, 1989, to June 15, 1989, because he was not sentenced to a state correctional facility under the supervision of the Department of Corrections, as required by 16-11-306, C.R.S. (1991 Cum.Supp.). Consequently, it also concluded that defendant was not entitled to good-time credit for the same period. In addition, the court noted that the community corrections board had eliminated the awarding of good-time credit for those persons sentenced after May 18, 1989, and it determined that such action was within its broad authority. Hence, relying on § 17-22.5-201, C.R.S. (1986 Repl.Vol. 8A) and the board's authority, the trial court found that defendant was not entitled to good-time credit for the entire time served in residential community corrections because he was not confined in a correctional facility of the Department of Corrections. The trial court reasoned that the granting of presentence confinement credit and good-time credit required additional record keeping and additional personnel which would divert funds. Additionally, granting the credit could result in a defendant being under the jurisdiction of the program for too short a time for him to receive its benefits. I. Defendant contends that he is entitled to both confinement credit and good-time credit for the period between January Page 605 27, 1989, and June 15, 1989. He maintains that failure to award him credit impermissibly increased the length of his original sentence in violation of § 17-27-114(2), C.R.S. (1991 Cum.Supp.). We agree. A defendant sentenced directly to a community corrections facility may be resentenced to the Department of Corrections if initial acceptance in the facility is revoked. People v. Saucedo, 796 P.2d 11 (Colo.App.1990). If a defendant is rejected after initial acceptance by a community corrections facility, then, under §§ 17-27-103(3) and 17-27-114(2), C.R.S. (1991 Cum.Supp.) , the sentencing court is authorized to resentence the defendant and impose any sentence which might originally have been imposed "without increasing the length of the sentence." People v. Kastning, 738 P.2d 807 (Colo.App.1987). Upon resentencing to the Department of Corrections, a defendant must receive credit for time served on direct sentence to community corrections. People v. Washington, 709 P.2d 100 (Colo.App.1985). A court's failure... 2 practice notes Beecroft v. People, No. 93SC357 United States Colorado Supreme Court of Colorado May 16, 1994 ...resident, the sentence is a term of imprisonment, but one served in a local facility rather than in a DOC facility. See People v. Galvin, 835 P.2d 603 , 605 (Colo.App.1992); People v. Saucedo, 796 P.2d 11, 12 (Colo.App.1990). Accordingly, if an offender spends time in a community correctiona...... People v. Pimble, Court of Appeals No. 14CA0770 United States Colorado Court of Appeals of Colorado August 13, 2015 ...7 When a court revokes a sentence to community corrections, it is authorized to resentence the defendant to DOC custody. People v. Galvin, 835 P.2d 603 , 605 (Colo.App.1992). A defendant so resentenced is entitled to PSCC for any time served in a residential community corrections facility. P...... 2 cases Beecroft v. People, No. 93SC357 United States Colorado Supreme Court of Colorado May 16, 1994 ...resident, the sentence is a term of imprisonment, but one served in a local facility rather than in a DOC facility. See People v. Galvin, 835 P.2d 603 , 605 (Colo.App.1992); People v. Saucedo, 796 P.2d 11, 12 (Colo.App.1990). Accordingly, if an offender spends time in a community correctiona...... People v. Pimble, Court of Appeals No. 14CA0770 United States Colorado Court of Appeals of Colorado August 13, 2015 ...7 When a court revokes a sentence to community corrections, it is authorized to resentence the defendant to DOC custody. People v. Galvin, 835 P.2d 603 , 605 (Colo.App.1992). A defendant so resentenced is entitled to PSCC for any time served in a residential community corrections facility. P......	https://case-law.vlex.com/vid/people-v-galvin-90ca0321-892139933
IJERPH \| Free Full-Text \| Motor Competence and Attainment of Global Physical Activity Guidelines among a Statewide Sample of Preschoolers Global physical activity guidelines for preschoolers include 60 min of moderate-to-vigorous physical activity (MVPA) daily. This study, based on the developmental model of motor skill competence, examines how motor competence relates to preschoolers’ likelihood of meeting global guidelines using ankle accelerometry. We measured physical activity using 24-h ankle-placement accelerometry (Actical) for at least two consecutive days (87% with six-seven days), motor competence using the Test of Gross Motor Development-2 (TGMD-2), and BMI-for-age z-scores (BMIz) using anthropometry and age- and sex-specific CDC norms. Caregivers provided demographic characteristics of children’s age, sex, and race. We used multivariable logistic regression to examine how motor competence, BMIz weight status, and demographic characteristics related to meeting global physical activity guidelines. The sample included 588 preschoolers, age 3–5 years; 55% male; 60% white; and 28% overweight/obese; 75% attained the recommended 60 min of MVPA per day. The odds of meeting MVPA guidelines were associated with higher gross motor quotient, higher object control scores, sex (male), age (older), and race (white), but not with BMIz weight status. Findings support the use of 24-h ankle accelerometry among preschoolers and are consistent with the developmental model of motor competence applied to preschoolers, whereby object control competence relates positively to attaining global physical activity guidelines. Motor Competence and Attainment of Global Physical Activity Guidelines among a Statewide Sample of Preschoolers by Anthony Slaton 1,2 , Alysse J. Kowalski 1 , Amy Zemanick 1 , Ann Pulling Kuhn 1 , Erin R. Hager 1,3 and Maureen M. Black 1,3,4,* 2 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY 11549, USA 3 Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore, MD 21201, USA 4 RTI International, Research Triangle Park, Durham, NC 27709, USA * Author to whom correspondence should be addressed. Int. J. Environ. Res. Public Health 2020 , 17 (22), 8546; https://doi.org/10.3390/ijerph17228546 Received: 7 October 2020 / Revised: 6 November 2020 / Accepted: 13 November 2020 / Published: 18 November 2020 (This article belongs to the Special Issue Motor Competence and Physical Fitness in the Promotion of an Active and Healthy Lifestyle in Children and Adolescents ) Abstract Global physical activity guidelines for preschoolers include 60 min of moderate-to-vigorous physical activity (MVPA) daily. This study, based on the developmental model of motor skill competence, examines how motor competence relates to preschoolers’ likelihood of meeting global guidelines using ankle accelerometry. We measured physical activity using 24-h ankle-placement accelerometry (Actical) for at least two consecutive days (87% with six-seven days), motor competence using the Test of Gross Motor Development-2 (TGMD-2), and BMI-for-age z-scores (BMIz) using anthropometry and age- and sex-specific CDC norms. Caregivers provided demographic characteristics of children’s age, sex, and race. We used multivariable logistic regression to examine how motor competence, BMIz weight status, and demographic characteristics related to meeting global physical activity guidelines. The sample included 588 preschoolers, age 3–5 years; 55% male; 60% white; and 28% overweight/obese; 75% attained the recommended 60 min of MVPA per day. The odds of meeting MVPA guidelines were associated with higher gross motor quotient, higher object control scores, sex (male), age (older), and race (white), but not with BMIz weight status. Findings support the use of 24-h ankle accelerometry among preschoolers and are consistent with the developmental model of motor competence applied to preschoolers, whereby object control competence relates positively to attaining global physical activity guidelines. Keywords: preschooler ; physical activity ; motor competence 1. Introduction Excess weight gain in preschool-age children (3–5 years of age) is generating widespread interest due to its association with obesity-related comorbidities later in life [ 1 , 2 ]. In the United States, 13.9% of children ages 2–5 have obesity [ 3 ]. Identifying the factors that underlie the current obesity epidemic is a public health priority. Limited physical activity is regarded as an early risk factor for obesity [ 4 , 5 ]. As such, obesity prevention efforts that target physical activity in young children have the potential to reduce children’s lifelong obesity risk. Adequate physical activity during early childhood not only reduces the risk of obesity but also plays an important role in social development, cognition, and emotional well-being [ 4 , 5 ]. The promotion of physical activity in preschoolers requires a thorough understanding of the multiple factors that influence children’s movement behavior, including motor competence, weight status, and demographic variables, including sex, age, and race/ethnicity. The developmental model of motor skill competence introduced by Stodden and colleagues suggests that there is a synergistic relationship between motor skill competence and physical activity during childhood, with advances in one impacting the other [ 6 ]. Motor skill competence is defined as the development of object control skills (e.g., kicking, throwing) and locomotor skills (e.g., running, skipping) [ 6 ]. A recent review found that preschoolers who demonstrated mastery of locomotor and object control motor skills were more likely to be physically active [ 7 ]. Basic motor skills developed in early childhood provide the foundation for more complex movements required for participation in sports and other organized activities later in adolescence [ 8 ]. The importance of motor competence in physical activity is reflected in the National Association for Sport and Physical Education’s (NASPE) Active Start guidelines which explicitly state that motor skill development should be an integral component of early childhood education [ 9 ]. Despite these guidelines, recent evidence suggests that the heterogeneity in motor competence may reflect differences in children’s, sex, age, race/ethnicity and weight status [ 10 , 11 , 12 , 13 , 14 ], indicating a need to further explore these relationships. A key issue with much of the literature regarding physical activity in young children is that it relies on data collected in structured environments, such as childcare centers, where a caregiver or teacher directs children’s daily activity. In a sample of same-sex twin pairs, Fisher and colleagues found that children’s environment was the most significant predictor of physical activity [ 11 ]. As such, there is a need for studies that measure physical activity throughout an entire 24-h period to elucidate individual differences that potentially influence motor development. The current study aims to assess 24-h physical activity among preschoolers across multiple contexts (preschool and home) that include structured and unstructured physical activity. This is accomplished by using ankle accelerometers to track children’s movement for a 7-day period. Placement of the accelerometer on the ankle allows investigators to examine relations among motor competence, physical activity, environmental, and child characteristics throughout multiple activities. The World Health Organization and the NAPSE recommend that preschoolers engage in at least 60 min of moderate-to-vigorous physical activity (MVPA) per day [ 9 , 10 ]. Despite these guidelines, the proportion of children engaging in 60 min of MVPA per day varies greatly across studies depending on the measurement method used. For example, Guinhouya and colleagues found that the proportion of children engaging in 30 min of MVPA varied from 34.8% to 100% depending on the methodology selected [ 15 ]. Objective monitoring of physical activity using accelerometry is the most accurate method to measure physical activity. Still, there is little consensus on accelerometer cut points most acceptable to signify MVPA among preschoolers [ 16 ]. The use of different cut points could have significant impacts on reporting as the selection of cut point thresholds influences the proportion of children who meet MVPA guidelines [ 15 , 17 , 18 ]. Consequently, physical activity measurement among preschoolers is not well understood. The purpose of this study is to examine how motor competence and demographic characteristics relate to preschoolers’ likelihood of engaging in 60 min of MVPA per day, assessed via 24-h ankle accelerometry. 2. Materials and Methods As a preliminary step, we conducted a search of cut points used with Actical accelerometers. We identified 24 papers: 21 used right hip placement, two used ankle placement, and one used wrist placement. We could not identify a current threshold for ages 3–5 on ankle placement, therefore we applied the ankle thresholds validated by indirect calorimetry for ages 12–36 [ 19 ]. All children in the validation sample walked independently, the mean age was 24.5 months (range 14.7–35.5), 58.3% were males, and they engaged in six specific activities: (1) watching TV (sitting), (2) listening to a book (sitting), (3) table games (standing), (4) imaginary play (walking), (5) ball games (running), and (6) chase (running) [ 19 ]. 2.1. Participants Data were collected from children in 54 childcare centers in ten Maryland counties as part of a larger three-arm cluster randomized controlled childhood obesity prevention trial: Creating Healthy Habits Among Maryland Preschoolers (CHAMP) [ 20 ]. Childcare centers that served low- and middle-income communities in urban, semi-urban and rural areas were eligible if they accepted childcare vouchers, participated in the Child and Adult Care Food Assistance Program, or cost less than $ 300/week per child. Head Start centers were excluded because many were already engaging in health promoting activities. Children were eligible if they were between 3–5 years of age, attended childcare at least 3 days per week, were English-speaking, intended to be enrolled in the center through the spring, and were without developmental delays that interfered with assessment. The current study examined data collected at baseline evaluations prior to intervention. Evaluations occurred on site at the childcare centers. All parents gave their informed consent for their child’s inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, approved by the Ethics Committee of the University of Maryland School of Medicine (HP-00065933), and registered at https://clinicaltrials.gov/ct2/show/NCT03111264 . 2.2. Measures 2.2.1. Anthropometry and Demographics Height was measured with a portable stadiometer (Shorr Productions, Olney, MD, USA) to the nearest 1 cm. Weight was measured with TANITA BWB-800 (TANITA, Tokyo, Japan) digital scales to the nearest 0.1 kg. Two independent measurements were taken and repeated if the two initial measures were not identical. We used height (meters, m) and weight (kilograms, kg) measurements to calculate BMI (weight/height 2 , kg/m 2 ) and BMI-for-age z-scores (BMIz), based on the age- and sex-specific 2000 CDC norms [ 21 ]. Children with BMIz scores: z < −1, −1 ≤ z ≤ 1, and z > 1 were considered to be underweight, healthy weight, and overweight/obese, respectively. Caregivers reported demographic characteristics of the child in an online survey administered through Qualtrics. We coded demographic characteristics as: sex (0 male, 1 female) and race (0 white, 1 other). 2.2.2. Physical Activity Children’s physical activity was assessed via 24-h accelerometers (Actical, Phillips Respironics, Inc.). At the childcare center, accelerometers were secured to the lateral malleolus of each child’s non-dominant ankle, under socks, using a non-removable band. Children wore the accelerometer for 7 days. Protocol and data handling were based on prior studies that used the device to measure physical activity and sleep in young children [ 19 ]. Data were collected by the accelerometers in 15-s epochs. We applied cut points to calculate time spent in MVPA −550 counts per 15 s [ 22 , 23 ]. We retained data for children with at least two days of valid data (87% had valid data for at least six days). Preschoolers engaging in at least 60 min of MVPA per day were coded as having met MVPA guidelines (0 did not meet guidelines, 1 met guidelines) [ 9 , 10 ]. 2.2.3. Gross Motor Skill We administered the Test of Gross Motor Development-2 (TGMD-2) to assess children’s gross motor skill development. The TGMD-2 is comprised of two subtests – object control and locomotor [ 24 ]. The object control subtest measured children’s mastery of skills such as throwing and catching a ball. The locomotor subtest measured children’s mastery of fluid coordinated movements from one point to another. Trained research assistants observed each child individually perform a series of items (movements) such as throwing a ball, skipping, running, and hopping. Each item was performed twice and assigned a score of “1” for accurate completion or “0” for non-completion. Items were summed to produce raw scores. We selected TGMD-2 because it provides a granular assessment of the child’s motor development-based upon a discrete set of criteria for each skill. For example, locomotor development is assessed by observing a child run, gallop, hop, leap, slide, and jump horizontally. Running, for instance, is then further deconstructed into a specific set of performance criteria: moving arms in opposition to legs, striding with both feet off the ground for a brief period of time, narrow foot placement, and stepping with the non-support leg bent at 90 degrees. The individual performance criteria are then scored 0 or 1 for completion, while the overall subtest score—used in the linear regression—is a composite of the entire set of items for the various movements. This process provides a quantitative assessment of the child’s motor development on a scale of 1–20 after adjustments for sex and age. The TGMD has good to excellent inter-rater reliability [ 24 ]. In our sample, the mean inter-class correlation coefficient (ICC) was 0.98. Gross motor skill development is influenced by biological maturation, with male sex associated with better development [ 25 ]. Some evidence suggests that there are pre-maturational biological differences favoring males in skills such as throwing and striking [ 26 ]. To adjust for potential biological differences, we converted raw scores to age- and sex-adjusted standard scores on the TGMD-2, as recommended. We combined the standardized subtest scores to create an overall performance score, the Gross Motor Quotient (GMQ), which is a valid and reliable measure of children’s current gross motor development. GMQ scores <17, 17–23, and 24–40 reflect poor to below average, average, and above average to superior gross motor development, respectively [ 27 , 28 ]. 2.3. Statistical Analysis We included participants with gross motor development and physical activity measures in the analysis. We characterized the sample using frequencies for categorical measures and mean ± standard deviation for continuous measures. Using the ankle cut-point of ≥550 counts per 15 s to signify MVPA, we calculated average daily minutes spent in MVPA for each child [ 22 ]. Based on prior literature involving young children, we considered age, sex, race, BMIz weight status, object control, locomotor, and GMQ as a priori predictors of time spent in MVPA. We conducted simple linear regression with minutes of MVPA per day for each predictor. Predictors that were significantly associated with minutes of MVPA per day in unadjusted models were included in a multivariable linear regression model. Using unadjusted logistic regression, we examined associations of demographic characteristics and motor competence with meeting MVPA guidelines. Significant predictors were included in multivariable models. We conducted statistical analyses using STATA (version 14) and considered p < 0.05 statistically significant. 3. Results Child demographic characteristics and performance on the TGMD-2 test are displayed in Table 1 . Of the 588 preschoolers with gross motor development and physical activity measures, 55% were male, 60% identified as white, and 28% had overweight or obesity. On average, preschoolers engaged in 76.5 min of MVPA each day. Over half (54%) of preschoolers scored above average for their age on the TGMD-2 while 8% performed below average. Almost three-quarters of preschoolers ( n = 439/588, 74.7%) reached recommended levels of MVPA per day when ankle placement cut points were applied. Table 1. Descriptive characteristics of CHAMP participants with physical activity and gross motor development measures ( N = 588) a . Linear regression results are displayed in Table 2 . Preschoolers who were older, male, and white spent more time in MVPA compared to younger, female, and non-white preschoolers in unadjusted and adjusted models; and weight status was not associated with time spent in MVPA. Object control, locomotor scores, and GMQ were not associated with minutes of MVPA/day in unadjusted or adjusted linear models. In multivariable logistic regression, increased GMQ was associated with slightly increased odds of meeting MVPA guidelines (OR = 1.05, 95% CI: 1.00, 1.09) ( Table 3 ). This was driven by object control which was positively associated with meeting MVPA guidelines (OR = 1.10, 95% CI: 1.01, 1.19). Locomotor was not associated with meeting MVPA guidelines in unadjusted or adjusted models. The odds of meeting MVPA guidelines were twice as high for males compared to females and twice as high for white preschoolers compared to non-white preschoolers. Weight status was not associated with meeting MVPA guidelines. Table 2. Unadjusted and adjusted linear associations of gross motor development and child demographic characteristics with mean minutes of moderate-to-vigorous physical activity per day. Table 3. Unadjusted and adjusted logistic associations of gross motor development and child demographics with meeting moderate-to-vigorous physical activity guidelines per day. 4. Discussion Guided by the development model of motor skill competence and using objectively measured 24-h physical activity data from ankle placement, this study had three primary findings. First, 75% of preschoolers met the criterion of 60 min of daily MVPA. Second, object control skill competence, but not locomotor, was significantly associated with meeting the criterion of 60 min of daily MVPA. Third, sex (male), older age, and white race, but not weight status, were significant predictors of 60 min of daily MVPA. To compare the proportion of preschoolers in our study meeting the global guidelines of 60 min of daily MVPA, we reviewed the Canadian 24-Hour Movement Guidelines for the Early Years that found nearly all (62–84%) of Canadian preschoolers reached recommended levels of MVPA [ 29 , 30 ]. We also referenced a recent report from the International Children’s Accelerometry Database (ICAD) [ 31 ]. The analysis included 1052 preschoolers (ages 3 and 4 years) from six studies in four high-income countries (Canada, Australia, United States, and United Kingdom), using waist-worn, uniaxial Actigraph accelerometers. Overall, 78.8% of children in the ICAD study met the criterion of 60 min of daily MVPA. Using cut points established by Pate [ 32 ], at least three studies examined the prevalence of preschoolers meeting the criterion of 60 min of MVPA. In one study, the prevalence varied from 77.6% (weekends) to 93.5% (weekdays) [ 33 ]. In a second study, the prevalence was 52.9% among girls and 65.6% among boys [ 17 ]. In a third study conducted among preschoolers having a BMI above the 85th percentile who were referred for treatment for overweight/obesity, the prevalence was 80% [ 34 ]. Thus, our findings of 75% were congruent with the literature. The finding that object control skills, including ball handling, positively predicted preschoolers’ attainment of 60-min of daily MVPA is consistent with the developmental model of motor competence and with other studies that have found positive relationships between motor competence and physical activity [ 6 , 35 ]. Among preschoolers, object control represents a basic skill that children need to be physically engaged in preschool activities, such as ball handling [ 25 ]. Beyond the biological maturation required to learn basic motor skills, opportunities to learn and practice motor skills are needed to advance motor skills [ 25 ]. The developmental mode of motor skill competence, informed by Ecological Systems Theory [ 36 ] and Achievement Goal Theory [ 37 ], posits that the environmental context influences opportunities to gain object control skills and to increase children’s confidence and perceptions of their object control skills. Based on the developmental model of motor competence, children’s perception of their motor skills mediates the association between object control skills and physical activity, such that gaining object control skills enhances self-perception and enjoyment, which increase the likelihood of seeking out opportunities for subsequent physical activity. The relation between motor competence and physical activity among preschoolers has been mixed. In a study among preschool-age children in low-income communities in Brazil, 72% of girls and 84% of boys achieved 60 min of daily MVPA, but meeting physical activity guidelines was not associated with overall motor competence [ 38 ]. Another study found a relationship between MVPA and locomotor skills, but not object control skills [ 31 ]. A third study found that male object control skills were associated with physical activity, while female locomotor skills were associated with physical activity [ 35 ]. Finally, a meta-analysis reported consistent relations among object control and MVPA [ 39 ]. These findings suggest that among preschoolers, exposure to specific activities and skills may contribute to increases in motor competence, particularly object control, which in turn is associated with increases in physical activity. This pattern is consistent with the synergism proposed by the developmental model of motor competence [ 6 ]. Our initial set of analyses were consistent with previous literature that MVPA was greater among male preschoolers compared to females [ 35 ] and among older compared to younger preschoolers [ 40 ]. There are at least two possible explanations for these findings. First, older age and male sex have been consistently related to object control skills [ 41 ], suggesting that age and sex differences in preschoolers’ MVPA may be associated with differences in object control skills. Second, when environmental and sociocultural factors are considered, preschoolers’ physical activity is largely associated with the availability of open spaces for play, and family involvement, encouragement, and expectations related to physical activity, which is often higher for male compared to female preschoolers [ 42 , 43 ]. Although at least one other study has found racial differences related to physical activity among preschoolers, most reviews have not reported racial differences in MVPA among preschoolers, particularly when environmental and sociocultural variables were considered [ 40 ]. Our finding that preschoolers’ weight status was not related to meeting the criterion of 60 min of MVPA daily is consistent with findings from a systematic review of physical activity [ 44 ] and a meta-analysis of motor competence [ 25 ] that among preschoolers, BMIz was not related to either. However, a systematic review showed that preschool interventions that promote physical activity are effective in improving children’s weight status, illustrating the beneficial effects of incorporating physical activity into obesity prevention [ 45 ]. Overall, these findings suggest that limited physical activity in early childhood could exacerbate health disparities in obesity-related comorbidities found in adult populations. Although all preschoolers should have opportunities to advance their motor skill competence and engage in physical activity, younger, female preschoolers may benefit from additional initiatives. Providing preschoolers with opportunities to engage in and improve their motor competencies is important for participating in healthy physical activity patterns throughout life [ 8 ]. This study yields several recommendations for future investigations. First, gross motor competency is a general term that includes multiple proficiencies, including object control, locomotor skill, and coordination. Clarifying the factors associated with specific types of motor competency would reduce confusion. Second, as suggested by the developmental model of motor competence, future research among preschoolers should examine the mechanisms linking environmental opportunities and preschoolers’ perception of their motor competence to motor competence and physical activity. Third, future research among preschoolers should examine associations among demographic, environmental, and sociocultural factors related to motor competence and physical activity longitudinally. Research can also examine underlying reasons for differences in motor competencies such as the type of sport or activity participation or physical education curricula, as well as examine what type of physical activity is important for motor development [ 46 ]. There have been at least two reviews of interventions to promote physical activity among preschoolers, which is particularly relevant with increases in preschool enrollment [ 47 , 48 ]. One recommended that interventions for preschool children be theory-driven, involve children and parents, and include a structured activity delivered by experts [ 47 ]. Another recommended that preschoolers need developmentally appropriate instruction in motor competence, as well as opportunities to practice and develop a positive self-perception of their motor competencies [ 48 ]. Both endorsed the importance of the preschool period as an ideal time to help children develop motor competence and an affinity for physical activity. Strengths and Limitations There were several strengths and limitations to this study. The focus on the association between motor skill competence and physical activity among preschoolers represents an understudied topic during a period when young children are establishing habits that can influence their health and well-being across the life-course. Direct measurement of MVPA through accelerometry and motor competence through the TGMD-2 avoids self-report biases. The inclusion of statewide data from preschoolers in low- and middle-income families from urban, semi-urban, and rural areas is wide representation. Although ankle accelerometry allows for 24-h continuous wear and reduces participant burden, it introduces the burden of wearing a device, may not capture activity conducted while seated, and may over-estimate fidgeting involving the ankle. A validation study should be conducted among preschoolers. Additional limitations include a cross-sectional design, thus not permitting the examination of the temporality of motor skill competence and physical activity, and the lack of data on important covariates, including household family socioeconomic variables [ 49 ]. 5. Conclusions Motor skill competence and physical activity play critical roles in early childhood in promoting cognition, school readiness, and habits that facilitate health and well-being throughout life [ 5 ]. The benefits associated with adequate physical activity levels can be seen across a broad spectrum of physical, social, and cognitive indicators in children [ 50 ]. Interventions that promote physical activity habits have been effective in preventing obesity among preschoolers [ 45 ], illustrating the relevance of understanding the mechanisms that underpin physical activity among preschoolers. Overall, our study provides insight into the association between motor competence and physical activity, the role of ankle accelerometry in providing 24-h measurement, and the need to promote interventions that target improving object control skills in preschoolers. Author Contributions Conceptualization, M.M.B.; Formal Analysis, A.S., A.J.K.; Data Curation, A.Z.; Writing—Original Draft Preparation, A.S.; Writing—Review & Editing, A.S., A.J.K., A.Z., A.P.K., E.R.H., M.M.B.; Funding Acquisition, M.M.B. All authors have read and agreed to the published version of the manuscript. Funding The study was funded by the National Institute for Diabetes, Digestive, and Kidney Diseases, grant numbers R01 DK107761 and T32 DK095737. The APC was funded by grant number R01 DK107761. Acknowledgments The authors acknowledge the participating preschoolers, parents, and childcare centers and other members of the research team. Conflicts of Interest The authors declare no conflict of interest. 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Demographic Characteristic N n % Age 588 3 years-old 257 44% 4 years-old 290 49% 5 years-old 41 7% Sex 588 Male 321 55% Female 267 45% Race 538 White 321 60% Other 217 40% BMIz weight status 561 Underweight (z < −1) 49 9% Healthy weight (−1 ≤ z ≤ 1) 356 63% Overweight or obese (z > 1) 156 28% MVPA Minutes SD Average per day 588 76.5 29.3 Motor Competence N % TGMD-2: Gross Motor Quotient 588 Above Average–Superior (24–40) 316 54% Average (17–23) 227 39% Below Average–Very Poor (2–16) 45 8% Average SD TGMD-2: Object Control Subtest Standardized Score 588 3 years-old 12.5 3.0 4 years-old 12.4 2.4 5 years-old 11.5 3.0 TGMD-2: Locomotor Subtest Standardized Score 588 3 years-old 11.1 3.4 4 years-old 12.1 3.2 5 years-old 11.3 3.3 a Presented as N (%) or mean ± SD. Abbreviations: BMIz, body mass index z-score; MVPA, moderate-to-vigorous physical activity; TGMD-2, Test of gross motor development-2. Table 2. Unadjusted and adjusted linear associations of gross motor development and child demographic characteristics with mean minutes of moderate-to-vigorous physical activity per day. Characteristic β (95% CI) a p β adj (95% CI) b p β adj (95% CI) b p Sex Male 11.23 (6.56, 15.9) <0.01 11.46 (6.61, 16.3) <0.01 11.14 (6.33, 15.95) <0.01 Age 0.55 (0.22, 0.87) <0.01 0.6 (0.27, 0.94) <0.01 0.57 (0.24, 0.9) <0.01 Race White 8.94 (3.96, 13.93) <0.01 8.31 (3.43, 13.19) <0.01 8.58 (3.72, 13.44) <0.01 BMIz weight status Underweight 5.44 (−3.28, 14.17) 0.22 -- -- Healthy weight Ref -- -- Overweight 1.2 (−4.3, 6.71) 0.67 -- -- TGMD-2 Object Control 0.58 (−0.28, 1.45) 0.19 0.8 (−0.21, 1.81) 0.12 -- Locomotor 0.3 (−0.42, 1.01) 0.42 −0.07 (−0.91, 0.78) 0.88 -- Gross Motor Quotient 0.28 (−0.17, 0.74) 0.22 -- 0.31 (−0.16, 0.78) 0.19 a Models are unadjusted. b Models are adjusted for other characteristics in column. Abbreviations BMIz, body mass index z-score; TGMD-2, Test of gross motor development-2. Characteristic OR (95% CI) a p OR (95% CI) b p OR (95% CI) b p OR (95% CI) b p Sex Male 2.18 (1.49, 3.19) <0.01 2.26 (1.5, 3.42) <0.01 2.4 (1.59, 3.66) <0.01 2.34 (1.55, 3.55) <0.01 Age 1.06 (1.03, 1.09) <0.01 1.07 (1.04, 1.1) <0.01 1.07 (1.04, 1.1) <0.01 1.06 (1.03, 1.1) <0.01 Race White 2.21 (1.49, 3.28) <0.01 2.26 (1.51, 3.41) <0.01 2.16 (1.43, 3.28) <0.01 2.22 (1.47, 3.35) <0.01 BMIz weight status Underweight 1.07 (0.54, 2.27) 0.86 -- -- -- Healthy weight Ref -- -- -- Overweight 0.93 (0.6, 1.44) 0.73 -- -- -- TGMD-2 Object Control 1.08 (1.01, 1.16) 0.03 -- 1.1 (1.01, 1.19) 0.04 -- Locomotor 1.05 (0.99, 1.11) 0.11 -- 1.01 (0.94, 1.08) 0.87 -- Gross Motor Quotient 1.04 (1, 1.08) 0.03 -- -- 1.05 (1, 1.09) 0.03 a Models are unadjusted. b Models are adjusted for other characteristics in column. Abbreviations: OR, odds ratio; BMIz, body mass index z-score; TGMD-2, Test of gross motor development-2. 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Molecules \| Free Full-Text \| A QM/MM–Based Computational Investigation on the Catalytic Mechanism of Saccharopine Reductase Saccharopine reductase from Magnaporthe grisea, an NADPH-containing enzyme in the α-aminoadipate pathway, catalyses the formation of saccharopine, a precursor to L-lysine, from the substrates glutamate and α-aminoadipate-δ-semialdehyde. Its catalytic mechanism has been investigated using quantum mechanics/molecular mechanics (QM/MM) ONIOM-based approaches. In particular, the overall catalytic pathway has been elucidated and the effects of electron correlation and the anisotropic polar protein environment have been examined via the use of the ONIOM(HF/6-31G(d):AMBER94) and ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94) methods within the mechanical embedding formulism and ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94) and ONIOM(MP2/6-311G(d,p)//HF/6-31G(d):AMBER94) within the electronic embedding formulism. The results of the present study suggest that saccharopine reductase utilises a substrate-assisted catalytic pathway in which acid/base groups within the cosubstrates themselves facilitate the mechanistically required proton transfers. Thus, the enzyme appears to act most likely by binding the three required reactant molecules glutamate, α-aminoadipate-δ-semialdehyde and NADPH in a manner and polar environment conducive to reaction. A QM/MM–Based Computational Investigation on the Catalytic Mechanism of Saccharopine Reductase by Joel N. Almasi , Eric A.C. Bushnell and James W. Gauld * Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada Author to whom correspondence should be addressed. Molecules 2011 , 16 (10), 8569-8589; https://doi.org/10.3390/molecules16108569 Received: 5 September 2011 / Revised: 27 September 2011 / Accepted: 30 September 2011 / Published: 12 October 2011 Abstract : Saccharopine reductase from Magnaporthe grisea , an NADPH-containing enzyme in the α-aminoadipate pathway, catalyses the formation of saccharopine, a precursor to L-lysine, from the substrates glutamate and α-aminoadipate-δ-semialdehyde. Its catalytic mechanism has been investigated using quantum mechanics/molecular mechanics (QM/MM) ONIOM-based approaches. In particular, the overall catalytic pathway has been elucidated and the effects of electron correlation and the anisotropic polar protein environment have been examined via the use of the ONIOM(HF/6-31G(d):AMBER94) and ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94) methods within the mechanical embedding formulism and ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94) and ONIOM(MP2/6-311G(d,p)//HF/6-31G(d):AMBER94) within the electronic embedding formulism. The results of the present study suggest that saccharopine reductase utilises a substrate-assisted catalytic pathway in which acid/base groups within the cosubstrates themselves facilitate the mechanistically required proton transfers. Thus, the enzyme appears to act most likely by binding the three required reactant molecules glutamate, α-aminoadipate-δ-semialdehyde and NADPH in a manner and polar environment conducive to reaction. Keywords: Schiff base ; saccharopine reductase ; α-aminoadipate-δ-semialdehyde ; saccharopine ; imine formation ; carbinolamine ; QM/MM ; computational Graphical Abstract 1. Introduction The genetic material of organisms contains the codons for twenty “standard” α-amino acids. Despite their central importance for the construction of cellular proteins and enzymes, however, not all cells are able to synthesize all twenty de novo . For instance, the ability to biosynthesize the essential amino acid L-lysine is limited to some green plants, bacteria, fungi, and cyanobacteria [ 1 , 2 ]. In addition, it has been observed to occur via just two distinct routes: (i) the diaminopimelate (green plants, bacteria, and lower fungi), and (ii) the α-aminoadipate (cyanobacteria and higher fungi) pathways [ 3 ]. For example, the fungal species, Candida albicans , Cryptococcus neoformans , Aspergillus fumigatus , Saccharomyces cerevisiae and Magnaporthe grisea have all been shown to utilise the α-aminoadipate pathway [ 1 ]. The former three are all human fungal agents and pose a risk to those with compromised immune systems such as AIDS, cancer, and transplant patients [ 4 ]. Magnaporthe grisea , on the other hand, affects many grass and crop species’ and is perhaps best known for causing rice blast disease [ 5 ]. Thus, this pathway represents an attractive target for the development of new fungicides [ 6 ]. Saccharopine reductase is a key enzyme in the α-aminoadipate pathway. Specifically, it catalyses the condensation of α-aminoadipate-δ-semialdehyde (AASA) with glutamic acid and subsequent reduction by NADPH of the resulting Schiff base to give the L-lysine precursor saccharopine [ 1 ]. It has been found that the substrates of saccharopine reductase bind in the order of NAPDH, AASA and lastly glutamate [ 1 ]. However, after the binding of the substrates, two possible catalytic mechanisms have been proposed for saccharopine reductase [ 1 , 4 ]. Johansson et al. [ 4 ] obtained X-ray crystal structures of the apo-enzyme and an enzyme…saccharopine/NADPH complex. Based on these structures they suggested that there are no suitable active-site acid/base residues able to facilitate the mechanistically required proton transfers. Hence, they concluded that the observed catalytic rate enhancement of saccharopine reductase is instead due to favourable positioning of the substrates with respect to each other within the active-site [ 4 ]. Consequently, they proposed the catalytic mechanism outlined in Scheme 1 . Notably, the α-amino of the glutamic acid is initially neutral, while the α-carboxylate groups are both ionised. Thus, the first step in the overall mechanism is nucleophilic attack of the Glu-NH 2 nitrogen ( Glu N) at the R-group carbonyl carbon ( AASA C) of AASA. This occurs with concomitant transfer of a proton to AASA’s R-group carbonyl oxygen ( AASA O) and loss of a proton from the bridging amine to give a carbinolamine intermediate. The latter then formally undergoes a 1,3-intramolecular proton transfer from its - Glu NH- moiety to the newly formed hydroxyl ( AASA OH) group, resulting in loss of water and formation of an unprotonated-Schiff base intermediate. In the third and final step the Schiff base is reduced via hydride transfer from the NADPH cofactor with a concomitant protonation by an unknown moiety to give saccharopine. More recently, Vashishtha et al. [ 1 ] experimentally examined pH-rate profiles and solvent deuterium kinetic isotope effects of saccharopine reductase from S. cerevisiae . Based on their observations, they concluded that it utilises an acid/base mechanism involving two active-site residues and proposed the catalytic mechanism outlined in Scheme 2 . Specifically, an active-site base ( B1 ), estimated [ 1 ] to have a p K a in the range of 5.6–5.7, initially deprotonates the glutamates protonated α-amino group. However, as noted by Johannson et al. [ 4 ] it is not clear what group may act as this general base. As a result, the Glu N centre is then able to nucleophilically attack at the AASA C centre. However, in contrast to that proposed by Johansson et al. [ 4 ] this occurs concomitant protonation of the AASA O centre by an acidic active site residue ( H:B2 ) with an estimated p K a of 7.8–8. Based on their X-ray crystal structure of the enzyme-product complex, Johannson et al. [ 4 ] concluded that no obvious active site residue exists to facilitate this protonation. However, Vashishtha et al. [ 1 ] have alternatively suggested that an aspartyl (Asp126) may be able to protonate the oxyanion formed during nucleophilic attack of the glutamates amine. This results in formation of a Glu N-protonated carbinolamine intermediate. Subsequently, B2 abstracts a proton from the intermediate’s - Glu NH 2 + - moiety before transferring it onto the newly formed nearby AASA OH group, resulting in formation of a protonated-Schiff base intermediate with loss of water (see Scheme 2 ). The Schiff-base is then reduced by hydride transfer from the NADPH cofactor onto the imines carbon centre, thus giving saccharopine. In the last two steps the initial active-site is regenerated with assistance of the product itself; H:B1 transfers its proton to B2 via the saccharopine’s - Glu NH- group to reform B1 and H:B2 , i.e. , their initial states. Unfortunately, they were unable to identify the exact active-site acid/base residues involved. Scheme 1. The catalytic mechanism of saccharopine reductase as proposed by Johansson et al. [ 4 ]. Scheme 1. The catalytic mechanism of saccharopine reductase as proposed by Johansson et al. [ 4 ]. Scheme 2. The general acid/base catalytic mechanism as proposed by Vashishtha et al. [ 1 ]. Scheme 2. The general acid/base catalytic mechanism as proposed by Vashishtha et al. [ 1 ]. At present, there have been no computational investigations on the catalytic mechanism of saccharopine reductase. However, Schiff base formation has been extensively studied both experimentally and computationally due in part to their common occurrence as reaction intermediates in biochemistry and chemistry [ 4 , 7 , 8 , 9 ]. From these studies it has been shown that Schiff base formation depends on several factors including the solvent, pH, and the chemical nature of the reactants [ 7 , 10 , 11 , 12 , 13 , 14 , 15 ]. Mechanistically, it can be thought of occurring in two stages: (i) initial formation of a carbinolamine-type intermediate via nucleophilic attack of an amino group at a carbonyl carbon, followed by (ii) loss of its carbinolamine hydroxyl as water to give the corresponding imine. Overall, Schiff base formation is favoured at neutral pH. However, markedly lower reaction barriers are obtained if a water or some other suitable moiety facilitates the required proton transfers [ 7 ]. In contrast, under acidic conditions, i.e. , those in which the attacking amino group is initially protonated, the first stage is slow as it requires deprotonation of the amino group while the subsequent stage, loss of water, is quite rapid. Elucidation of an enzymes catalytic mechanism is central to a complete understanding of its biochemical role and the development of effective inhibitors. In this present study we have used ONIOM quantum mechanics/molecular mechanics (QM/MM) computational methods to investigate the overall mechanism of saccharopine reductase. In particular, we have examined the initial protonation states of key substrate functional groups and possible mechanistic roles of the substrates own acid/base groups. 2. Computational Methods For all calculations the combined quantum mechanical and molecular mechanical (QM/MM) method in the ONIOM [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ] formalism was applied as implemented within the Gaussian 09 program suite [ 25 ]. Density functional theory (DFT) is a common tool for investigating biochemical reactions [ 26 ]. However, it has a tendency to underestimate barriers, in particular, those corresponding to proton transfers [ 27 ]. In contrast, Hartree-Fock (HF) tends to overestimate barriers for proton transfer [ 27 ]. However, in a related computational investigation Williams [ 28 ] studied the condensation reaction between ammonia and formaldehyde at the HF/3-21G level of theory. They found that for nucleophilic attack of the amino at the carbonyl carbon, the lowest barrier to formation of the carbinolamine intermediate was obtained when two water molecules were involved in the reaction, in agreement with experimental predictions [ 28 ]. Later, as part of a computational study on Schiff base formation in the same chemical system, Hall and Smith [ 29 ] re-examined the reaction steps leading to formation of the carbinolamine intermediate at the considerably higher G2(MP2,SVP) level of theory. Importantly, they obtained the same series of reaction steps leading to formation of the carbinolamine intermediate as previously found by Williams [ 28 ]. although the relative energies differed [ 28 ]. Thus, all geometry optimizations were performed at the ONIOM(HF/6-31G(d):AMBER94) level of theory within the mechanical embedding (ME) formalism [ 30 ]. Harmonic vibrational frequency calculations of stationary points along the potential energy surface (PES) were performed at the same level of theory in order to characterize them as minima or transition structures and to calculate Gibbs free energy corrections at standard ambient temperature and pressure (SATP). Relative energies were then obtained by performing single point (SP) calculations at higher levels of theory based on the above-optimized geometries, with inclusion of the appropriate free energy correction. Specifically, SP calculations were performed at the; (i) ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME; (ii) ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94) within the electronic embedding (EE) formalism; and (iii) ONIOM(MP2/6-311G(d,p)//HF/6-31G(d):AMBER94)-EE levels of theory. These were chosen in order to enable systematic consideration of the effects of (i) incorporation of electron correlation, (ii) the anisotropic protein environment on the reactive core ( i.e. , QM layer) and (iii) increasing the basis set size, respectively. It is noted that all energies reported herein have been corrected by adding the necessary Gibbs corrections discussed above. Figure 1. (a) The X-ray crystal structure (PDB ID: 1E5Q)-derived QM/MM model used to investigate the catalytic mechanism of saccharopine reductase. (b) Schematic representation of the QM/MM model: groups in the inner and outer circles have been modelled at the HF/6-31G(d) and AMBER94 levels of theory, respectively. Note, residues, waters and functional groups in black have been included in the model in their entirety, while residues in red have only had their peptide backbone included. Figure 1. (a) The X-ray crystal structure (PDB ID: 1E5Q)-derived QM/MM model used to investigate the catalytic mechanism of saccharopine reductase. (b) Schematic representation of the QM/MM model: groups in the inner and outer circles have been modelled at the HF/6-31G(d) and AMBER94 levels of theory, respectively. Note, residues, waters and functional groups in black have been included in the model in their entirety, while residues in red have only had their peptide backbone included. A large active-site model for saccharopine reductase from M. grisea was obtained from an X-ray crystal structure [PDB: 1E5Q] of the enzyme co-crystallized with the saccharopine product and is shown in Figure 1 . Specifically, both the glutamate and α-aminoadipate-δ-semialdehyde (AASA) substrates and reactive moiety of the NADPH cofactor were included in the QM layer. All residues and waters within 15 Å of the cosubstrates were included in the MM layer either in their entirety or only including their peptide backbone component ( i.e. , the residue was modelled as -NHCH 2 CO-). The saccharopine moiety in the X-ray crystal structure was replaced by the two cosubstrates accordingly. Specifically, the C-N bond was cleaved and hydrogens added to the nitrogen to regenerate the initial glutamate substrate while an oxygen was added to the carbon centre thus reforming the initial α-aminoadipate-δ-semialdehyde cosubstrate. Hydrogens were added to the active-site model with all ionisable functional groups being modelled in their most likely protonation state at pH = 7. To ensure the integrity of the model during calculations the α-carbon of each residue was held fixed at its crystal structure position. It should be noted that residue Tyr100 was included in the QM layer for the examination of the initial protonation state of the Glu-NH 2 moiety and in the MM layer for the mechanism studies (see below). 3. Results and Discussion 3.1. The pK a of the Substrate Glutamate’s α-Amine It has been suggested [ 1 ] that for favourable binding, the amines of both the glutamate and AASA substrates must initially be protonated. Then, once bound, the glutamate’s α-NH 3 + group deprotonates thus enabling it to act as a nucleophile [ 1 ]. Hence, prior to an investigation of the catalytic mechanism the likely initial protonation state of the glutamate’s α-amine (Glu-NH 2 ) was examined. In particular we have considered the proton affinities (PAs) of the α-amine of glutamate and AASA in aqueous solution and when bound in the active site, and that of H 2 O (aq) , i.e. , a water in the bulk aqueous environment. It is noted that the PA of an acidic group is simply the difference in electronic energy between a base (X − ) and its conjugate acid (HX) as shown in Equation 1: PA = E(X − ) − E(HX) (1) More specifically, the PAs of AASA-NH 2(aq) , Glu-NH 2(aq) and H 2 O (aq) were obtained at the IEF-PCM(ε = 78.3553)/MP2/6-311 + G(2df,p)//HF/6-31G(d) level of theory. The PAs of AASA-NH 2 and Glu-NH 2 when bound within the active site were obtained at the ONIOM(MP2/6-311+G(2df,p)//HF/6-31G(d):AMBER94) level of theory within the electronic embedding formulism. It is noted that in each of these “bound systems” the substrates carboxylates were modelled in their ionised forms ( i.e. , -COO − ). The PAs obtained are illustrated in Figure 2 . Figure 2. The PAs for the α-amines of AASA and Glu with respect to the local environment. The horizontal dashed line represents the PA of H 2 O in solution. Figure 2. The PAs for the α-amines of AASA and Glu with respect to the local environment. The horizontal dashed line represents the PA of H 2 O in solution. In aqueous solution the PA of AASA-NH 2 is calculated to be 1,216.1 kJ mol −1 , which is significantly greater than that calculated for H 2 O (aq) (1,034.0 kJ mol −1 ). Given the similarities in the α-amines of Glu and AASA, their PAs are expected to be in close agreement. Thus, in aqueous solution both AASA-NH 2 and Glu-NH 2 are likely protonated. As noted by Vashishtha et al. [ 1 ] the NADPH binds within the active site first to give an E•NADPH complex, followed by AASA and then Glu. From Figure 2 it can be seen that upon binding of AASA to E•NADPH the PA of its α-amine ( AASA-N (E•NADPH) ) drops significantly to 910.6 kJ mol −1 . In fact, it is now lower than that of H 2 O (aq) , thus suggesting that once bound the AASA-NH 3 + group could readily donate a proton to the bulk solution. The next step is binding of Glu to the E•NADPH•AASA complex. As noted above, it has been suggested [ 1 ] that for binding the α-amine of Glu must be protonated. From Figure 2 it can be seen that upon binding of Glu-NH 3 + the PA of AASA-NH 2 ( AASA-N (E•NADPH•Glu-NH3+) ) increases to 944.4 kJ mol −1 . In order for the α-amine of Glu to act as a nucleophile it must be neutral, i.e. , Glu-NH 3 + must lose a proton. As noted by Johannson et al. [ 4 ] there appears to be no suitable base within the active site to deprotonate Glu-NH 3 + . However, from Figure 2 it can be seen that deprotonation of the glutamates α-amine results in a significant increase inthe PA of AASA-NH 2 to 1,125.2 kJ mol −1 . In contrast, the PA of the resulting Glu-NH 2 moiety is lower at 1,079.0 kJ mol −1 . Importantly, both of these PAs are now larger than that of H 2 O (aq) . This suggests that it is unlikely for the α-amine of both substrates (AASA and Glu) to be at least simultaneously neutral; in such a case they both can potentially accept a proton from the bulk aqueous solution. However, if the more basic AASA-NH 2 group does take up a proton, i.e. , becomes AASA-NH 3 + , the PA of the Glu-NH 2 decreases considerably to 898.2 kJ mol −1 , and is now in fact lower than that of H 2 O (aq) . Furthermore, it has the lowest PA of all possible both-substrates-bound configurations considered herein. That is, the preferred configuration of the fully bound active site has a neutral Glu-NH 2 and protonated AASA-NH 3 + . 3.2. Mechanism for Formation of Saccharopine The overall potential energy surface (PES) obtained for the catalytic mechanism of saccharopine reductase at the ONIOM(HF/6-31G(d):AMBER94)-ME level of theory with inclusion of Gibbs free energy corrections is presented in Figure 3 . The optimized geometries of the corresponding reactant, product, intermediate complexes and transition structures, with selected distances, are presented in Figure 4 , Figure 5 and Figure 6 . In the optimized structure of the reactant complex ( RC ) both cosubstrates form intramolecular hydrogen bonds. Specifically, in the glutamate moiety its α-amino and -carboxylate groups form a reasonably strong hydrogen bond with an NH…O distance of 2.12 Å ( Figure 4 ). Meanwhile, in the α-aminoadipate-δ-semialdehyde (AASA) cosubstrate its R-group carbonyl oxygen weakly hydrogen bonds with its protonated α-amino group with an AASA CO…H 3 N + -AASA distance of 3.05 Å. More importantly, however, the distance between the nitrogen centre of Glu-NH 2 and the R-group carbonyl carbon of AASA ( AASA C), i.e. , r (Glu-N(H 2 )…(O)C AASA ), is 3.58 Å. While this distance is quite long, it is shorter than that observed between these same two centres in gas-phase calculations on the complexed isolated substrates ( i.e. in the absence of active-site and NADPH); 3.83 Å (not shown). It is also noted that the distance from the hydrogen on NADPH to be transferred later in the mechanism as a hydride to AASA C is quite long at 4.38 Å (see Figure 4 ). Thus, at least initially the two co-substrates and cofactor appear to interact only weakly within the active-site. However, they all appear to be suitably positioned to react further. Figure 3. Overall PES for the catalytic mechanism of saccharopine reductase obtained at the ONIOM(HF/6-31G(d):AMBER94)-ME level of theory with inclusion of Gibbs corrections. Figure 3. Overall PES for the catalytic mechanism of saccharopine reductase obtained at the ONIOM(HF/6-31G(d):AMBER94)-ME level of theory with inclusion of Gibbs corrections. Figure 4. Optimized structures obtained at the ONIOM(HF/6-31G(d):AMBER94)-ME level of theory of the reactant complex ( RC ), transition structure ( TS1 ) and the carbinolamine intermediate I1 with selected distances shown (in Angstroms). Figure 4. Optimized structures obtained at the ONIOM(HF/6-31G(d):AMBER94)-ME level of theory of the reactant complex ( RC ), transition structure ( TS1 ) and the carbinolamine intermediate I1 with selected distances shown (in Angstroms). Figure 5. Optimized structures of TS2 , I2 , TS3 , I3 , TS4 and I4 obtained at the ONIOM(HF/6-31G(d):AMBER94)-ME level of theory with selected distances shown (in Angstroms). Figure 5. Optimized structures of TS2 , I2 , TS3 , I3 , TS4 and I4 obtained at the ONIOM(HF/6-31G(d):AMBER94)-ME level of theory with selected distances shown (in Angstroms). Figure 6. Optimized structures of TS5 , I5 , TS6 and PC obtained at the ONIOM(HF/6-31G(d):AMBER94)-ME level of theory with selected distances shown (in Angstroms). Figure 6. Optimized structures of TS5 , I5 , TS6 and PC obtained at the ONIOM(HF/6-31G(d):AMBER94)-ME level of theory with selected distances shown (in Angstroms). 3.2.1. Formation of a Carbinolamine Intermediate The first step in the overall pathway is nucleophilic attack of the glutamates α-amino nitrogen at the R-group carbonyl carbon centre of the cosubstrate AASA. This occurs via transition structure TS1 at a cost of 102.5 kJ mol −1 at the ONIOM(HF/6-31G(d):AMBER94)-ME + Gibbs corrections level of theory ( Figure 3 ). In TS1 the Glu N…C AASA distance has shortened markedly to 2.00 Å while concomitantly the O-C AASA bond has lengthened to 1.24 Å, i.e. , has reduced double-bond character ( Figure 4 ). The nucleophilicity of the attacking amine nitrogen is likely slightly enhanced by the modest decrease in the length of the glutamates intramolecular α-NH…–OOC-Glu hydrogen bond to 2.09 Å. In addition, however, the electrophilicity of the AASA C centre is enhanced by the significant decrease in the intramolecular AASA CO…H 3 N + -AASA hydrogen bond to just 1.70 Å. In the resulting carbinolamine intermediate I1 , lying 50.6 kJ mol –1 lower in energy than RC , the newly formed AASA C-N Glu bond has a length of 1.53 Å, slightly longer than a typical C-N single bond (HF/6-31G(d): r (CH 3 -NH 2 ) = 1.46 Å). Concomitantly, the AASA C-O bond has lengthened to 1.37 Å and a proton has now been transferred onto its oxygen centre from the + H 3 N-AASA group. While this is a substantial increase from that observed in RC , it is still shorter than for a typical C-O single bond (HF/6-31G(d): r (CH 3 -OH) = 1.40 Å). This is likely due to the fact that the newly formed AASA COH group maintains a short, strong hydrogen bond with the AASA-NH 2 nitrogen centre ( Figure 4 ). It should be noted that the Glu NH…–OOC-Glu hydrogen bond has also shortened to 1.88 Å. Furthermore, the distance between the mechanistically important NADPH hydrogen and the intermediates AASA C centre has decreased markedly by 1.26 Å to 3.12 Å in I1 . Vashishtha et al. [ 1 ] have suggested that an acidic residue within the active-site with a p K a of 7.8–8.0, possibly an aspartate (Asp126), protonates the oxyanion formed during nucleophilic attack of the glutamates amine. In the optimized structure of RC , the side chain of Asp126 hydrogen bonds with that of Arg243 and thus, it would seem unlikely to be able to act as a general acid. Furthermore, the p K a of an aspartate R-group carboxylate in aqueous solution is 3.8. Hence, the protein environment would have to significantly perturb its p K a upwards by approximately 4 or more units. In addition, in the optimized structure of RC the side chains of Asp126 and Arg243 form a hydrogen bonded ion pair and thus, Asp126 is unlikely to be able to act as a general acid. In contrast, in aqueous solution primary amines such as that of the cosubstrate AASA (AASA-NH 3 + ) typically have p K a ’s in the range of 9–10 and these values can be lowered when placed within the less polar environment of a protein’s active site. Indeed, the p K a measured by Vashishtha et al. [ 1 ] is only slightly lower than what one would anticipate for AASA-NH 3 + , the acidic group that protonates the AASA O centre in our present mechanism, in aqueous solution. 3.2.2. Rearrangement of the Carbinolamine Intermediate I1 Before Schiff base formation the carbinolamine intermediate I1 must undergo a rearrangement to allow for loss of H 2 O; specifically, deprotonation of the bridging -NH 2 + - moiety and inversion of the resulting -NH- group.[ 7 ] In saccharopine reductase this proceeds in a stepwise manner with the first being transfer of a proton from the bridging - Glu NH 2 + - group onto what was initially the glutamate’s carboxylate group. This occurs via TS2 with a quite low barrier of only 20.5 kJ mol −1 relative to I1 ( Figure 3 ) The resulting “neutral” carbinolamine intermediate I2 lies significantly lower in energy than I1 by 56.9 kJ mol −1 , most likely due to the neutralisation of charges. As can be seen in Figure 5 , in I2 the Glu N-C AASA bond has shortened considerably by 0.07 Å to 1.46 Å; a typical C-N single bond length (see above). Concomitantly, the C-OH bond has lengthened by 0.04 Å to 1.41 Å which similarly, is a length more typical of a C-O single bond (see above). The mechanistically important NADPH hydrogen is also now significantly closer by 0.15 Å to the intermediates AASA C centre. It should be noted, that the proton transferred onto the glutamate’s carboxylate now forms a bifurcated hydrogen bond with both the bridging - Glu NH- nitrogen and the oxygen of the AASA C-OH moiety ( Figure 5 ). Furthermore, the Glu-COOH…N Glu interaction inhibits the bridging - Glu NH- group from inverting. As noted in the Introduction, Vashishtha et al. [ 1 ] have suggested that a general base with a p K a in the range of 5.6–5.7 deprotonates the α-amine of glutamate prior to nucleophilic attack. However, as detailed above, upon binding the Glu-NH 3 + group appears able to readily lose a proton to the bulk aqueous solution. The above results suggest that the carboxylate originating from the substrate glutamate may be the acid/base group measured. Indeed, while the p K a of the α-COO − of glutamate in aqueous solution is 2.1, that of acetic acid is markedly higher at 4.8. Furthermore, as noted above, the low polarity of the protein environment can also induce a shift in measured p K a ’s. Thus, the next step is transfer of the Glu-COOH proton onto the carbinolamine’s AASA C-OH hydroxyl group, which itself simultaneously donates its proton to the nearby H 2 N-AASA amino moiety. This double proton transfer proceeds via TS3 at a cost of 99.1 kJ mol −1 with respect to I2 . It is noted that in TS3 the -OH proton is essentially almost wholly transferred onto the H 2 N-AASA moiety while that of the Glu-COOH lies almost equidistant between both the carboxylate and carbinolamine oxygen’s (see Figure 5 ). The resulting “charged” carbinolamine intermediate I3 lies 75.7 kJ mol −1 higher in energy than I2 , which is still 31.8 kJ mol –1 lower than that of the initial reactant complex RC ( Figure 3 ). Importantly, this reaction has now removed the Glu-COOH…N Glu interaction. It is noted that we were unable to obtain any carbinolamine intermediate that contained a neutral Glu-COOH group that did not have a Glu-COOH…N Glu hydrogen bond. The bridging - Glu NH- moiety is then able to undergo an inversion as is required to enable loss of the carbinolamine -OH group as H 2 O to form the Schiff base.[ 7 ] This inversion allows for the overlap in the non-bonding MO containing the nitrogen’s lone pair and the anti-bonding MO of the C-O bond. Such an overlap weakens the C-O leading to a more facile bond cleavage process. The process of inversion occurs via TS4 with a barrier of 12.6 kJ mol − 1 with respect to I3 , to give the alternate carbinolamine intermediate I4 lying 10.9 kJ mol − 1 higher in energy than I3 . As can be seen in Figure 5 , in I4 a marginal shortening and lengthening of the AASA C-N and AASA C-O bonds, respectively is observed. In addition, the distance between the mechanistically important NADPH hydrogen and AASA C centre has decreased further to 2.86 Å ( Figure 5 ). 3.2.3. Formation of the Schiff Base and its Reduction Once the bridging - Glu NH- has inverted, formation of the corresponding “N-protonated” Schiff base I5 can then occur via loss of the carbinolamine -OH as water. This is achieved in one step by transfer of a proton from the AASA-NH 3 + group onto the AASA C-OH oxygen centre and occurs via TS5 with a barrier of only 34.7 kJ mol −1 with respect to I4 ( Figure 3 ). The resulting imine intermediate I5 lies markedly lower in energy than I4 by 72.0 kJ mol −1 . It is noted that in I5 the bridging Glu N- AASA C bond has shortened significantly to 1.27 Å while the water that was released remains hydrogen bonded to both the α-amino and -carboxylate of the initial AASA cosubstrate. In addition, while the distance between the NADPH hydrogen and the AASA C centre has increased by 0.16 Å to 3.02 Å, it is still significantly closer than observed in RC ( cf. Figure 4 ). The final step in the overall catalytic pathway is formation of the saccharopine product via reduction of the Schiff base by a hydride transfer from NADPH onto the AASA C centre of I5 . It is noted that experimentally it has been found that nucleophilic attack of the N=C double bond only occurs when the Schiff base is protonated ( i.e. , when in its iminium form) as is the case for I5 [ 29 , 31 ]. This H − transfer step proceeds via TS6 with a barrier of 107.5 kJ mol −1 with respect to RC at the ONIOM(HF/6-31G(d):AMBER94)-ME + Gibbs corrections level of theory. This barrier is lower than the generally accepted upper thermodynamic limit for enzymatic reactions of approximately 120 kJ mol −1 [ 32 ]. However, it corresponds to a reaction barrier of 200.4 kJ mol –1 relative to I5 The final active-site bound-saccharopine complex (PC) is −72.0 kJ mol −1 lower in energy than the initial active-site bound-reactant complex RC. Thus, overall, the pathway is calculated to be exothermic and thus thermodynamically favoured at the ONIOM(HF/6-31G(d):AMBER94)-ME + Gibbs corrections level of theory ( Figure 3 ). 3.3. Obtaining More Accurate and Reliable Energies for the Mechanism of Saccharopine Reductase As noted in the Computational Methods, previous studies have shown that the Hartree-Fock level of theory can provide a reliable mechanistic pathway for Schiff base formation, although the associated relative energies may be less accurate. However, by careful choice of higher levels of theory one can systematically consider the effects of, for example, electron correlation and the polarity of the protein environment surrounding the reactants and enzyme active-site. This is usually done by performing single-point (SP) calculations at higher levels of theory that are based on the geometries optimized at a lower level of theory, in this case ONIOM(HF/6-31G(d):AMBER94)-ME. These provide more accurate relative energies and hence, potential energy surfaces. Thus PES’s were then obtained at several systematically higher levels of theory and which are presented in Figure 7 . In order to facilitate comparison with the PES in Figure 3 , the relative energy of RC at all levels of theory have been set to zero. 3.3.1. The Inclusion of Electron Correlation Effects In the ONIOM(HF/6-31G(d):AMBER94)-ME approach the key reactive region, the QM-region, is described by the Hartree-Fock method. This method, however, lacks inclusion of electron correlation effects which can be important in describing bond making and breaking processes. Thus, relative energies were obtained at the higher ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME level of theory with inclusion of Gibbs corrections. That is, single-points were performed in which the key QM-region is now described using the conventional electron correlation approach MP2/6-31G(d). The resulting PES obtained is shown in Figure 7 ; dashed blue line. Figure 7. Overall PES’s obtained for the catalytic mechanism of saccharopine reductase at the (i) ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME + Gibb’s Corrections (dashed blue line), (ii) ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-EE + Gibb’s Corrections (dotted pink line), and (iii) ONIOM(MP2/6-311G(d,p)//HF/6-31G(d):AMBER94)-EE + Gibb’s Corrections (solid black line) levels of theory. Figure 7. Overall PES’s obtained for the catalytic mechanism of saccharopine reductase at the (i) ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME + Gibb’s Corrections (dashed blue line), (ii) ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-EE + Gibb’s Corrections (dotted pink line), and (iii) ONIOM(MP2/6-311G(d,p)//HF/6-31G(d):AMBER94)-EE + Gibb’s Corrections (solid black line) levels of theory. It can be seen clearly that a number of significant changes in relative energies occur along the catalytic pathway. In particular, those of the intermediates and product complex all decrease by 0.9–15.5 kJ mol −1 with respect to RC . However, the largest effects are observed for the transition structures (TS’s) which all decrease considerably by 23.3–94.9 kJ mol −1 with respect to RC . For example, the reaction barrier for the initial nucleophilic attack of the Glu-NH 2 nitrogen at the R-group carbonyl carbon of AASA is significantly reduced by 42.5 kJ mol −1 to 60.0 kJ mol −1 ; namely is, the relative energy of TS1 for formation of the Glu N-C AASA bond decreases. In fact, at this level of theory this reaction step now represents the rate-limiting step of the overall catalytic mechanism. The resulting “N-protonated” carbinolamine I1 lies lower in energy than RC by –66.1 kJ mol –1 , a modest lowering of 15.5 kJ mol −1 (cf. Figure 3 ). The subsequent proton transfer from the bridging - Glu NH 2 + - moiety to the Glu-COO − group now occurs essentially without a barrier via TS2 to give the “neutralized” carbinolamine intermediate I2 . Therefore, I1 has become kinetically and thermodynamically unstable with respect to rearrangement to I2 . Indeed, re-optimization of I1 at the ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME level of theory gave I2 directly (not shown). Notably, I2 is again the lowest energy intermediate along the catalytic pathway with respect to RC and now has a relative energy of −108.4 kJ mol −1 . This corresponds to a marginal decrease of just 0.9 kJ mol −1 , the smallest observed of any intermediate upon inclusion of electron correlation effects. A large reduction in the calculated barrier for the subsequent double-proton transfer via TS2 to give the alternate carbinolamine intermediate I3 is also observed. Specifically, it has been reduced by 54.4 kJ mol −1 . Consequently, similar to that observed for I1 at the same level of theory, I3 which now has a relative energy of −47.2 kJ mol −1 with regards to RC , is kinetically and thermodynamically unstable with respect to rearrangement back to I2 . Indeed, as for I1 , re-optimization of I3 at the ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME level of theory directly gave I2 (not shown). The reaction barrier for inversion of the bridging - Glu NH-; namely, rearrangement of I3 to give the alternate carbinolamine intermediate I4 via TS4 , is calculated to be just 14.7 kJ mol − 1 with respect to I3 ( Figure 7 ). Notably, the resulting “inverted carbinolamine” intermediate I4 is calculated to be only slightly stable with respect to rearrangement back to I3 by 1.3 kJ mol − 1 . The subsequent loss of water via TS5 is found to occur at a very low cost of 5.0 kJ mol − 1 with respect to I4 ( Figure 7 ). Thus, while the energy of TS4 relative to RC has decreased by 38.1 kJ mol − 1 upon inclusion of electron correlation effects, this corresponds to a decrease in the actual reaction barrier height of just 2.1 kJ mol − 1 ( cf. Figure 3 ). Similar to that obtained at the lower ONIOM(HF/6-31G(d):AMBER94)-ME + Gibbs corrections level of theory, the resulting Schiff base intermediate I5 is calculated to lie very low in energy relative to RC . Indeed, it has only modestly decreased by 10.4 kJ mol −1 to −103.3 kJ mol −1 . The largest impact of including the effects of electron correlation, however, are observed in the final step of the overall pathway; reduction of the Schiff base I5 via hydride transfer from NADPH onto the intermediates AASA C centre to give the desired saccharopine product. Specifically, as can be seen in Figure 7 , the relative energy of TS6 with respect to RC decreases by 94.9 kJ mol −1 . As a result, the barrier for this final step is markedly reduced to 115.9 kJ mol −1 with respect to I5 and in fact, is now predicted to be enzymatically and kinetically feasible [ 32 ]. The overall mechanism is again predicted to be exothermic with the final saccharopine-bound active-site complex PC lying lower in relative energy by 83.3 kJ mol −1 than the initial reactant-bound active-site complex RC ( Figure 7 ). 3.3.2. The Effects of the Protein’s Anisotropic Polar Environment In the ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME approach above the surrounding protein environment and its effects on the reactive QM region are only treated at the molecular mechanics (MM) level of theory. In contrast, in an electronic embedding (EE) formalism the point charges of the MM protein environment are included in the self-consistent optimization of the wave function. Consequently, it enables one to examine the effects of polarization on the reactive region (QM layer) by the anisotropic protein environment. Thus, relative energies were then also obtained at the ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-EE + Gibbs corrections level of theory. The resulting PES obtained is shown in Figure 7 ; dotted pink line. Comparison with the PES obtained at the ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME + Gibbs corrections level of theory ( Figure 7 , dashed blue line) provides insight into the protein environment’s influence on the catalytic mechanism. As can be seen in Figure 7 , inclusion of the polarizing effects of the protein environment has a tremendous influence on the overall pathway. More specifically, the relative energy of almost all intermediates, transition structures and the product complex are now significantly raised with respect to RC by 27.7–161.4 kJ mol −1 . The only exception occurs for the initial nucleophilic attack of Glu-NH 2 at the AASA C centre via TS1 for which the barrier is instead reduced by 9.8 kJ mol −1 to 50.2 kJ mol −1 . Importantly, as a result, this step is no longer rate-limiting in the overall pathway (see below). Significant changes are also observed for the carbinolamine intermediates I1 , I2 and I3 and the proton transfer reactions via TS2 and TS3 through which they interconvert. In particular, the initial “N-protonated” carbinolamine intermediate I1 formed is now in fact slightly higher in energy than RC by 9.4 kJ mol −1 . Furthermore, it is stable with respect to rearrangement to the subsequent “neutralised” carbinolamine I2 (see below). In contrast, I2 now has the highest relative energy with respect to RC , 53.0 kJ mol −1 , of the three carbinolamine intermediates I1 , I2 and I3 . In addition, it is thermodynamically and kinetically unstable with respect to rearrangement back to I1 or to the subsequent “charged” carbinolamine I3 . This is indicated by the fact that both TS2 and TS3 now have lower relative energies than I2 of 24.5 and 30.0 kJ mol −1 , respectively ( Figure 7 ). The complex I3 continues to lie lower in energy than RC , but by a lesser margin of 15.0 kJ mol −1 . However, as a result it is now the lowest energy carbinolamine intermediate of all three and in fact, is the lowest energy intermediate obtained along the entire catalytic pathway. A possible explanation for these observed changes may be found by considering the substrate glutamate’s carboxylate and the active-site residues with which it interacts. In particular, in I2 the Glu-COO − group hydrogen bonds to the guanidinium of an arginyl (Arg224) and phenolic R-group of a tyrosyl (Tyr78). At the previous level of theory considered, ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME, the Glu-COO − …Arg224/Tyr78 interactions were modelled at the MM level and thus, in effect, were modelled as a steric interaction. However, by now considering the polarizing effects of the protein environment these interactions are preferred when the Glu–COO - group is anionic as in I2 and I3 . Furthermore, the lower relative energy for I3 may reflect that there is also preference for having the positive charge on the intermediate further removed from the carboxylate and the positively charged Arg224 residue; in I1 the Glu-COO − hydrogen bonds directly with the bridging - Glu NH 2 + - group while in I3 it indirectly hydrogen bonds with the AASA-NH 3 + group via the carbinolamine -OH moiety. In addition, the predicted instability of I2 suggests that it may resemble a transition structure for Glu-COO − -assisted proton transfer from - Glu NH 2 + - to the carbinolamine hydroxyl oxygen, which would otherwise require an inherently high energy four-membered ring transition structure [ 7 , 29 ]. This is analogous to previous studies that have found lower barriers in related systems for a water-assisted proton transfer from the bridging -NH 2 + - to the carbinolamine oxygen [ 28 , 29 , 33 ]. Inversion of the bridging - Glu NH- moiety via TS4 is calculated to have now a decidedly higher barrier of 49.4 kJ mol − 1 with respect to I3 . This corresponds to an increase of 34.7 kJ mol − 1 compared to that obtained within the mechanical embedding formulism at the same level of theory (see above). Thus, the protein environment has a greater effect on this reaction step than does the inclusion of electron correlation which resulted in a comparatively slight increase of 2.1 kJ mol − 1 . Considerable changes upon inclusion of the polarizing effects of the protein environment are also observed for the subsequent loss of water via TS5 to give the Schiff base intermediate I5 . In particular, the barrier for this step is now 51.5 kJ mol − 1 with respect to I4 , a ten-fold increase compared to that obtained using the ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME approach. In fact, this process now represents the overall rate-limiting step along the catalytic pathway. Furthermore, I5 lies higher in energy than RC by 33.8 kJ mol − 1 and importantly, is thermodynamically and kinetically unstable with respect to further reaction via TS6 to give the final product complex PC ( Figure 7 ). Therefore, hydride transfer from the NADPH cofactor to the AASA C centre of the imine now essentially occurs without a barrier. The complex PC is calculated to be marginally endothermic compared to RC by 2.6 kJ mol − 1 . 3.3.3. The Effects of Increasing the Basis Set Size In any computational study it is important to use a basis set that adequately describes the chemical system being studied. This is particularly true when examining bond making and breaking process or those systems that involve weak, long-range or charged interactions. Thus, we also chose to examine the effects of increasing the basis set size for the reactive region, the QM layer. Specifically, the PES for the overall catalytic mechanism was obtained at the ONIOM(MP2/6-311G(d,p)//HF/6-31G(d): AMBER94)-EE + Gibbs corrections level of theory and is shown in Figure 7 (solid black line). This approach also represents the best, or benchmark, level of theory used in this present study. One can clearly see that improving the basis set used for the QM layer from 6-31G(d) to 6-311G(d,p) does not change the overall reaction pathway. Indeed, for almost all of the intermediates, transition structures and product complex, their relative energy with respect to RC decreases by just −4.7–−37.5 kJ mol −1 . The only exception is again observed for TS1 , i.e. , nucleophilic attack of Glu-NH 2 at the AASA C centre, which instead increases by 7.5 kJ mol −1 to 57.7 kJ mol −1 . For example, the carbinolamine I1 is again predicted to lie just slightly higher in energy than RC by 4.6 kJ mol −1 . Similarly, I3 is again calculated to lie lower in energy than RC , though now by 20.9 kJ mol −1 , a 5.9 kJ mol −1 decrease ( Figure 7 ). Furthermore, it is still the lowest energy intermediate along the overall pathway. In addition, despite a decrease in its relative energy of 17.0 kJ mol −1 to 36.0 kJ mol −1 , I2 is still predicted to be thermodynamically and kinetically unstable with respect to rearrangement back to I1 or on to I3 . A marginal increase in the barrier of just 1.2 kJ mol −1 to 50.6 kJ mol −1 is observed for inversion of the bridging - Glu NH- moiety via TS4 , i.e. , interconversion of I3 and I4 . In contrast, there is a modest reduction in the subsequent barrier height for loss of the carbinolamine -OH group as water via TS5 . Specifically, the barrier is reduced by 7.4 kJ mol −1 to 74.1 kJ mol −1 with respect to RC . However, this reaction process again remains the overall rate-limiting step in the catalytic mechanism of saccharopine reductase. It is noted that despite this relative decrease in the barrier height of TS5 , the energy difference between I3 and TS5 , the lowest energy intermediate and highest barrier respectively, remains fairly constant upon increasing the basis sets size. Indeed, this difference decreases by just 1.5 kJ mol −1 to 95.0 kJ mol −1 ( Figure 7 ). The resulting Schiff base intermediate I5 now lies 17.2 kJ mol −1 higher in energy than RC , but again can essentially undergo a barrierless hydride transfer from the NADPH cofactor to the its AASA C centre to give the final saccharopine-bound active-site product complex ( PC ). It is noted that upon increasing the basis set size the overall mechanism has once again become slightly exothermic with PC lying 18.4 kJ mol −1 lower in energy than the initial reactant-bound active-site complex RC . It is interesting to note that we also used the first principles quantum and statistical mechanics approach outlined by Llano and Eriksson [ 34 ], in combination with small chemical models consisting of only the Schiff base itself in I5 , i.e. , no active-site, and the NADPH ring from which the hydride is donated. It was predicted that the inherent free energy change for hydride transfer favoured the reduced imine product by 33.3 kJ mol −1 . Within the active-site, at our presently used highest level of theory ONIOM(MP2/6-311G(d,p)//HF/6-31G(d):AMBER94)-EE + Gibbs corrections, PC lies 35.6 kJ mol −1 lower in free energy than I5 . This suggests that for this final mechanistic step the enzyme does not aim to target distinctly or favour binding of the product over the preceding Schiff base. Rather, it simply utilises the inherent favourable free energy change for the hydride transfer. 4. Conclusions A series of systematically higher level ONIOM-based computational methods have been used in order to examine the overall catalytic mechanism of saccharopine reductase and the effects of electron correlation and the anisotropic polar protein environment on the mechanism. The enzymes overall mechanism was elucidated using the quantum mechanics/molecular mechanics (QM/MM) ONIOM(HF/6-31G(d):AMBER94) method within the mechanical embedding (ME) formulism. The present results suggest that the catalytic mechanism does not require the direct involvement of active-site residues in the required proton transfer processes. For example, the protonated α-amine (AASA-NH 3 + ) of the cosubstrate α-aminoadipate-δ-semialdehyde (AASA) is able to act as an acid. Specifically, during nucleophilic attack of the Glu-NH 2 group at the R-group aldehyde carbon of AASA it protonates the forming oxyanion centre. In addition, the glutamate’s carboxylate (Glu-COO − ) is able to assist the proton transfer from the bridging - Glu NH 2 + - moiety in the formed initial carbinolamine intermediate ( I1 ) to the nearby carbinolamine hydroxyl oxygen. Notably, at the ONIOM(HF/6-31G(d):AMBER94)-ME + Gibb’s corrections level of theory the lowest energy intermediate along the overall pathway is calculated to be the “neutralised” carbinolamine intermediate I2 in which both the α-carboxylate and α-amino of the initial glutamate and AASA cosubstrates respectively are neutral. The overall rate-limiting step was calculated to be hydride transfer via TS6 from the NADPH cofactor onto the bridging -NH + =C- carbon centre of the Schiff base intermediate I5 to give the final product bound active-site complex PC . In particular, it lies 107.5 kJ mol −1 higher in energy with regards to the initial reactant complex RC , but is 200.4 kJ mol −1 higher in energy than the preceding Schiff base intermediate I5 ( Figure 3 ). The inclusion of electron correlation effects, on the key reactive region (QM layer) by increasing the level of theory to ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94)-ME + Gibb’s corrections, leads to considerable changes along the catalytic pathway. In particular, with respect to the initial reactant complex RC the relative energies of the mechanistic intermediates and product complex all decreased by 0.9–15.5 kJ mol −1 while those of the transition structures (TS’s) all decreased by 23.3–94.9 kJ mol −1 . As a result, while the “neutralised” carbinolamine I2 remains the lowest energy intermediate along the pathway (−108.4 kJ mol −1 ), the thermodynamic rate-limiting step is now nucleophilic attack of GluNH 2 at the R-group aldehyde carbon ( AASA C) of the AASA cosubstrate via TS1 at a cost of 60.0 kJ mol −1 ( Figure 7 ). The largest single reaction step barrier again occurs for reduction of the Schiff base intermediate via TS6 , though now greatly reduced at 115.9 kJ mol −1 . Re-examination of the PES at the ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94) within the electronic embedding (EE) formulism with inclusion of Gibb’s corrections enabled the effects of the polarizing protein environment on the reactive region (QM layer) to be investigated. Importantly, it was found that relative to the initial reactant complex RC almost all intermediates, transition structures and product complex were destabilized by 27.7–161.4 kJ mol −1 ; namely, their relative energy was raised. The only exception occurred for the initial nucleophilic attack of Glu-NH 2 on the AASA cosubstrate via TS1 for which the barrier decreased by 9.8 kJ mol −1 . Consequently, the carbinolamine I3 lying 15.0 kJ mol −1 lower in energy than RC was now found to be the lowest energy intermediate along the overall pathway. Furthermore, the rate limiting step is now loss of water from the “inverted” carbinolamine I4 via TS5 , at a cost of 81.5 kJ mol −1 with respect to RC, to give the Schiff base I5 . In addition, the subsequent and final step in the overall pathway, reduction of the Schiff base, is found to occur now essentially without a barrier. Increasing the size of the basis set used to describe the key QM layer from 6-31G(d) to 6-311G(d,p) was also considered by the use of the ONIOM(MP2/6-311G(d,p)//HF/6-31G(d):AMBER94)-EE method with inclusion of Gibb’s corrections. In general, only comparatively modest decreases of 4.7–37.5 kJ mol −1 in the relative energy of all intermediates, transition structures and product complex with respect to RC were observed. The only exception being for TS1 whose relative energy increased by 7.5 kJ mol −1 . This was also the highest level of theory used in this present study. The carbinoalamine I3 is again the the lowest energy intermediate along the catalytic pathway being 20.9 kJ mol −1 lower in energy than RC. The overall rate-limiting step is the loss of water to give the Schiff base intermediate I5 which occurs via TS6 at a cost of 74.1 kJ mol −1 with respect to RC. A subsequent barrierless hydride transfer reduces I5 to the final saccharopine product. Experimentally, it has been suggested that two active site acid/base residues with p K a ’s of 5.6–5.7 and 7.8–8.0 facilitate the mechanistically required proton transfers [ 1 ]. However, it has also been experimentally suggested that there are no active site acid/base residues available and thus, the enzyme functions by orientating and positioning the substrates for reaction [ 4 ]. The present results suggest that acid/base functional groups within the substrates themselves, specifically the α-amine of α-aminoadipate-δ-semialdehyde and α-carboxylate of glutamate, are able to catalyse the mechanistically required proton transfer reactions, in support of previous suggestions by Johansson et al. 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Carbon and nitrogen co-doping enhances phase stability and mechanical properties of a metastable high-entropy alloy \| Request PDF Request PDF \| Carbon and nitrogen co-doping enhances phase stability and mechanical properties of a metastable high-entropy alloy \| To probe the significant interstitial effects coupling with metastability design of high-entropy alloys (HEAs), we introduced both interstitial C... \| Find, read and cite all the research you need on ResearchGate Article Carbon and nitrogen co-doping enhances phase stability and mechanical properties of a metastable high-entropy alloy August 2020 Journal of Alloys and Compounds831:154799 DOI: 10.1016/j.jallcom.2020.154799 Authors: <here is a image f2f62089ad6ff61c-d19572ff1996375a> Wanying Zhang Wanying Zhang <here is a image 68c43dacfeb6b96f-677b603968d117e4> Dingshun Yan Central South University <here is a image dca644a6dae250b6-89e737c3df01ea55> Wenjun Lu Southern University of Science and Technology <here is a image 0774f601d4f56c6f-571180ddf8f5c1e5> Zhiming Li Central South University Abstract To probe the significant interstitial effects coupling with metastability design of high-entropy alloys (HEAs), we introduced both interstitial C and N into a representative metastable HEA. The mechanical behavior of the novel C-N co-doped interstitial HEA (iHEA) with nominal composition Fe48.5Mn30Co10Cr10C0.5N1.0 (at. %) in different grain sizes has been investigated via digital image correlation (DIC) assisted tensile testing. The microstructure characteristics prior to and after tensile deformation with different local strain levels were probed by various techniques. The C-N co-doped iHEA shows a face-centered cubic (FCC) matrix without hexagonal closed packed (HCP) martensite after annealing plus the subsequent quenching, different from the reference metastable FCC-HCP dual-phase HEA without interstitials. Upon tensile deformation, dislocation slip and twinning prevail, and the new iHEA does not show phase transformation which is the primary deformation mechanism in the reference interstitial-free metastable HEA. This further confirms the enhanced FCC phase stability due to C-N co-doping. The interstitial effect coupling with the multiple strengthening mechanisms including twinning induced plasticity (TWIP) and nano-particle strengthening due to nano-sized carbonitrides leads to significantly higher yield strength (753 MPa) and ultimate tensile strength (1038 MPa) at good ductility (48.0%) compared to that of the reference interstitial-free metastable HEA (∼250 MPa, ∼850 MPa and ∼70%, respectively) at a similar grain size of ∼4 μm. Accordingly, our work demonstrates the significant capability of interstitials including C and N for tuning the phase stability and enhancing mechanical properties of HEAs. ... Therefore, the BCC phase was transformed into HCP phase at the start and then gradually transformed into FCC and the subsequent HCP/FCC nano-laminates, which improved the plasticity through strain partitioning. For the sake of clear understanding, Fig. 8 represents the yield strength versus elongation for the single interstitially doped HEAs, co-doped HEA and multiple-interstitially doped HEA taken from literature [22,85,87,93,95,96,[104][105][106][107][108][109] [110] [111]. ... ... Therefore, the GB act as an effective source of strengthening as it [22,86,87,93,95,96,104,[107][108][109] [110] [111], multiple-interstitially doped HEAs [106], and co-doped HEAs [105,110]. ... ... Therefore, the GB act as an effective source of strengthening as it [22,86,87,93,95,96,104,[107][108][109][110][111], multiple-interstitially doped HEAs [106], and co-doped HEAs [105, 110] . ... Strengthening mechanisms in high entropy alloys: A review Oct 2022 <here is a image 67fe3631c8939084-3881a22ed9f7924c> Naqash Ali Liqiang Zhang <here is a image 2b67bf2883ddfcd8-a397244156fa7030> D. M. Liu Jinjun Cheng High entropy alloys (HEAs) is a new generation of alloys with multi-component systems and emerged as a potential candidate for the industrial applications due to their excellent mechanical properties at cryogenic, ambient and elevated temperatures. The chemistry changes through microstructural heterogeneities leads to a significant strength increment in HEAs as compare to the conventional solid solutions. However, the strength increment is often related to the ductility loss and vice-versa, which is known as strength-ductility trade-off. Therefore, the modifications in the conventional strengthening mechanisms are required to overcome this dilemma. The conventional strengthening mechanisms have been revisited and revised by the materials scientists to break these trade-offs through adjusting the stacking fault energy, twins formation and phase transformation in multicomponent systems. Herein, the different strengthening mechanisms including, solid solution strengthening, grain boundary strengthening, precipitation strengthening and phase transformation strengthening are systematically reviewed with regard to overcome the strength-ductility trade-off in HEAs. ... Recently, the concept of HEAs has been expanded to include non-equiatomic variants containing four or more principal elements [4]. Apart from the single-phase stable HEA systems, several additional alloy systems including multi-phase [5], metastable [6,7] and interstitial HEAs [8] [9] [10] have been developed to date through adjusting the chemical compositions, and many of them exhibit desirable mechanical and/or functional properties. ... ... By inputting the attained yield strength and grain size values of the tested samples into eqn. (9) , the values of k y and σ 0 for the FeNiCoCr-AlTiCuSi alloy are estimated as ~675 MPa⋅μm 1/2 and 125 MPa, respectively. It is seen that the present multiple minor elements decorated FeNiCoCr-AlTiCuSi alloy exhibits higher Hall-Petch coefficient and lattice friction stress compared to the undecorated reference alloy (~628.5 MPa⋅μm 1/2 and 79.4 MPa, respectively) [31]. ... ... In addition, the doping of the multiple minor elements (Al, Ti, Cu and Si) enhances the lattice distortion in the material as discussed above, which leads to a higher friction stress against the motion of Shockley partials. It has been reported in the interstitial HEAs that the significant drag effect by interstitial atoms can strongly suppress the mobility of the neonatal mobile partials [14], and thus severely constrains the width of SFs and lowers the probability of the formation of SFs on the neighboring atomic planes [9] . Analogically, the retarding effect on the movement of partial dislocations by the enhanced lattice friction stress from the additional multiple minor elements would suppress the generation of mechanical twins at the early deformation stages in the current FeNiCoCr-AlTiCuSi alloy. ... Multiple minor elements improve strength-ductility synergy of a high-entropy alloy Feb 2022 MAT SCI ENG A-STRUCT <here is a image d1fb82583fdfa3e2-27d7caf729e4f754> Shuya Zhu <here is a image ed823b8e1ad7c97f-ffb1f6ff53a90220> Kefu Gan <here is a image 68c43dacfeb6b96f-677b603968d117e4> Dingshun Yan <here is a image 0774f601d4f56c6f-571180ddf8f5c1e5> Zhiming Li The developments of multicomponent high-entropy alloys usually put emphasis upon the roles of multiple principal elements in optimizing the various properties. Instead of tuning the principal elements, here we propose to use multiple minor alloying elements to improve performance of HEAs. To this end, the microstructure and mechanical behavior of a newly developed alloy, i.e., Fe35Ni20Co20Cr20Al2.5Ti1.0Cu1.0Si0.5 (at. %), have been investigated. The alloy decorated by the multiple minor alloying elements (i.e., Al, Ti, Cu and Si) exhibits a single face-centered cubic (FCC) γ phase in fully recrystallized state. Compared with the undecorated Fe40Ni20Co20Cr20 (at. %) counterpart with similar grain size, the yield strength of the decorated alloy sample with multiple minor elements is enhanced by ∼19% at a high elongation of ∼74%. Microstructural characterizations indicate that dislocation slip prevails at the early stages of plastic deformation while mechanical twins are observed to occur at the late deformation stage. The local stress field caused by the atomic size mismatch and elastic mismatch originated from the multiple minor elements significantly impedes the movement of dislocations thus improves the strength. Such retarding effect of the multiple minor elements on mobile dislocation further hinders the generation of stacking faults on adjacent atomic planes and thereby increases the FCC-γ phase stability, which also postpones the deformation twinning upon tension. This work demonstrates the practical significance of introducing multiple minor alloying elements with their synergistic effect into HEAs, and the design strategy enlarges the space for compositional design of advanced alloys. ... In this respect, the metastable transformation-induced plasticity (TRIP) assisted dual-phase HEAs, e.g., Fe 50 Mn 30 Co 10 Cr 10 (at%), have been developed to enhance both of strength and ductility by combining the massive substitutional solid solution strengthening and transformation-induced hardening effects [9][10][11]. In order to combine more strengthening mechanisms and further improve the mechanical properties, interstitial elements such as C and/or N were added into the HEAs for developing a novel class of interstitial high-entropy alloys (iHEAs), e.g., Fe 49.5 Mn 30 Co 10 Cr 10 C 0.5 (at%) [12][13][14] and Fe 48.5 Mn 30-Co 10 Cr 10 C 0.5 N 1.0 (at%) [15] [16] [17]. In these typical iHEAs, multiple strengthening mechanisms including TRIP, twinning-induced plasticity (TWIP), interstitial solid solution strengthening and precipitation hardening can be activated. ... ... Nano-carbides (~200 nm) and dislocations randomly distribute in the FCC-γ matrix ( Fig. 1b 4 ). C-N co-doping further increases the phase stability and SFE of the FCC-γ matrix [16] , thus resulting in a single FCC-γ phase. The dislocations in the C 0.5 N 1.0 iHEA matrix arrange in planar arrays ( Fig. 1c 4 ), instead of random distribution observed in the C 0.5 iHEA. ... ... We also note that the temperature corresponding to the second peak in C-N free metastable HEA is ~50 ℃ higher than that of the other two HEAs, suggesting different trapping sites. Nano carbides in the C 0.5 iHEA and carbonitrides in C 0.5 N 1.0 iHEA have been observed (Fig. 1b 4 -c 4 ) [14, 16] , which can act as the irreversible hydrogen traps. On the other hand, the fraction of TBs in C 0.5 and C 0.5 N 1.0 iHEAs obtained by the EBSD analysis are 0.712 and 0.857, respectively. ... Effects of interstitial C and N on hydrogen embrittlement behavior of non-equiatomic metastable FeMnCoCr high-entropy alloys <here is a image d1fb82583fdfa3e2-27d7caf729e4f754> Shuya Zhu <here is a image 0774f601d4f56c6f-571180ddf8f5c1e5> Zhiming Li The hydrogen embrittlement behavior of C-doped and C-N co-doped non-equiatomic FeMnCoCr high-entropy alloys were investigated by slow strain rate tensile tests (1×10⁻⁵ s⁻¹) under in-situ electrochemical hydrogen charging. Multi-scale microstructural analysis suggests that appropriate phase stability and stacking fault energy adjusted by C-doping provide the alloy with slightly greater resistance to hydrogen embrittlement with the formation of abundant deformation-induced twins and ε-martensite during deformation. The C-N free alloy shows grain boundary and ε/γ interface cracking even though the γ and ε phases have high deformability. C-N co-doping promotes planar dislocation slip, assisting grain- and twin-boundary cracking under deformation in hydrogen. ... The concept of high entropy alloys (HEAs) containing multiple principal elements has worked as a breakthrough to traditional alloy design based on one or two principal elements [1][2] [3] [4][5][6] . At beginning, single-phase HEAs were developed according to the principle of maximum configuration entropy, such as facecentered cubic (FCC) CoCrFeMnNi [7] , body-centered cubic (BCC) TiNbTaZrHf [8] and hexagonal close-packed (HCP) YGdTbDyHo [9] . ... ... At beginning, single-phase HEAs were developed according to the principle of maximum configuration entropy, such as facecentered cubic (FCC) CoCrFeMnNi [7] , body-centered cubic (BCC) TiNbTaZrHf [8] and hexagonal close-packed (HCP) YGdTbDyHo [9] . However, a high configuration entropy is not a guarantee for the validness of stable solid-solution phase, but in fact the compe-after a co-doping of 0.5 at.% carbon plus 1.0 at.% nitrogen, the asachieved Fe 48.5 Mn 30 Co 10 Cr 10 C 0.5 N 1.0 (at.%) iHEA shows further enhanced strength at maintained ductility; it is also found that dislocation slip and twinning prevail but displacive phase transformation from FCC γ to HCP ε phase does not occur in the carbon and nitrogen co-doped iHEA during tension experiments [3] . This indicates that interstitial carbon and nitrogen enhance phase stability through increasing stacking fault energy (SFE) of the present FeM-nCoCr system. ... ... In this view, a pop-in is an indicator to plasticity and highly associated with the intrinsic motions of defects in the sheared volume [32][33][34][35] . For examples, Chiu and Ngan [20] applied nanoindentation tests on Ni 3 Al crystal and employed continuum mechanical descriptions for dislocation loop energy under intense shears, to determine the critical shear stress favoring dislocation nucleation. Schuh et al. [36] studied the dislocation nucleation from high-temperature nanoindentation tests and proposed statistical methods for examining the incipient plasticity of crystals. ... Interstitial effects on the incipient plasticity and dislocation behavior of a metastable high-entropy alloy: Nanoindentation experiments and statistical modeling <here is a image d1fb82583fdfa3e2-27d7caf729e4f754> Shuya Zhu <here is a image 0774f601d4f56c6f-571180ddf8f5c1e5> Zhiming Li Owing to the partial dislocation assisted twinning and/or displacive transformation upon stress loading, metastable high-entropy alloys (HEAs) and their interstitial variants have shown excellent strength-plasticity synergy. However, the fundamental mechanisms of the dislocation nucleation and the onset of plasticity in these emerging materials remain unclear. The present study is to provide quantitative insights into the dislocation nucleation in the metastable HEAs and reveal the corresponding effects of interstitial alloying elements through combined instrumented nanoindentation experiments and statistical physical modeling. The results indicate that dislocation nucleation in a representative metastable non-equiatomic FeMnCoCr HEA is triggered by the thermally activated displacement of single principal atom, suggesting a dominant homogeneous mode of dislocation nucleation according to a continuum mechanical description for neonatal dislocation loop energy. Also, minor heterogeneous nucleation via monovacancy-atom exchange is possible according to a quantitative analysis for the potential effects of pre-existing defects. The activation volume necessary for dislocation nucleation in the metastable HEA is increased upon dissolving 0.5 at.% C plus 1.0 at.% N into the face-centered cubic structure. Statistical modeling and experimental nanoindentation results suggest that interstitial C and N atoms are prone to facilitate the nucleation rate of Shockley partials under intense shears. Yet, the significant drag effect by interstitial atoms can trap those neonatal mobile partials and reduce their mean free path before exhaustion. Thus, the width of stacking faults (SFs) formed by slip of such partials is severely constrained, which hinders the generation of SFs on multiple atomic layers and further inhibits the displacive phase transformation during deformation of the C-N co-doped metastable HEAs. ... However, high volume fractions of B2 NiAl lead to undesirable embrittlement [23]. Other methods to increase strength are interstitial alloying elements such as C [33] [34] [35], N [33,36,37,34,38,39] and B [40], which increase strength effectively even at low contents. Especially the addition of C is interesting as it is extensively and effectively used for strengthening in FCC-based alloys, both for precipitation [41] and solid solution hardening [42]. ... ... However, high volume fractions of B2 NiAl lead to undesirable embrittlement [23]. Other methods to increase strength are interstitial alloying elements such as C [33][34][35], N [33,36,37, 34, 38,39] and B [40], which increase strength effectively even at low contents. Especially the addition of C is interesting as it is extensively and effectively used for strengthening in FCC-based alloys, both for precipitation [41] and solid solution hardening [42]. ... Thermodynamics, microstructure evolution and mechanical properties of Al- and C-added CoFeMnNi multi-principal element alloys <here is a image 1863cc4940c38e5a-327115cb1f9b2e9b> Fabian Kies <here is a image 3b46aac327e55cdb-6468e2667be7fa27> Simon Ewald Navigating through the phase space of multi-principal element alloys (mpeas) with desired microstructures and outstanding properties is challenging due to extremely high degrees of freedom in alloy composition and processing conditions. Separate Al and C additions and the resulting precipitation of hard phases are commonly used to strengthen CoCrFeMnNi-type alloys. However, the combined alloying effect and especially the high hardening potential of C in solid solution of mpeas are rarely investigated, but the few existing investigations reveal a high potential. Therefore, the properties of the Al0-22.1C0-2.3(CoFeMnNi)100-75.6 (at%) system were comprehensively investigated, where Cr was intentionally removed to keep C in solid solution. For theoretical and experimental screening of the system, a custom calphad database was extended, samples were manufactured by additive manufacturing (am) and annealed between temperatures of 1150 and 550°C. Detailed microstructural and mechanical analysis on 40 different revealed the properties of the equiatomic CoFeMnNi alloy and the effect of the separate and combined additions of Al and C, including comprehensive precipitate characterization. The system was especially potent in its room temperature tensile properties in the Al- and C-added fcc-based region, where it caused the activation of twinning-induced plasticity (twip) and combined high strength and ductility increases. ... Co-doping the interstitial elements can synergistically enhance the mechanical properties. In a case study, co-doping of C and N in an iHEA resulted in phase stability enhancement and multiple strengthening mechanisms such as twinning induced plasticity (TWIP), solid solution strengthening, and nano-particle strengthening [26] . In this regard, the co-doping of B and N with the aim of forming boron nitride (BN) precipitates could be beneficial for both room-and high-temperature properties due to the phase stability of BN [27]. ... A facile strengthening method by co-doping boron and nitrogen in CoCrFeMnNi high-entropy alloy <here is a image 6118bc332d456ece-6b45887a767e0a13> Peyman Asghari-Rad <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hyoung Seop Kim This work aims to investigate the multiple strengthening mechanisms in the B–N co-doped CoCrFeMnNi high-entropy alloy. B–N co-doping induces the fine grain size and leads to Cr2B and BN precipitate formations. The B–N co-doped CoCrFeMnNi exhibits enhanced yield strength by ∼95% with sustaining the considerable ductility of ∼49.8%, resulting from solid solution strengthening, precipitation strengthening, and grain boundary strengthening. ... It has been reported that the interstitial atoms added include C, N, O, and B atoms. [15][16][17][18][19][20] [21] [22] Gradually, the HEAs with interstitial atoms have become an important branch of the HEA research area. Contrary to the expectation of developing complicated microstructures due to the presence of multiple elements, these alloys form solid-solution phases rather than intermetallic compounds. ... Phase Stability in High-Entropy Alloys: The Role of Configurational Entropy <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ye Zhenhua <here is a image 27e38251b04ca56a-b5788a934ed03dc4> Chuanwei Li <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jianfeng Gu High-entropy alloys (HEAs) have been attracted the attention of many researchers and have exhibited excellent performance due to their structures. Many researchers take the view that the unique structure of HEAs is closely related to configurational entropy (Smix). Hence, it is of great significance to assess the role of configurational entropy on the phase stability for designing HEAs. A model for calculating the Smix of HEAs, including that containing interstitial atoms, has been proposed in this work. The results demonstrate that the true mixing entropy (ST) deviates from the ideal mixing entropy, and is controlled by the mismatch of the atomic size and mixing enthalpy. Hence, the ST of HEAs decreases with decreasing temperature, which reduces the stability of solid solutions. Moreover, introducing very different atoms, such as carbon, would exacerbate this trend. This means that it is still difficult to obtain high solid solubility for such atoms in HEAs even at high temperature, which is consistent with the experimental results. It is demonstrated that the role of entropy was reflected in the driving force of intermetallic compounds and the entropy-related diffusion coefficient. The work is helpful in understanding the effect of configurational entropy on the microstructure and properties of HEAs. ... Metallic materials strengthened by conventional strengthening mechanisms generally suffer from a strength-ductility trade-off [16] . To overcome the trade-off in HEAs, extensive research has focused on activation of various strengthening mechanisms such as second phase strengthening [17][18][19][20] , solid solution hardening [21] [22][23] , microband-induced plasticity (MBIP) [24][25][26] , twinninginduced plasticity (TWIP) [ 27 , 28 ], and the TRIP effect [ 12 , 29 ]. The novel concept of hetero-deformation induced (HDI) strengthening or back stress strengthening mechanism has been proposed [ 30 , 31 ]. ... Hierarchical precipitates, sequential deformation-induced phase transformation, and enhanced back stress strengthening of the micro-alloyed high entropy alloy <here is a image 4cb9f9a5f62496d0-97d4d7e6bde99abc> Jin-Kyung Kim We report the annealing time-dependent microstructures and deformation mechanisms of the novel face-centered cubic Fe49.5Mn30Co10Cr10C0.2Ti0.1V0.1Mo0.1 HEA. Three types of precipitates, σ-phase, Cr-rich MC-type carbides, and nano-scale (Ti, V, Mo)C, are present in the annealed materials at 600°C. Such hierarchical precipitates could lead to sluggish recrystallization and grain growth upon annealing. The partially recrystallized microstructures and hierarchical precipitates could lead to a high yield strength even for prolonged annealing conditions. Deformation mechanisms also change with annealing time. The materials annealed for short times (< 2 h) are deformed by dislocation glide, deformation twinning, and deformation-induced ε phase. A longer annealing time (> 10 h) triggers a multi-variant ε phase, reverse transformation from ε to γ, and the multi-step sequential transformation, γ → ε → reverse transformed γ from ε → ε transformed from the reverse transformed γ. Further, the back stress analysis shows a higher contribution of back stress strengthening in materials annealed for longer times, which could be attributed to the increase in γ/ε and γ/σ interfaces. The activation of various deformation mechanisms and high back stress strengthening could lead to a superior strain hardening capacity and strength-ductility combination (YS: 699 MPa, UTS: 1041 MPa, TE: 45%) of the material annealed for 10 h. The present work provides the novel microstructure design solution of the metastable high entropy alloys with exceptional mechanical properties, utilizing hierarchical precipitates, sequential deformation-induced phase transformation, and enhanced back stress strengthening. ... Furthermore, the displacive phase transformation was found to be suppressed in the C-N co-doped Fe48.5Mn30Co10Cr10C0.5N1.0 (at. %) on tension, which suggested that the high content of interstitial atoms efficiently enhanced the SFE of the metastable HEA [97] . Note that such C and N co-doped HEA subjected to severe deformation would exhibit the martensite transformation again [98], indicating that the phase metastability could be awakened by modifying the strain state. ... The Temperature Dependence of Deformation Behaviors in High-Entropy Alloys: A Review <here is a image 68c43dacfeb6b96f-677b603968d117e4> Dingshun Yan <here is a image 0774f601d4f56c6f-571180ddf8f5c1e5> Zhiming Li Over the past seventeen years, deformation behaviors of various types of high-entropy alloys (HEAs) have been investigated within a wide temperature range, from cryogenic to high temperatures, to demonstrate the excellent performance of HEAs under extreme conditions. It has been suggested that the dominated deformation mechanisms in HEAs would be varied with respect to the environmental temperatures, which significantly alters the mechanical properties. In this article, we systematically review the temperature-dependent mechanical behaviors, as well as the corresponding mechanisms of various types of HEAs, aiming to provide a comprehensive and up-to-date understanding of the recent progress achieved on this subject. More specifically, we summarize the deformation behaviors and microscale mechanisms of single-phase HEAs, metastable HEAs, precipitates-hardened HEAs and multiphase HEAs, at cryogenic, room and elevated temperatures. The possible strategies for strengthening and toughening HEAs at different temperatures are also discussed to provide new insights for further alloy development. ... As this system is already stable, C and N may change the stacking fault energy, affecting slightly the deformation mechanisms, for example the critical resolved shear stress for twinning, twin thickness, among others. For metastable austenites of the system Fe 48.5 Mn 30 Co 10 Cr 10 C 0.5 N 1.0 [22] , the combined addition of C and N reduces the formation of -martensite, increases strength but reduces ductility. ... CrMnFeCoNi high entropy alloys with carbon and nitrogen: mechanical properties, wear and corrosion resistance <here is a image 45c5607c97c3a845-61fde44d9bcc03fc> Lais Mujica Roncery <here is a image 11a45ee025b3aa8d-794ceba7c6721bee> Philipp Niederhofer The use of interstitial elements has been a key factor for the development of different kinds of steels. However, this aspect has been little explored in the field of high entropy alloys (HEAs). In this investigation, the effect of carbon and nitrogen in a near-equiatomic CrMnFeCoNi HEA is studied, analyzing their impact on the microstructure, and mechanical properties from 77K to 673K, as well as wear, and corrosion resistance. Carbon and nitrogen are part of the FCC solid solution and contribute to the formation of precipitates. An increase in the yield and ultimate tensile strength accompanied with a decrease in the ductility are the main effects of C and N. The impact toughness of the interstitial-free material is higher than that of C and C+N alloyed systems. Compared to CrNi and CrMn austenitic steels, the wear resistance of the alloys at room temperature is rather low. The surface corrosion resistance of HEAs is comparable to austenitic steels; nevertheless HEAs are more susceptible to pitting in chloride containing solutions. ... Recently, solid solution strengthening by interstitial introduction has been included in HEA design strategies. The introduction of foreign interstitials, such as C, N, B and/or H, has been found to surprisingly improve the strength significantly without sacrificing the ductility [14][15][16][17][18] [19] [20] . In traditional alloys, foreign interstitials, such as C and N usually induce spatial lattice fluctuations (much higher lattice distortions/local strain distributions than substitutional atoms), affecting the interaction between interstitial species and dislocations [ 21 , 22 ]. ... Enhancement of vacancy diffusion by C and N interstitials in the equiatomic FeMnNiCoCr high entropy alloy <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Eryang Lu <here is a image ee0bcccf739aa66c-4c46c947ebd22f8b> Junlei Zhao <here is a image 19f0eabd8c56baa9-96f754d9598c1d41> Ilja Makkonen <here is a image afa64548efe7d29c-b21f1a09c1664bf5> Filip Tuomisto We present evidence of homogenization of atomic diffusion properties caused by C and N interstitials in an equiatomic single-phase high entropy alloy (FeMnNiCoCr). This phenomenon is manifested by an unexpected interstitial-induced reduction and narrowing of the directly experimentally determined migration barrier distribution of mono-vacancy defects introduced by particle irradiation. Our observation by positron annihilation spectroscopy is explained by state-of-the-art theoretical calculations that predict preferential localization of C/N interstitials in regions rich in Mn and Cr, leading to a narrowing and reduction of the mono-vacancy size distribution in the random alloy. This phenomenon is likely to have a significant impact on the mechanical behavior under irradiation, as the local variations in elemental motion have a profound effect on the solute strengthening in high entropy alloys. ... On the other hand, interstitial N would introduce solid solution strengthening, leading an enhanced yield strength. Indeed, this expected N impact is found in experiments for the Cr 0:1 Mn 0:3 Fe 0:5 Co 0:1 alloy containing interstitial C and N. [77] 3.2 Impact of Local Environment Around N We next analyze the dependence of DE sol on the local environment around the interstitial N atom in more detail. For the first qualitative measure, we focus on ''M-rich environments'' (M = Cr, Mn, Fe, Co, Ni) where the element M occupies half or more of the 1NN atomic sites around an N atom. ... Impact of N on the Stacking Fault Energy and Phase Stability of FCC CrMnFeCoNi: An Ab Initio Study Interstitial alloying has become an important pillar in tuning and improving the materials properties of high-entropy alloys, e.g., enabling interstitial solid-solution hardening and for tuning the stacking fault energies. In this work we performed ab initio calculations to evaluate the impact of interstitial alloying with nitrogen on the fcc–hcp phase stability for the prototypical CrMnFeCoNi alloy. The N solution energies are broadly distributed and reveal a clear correlation with the local environments. We show that N addition stabilizes the fcc phase of CrMnFeCoNi and increases the stacking fault energy. ... This behavior was mainly attributed to the development of deformation-induced twining causing twinninginduced plasticity (TWIP) in a face-centered cubic (fcc) solid solution. To reduce the cost of the alloy, some modifications to the equiatomic proportion aiming to decrease the percentage of expensive elements were suggested; besides this, an addition of interstitial elements can increase the strength of the material [6][7][8][9] [10] [11][12]. Some of the obtained alloys demonstrate rather high strength due to the activation of several strengthening mechanisms (e.g., solid-solution-strengthening or precipitation hardening); besides this, some of those mechanisms (specifically, so-called dynamic Hall-Peth strengthening due to TWIP and/or TRIP transformation-induced plasticity (TRIP) effects) provide a considerable improvement in ductility [13]. ... Friction Stir Welding of a TRIP Fe49Mn30Cr10Co10C1 High Entropy Alloy <here is a image 9e4bc1b5051c44bb-134a6b1a059a0d5f> N. D. Stepanov <here is a image 05789443416fba81-b121391cbdc060cc> Sergey Zherebtsov The effect of friction stir welding parameters on the structure and properties of Fe49Mn30Cr10Co10C1 high-entropy alloy welds was studied. Due to the development of the TRIP effect, the mechanical behaviour of this alloy was associated with the γ fcc - to - ε hcp martensitic transformation. In the initial condition, the microstructure of the program alloy comprised equiaxed fcc grains and small fractions of the hcp ε-martensite (~5%) and М23С6 carbides (~4%). Friction stir welding of the program alloy resulted in recrystallization of the stir zone and a decrease in the fraction of the carbides to 1–2%; however, the percentage of the hcp phase remained at nearly the same level as that in the initial condition. Post-welding tests showed a considerable increase in the strength and microhardness of the welds both due to the recrystallization-induced decrease in grain size and martensitic transformation. ... AlCoCuFeNi is selected as the subject of this research as it is frequently-used in the experiment, which can be used to compare with our simulation results. HEAs are generally prepared in the vacuum environment, although there may be few contaminant elements, e.g., O, C, H, N left after the vacuum processing or in the metal materials, the amount of contaminant elements is too small, and few effects of residual contaminant elements were found in the experiments now, so the influence of residual contaminant elements do not be considered during solidification process [28] [29] [30]. ... Impact of local chemical order on the structure evolution of dual-phase high-entropy alloy during solidification process Local chemical order (LCO) may have an important influence on the formation of phase structure in the dual-phase high-entropy alloys (HEAs), so this paper studies the solidification process of AlCoCuFeNi with molecular dynamics simulation. In the melt, there are three obvious chemical orders: Co-Ni, Cu-Fe and Al-Fe. Co, Ni, Cu tend to form FCC phase, Al and Fe tend to form BCC phase. The region with rich Co and Ni is easier to nucleate, so at the initial stage of crystallization, FCC phase is more stable than BCC phase. As the internal energy of Cu is much higher than other elements, which leads to higher Gibbs free energy of FCC phase, during the subsequent crystallization process, BCC phase tends to be more stable. At the end of solidification, the system is composed of BCC phase and FCC phase, BCC phase has more Al, FCC phase has more Cu, and the results are consistent with the experimental results. ... However, while the carbon produced a large increase in strength, it is not possible to assess the interstitial strengthening since the undoped alloy was 28% hexagonal-close-packed. Later, Zhang et al. [46] replaced an additional 1 at.% iron in this HEA with nitrogen to produce the f.c.c. ... Interstitials in f.c.c. High Entropy Alloys	https://www.researchgate.net/publication/339960304_Carbon_and_nitrogen_co-doping_enhances_phase_stability_and_mechanical_properties_of_a_metastable_high-entropy_alloy
Overexpression of Cyclin D1 and Underexpression of p27 Predict Lymph Node Metastases in Papillary Thyroid Carcinoma Download Citation \| On Apr 1, 2002, M. L. C. Khoo published Overexpression of Cyclin D1 and Underexpression of p27 Predict Lymph Node Metastases in Papillary Thyroid Carcinoma \| Find, read and cite all the research you need on ResearchGate Article Overexpression of Cyclin D1 and Underexpression of p27 Predict Lymph Node Metastases in Papillary Thyroid Carcinoma April 2002 The Journal of Clinical Endocrinology and Metabolism87(4):1814-1818 DOI: 10.1210/jc.87.4.1814 Authors: <here is a image f2f62089ad6ff61c-d19572ff1996375a> M. L. C. Khoo M. L. C. Khoo ... Furthermore, some of those reports have found higher expression in anaplastic and poorly differentiated tumors [5,6], whereas others failed to demonstrate this correlation [4,11]. On the other hand, some authors have shown that p27 kip1 protein expression, another CIP/ KIP family member, is decreased in papillary thyroid carcinoma (PTC) in comparison with follicular carcinoma and benign thyroid lesions [11,[13][14][15][16][17] [18] [19][20][21]. Moreover, p27 kip1 underexpression could predict lymph node metastasis [18][19][20] and more aggressive tumors [16] in PTC. ... ... On the other hand, some authors have shown that p27 kip1 protein expression, another CIP/ KIP family member, is decreased in papillary thyroid carcinoma (PTC) in comparison with follicular carcinoma and benign thyroid lesions [11,[13][14][15][16][17][18][19][20][21]. Moreover, p27 kip1 underexpression could predict lymph node metastasis [18] [19][20] and more aggressive tumors [16] in PTC. ... ... In our series, 30% of the samples were positive, and we did not find any relationship with the clinical or histological parameters. p27 kip1 , another CIP/KIP member, has also been analyzed in papillary cancer [7,11,[13][14][15][16][17] [18] [19][20][21]. Most authors have found a significant reduction in p27 kip1 staining compared to normal thyroid tissue [13,21], benign thyroid tumors [14,15,17,21], and follicular thyroid carcinoma [7]. ... Expression of p21cip1, p27kip1, and p16INk4a Cyclin-Dependent Kinase Inhibitors in Papillary Thyroid Carcinoma: Correlation with Clinicopathological Factors Article Full-text available Sep 2008 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Carles Zafon <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Gabriel Obiols <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Josep Castellvi <here is a image 092bff6d06fc3ea1-4ec10e723a9bd0e6> Jordi Mesa In a variety of human malignancies, aberrant expression of proteins involved in the control of cell-cycle progression has been reported. In this study, p21cip1, p27kip1, and p16INk4a cyclin-dependent kinase inhibitors were analyzed to evaluate their usefulness in clinical management of papillary thyroid carcinoma (PTC). Archived material derived from 46 cases of PTC was analyzed immunohistochemically. Protein expression was ascertained on tissue microarrays, and results were correlated with clinicopathological features of the patients. Positive immunostaining was observed in 14 (30,4%) p21cip1, 26 (56,5%) p27kip1, and 14 (30,4%) p16INk4a cases. No significant correlation between p21cip1 or p27kip1 and clinical factors was found. In contrast, p16INk4a expression showed a significant correlation with initial extension of the disease. Therefore, 45.8% of patients with loco-regional extension were p16INk4a positive, whereas overexpression was only seen in 15.7% of cases with intrathyroid disease (p < 0.05). Moreover, all patients with simultaneous p16INk4a positivity and lack of p27kip1 staining (four patients) presented lymph node metastases. In contrast, only 12 (28.5%) of the remaining patients showed lymph node tumor involvement. In conclusion, p16INk4a expression suggests extrathyroid neck extension of PTC. This effect is enhanced when p27kip1 is negative. We think that their analysis by immunohistochemistry could be useful in the management of patients with PTC. ... Strong cyclin D1 expression was found in both the thyroid and lymph nodes of all 3 of our cases. Work from our laboratory and others has linked cyclin D1 overexpression in PTC to aggressive behavior and lymph node metastases [3] [4] [5] [6] [7] [8] [9]. Some studies have actually proposed cyclin D1 as a marker to predict the occurrence of lymph node metastases in patients with PTC, including those with mPTC [4] [5] [6] [7]. ... ... Work from our laboratory and others has linked cyclin D1 overexpression in PTC to aggressive behavior and lymph node metastases [3] [4] [5] [6] [7] [8] [9]. Some studies have actually proposed cyclin D1 as a marker to predict the occurrence of lymph node metastases in patients with PTC, including those with mPTC [4] [5] [6] [7]. We found particularly impressive (and quoted it in our manuscript, ref. 35) the work by Khoo et al [4], who identified cyclin D1 overexpression in 20 of the 22 mPTCs in patients who—like ours—presented clinically with regional lymph node metastases. ... Papillary thyroid microcarcinoma associated with metastasis and fatal outcome: Is the microcarcinoma an incidental finding? - Reply Article Sep 2013 Simonetta Piana <here is a image e69dcb9b3574aeda-2a25e4cf146e2212> Moira Ragazzi <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Giovanni Tallini Juan Rosai ... Several studies have investigated the role of the BRAF V600E mutation in PTC [24][25][26] [27] [28][29][30] , and several of them, 17,18 though not all, 16,20 have reported a significant association of this mutation with metastasis and local invasion. These differences may be explained by the low number of cases composing the cohort 16,20 and the different histotype composition of the PTC, 20 which may obscure the association between some poor clinicopathological outcomes and BRAF V600E mutation; several studies, however, have reported BRAF V600E mutation at a higher rate in PTC with invasive and metastatic potential than in noninvasive tumors, although without statistical significance. ... ... These findings are in line with previous studies on p27 Kip1 protein expression in thyroid papillary microcarcinomas. 26, 27 Previous studies have not, however, included an examination of p27 Kip1 expression in LN metastases and paired PTCs. It should be noted that we ourselves have evaluated the potential role of p27 Kip1 in the process of LN metastasis. ... BRAFV600E mutation and p27kip1 expression in papillary carcinomas of the thyroid ≤1 cm and their paired lymph node metastases Article Aug 2007 CANCER-AM CANCER SOC <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Vito Rodolico <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Daniela Cabibi <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Giuseppe Pizzolanti <here is a image d0448e28c9030141-5e5a0591e85a762c> Carla Giordano BACKGROUND.BRAFV600E mutation and p27kip1 expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas.METHODS.Tissue samples from 214 consecutive patients who underwent total or near-total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) ≤1 cm were analyzed for BRAFV600E mutation by a real-time, allele-specific amplification and for p27kip1 expression by immunohistochemistry.RESULTS.The BRAFV600E mutation was detected in 88 of the tumors examined, with significant differences between groups with and without lymph node (LN) metastases; the mean age of patients with BRAFV600E mutation was significantly higher than that of patients without mutations. A significant association was found between low p27Kip1 protein expression and multifocality, bilaterality, and extrathyroidal extension, in addition to LN metastasis. In 42 cases with LN metastases, 23 harbored the BRAFV600E mutation in the metastatic tumor and presented a wider diameter of the largest metastatic area, a higher number of involved LNs, and a higher percentage of metastatic lesions with extracapsular extension of LN (ECE-LN). A significantly lower mean value of p27Kip1 was observed in LNs harboring the BRAFV600E mutation and in ECE-LN; an inverse correlation was found between p27Kip1 and the number of metastatic LNs, as well as the diameter of the largest metastatic area in LN.CONCLUSIONS.The authors' data suggested that BRAFV600E mutation and p27Kip1 down-regulation in cancer cells of PTC ≤1 cm may be factors that facilitate tumor-cell growth and progression once these are seeded in the LNs. Cancer 2007. © 2007 American Cancer Society. ... Negative control was employed by substituting primary antibody. Cyclin D1 scored as: negative, 1+ (weak) = less than 10%, 2+ (moderate) = 11 to 50% and 3+ (strong) = more than 50% nuclear tumor cells stained positive, [8] while the scoring of DJ-1 was based on intensity. Four areas per tissue were evaluated using the following scale: 0, no staining; 1, faint staining; 2, moderate intensity staining; and 3, and intensity staining. ... Impact of cyclin D1 and DJ-1 on diagnosis, clinico-pathological features and outcome in prostate cancer and benign prostatic hyperplasia Article Full-text available Apr 2020 <here is a image 44939ccd98d8fd8d-6c2ccb49b78bfcbf> Amrallah A Mohammed Hanna M. Ibrahim <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hanaa Atwa <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Amira Elwan Background Disturbance in cell cycle regulatory genes is a common finding among many types of cancers. The aim of this study is to evaluate the role of cyclin D1 and DJ-1 in benign prostatic hyperplasia (BPH) and prostate cancer (PC). Method The current study enclosed 40 patients diagnosed with PC and 40 cases of BPH. The expression level of cyclin D1 and DJ-1 were evaluated by immunohistochemistry (IHC). Cyclin D1 scored depending on the percentage of stained nuclear tumor cells. While scoring of DJ-1 was based on intensity. The results were correlated with clinicopathological features and outcome. Results In the PC group, cyclin D1 was detected in 95% and overexpressed in 42.5%, DJ-1 was positively stained in 85% and overexpressed in 47.5%. Meanwhile, in the BPH group, cyclin D1 was not detected and DJ-1 stained in only 2.5%. There was a statistically significant difference in Gleason score (GS), tumor stage, size, and treatment failure (p =< 0.001). In the terms of PC diagnosis prediction, although cyclin D1 was more specific (100%), DJ-1 is more sensitive than cyclin D1 (80%, 70%, respectively) (p = 0.000). Conclusions Cyclin D1 and DJ-1 may emerge as a promising way for diagnosis of PC in certain circumstances, as the presence of insufficient tissue sampling, small foci of carcinoma or benign lesions mimic PC. This is in addition to the known role of cyclin D1 and DJ-1 in PC prognosis. ... Cyclin D1 serves a vital role in promoting cancer cell proliferation (27), and has been considered as a pivotal element of malignant transformation in human cancer (28). A previous study also found that cyclin D1 was downregulated by silenced PVT1 in thyroid cancer (29) . Taken together, these results indicated that downregulated cyclin D1 may be associated with the suppression of melanoma cell proliferation via the arrest of the cell cycle at the G0/G1 stage. ... Effect of long non-coding RNA PVT1 on cell proliferation and migration in melanoma Article Full-text available Dec 2017 Lamei Chen Dongmei Ma Yuanyuan Li Yali Song The present study aimed to investigate the potential role of the long non‑coding RNA (lncRNA) Pvt1 oncogene (non‑protein coding) (PVT1) in the progression and metastasis of malignant melanoma, and to reveal its possible molecular mechanisms. The expression of lncRNA PVT1 in melanoma tissues and adjacent normal skin from patients with melanoma, and in the melanoma A‑375 and sk‑mel‑5 cell lines, was analyzed using reverse transcription‑quantitative polymerase chain reaction and western blot analyses. The effects of PVT1 expression on cell proliferation, the cell cycle, cell migration and cell invasion were analyzed using MTT assay, flow cytometry, Transwell and scratch assays, respectively. The interaction between PVT1 and enhancer of zeste homolog 2 (EZH2) in melanoma cells was analyzed using RNA immunoprecipitation (RIP) assay. The effect of PVT1 on microRNA‑200c (miR‑200c) expression was analyzed by chromatin immunoprecipitation (ChIP) assay. PVT1 was highly expressed in the melanoma tissues and cells. Silencing of PVT1 significantly inhibited cell proliferation, migration and invasion, and arrested the cell cycle at the G0/G1 stage. Additionally, PVT1 silencing significantly decreased the cyclin D1 expression in the melanoma cells. The expression of E‑cadherin was significantly increased and the expression of N‑cadherin and vimentin was significantly decreased in the PVT1‑silenced group. The RIP assay found that endogenous PVT1 was highly enriched by EZH2 RIP compared with that of the negative control. The ChIP assay revealed that the expression of miR‑200c was decreased significantly in the PVT1‑silenced group compared with the controls. Overall, the present study demonstrated that the lncRNA PVT1 may contribute to the tumorigenesis and metastasis of melanoma through binding to EZH2 and regulating the expression of miR‑200c. lncRNA PVT1 may serve as a potential target for the therapy of melanoma. ... In PTC, a possible mechanism associating low levels of miR-9 and metastasis could include cyclin D1 and p27 regulation. Overexpression of cyclin D1 and underexpression of p27 have been shown to predict lymph node metastases in PTC [85] . Cyclin D1 is reportedly a miR-9 target [42], while p27 has been shown to interact with Stathmin (STMN1), also a miR-9 target [86], in such a way that higher levels of STMN1 lead to decreased expression of p27 [87]. ... MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer Article May 2015 CLIN EXP METASTAS Adriana Sondermann <here is a image 88239d196b935d32-1951dcf639403ebe> Flavia M Andreghetto Ana Carolina Bernardini Moulatlet <here is a image 9b7b7bc019ccf2e5-e43ed0a4263f2239> Patricia Severino Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma recurrence. Using macro-dissection followed by quantitative real-time PCR, we measured miR-9, miR-10b, miR-21 and miR-146b expression levels in formalin-fixed, paraffin-embedded samples of 66 patients with papillary thyroid carcinoma categorized into two groups: the recurrent group (n = 19) and the non-recurrent group (n = 47). All patients underwent total thyroidectomy and were followed for at least 120 months after surgery to be considered recurrence-free. Univariate and multivariate analysis were performed using the Cox proportional hazard model in order to identify associations between multiple clinical variables and microRNA expression levels and papillary thyroid carcinoma recurrence. MiR-9 and miR-21 expression levels were found to be significant prognostic factors for recurrence in patients with papillary thyroid carcinoma (HR = 1.48; 95 % CI 1.24-1.77, p < 0.001; and HR = 1.52; 95 % CI 1.18-1.94, p = 0.001; respectively). Multivariate analysis involving the expression level of miR-9 and miR-21 and various clinical parameters identified the expression of these microRNAs as independent prognostic factors for papillary thyroid cancer patients. In conclusion, our results support the potential clinical value of miR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid carcinoma. ... A vizsgálatban azt az eredményt kapták, hogy a daganatok 63,2% expresszálta a cyclin D1-t, az egyes alcsoportok közül szignifikánsan nagyobb arányban azok, amelyeknél nyirokcsomó metastasis is jelentkezett; ugyanakkor a p27 gén expressziójának szignifikánsan alacsonyabb szintje volt észlelhető a metastatizáló pajzsmirigy carcinomákban. A szerzők a vizsgálatok eredményéből azt a következtetést vonták le, hogy a p27 gén expressziójának csökkenése, valamint a cyclin D1overexpressziója együttesen a papillaris carcinoma nyirokcsomóáttét-képzésének független prediktív faktora (73) . ... A PAJZSMIRIGY MICROCARCINOMA EPIDEMIOLÓGIÁJA ÉS BIOLÓGIAI TULAJDONSÁGAI PhD értekezés Article Gábor Kovács László ... Transcriptional activation of the cyclin D1 gene is a key step in cell proliferation: cyclin D1 is normally expressed during G1 and regulates the transition from G1 to S phase (30). Deregulated expression of cyclin D1 is frequently an early step in neoplastic transformation in various human cancers including thyroid tumors (30,(41)(42)(43)(44). Interestingly, several studies have also reported correlations between cyclin D1 overexpression and poor clinical prognostic characteristics, including advanced tumor stage, tumor recurrence, and metastatic spread in papillary thyroid (45, 46). Although the copy number of cyclin D1 gene is amplified in a number of human neoplasms, neither major genetic alterations nor amplification of this gene has been found in thyroid cancers, but mainly a strong nuclear cyclin D1 localization (47,48). ... Effects of the Smad4 C324Y mutation on thyroid cell proliferation Article Full-text available Apr 2013 INT J ONCOL <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sonia D'Inzeo <here is a image 73679b950e1cfd5f-abcfe38c508a9e58> Arianna Nicolussi <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Francesco Nardi <here is a image 48d6bd0e603d1d72-ede18e40a8e9d1ab> Anna Coppa Smad4 is a key mediator of the transforming growth factor-β (TGF-β) superfamily that is involved in the control of cell proliferation and differentiation. We recently demonstrated that a Smad4 mutation, Smad4 C324Y, isolated from nodal metastases of papillary thyroid carcinoma, causes an increase of TGF-β signaling, responsible for the acquisition of transformed phenotype and invasive behaviour in thyroid cells stably expressing this mutation. In this paper, we demonstrate that the stable expression of Smad4 C324Y mutation in FRTL-5 cells is responsible for TSH-independent growth ability. Our data show that the Smad4 C324Y mutation interacts with P-Smad3 more strongly than Smad4 wt, already in basal condition; this interaction is responsible for TGF-β signaling and PKA activation that, in turn, determines an increased phosphorylation of CREB, necessary for the mitogenic actions of TSH. The expression of cyclin D1 also increases in all cells overexpressing the Smad4 C324Y mutation. All together, these data demonstrate that Smad4 C324Y mutation, interacting with the PKA pathway, gives cells the ability to proliferate independently from TSH. ... The value of novel molecular markers in determining the prognosis of differentiated thyroid cancer remains to be established. Alterations in cell cycle control elements including cyclin D1 over-and underexpression of the cyclin-dependent kinase inhibitor p27 predict metastatic thyroid cancer growth (Khoo et al., 2002; Kondo et al., 2006). ... Endocrine Organs Chapter Full-text available Oct 2007 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Shereen Ezzat <here is a image d8371981a279abf6-6ec84582f057800b> Sylvia L Asa Endocrine organ dysfunction can explain sudden and unexpected death, although this is rarely the case in forensic practice (Püschel 2004). ... p27 is a CDK-inhibitor protein that controls cell proliferation in the G1-S phase by binding to and regulating the activity of cyclin-dependent kinases (CDKs) [36]. Several studies have shown that low p27 expression is associated with a variety of human neoplasms, including those originating in the cervical, gastric, and oral regions [15, 29, 30,35]. The evaluation of p27 expression has been considered clinically relevant to HNSCC. ... Possible implication of Mdm2 as a prognostic marker in invasive laryngeal carcinoma Full-text available Feb 2012 Eur Arch Oto Rhino Laryngol Marcela Kazue Hassumi-Fukasawa <here is a image fdbacf93b91dc7f1-52570ce0471daa0f> Miranda F. A. Márcia C M Guimarães Edson Garcia Soares Laryngeal squamous cell carcinoma is one of the most common malignant neoplasms of the head and neck. In Brazil, laryngeal tumors represent 2% of all cancers and are associated with approximately 3,000 deaths annually. Human papillomavirus (HPV) has been reported to play an important role in the etiology of laryngeal cancer. The aim of the present study was to evaluate the expression of p53, p27, and Mdm2 in laryngeal carcinomas. Sixty-three larynx biopsies were selected for the study, including 9 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastasis and 27 laryngeal carcinomas with metastasis. Twenty-seven cervical lymph nodes from patients with metastatic lesions were also evaluated. The expression levels of p53, p27, and Mdm2 were assessed by immunohistochemistry using a computer-assisted system. HPV detection and typing were performed using PCR, and the HPV types that were evaluated included HPV 6, 11, 16, 18, 31 and 33. Out of 63 patients, 53 (84.1%) were positive for β-globin (internal control), and 10 (15.9%) were β-globin negative and therefore excluded from the evaluation. Thus, 7 (13.2%) out of 53 patients were HPV positive, and 46 (86.8%) out of 53 patients were HPV negative. Statistically significant differences (p < 0.05) in Mdm2 expression levels were observed in the in situ laryngeal carcinoma samples compared with the laryngeal carcinoma samples with metastasis. No statistically significant differences (p > 0.05) in either p53 or p27 expression levels were detected. These findings suggest that Mdm2 may be associated with the invasiveness and aggressiveness of laryngeal carcinomas. ANÁLISE IMUNOISTOQUÍMICA DO BIOMARCADOR CICLINA D1 NOS CARCINOMAS PAPILÍFEROS DE TIREOIDE E BÓCIOS MULTINODULARES Preprint Full-text available May 2022 Ivan José Paredes Bartolomei Carmen Australia Paredes Marcondes Ribas Maria Augusta Karas Zella Paulo Afonso Nunes Nassif Racional - Os carcinomas papilíferos são os mais prevalentes e menos agressivos de tireoide (CPT). Em alguns casos, o diagnóstico é duvidoso e o prognóstico ruim. A busca de biomarcadores teciduais que permitam assegurar tanto o diagnóstico para casos indeterminados, quanto o prognóstico, identificando os casos de maior agressividade, têm sido estudadas nas últimas décadas. Objetivo: Analisar a ciclina D1 nos CPT e nos bócios multinodulares (BMN) e verificar a correlação da marcação com as características clinicopatológicas. Métodos: Foram selecionados 118 tecidos de pacientes adultos submetidos àa tireoidectomia por CPT e 40 BMN como grupo controle. Realizou-se imunocoloração tecidual com ciclina D1 com subsequente análise imunoistoquímica em ambos grupos, avaliando-se a expressão do marcador (intensidade e distribuição). No grupo dos CPT os dados da imunocoloração foram também cruzados com os dados clinicopatológicos. Resultados: A maioria (93,3%) expressou a coloração da ciclina D1 com intensidades variadas (fraca, moderada e forte) e distribuição predominantemente difusa (71,2%). O grupo controle dos BMN, expressou coloração para ciclina D1 em 57,5%, com intensidade fraca (47,5%) e distribuição esparsa (37,5%). A diferença entre os grupos (estudo e controle) foi estatisticamente significante (p<0,001). No grupo dos CPT, os cruzamentos clinicopatológicos não evidenciaram diferenças quanto à idade, sexo, tipo e tamanho tumoral, estado linfonodal, focalidade e invasão angiolinfática. Conclusão: A ciclina D1 foi expressa na grande maioria dos CPT sendo a distribuição difusa predominante. Não houve correlação entre a expressão delacom qualquer característica clinicopatológica dos CPT. MicroRNA profiling predicts positive nodal status in papillary thyroid carcinoma in the preoperative setting Background: The molecular characterization of thyroid nodules in cytological samples has so far been focused on discriminating between benign and malignant forms in a purely diagnostic setting. The evidence on the impact of molecular biomarkers to determine the risk of aggressiveness in cytologically "neoplastic" lesions is limited to genomic alterations (such as BRAF and TERT mutations). The aim of our study was to assess the preoperative role of microRNAs (miRNAs) in predicting the nodal status of patients with papillary thyroid cancer. Methods: A pilot series of histological samples of papillary thyroid carcinoma with (6 cases) or without (6 cases) lymph node metastases, matched for other major clinical and pathological features, was analyzed for global miRNA expression in a screening phase. A set of miRNAs was then validated in a series of 63 consecutive cytological samples of papillary carcinomas: 48 pN-negative and 15 pN-positive at histology. Results: Unsupervised cluster analysis segregated surgical pN-negative and pN-positive samples, except for 1 case. The 45 differentially expressed miRNAs in pN-positive versus pN-negative cases were predicted to regulate a wide range of cellular pathways, enriched for Wnt, gonadotropin-releasing hormone receptor, and cerulein/cholecystokinin receptor signaling. In agreement with their profiles in surgical samples, 4 miRNAs of the 10 selected for validation (miR-154-3p, miR-299-5p, miR-376a-3p, and miR-302E) had a significant differential expression in cytological samples of papillary carcinoma with lymph node metastases and predicted the positive nodal status with a relatively good performance. Conclusions: MiRNA profiling is a potential promising strategy to define papillary carcinoma aggressiveness in the preoperative setting. Expression of Cyclin D1, Cytokeratin 7, Cytokeratin 20 and Vimentin in Papillary Thyroid Cancer and Relationship with Patient's Prognostic Factors Association of BRAF V600E Mutation with Poor Clinical Prognostic Factors and Ultrasonographic Findings in Cases of Papillary Thyroid Carcinoma Purpose: This study evaluated the association of the BRAFV600E mutation with known prognostic factors and ultra-sonographic characteristics in cases of papillary thyroid carcinoma. Methods: Subjects included 169 patients who received thyroi-dectomy at Wonju Christian Hospital under the diagnosis of papillary thyroid cancer from February 2010 to October 2011.Results: Of the total patients who received thyroidectomy, there were 128 cases (75,7%) of BRAFV600E mutation. Neither age nor sex were associated with the BRAFV600Emutation. Tumor size, shape, margin, extrathyroidal ex-tension, central node metastasis and lateral node meta-stasis were found not to be associated with the BRAFV600Emutation. Tumor calcification, echogenicity and vascularity were also not associated with the mutation.Conclusion: As debate remains about the association be-tween the BRAFV600E mutation and clincopathologic factors and ultrasonographic characteristics in cases of papillary thyroid carcinoma, further study is needed The Relationship between the p27 Expression of Papillary Thyroid Cancer Cells Obtained by FNA and Cervical Lymph Node Metastasis The evolution of differentiated thyroid cancer Differentiated thyroid tumours of follicular cell derivation have traditionally been classified based on architecture, cytology, or both. The features that distinguish the various entities are controversial and diagnostic criteria are inconsistent and often irreproducible. The complexity of classification schemes has not been substantiated by molecular profiling. In this review, a simplistic approach to the diagnosis of well differentiated thyroid neoplasia is provided to challenge the dogma. The proposed classification matches the molecular profiles of these lesions and simplifies the criteria for diagnosis. This approach can be used to support rational treatment algorithms. RASSF1A promoter methylation is associated with increased risk of thyroid cancer: A meta-analysis Objective Previous studies have reported that Ras-associated domain family 1A (RASSF1A), the most commonly silenced tumor suppressor via promoter methylation, played vital roles in the development of carcinogenesis. The purpose of this meta-analysis was to determine whether RASSF1A promoter methylation increased the risk of thyroid cancer. Methods PubMed, Embase, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure databases were searched to obtain eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations, using Stata 12.0 software. The methodological quality of included studies was evaluated using Newcastle–Ottawa scale table. Egger’s test and Begg’s test were applied to detect publication biases. TSA 0.9 software was used to calculate the required information size and whether the result was conclusive. Results A total of 10 articles with 12 studies that included 422 thyroid cancer patients, identifying the association of RASSF1A promoter methylation with thyroid cancer risk, were collected in this meta-analysis. Overall, RASSF1A promoter methylation significantly increased the risk of thyroid cancer (total, OR=8.27, CI=4.38–15.62, P<0.05; Caucasian, OR=9.25, CI=3.97–21.56, P<0.05; Asian, OR=7.01, CI=2.68–18.38, P<0.05). In the subgroup analysis based on sample type, a significant association between thyroid cancer group and control group was found (normal tissue, OR=9.55, CI=4.21–21.67, P<0.05; adjacent tissue, OR=6.80, CI=2.49–18.56, P<0.05). The frequency of RASSF1A promoter methylation in follicular thyroid carcinoma was higher than in control group (OR=11.88, CI=5.80–24.32, P<0.05). In addition, the results indicated that the RASSF1A promoter methylation was correlated with papillary thyroid carcinoma in Caucasians and Asians (total, OR=8.07, CI=3.54–18.41, P<0.05; Caucasian, OR=11.35, CI=2.39–53.98, P<0.05; Asian, OR=6.67, CI=2.53–17.64, P<0.05). On the basis of the trial sequential analysis, the significant association of RASSF1A promoter methylation with thyroid cancer risk was found, and there was no need to perform further studies. Conclusion This meta-analysis confirms that RASSF1A promoter methylation is a risk factor for thyroid tumor. Do Helper T Cell Subtypes in Lymphocytic Thyroiditis Play a Role in the Antitumor Effect? Background: Papillary thyroid carcinoma (PTC) is frequently accompanied by lymphocytic thyroiditis (LT). Some reports claim that Hashimoto's thyroiditis (the clinical form of LT) enhances the likelihood of PTC; however, others suggest that LT has antitumor activity. This study was aimed to find out the relationship between the patterns of helper T cell (Th) cytokines in thyroid tissue of PTC with or without LT and the clinicopathological manifestation of PTC. Methods: Fresh surgical samples of PTC with (13 cases) or without (10 cases) LT were used. The prognostic parameters (tumor size, extra-thyroidal extension of PTC, and lymph node metastasis) were analyzed. The mRNA levels of two subtypes of Th cytokines, Th1 (tumor necrosis factor α [TNF-α], interferon γ [IFN-γ ], and interleukin [IL] 2) and Th2 (IL-4 and IL-10), were analyzed. Because most PTC cases were microcarcinomas and recent cases without clinical follow-up, negative or faint p27 immunoreactivity was used as a surrogate marker for lymph node metastasis. Results: PTC with LT cases showed significantly higher expression of TNF-α (p = .043), IFN-γ (p < .010), IL-4 (p = .015) than those without LT cases. Although the data were not statistically significant, all analyzed cytokines (except for IL-4) were highly expressed in the cases with higher expression of p27 surrogate marker. Conclusions: These results indicate that mixed Th1 (TNF-α, IFN-γ , and IL-2) and Th2 (IL-10) immunity might play a role in the antitumor effect in terms of lymph node metastasis. Oncogenesis and Molecular Targeted Therapy in Thyroid Cancer Identification of Differentially Expressed Kinase and Screening Potential Anticancer Drugs in Papillary Thyroid Carcinoma Aim . We aim to identify protein kinases involved in the pathophysiology of papillary thyroid carcinoma (PTC) in order to provide potential therapeutic targets for kinase inhibitors and unfold possible molecular mechanisms. Materials and Methods . The gene expression profile of GSE27155 was analyzed to identify differentially expressed genes and mapped onto human protein kinases database. Correlation of kinases with PTC was addressed by systematic literature search, GO and KEGG pathway analysis. Results . The functional enrichment analysis indicated that “mitogen-activated protein kinases pathway” expression was extremely enriched, followed by “neurotrophin signaling pathway,” “focal adhesion,” and “GnRH signaling pathway.” MAPK, SRC, PDGFRa, ErbB, and EGFR were significantly regulated to correct these pathways. Kinases investigated by the literature on carcinoma were considered to be potential novel molecular therapeutic target in PTC and application of corresponding kinase inhibitors could be possible therapeutic tool. Conclusion . SRC, MAPK, and EGFR were the most important differentially expressed kinases in PTC. Combined inhibitors may have high efficacy in PTC treatment by targeting these kinases. Long noncoding RNA PVT1 modulates thyroid cancer cell proliferation by recruiting EZH2 and regulating thyroid-stimulating hormone receptor (TSHR) The purposes of this study were to investigate the potential roles of long noncoding RNA (lncRNA) PVT1 in thyroid cancer cell proliferation and to explore their possible mechanisms. A total of 84 patients who were diagnosed as having thyroid cancer (papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and anaplastic thyroid carcinoma (ATC)) in Renji Hospital were enrolled in this study. Expressions of lncRNA PVT1 in thyroid cancer tissues and cell lines (IHH-4, FTC-133, and 8505C) were analyzed using RT-polymerase chain reaction (PCR) and western blotting analysis. The effects of lncRNA PVT1 expression on thyroid cancer cell proliferation and cell cycle were analyzed using flow cytometry. Furthermore, the effects of lncRNA expression on thyroid-stimulating hormone receptor (TSHR) expression and polycomb enhancer of zeste homolog 2 (EZH2) were also analyzed using RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay, respectively. Compared to the controls, lncRNA PVT1 was significantly up-regulated in thyroid tissues, as well as in three kinds of tumor cell lines (P < 0.05). Silenced PVT1 significantly inhibited thyroid cell line IHH-4, FTC-133, and 8505C cell proliferation and arrested cell cycle at G0/G1 stage and significantly decreased cyclin D1 and TSHR expressions (P < 0.05). Moreover, lncRNA PVT1 could be enriched by EZH2, and silencing PVT1 resulted in the decreased recruitment of EZH2. This study suggested that lncRNA PVT1 may contribute to tumorigenesis of thyroid cancer through recruiting EZH2 and regulating TSHR expression. <here is a image 16e0e722933f6a34-bac3cedf7b6b28b5> Peyker Temiz <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Gizem Akkas Nalan Neşe Yamaç ERHAN Background/aim: To identify the role of gene products associated with apoptosis and cell cycle in the pathogenesis of thyroid follicular neoplasm. Materials and methods: Thirty follicular adenomas (FAs), 16 follicular carcinomas (FCs), and 20 adenomatous nodules (ANs) were investigated with immunohistochemical staining of p16, p21, p27, p53, Bcl-2, Bax, Bcl-xL, and cyclin D1 via a tissue microarray method. Results: Bcl-2 showed a significant difference between the benign groups (AN and FA) and the malignant group (FC). Bax was significantly higher in the FC group. p53 was lowest in the AN group and highest in the FC group with significant differences between the groups. p16 was significantly higher in the FC group than in the other groups. There was a significant difference between the AN group and neoplastic lesions in terms of p21 staining. The number of cases with positive p27 was lower in the AN group than the neoplastic groups. There was no significant difference in terms of Bcl-xL and cyclin D1. Conclusion: Cell cycle modulators, led by the Bcl-2 family, played an important role in the pathogenesis of thyroid follicular neoplasm, and p53, p16, and p21 in particular played a role in the carcinogenesis of FC. Jae Yeon Seok Dong Hae Chung <here is a image 0a4f22767a593143-cd1485e49f1c58a3> yoo seung Chung <here is a image 3b88db4c9fcf12f8-4f084c6a77993bba> Young Don Lee ENDOCR PATHOL Sung-Im Do Kyungeun Kim Hyunjoo Lee Jung-Soo Pyo Magdy Hassan Kotb Ahmed Mohamed Zaher <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mai Amr <here is a image ddf6727504e269f6-3394ad3b37386500> Shahenda Salem Update Canc Therapeut Rebecca L Brown Ezra E W Cohen <here is a image b9ba603aa21d8058-8b2e02301ea59bbf> Chantal Mathieu Isabelle Clinckspoor <here is a image d88e1adf3cb78e9c-ffff67d0c9242f66> Lieve Verlinden Brigitte Decallonne Besides its classical role in bone and calcium homeostasis, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has many non-classical effects; antiproliferative, anti-apoptotic and prodifferentiating effects of 1,25(OH)2D3 have been described in several tumour types in preclinical models. This review focuses on the insights gained in the elucidation of the role of 1,25(OH)2D3 in the normal thyroid and in the pathogenesis, progression and treatment of thyroid cancer, the most common endocrine malignancy. An increasing amount of observations points towards a role for impaired 1,25(OH)2D3-VDR signalling in the occurrence and progression of thyroid cancer, and a potential for structural analogues in the multimodal treatment of dedifferentiated iodine-resistant thyroid cancer. A role for vitamin D in thyroid-related autoimmunity is less convincing and needs further study. Altered 1,25(OH)2D3-VDR signalling does not influence normal thyroid development nor thyrocyte function, but does affect C-cell function, at least in rodents. If these findings also apply to humans deserves further study. Carcinoma de tiroides. Clasificaci?n. Manifestaciones cl?nicas. Diagn?stico. Actitudes terap?uticas. TSHrh y tiroglobulina s?rica en el manejo del carcinoma diferenciado tiroideo Genetic mutations, molecular markers and future directions in research Recent molecular studies have described a number of abnormalities associated with the pathogenesis of thyroid carcinoma. These distinct molecular events are often associated with specific stages of tumor development and may serve as prognostic factors and therapeutic targets. A better understanding of the mechanisms involved in thyroid cancer pathogenesis, will hopefully help translate these discoveries to improved patient care. Correlation of Immunohistochemical Markers and BRAF Mutation Status with Histological Variants of Papillary Thyroid Carcinoma in the Korean Population Several pathologic characteristics are associated with an adverse clinical outcome in papillary thyroid carcinoma (PTC), including the histological variant. This study aimed to investigate immunohistochemical expression and BRAF mutation status based on the histological variant and evaluated potential markers of aggressive behavior of PTC in Korean patients. In all, 407 PTC cases were classified to each histological variant, and the 94 representative cases were subjected to immunohistochemistry and BRAF mutation analysis. The classic type, follicular variant (FV) and tall cell variant (TCV) represented 76.9%, 14.2% and 6%, respectively. TCV showed a larger tumor size (P = 0.009), frequent extrathyroidal extension (P = 0.022) and cervical lymph node (LN) metastasis (P = 0.018). TCV and FV showed the reduced expression of galectin-3 (P = 0.003) and HBME1 (P = 0.114). Regardless of histology, PTEN loss and diffuse S100A4 expression were associated with LN metastasis (P = 0.007, P = 0.013). All TCVs harbored BRAF V600E mutation, and FV harbored less BRAF V600E mutation (P = 0.043). Immunohistochemical evaluation showed characteristic patterns in histological variants. PTEN and S100A4 expression are suggested as indicators of regional lymph node metastasis. BRAF (V600E) associates with cytoplasmatic localization of p27kip1 and higher cytokeratin 19 expression in papillary thyroid carcinoma The genetic alterations are responsible for the altered protein expression in tumors. The knowledge of the link between the altered protein expression and genetic alterations may provide potentially important biological and clinical information. In this study, the expression of some protein markers (Gal-3, p21Kip1, CK19) known to be associated to the papillary thyroid carcinoma (PTC) was assessed in a series of surgical samples by immunohistochemistry, and the association between expression of these markers and the BRAF ( V600E ) mutation was investigated. Gal-3 positive staining was evident in 26 % of benign nodules. The BRAF ( V600E ) mutation and Gal-3 expression, were found in 55.5 and 87 % of PTC respectively, and were unlinked. The expression of CK19 in benign nodules was weak and limited to scattered follicular cells. Diffuse cytoplasmatic expression of CK19 was present in malignant tumors in a variable percentage of cells. A higher percentage of CK19 expressing cells was associated with BRAF ( V600E ) (P ≤ 0.001). All benign nodules displayed nuclear p27kip1 in more than 15 % of the cells. Twenty-nine PTC showed a cytoplasmatic staining with negative nuclei. PTC with cytoplasmatic or 0-5 % of cells with nuclear staining, 6-15 % or >15 % of cells with nuclear staining were 72 (66.7 %), 24 (22.2 %), and 12 (11.1 %) respectively. In BRAF ( V600E ) positive tumors, the cytoplasmatic localization of p27kip1 was significantly more frequent (P = 0.024). In conclusion, we provide evidences that BRAF ( V600E ) is non-associated with Gal-3 expression, whereas it is associated with cytoplasmatic localization of p27kip1 and higher CK19 expression in PTC. Pitfalls in the Diagnosis of Follicular Epithelial Proliferations of the Thyroid The diagnosis of follicular epithelial neoplasms is an area of controversy. We provide our experience with common problems that practising pathologists face when confronted with follicular epithelial proliferations. One of the major issues is the recognition of the diagnostic nuclear features of papillary thyroid carcinoma and reactive cytologic atypia. We discuss the definitions of capsular invasion, vascular invasion, and extrathyroidal extension and their implications in cancer diagnosis and staging. We propose unified terminology for benign follicular epithelial proliferations in the setting of multinodular goiter. We also review challenges related to oncocytic change, malignant transformation in benign nodules, focal dedifferentiation, and the application of ancillary tools in thyroid pathology. We believe that this review contains comprehensive and up to date information that will be of value to pathologists who practice surgical pathology of thyroid. Achiral Lanthanide Alkyl Complexes Bearing N,O Multidentate Ligands. Synthesis and Catalysis of Highly Heteroselective Ring-Opening Polymerization of rac-Lactide Alkane elimination reactions of amino-amino-bis(phenols) H2L1-4, Salan H2L5, and methoxy-β-diimines HL6,7 with lanthanide tris(alkyl)s, Ln(CH2SiMe3)3(THF)2 (Ln = Y, Lu), respectively, afforded a series of lanthanide alkyl complexes 1−8 with the release of tetramethylsilane. Complexes 1−6 are THF-solvated mono(alkyl)s stabilized by O,N,N,O-tetradentate ligands. Complexes 1−3 and 5 adopt twisted octahedral geometry, whereas 4 contains a tetragonal bipyramidal core. Bearing a monoanionic moiety L6 (L7), complex 7 (8) is a THF-free bis(alkyl). In complex 7, the O,N,N-tridentate ligand combined with two alkyl species forms a tetrahedral coordination core. Complexes 1, 2, and 3 displayed modest activity but high stereoselectivity for the polymerization of rac-lactide to give heterotactic polylactide with the racemic enchainment of monomer units Pr ranging from 0.95 to 0.99, the highest value reached to date. Complex 5 exhibited almost the same level of activity albeit with relatively low selectivity. In contrast, dramatic decreases in activity and stereoselectivity were found for complex 4. The Salan yttrium alkyl complex 6 was active but nonselective. Bis(alkyl) complexes 7 and 8 were more active than 1−3 toward polymerization of rac-LA, however, to afford atactic polylactides due to di-active sites. The ligand framework, especially the “bridge” between the two nitrogen atoms, played a significant role in governing the selectivity of the corresponding complexes via changing the geometry of the metal center. The NMR spectrum of the active species of the rac-lactide oligomer attached to complex 1 demonstrated a coordination−insertion mechanism. In addition it also confirmed that the geometry of the metal center of complex 1 in the solid state was retained in solution (THF) during the polymerization, which contributed significantly to the high selectivity of the complex. Villous Papillary Thyroid Carcinoma: a Variant Associated with Marfan Syndrome Marfan syndrome (MFS) is an autosomal dominant hereditary disorder of connective tissue associated with perturbations in transforming growth factor β (TGF-β) biology, most often due to mutations in FBN1 gene that encodes fibrillin-1. To our knowledge, there is no known association of MFS with thyroid carcinoma. We report a 46-year-old man with known history of MFS who developed an unusual histological variant of papillary thyroid carcinoma. The tumor exhibited a widely invasive florid papillary growth pattern with prominent long villous fronds. Immunohistochemical and molecular analysis revealed a BRAF(V600E) mutation, evidence of aggressive biomarker expression (positivity for HBME-1, cytokeratin 19, galectin-3 and cyclin D1, and loss of p27), and changes associated with TGF-β-related epithelial-to-mesenchymal transition with active phospho-SMAD signaling. We introduce a unique histological pattern of papillary thyroid carcinoma that is associated with MFS. The combination of BRAF(V600E) mutation in the setting of altered TGF-β signaling and weak connective tissue integrity associated with MFS may cooperate and possibly be responsible to form this unique villous morphology with epithelial-to-mesenchymal transition and invasive growth. Classification of papillary thyroid microcarcinoma according to size and fine‐needle aspiration cytology: Behavior and therapeutic implications The purpose of this study was to assess and classify cases of papillary microcarcinoma according to size (up to 0.5 cm and between 0.6 and 1.0 cm) and fine-needle aspiration cytology (FNAC). These results were then correlated with clinical and histopathologic factors of worse prognosis. A total of 448 cases of papillary thyroid carcinoma were studied retrospectively. Of the 448 patients, 173 presented with carcinomas of ≤0.5 cm and 275 patients presented with carcinomas sized between 0.6 and 1.0 cm (>0.5 cm). Lymph node metastasis was diagnosed in 6% of the carcinoma cases of ≤0.5 cm and in 16% of the cases with tumors of >0.5 cm. A total of 281 cases tested positive for papillary carcinoma by FNAC, and in 113 cases, the carcinoma was diagnosed during the histopathologic examination. A positive FNAC for carcinoma was correlated with a higher incidence of lymph node metastasis (16% vs 5%). The diagnosis of papillary carcinoma using the preoperative biopsy enables a more precise oncological procedure with greater chance of biological cure. © 2010 Wiley Periodicals, Inc. Head Neck, 2011 Papillary microcarcinoma in comparison with larger papillary thyroid carcinoma in BRAFV600E mutation, clinicopathological features, and immunohistochemical findings Papillary thyroid microcarcinoma (PMC; ≤1 cm) is thought to take a benign course during the lifetime. However, recent studies showed high recurrence rates for PMC. We analyzed the clinicopathological features, long-term prognosis, and some molecular characteristics including BRAFV600E mutation by retrospectively reviewing the records of 1150 patients with papillary thyroid carcinoma (PTC), 278 with PMC, and 868 with PTC >1 cm. The prevalence of extrathyroidal invasion (52.2%) and initial nodal metastasis (34.9%) in patients with PMC was surprisingly high and almost as high as that for patients with PTC (72.4% and 51.8%, respectively). The rate of recurrent or persistent disease did not differ between patients with PMC and PTC (recurrent or persistent disease, 6.1% vs 14.1%; 53.4- vs 84.2-month follow-up; n = 98 vs 647; corrected p = .112). The frequency of BRAFV600E mutation was similar in patients with PMC and PTC (65.6% vs 67.2%). Immunohistochemical staining showed no different expression pattern according to the tumor size. These results suggest that PMC is not an occult cancer and it can act like larger PTC. Therefore, PMC should not be underestimated in practice. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 Pathologie des Schilddr�senkarzinoms Thyroid carcinoma accounts for approximately 1% of all human malignancies and is thus a rather rare tumour. Both its differential diagnosis from benign lesions (thyroid hyperplasia and adenoma) and exact classification may cause substantial difficulties in daily routine diagnostic pathology. Due to their different biological behaviour the recently published WHO classification of thyroid tumours subdivides thyroid carcinomas of follicular cell origin into well-differentiated carcinomas (papillary and follicular carcinoma), poorly differentiated carcinomas and anaplastic carcinomas. Whereas papillary and follicular carcinomas are usually associated with good prognosis, poorly differentiated carcinoma shows a significantly less favourable and anaplastic carcinoma even a devastating outcome. Thyroid medullary carcinoma, originating from calcitonin-producing C cells, occurs in a sporadic and familial form; the familial type is inherited in an autosomal dominant manner and shows specific germ line mutations of the RET proto-oncogene. Molecular Pathogenesis of Thyroid Cancer The thyroid follicular epithelial cell (thyrocyte) responds to myriad growth-stimulating substances, including hormones, growth factors, cytokines, and other mitogens (1–15), as exemplified in Table 1. Thyrocyte responses to these factors are mediated by distinct signal transduction pathways (Figs. 1–3). Each pathway features a cell surface receptor that is linked to a specific cytoplasmic signal transduction cascade: 1. Receptor tyrosine kinase (RTK)/RAS/RAF/MEK/mitogenactivated protein kinase (MAPK) pathway (Fig. 1). 2. Thyrotropin (TSH) receptor/adenylate cyclase/protein kinase A (PKA) pathway (Fig. 2). 3. Receptor/phospholipase C (PLC)/protein kinase C (PKC) pathway (Fig. 3). Histone Deacetylase Inhibition Modulates E-Cadherin Expression and Suppresses Migration and Invasion of Anaplastic Thyroid Cancer Cells Anaplastic thyroid cancer cells are characterized by a mesenchymal phenotype, as revealed by spindle-shaped cells and absent or reduced levels of E-cadherin. Epigenetic silencing is considered one of the leading mechanisms of E-cadherin impairment, which causes the acquisition of the invasive and metastatic phenotype of anaplastic thyroid cancer. In this study we investigated the effects of histone deacetylase inhibition on E-cadherin expression, cell motility, and invasion in anaplastic thyroid cancer cell cultures. Three stabilized cell lines and primary cultures of anaplastic thyroid cancer were treated with various histone deacetylase inhibitors. After treatment, we evaluated histone acetylation by Western blotting and E-cadherin expression by RT-real time PCR. The proper localization of E-cadherin/β-catenin complex was assessed by immunofluorescence and Western blot. Transcription activity of β-catenin was measured by luciferase reporter gene and cyclin D1 expression. The effect on cell motility and invasion was studied both in vitro using scratch-wound and transwell invasion assays and in anaplastic thyroid carcinomas tumor xenografts in mice in vivo. Histone deacetylase inhibition induced the E-cadherin expression and the proper membrane localization of the E-cadherin/β-catenin complex, leading to reduced cancer cell migration and invasion. We here demonstrate an additional molecular mechanism for the anticancer effect of histone deacetylase inhibition. The antiinvasive effect in addition to the cytotoxic activity of histone deacetylase inhibitors opens up therapeutic perspectives for the anaplastic thyroid tumor that does not respond to conventional therapy. Altered Expression of Key Players in Vitamin D Metabolism and Signaling in Malignant and Benign Thyroid Tumors 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D, mediates antitumor effects in various cancers. The expression of key players in vitamin D signaling in thyroid tumors was investigated. Vitamin D receptor (VDR) and CYP27B1 and CYP24A1 (respectively activating and catabolizing vitamin D) expression was studied (RT-PCR, immunohistochemistry) in normal thyroid, follicular adenoma (FA), differentiated thyroid cancer (DTC) consisting of the papillary (PTC) and follicular (FTC) subtype, and anaplastic thyroid cancer (ATC). VDR, CYP27B1, and CYP24A1 expression was increased in FA and DTC compared with normal thyroid. However, in PTC with lymph node metastasis, VDR and CYP24A1 were decreased compared with non-metastasized PTC. In ATC, VDR expression was often lost, whereas CYP27B1/CYP24A1 expression was comparable to DTC. Moreover, ATC with high Ki67 expression (>30%) or distant metastases at diagnosis was characterized by more negative VDR/CYP24A1/CYP27B1 staining. In conclusion, increased expression of key players involved in local 1,25(OH)(2)D(3) signaling was demonstrated in benign and differentiated malignant thyroid tumors, but a decrease was observed for local nodal and especially distant metastasis, suggesting a local antitumor response of 1,25(OH)(2)D(3) in early cancer stages. These findings advocate further studies with 1,25(OH)(2)D(3) and analogs in persistent and recurrent iodine-refractory DTC. Advanced Bone Formation in Mice with a Dominant-negative Mutation in the Thyroid Hormone Receptor Gene due to Activation of Wnt/ -Catenin Protein Signaling Thyroid hormone (T3) acts in chondrocytes and bone-forming osteoblasts to control bone development and maintenance, but the signaling pathways mediating these effects are poorly understood. ThrbPV/PV mice have a severely impaired pituitary-thyroid axis and elevated thyroid hormone levels due to a dominant-negative mutant T3 receptor (TRβPV) that cannot bind T3 and interferes with the actions of wild-type TR. ThrbPV/PV mice have accelerated skeletal development due to unknown mechanisms. We performed microarray studies in primary osteoblasts from wild-type mice and ThrbPV/PV mice. Activation of the canonical Wnt signaling in ThrbPV/PV mice was confirmed by in situ hybridization analysis of Wnt target gene expression in bone during postnatal growth. By contrast, T3 treatment inhibited Wnt signaling in osteoblastic cells, suggesting that T3 inhibits the Wnt pathway by facilitating proteasomal degradation of β-catenin and preventing its accumulation in the nucleus. Activation of the Wnt pathway in ThrbPV/PV mice, however, results from a gain of function for TRβPV that stabilizes β-catenin despite the presence of increased thyroid hormone levels. These studies demonstrate novel interactions between T3 and Wnt signaling pathways in the regulation of skeletal development and bone formation. The Cyclin D1 (CCND1) A870G polymorphism predicts clinical outcome to lapatinib and capecitabine in HER2-positive metastatic breast cancer Prognostic value of oncoprotein expressions in thyroid papillary carcinoma The aim of this study was to evaluate the expressions of oncoproteins and to correlate the results with clinicopathologic parameters in papillary thyroid carcinoma (PTC). Papillary thyroid cancer (PTC) is the most common form and accounts for about 80% of all thyroid cancers. Although PTC generally has a good prognosis, some patients suffer from local recurrence and/or distant metastasis. Oncogenes have reported to be related not only in carcinogenesis but also in tumor prognosis, tumor type, differentiation and site of tumor in epithelial malignant tumors such as thyroid, breast, ovarian, and stomach cancer. This study was planned retrospectively and was performed in 87 patients (47 PTC, 40 benign lesions). The data of clinicopathologic parameters and tissue samples were collected from the archives. Sections stained with H&E were evaluated for each case and after confirming the diagnosis of PTC, oncoprotein expressions were determined by immunohistochemical analysis. The differences of oncoprotein expressions in PTC compared with control group were statistically significant. Cyclin D1 and p53 expressions were significantly increased in PTC. The expressions of bcl-2 and c-erbB-2 in PTC were found as increased, but the correlation between these proteins and poor prognostic parameters were not significant. We suggest that increased expressions of cyclin D1 and p53 could be used as prognostic factors in patients with PTC. A High-Throughput Proteomic Approach Provides Distinct Signatures for Thyroid Cancer Behavior Well-differentiated thyroid cancer (WDTC) is the most frequent form of endocrine neoplasia. One of the main challenges in the management of this disease is distinguishing low-risk patients who can be treated by surgical resection of the lesion from those with a high likelihood of recurrence who need a more extensive approach, including total thyroidectomy and radioiodine ablation. A tissue microarray (TMA) comprising 410 cases of WDTC was constructed with risk estimates for the following features: extrathyroidal extension, lymph node metastases, and vascular invasion. The variables examined were morphologic classification, candidate genetic, and proteomic biomarkers. BRAF (Raf kinase type B) mutant carriers showed increased risk of developing invasion compared with wild-type (WT) cases. However, when classified morphologically, classic papillary thyroid carcinomas (PTC) showed much higher risk estimates for invasive features compared with follicular variant PTCs (FVPTC); within these morphologic subgroups, BRAF mutational status did not provide independent risk estimates. Staining intensities for membranous galectin-3 (Gal3), HBME-1, and CK19 and nuclear Gal3 were statistically validated as markers of aggressive behavior. Estrogen receptor beta (ERβ) was overexpressed in lesions with invasive behavior. The utility of these biomarkers remained statistically significant in the FVPTC. In contrast, a different set of biomarkers proved effective in classic PTC where upregulation of cyclin D1, loss of p27, and overexpression of ERβ were associated with invasive behavior. Different proteomic signatures validate the distinction of classic and FVPTC and provide a practical clinical mechanism to predict the thyroid cancer behavior and stratify patients for clinical management. Warthin Tumor-Like Papillary Thyroid Carcinoma with a Minor Dedifferentiated Component: Report of a Case with Clinicopathologic Considerations <here is a image 36efbd95d5bbc3f9-e31574558b96da5a> Paolo Amico Salvatore Lanzafame <here is a image d5d216363ba6bb04-a8a4e0598da41309> Giovanni Li Destri <here is a image 5ba6c18b825355ae-ce0409235dd8a60e> Gaetano Magro Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course. Expression of cell-cycle regulators (cyclin D1, cyclin E, p27(kip1), p57(kip2)) in papillary thyroid carcinoma Mar 2010 OTOLARYNG HEAD NECK Sang Hyuk Lee Jong Kyu Lee Sung Min Jin <here is a image 1fcaa0b82a10bcf2-88f215dd209c0137> Dong Hoon Kim To evaluate the expression of cell-cycle regulators in papillary thyroid carcinoma in relation to lymph node metastatic features, and to determine whether immunohistochemical staining of cell-cycle markers can predict lymph node metastasis. Cross-sectional study of prior surgical specimens. Academic tertiary referral center. We reviewed the clinical records of patients who had undergone surgery for thyroid cancer and follicular adenoma between January 2005 and May 2008 at our clinic. Among these cases, 92 patients, comprising 28 patients with follicular adenoma, 32 with papillary thyroid carcinoma without lymph node metastasis, and 32 with papillary thyroid carcinoma with lymph node metastasis, were selected randomly. Formalin-fixed, paraffin-embedded tissues from the 92 patients were immunohistochemically stained for cyclin D1, cyclin E, p27(kip1), and p57(kip2), and protein expression levels were quantified and compared among the groups. Tumor specimens from the papillary thyroid carcinoma group had significantly higher expression levels of cyclin D1 and cyclin E, and cytoplasmic expression of p57(kip2) than the other two groups (P < 0.05). In particular, all malignant cases expressed cyclin D1, and cytoplasmic p57(kip2) was expressed only in malignant cases. Furthermore, differences in the grade of cyclin D1 expression according to lymph node metastasis were statistically significant (P < 0.05). Our results suggest that immunohistochemistry of certain cell-cycle regulators may be helpful in the diagnosis of papillary thyroid carcinoma, and that cyclin D1 in particular may be a useful marker for evaluating lymph node metastasis.	https://www.researchgate.net/publication/276944523_Overexpression_of_Cyclin_D1_and_Underexpression_of_p27_Predict_Lymph_Node_Metastases_in_Papillary_Thyroid_Carcinoma
NEW CLAUSE.—(Charge to tax in respect of provision for retirement or other benefits to directors and employees of bodies corporate.) (Hansard, 9 July 1947) NEW CLAUSE.& #x2014;(Charge to tax in respect of provision for retirement or other benefits to directors and employees of bodies corporate.) (Hansard, 9 July 1947) NEW CLAUSE.—(Charge to tax in respect of provision for retirement or other benefits to directors and employees of bodies corporate.) HC Deb 09 July 1947 vol 439 cc2369-87 §(1) Subject to the exemptions and provisions contained in the next succeeding section, where pursuant to a scheme for the provision of future retirement or other benefits for persons consisting of or including directors or employees of a body corporate (in this and the next four succeeding sections referred to as a "retirement benefits scheme") the body corporate in any year of assessment pays a sum with a view to the provision of any such benefits for any director or employee thereof, then (whether or not the accrual of the benefits is dependent on any contingency),— ( a)the sum paid, if not otherwise chargeable to income tax as income of the director or employee, shall be deemed for all the purposes of the Income Tax Acts to be income of that director or employee for that year of assessment and assessable to income tax under Schedule E; and ( b) where the payment is made under such an insurance of contract as is mentioned in section thirty-two of theIncome Tax Act. 1918 (which relates to relief for life insurance premiums, etc.). relief, if not otherwise allowable, shall be given to him under that section in respect of the payment to the extent, if any, to which such relief would have been allowable to him if the payment had been made. by him and the insurance or contract under which the payment is made had been made with him. §(2) Subject to the exemptions and provisions contained in the next succeeding section. where— ( a) an agreement is in force between a' body corporate and a director or employee 2370 thereof for the provision for him of any future retirement or other benefits afforded by a retirement benefits scheme, or a person is serving as a director or employee of a body corporate in connection wherewith there is a retirement benefits scheme relating to persons of the class within which he falls under which any such benefits will be provided for him; and ( b) the body corporate does not, or does not fully, secure the provision of the benefits by the payment of such sums as are mentioned in the preceding subsection; and ( c) the circumstances in which the benefits are to accrue are not such as will render the benefits assessable to income tax under Schedule E as emoluments of his office as a director or of his employment, then (whether or not the accrual of the benefits is dependent on any contingency), in each year of assessment in which the agreement is in force or the director or employee is serving as aforesaid, up to and including the year of assessment in which the benefits accrue or there ceases to be any possibility of the accrual thereof, a sum equal to the annual sum which the body corporate would have had to pay in that year under a contract with a third person which secured the provision by that third person of those benefits or, as the case may be, of those benefits so far as not already secured by the payment of such sums as are mentioned in the preceding subsection, shall be deemed for all the purposes of the Income Tax Acts to be income of the director or employee for that year and assessable to income tax under Schedule E. §(3) Where the body corporate pays any sum as mentioned in subsection (1) of this section in relation to several directors or employees, the sum so paid shall, for the purpose of that subsection, be apportioned among them by reference to the separate sums which would have had to be paid to secure the separate benefits to be provided for them respectively, and the part of the sum apportioned to each of them shall be deemed for that purpose to have been paid separately in relation to that one of them.—[ The Solicitor-General.] I beg to move, "That the Clause be read a Second time." This new Clause relates to retirement benefits. This is the first of a series of five Clauses which are designed to replace Clauses 14 to 18 of the Bill as it stands. I do not know whether it would be convenient if the Debate on this Clause were extended so that I could deal with the five Clauses together as they all hang together and form one single scheme. If it is the wish of the House that a general discussion should take place on this Clause, it might be the more convenient. I am much obliged to the House. What we have sought to do in framing these Clauses is to give effect to the various criticisms which were directed against the Clauses, which I have mentioned, by hon. Members when the Clauses of the present Bill were under discussion. In general terms the major criticism was directed most to Clauses 16 and 17 of the Bill. They were the Clauses which dealt with the voluntary payments, and it was urged that they would bear hardly upon non-whole-time directors and other directors and employees and impose a harsh and severe burden upon them. Only detailed criticism was directed to the first two Clauses, and it was felt during all the discussions that they were apt to remedy what was a serious abuse or potentially serious abuse. Therefore, what we have done in refraining the Clauses is virtually this. We have thrown overboard entirely what there was in Clauses 16 and 17 and we have confined the new Clauses to doing what was done in a slightly different form in Clauses 14 and 15. We have then gone on to deal with certain matters of detail. If I may review quite briefly what we have done it is as follows. Clauses 14 and 15 are Clauses which deal with schemes under which a company has paid various sums year by year to insurance companies or trustees to provide benefits. They deal also with conditions of service under which a company has undertaken to provide benefits. In both cases whether these benefits consist either of non-taxable lump sums or of annuities or pensions convertible into non-taxable lump sums, or which are wholly disproportionate and in excess of anything which might be described as a reasonable pension—in respect of those cases, which by common consent were cases which really required to be dealt with, what we have done is done by Clauses 14 and 15. We have said that the amount paid by the employer shall be treated as income and if no amount is paid and payment is to be found out of the funds of the company we take a notional figure, which shall be attributed to the employee as taxable income during the years of his employment. That is a principle to which I do not think any exception has been taken. It has been conceded to be fair and reasonable. But again, we have introduced exceptions which were introduced in the2372previous Bill but in a slightly larger and more generous form. The exceptions apply to statutory superannuation schemes. They apply to schemes approved under Section 32 of theFinance Actof 1921 and they also apply to schemes which are ad hocapproved by the Commissioners for the purposes of this Clause. Broadly speaking, the Commissioners are given power to approve, and indeed, it is made obligatory on them to approve certain schemes, provided the amount is paid by the company for an annuity and provided the schemes comply more or less—because there is a measure of discretion left to them—with certain requirements. These requirements, if I may summarise them as briefly as I can, are that the scheme should conform in outline, generally speaking, to what could be considered to be, in ordinary common parlance, a bona fidesuperannuation scheme. Any schemes falling within these three categories are not affected by the new Clauses, they are entirely outside, as they were before, but we have introduced further provisions to deal with points of criticism. First of all, we exempt altogether any scheme existing before April, 1944, the main benefit to be provided is a life pension or annuity. That is the first thing we propose. Because by that date, at any rate, all the schemes were known. There is a discretion in regard to later schemes. Any scheme which was pre-April, 1944, is a scheme known to the authorities and its qualities have been assessed and understood. We further do this. A question was asked whether anything could be done in regard to provident schemes designed to provide for lump sum payments. What we have done is to exempt small provident funds and endowment insurance schemes providing for small lump sum payments. We have fixed this limit that the employer must pay not more than 10 per cent. of the employee's remuneration to the fund or not more than £100, whichever is the less. We have accepted this. It was not done in the last Clause but was a point brought up in the discussion What we have also done is that we have2373made provision for tax to be reclaimable by an individual who can show, for example, that he has been dismissed or for some other reason will not get the benefit in respect of which the tax is paid. That point was also made during the discussion. My hon. Friend the Member for North-wich (Mr. J. Foster) raised a subtle and complicated point relating to employees overseas. He instanced the question of an Indian company which is paying pensions in India, and asked whether the Indian company's Indian employees would be covered? We have now exempted these and employees employed abroad who would not have come under Schedule E. We have made it possible for part of the scheme to be approved even if the whole scheme is not approved. It can be dissected and approved in part. Finally, we have said that, if a scheme which at present does not qualify for approval is changed, and changed before April, 1948, or any longer time which may be allowed by the Commissioners for that purpose—if it is not reasonably practicable to change it within that time—it can be approved retrospectively to April, 1947. We think that is a fair way to deal with the matter. It gives people an opportunity of adjusting the scheme to comply with the requirements which we have set out, and adjust it in such a way as will qualify for approval, not only from the date of adjustment but from April, 1947. All these Amendments are in the new Clauses which are rather long but which give effect to what I have been saying. We hope the House will agree that in so doing, we have met the criticisms which were advanced against the old Clauses and we hope also, that these are more easily intelligible than the others. Before the hon. and learned Gentleman sits down may I ask him this question? He spoke of the reclaiming where no benefit is to be derived. Can he say whether the ordinary six years' limit applies to reclaiming, or will it go back further? I am sure the House is indebted to the hon. and learned Gentleman for his clear explanations which we are now getting so used to receiving when he addresses us on technical matters that the Chancellor is putting into this Bill. These points have, of course, all arisen as the result of a promise the Chancellor made. There have been discussions with regard to this Clause and the result is now before us. The original Clauses which have been dropped, occupied no less than eight pages of theFinance Billas introduced. The new Clauses given to us look as if they will cover as much paper in the next stage as those for which they are being substituted. I am glad the Government have been able to modify the attitude which previously they had taken up, because we on this side of the House were with them at the start, when they said there were certain gross evasions taking place, as indeed we always would be in saying that these evasions must be dealt with. 11.45 p.m. While we did not specify, have not specified and do not intend to specify what the abuses were, we know what they are from discussions which have taken place. As I understand it, three things of real importance now emerge. As the hon. and learned Gentleman has said, first of all, all schemes which are pre-1944 are automatically exempted—obviously, if their main purposes are within the scope of what we are discussing. The second new point is that if a scheme falls within the conditions—and they are fairly hard conditions, if that is the right word—laid down in the third new Clause, then the Commissioners have to approve it: there is no option there. The third important point is that in spite of that, the Commissioners are given by the general effect of this new scheme a very wide discretion. In brief, all pre-1944 schemes are exempted, new schemes which come within the conditions of the third Clause have to be approved, and thirdly the Commissioners are given wide discretion. It seems to me—and I am no expert in this—that what one might call genuine schemes, whether existing or future, will2375really be all right. The genuine scheme will be all right even if lump sum payments—which were the chief cause of the mischief we are dealing with—are involved in schemes hereafter. Even it there are lump sum payments, that does not automatically disallow a scheme if the lump sum payment is in scale with that length of service, or the previous salary or pay of the person concerned. I understand this was really the intention of the previous Clause, although that did not emerge quite clearly at the time. I would like to ask the hon. and learned Gentleman one or two questions, the answers to which we would like to have quite definite and clear. I think, first of all, he can give me the assurance that powers under this new Clause would not be used to damnify a person who is given a pension related to his length of service and to the remuneration he has received, if such a pension is in line with schemes which the Revenue would view with favour. There may be cases—and this is the actual point I have in mind=—where, for example, a scheme is drawn up and some man does not fall within its scope for the very reason that the moment the scheme is going into effect, he is too old to take advantage of it, although he has long service, and his company wants to help him in his retirement. Such a person would not be damnified because he was not in the scheme—provided that what is given to him is in general line with what he would have got if he were in the scheme? I think that is the case and I hope when the right hon. Gentleman comes to reply he will give me that assurance because I understand it is for this that the new Clauses have appeared on the Paper. It is a point which has worried' a number of men, and women, too, who might be concerned. The second point which I think is clear from what the right hon. Gentleman said is that any penalties under these Clauses in schemes which fall foul of the views of the Commissioners or in favour of which they will not exercise discretion, will not be retrospective. We should like that stated definitely for the purpose of the record. I think it is also quite clear and implicit in what he said—that all these arrangements and plans are only intended to deal with schemes which are clearly designed, in the view of the Commissioners to avoid taxation. I think that is2376a fact, but if the right hon. Gentleman can put this assurance into words in a favourable sense I shall be very much obliged. What is the lesson we are to draw from all this? I think it is regrettably the case that in periods of high taxation there are some people—we need not necessarily admire them—who will go to great lengths to see if there are legal ways of avoiding taxation. That is a view which may be held by the Communist Party but it is not universally held. There is a high judicial decision that if it is legal to do so, and if taxation can be avoided legally, there is no reason why people should not take advantage of it. That is a decision, I think, of the highest courts: whatever the moral view of it may be is another matter. All I was saying was that there are some people who will try to avoid taxation when it gets to such a high scale, and this and other features will progressively diminish when happier times come and taxation can be reduced. The other point that emerges and to which I would draw the attention of the right hon. Gentleman, and the Financial Secretary, is that when it had been decided, as it was decided, to tackle this problem, there might have been a saving of time and trouble to a great number of people if, granted the intentions of the Government were known, the Government had taken into consultation some of the experts, whom they were good enough to consult between the Committee stage and the Report stage, before they introduced the Bill. If they had been able much earlier to get into contact with certain people who gave them help they might have been saved much trouble and anxiety. It would have been much less trouble, and I had hoped that that course might have been adopted— obviously, under the ban of confidential talks. At present a lump sum payment on retirement, as part of a contract of service, is taxable in full in the year it is received; and as regards insurance policies, if a company takes out an insurance on an employee, which is fully vested in him, that insurance is treated for tax as part of his income. There is an aspect of that2378 which is very important. It was realised by certain people that if contingencies could be imported into the arrangement the existing law could be avoided. I think this is a very important part of the new Clauses which the Chancellor has introduced. 12 m. The most prevalent type has been the purchase by companies of a very large endowment assurance for directors, which they receive on retirement and which is free of tax but the premium of which has been paid out of the trading expenses of the company. The method devised to deal with such cases was to see whether benefits which accrue would or would not depend on a contingency. Unfortunately, in dealing with existing abuses the Clauses were extended to deal with all sorts of situations which might arise and as I read the original five Clauses it seemed to me it was rather like casting a net to take a few pike out of the river and enmeshing all the salmon and trout. But the main changes which the Chancellor has seen fit to make in Clause 16, dealing particularly with part-time directors, which had been dropped altogether, and in the elimination of Clause 17, disposes of a very large number of objectionable aspects that we on this side found in the original Clauses. I want to make one or two point which I think are important. The first concerns the provision that has been made that the Commissioners shall look at these things. I think the Chancellor has shown great faith in them—that they will apply their wisdom and judgment to conditions on which a pension or annuity would be allowed. The main objection to the original Clauses has been removed, but I think there is failure to see that all the existing or future pensions funds of a genuine character will escape these Clauses. I do not want to be over-critical because as I say, and as has been said by my right hon. Friend on the Front Bench, we are very grateful for the changes that have been made, but I would like to ask the Solicitor-General to give heed to the third Clause to be moved by the Chancellor on the approval of retirement benefit schemes. If he will turn to Subsection (1), paragraph ( c) he will see that the proportion between the value of the pensions…and the value of all other benefits …as are commutable, that is, of course,2379 the capital sum. is to be determined on the basis of what is "reasonably comparable" to "statutory superannuation schemes." I have a great regard for these statutory schemes but I think they are based on the service of the individual concerned. In modern industry, where you get an individual moving from firm to firm, it is quite likely that an operative or executive with good ability moves from one firm to another until at the age of 45 he reaches a firm with which he will serve for the rest of his life. His firm may have no actual scheme. I suggest, with great respect, that the services he has rendered to industry, apart altogether from the years of service he has given, should be taken into account. I think that where the scheme says that it should be reasonably comparable, that fact should be taken into account. We have seen that this scheme which we are debating tonight is very intricate; and it is very hard to assess the exact significance of it. It has been subjected in Canada and elsewhere to an inquiry. While I very much appreciate the courtesy of the Chancellor in recommitting this, I think that if we look to Canada, where the authorities were confronted with a similar problem, we shall see that they set up a Royal Commission to inquire into retirement benefits, life assurance and the taxation of annuities. I suggest that this forms a portion of Income Tax law which might well be inquired into without reopening the whole field of Income Tax law. I end by repeating that I very much appreciate the fact that the Chancellor has withdrawn the whole of those Clauses, and that he has introduced five new Clauses which go a very long way to meeting the points that we raised; but I still think that this aspect of Income Tax law should be the subject of an inquiry, and I hope that such an inquiry will be held before this time next year. I should like the hon. and learned Gentleman to deal with one or two minor points on these new Clauses that he has drawn up in substitution for those formerly in the Bill. The first is in regard to the second new Clause. In line 4, the words occur (whether in whole or in part).I should be grateful if he would say exactly what those words are meant to2380effect. As this Clause is at present drafted it is not, as I read it, at all clear, and I think he should say something more on that subject. My right hon. and gallant Friend the Member for Gainsborough (Captain Crookshank) has mentioned the question of schemes that were excepted those prior to 1944. But I think the House ought to be told a little more about those schemes that are not going to be automatically excepted. Reference has been made to Subsection (2) of the second new Clause, but I should be grateful to hear from the hon. and learned Gentleman more about Subsection (2) of the fourth new Clause. It does seem to me that that fourth new Clause is very wide, and that it could well mean that, where several schemes are run by a body corporate, a good one, one such as would fall within the exceptions, could be ruled out because the others were bad. If I read it aright, it says that if, in general, the schemes were bad, a good one would fall as well as the bad ones. I think the hon. and learned Gentleman should make clear what the intentions of the Government are. on that point. In regard to the third new Clause I would ask a question about retirement In line 35 the new Clause deals with the case of a person who never expected to get any benefit whatever. The actual words are by repayment or otherwise as may be appropriate.I would like to know from the Solicitor-General what is the meaning of the words "or otherwise as may be appropriate." Does it mean that when a person is behind with Income Tax payments sums may be appropriated from him by the Treasury for the payment of other claims? If that is so it is a most dangerous precedent and one in legislation in this House we have always tried to avoid. I hope that we can have an assurance that that is not so. There is another point in line 38 where it deals with repayments in part and where the Commissioners are empowered to repay. I quote the exact words: as may seem to them just and reasonable.There should be some method of appeal from what the Commissioners may direct. As I read the Clause, where there is a sum of money due to a person under a scheme and the Commissioners make an allocation, there is no appeal whatsoever. I think that that is a bad thing. There2381should be a method whereby the person concerned has a right of appeal against the decision of the Commissioners. In the third new Clause very considerable discretion is allowed to the Commissioners and with that I agree, but again I would like to ask the hon. and learned Gentleman particularly with regard to this matter, if he would look at that Clause, for one of the main conditions is that none of the benefits can be commuted. Who is to determine in what circumstances the benefit cannot be commuted? It may be that a man wishes to complete the purchase of a house, for example, where an employee has paid on a house certain sums over years and he has to retire early, and wishes to use that benefit to pay off the sum remaining on the house. Would that be an infringement of these provisions, or would it be an infringement to assign part of the benefit for the education of his children or if he was to make a maintenance grant to some near relative, to, say, his sister-in-law or someone of that sort? Would that in fact be an infringement of the regulations? I agree that the Commissioners have wide powers of discretion but we would like to know something of the general principle which lies behind it. I would ask the hon. and learned Gentleman, in relation to this Clause, if there is any method whereby an individual can appeal particularly in regard to Subsection (2), which does seem to be very dangerous. Here the Commissioners can at any time withdraw their consent to a scheme for any reason that they decide to be a proper reason. It is perfectly possible that if a body corporate has entered into a scheme and then can be served with a notice, that the scheme is no longer appropriate. There is no appeal from that provision, and as far as I can see it might lead to very considerable trouble. Now with regard to the fifth Clause— the definition of a "controlling director". It starts by saying that he is one of the directors who control the company. Now the phraseology here is very different from that in theCompanies Bill. Is it intended that this phrase in line 5 of the fifth new Clause is to have the same effect as what is called "a director controlling a company" in theCompanies Bill, or if not, what interpretation is to be placed on these words—"a director having a2382controlling interest therein"? As drafted it might mean anything. Further what is the intention in introducing the words "more than five per cent."? As it reads at the moment, no director who has more than five per cent. beneficial interest in any company can claim that any scheme shall be to his advantage. He is ruled out automatically. I would like the hon. and learned Gentleman to think for a moment what that means. Take the thousand and one small businesses in the county towns and country towns of England. There, very often, a young person is offered an interest, but he is usually only offered an interest if he will put up capital for the business. In other words, he buys a partnership. It is not a partnership commercially, yet that is what it comes to. Under this Clause, that will be ruled out because anyone putting up five per cent. by which he takes a share, will, at the same time, be able to take no part in any superannuation, or any other, scheme. It seems to me that that is very bad, particularly for the development of small businesses. I cannot see any practical use in it. Of all the Clauses we have dealt with, this is the worst Clause which has been put before us, the retention of this five per cent. It can only be a great stumbling block to the development of small businesses. I must apologise to the House for putting so many questions.	https://hansard.millbanksystems.com/historic-hansard/commons/1947/jul/09/new-clause-charge-to-tax-in-respect-of
HB2196 HD1 HOUSE OF REPRESENTATIVESH.B. NO.2196THIRTIETH LEGISLATURE, 2020H.D. 1STATE OF HAWAII A BILL FOR AN ACT RELATING TO WATER QUALITY . BE IT ENACTED BY THE LEGISLATURE OF THE STATE OF HAWAII: PART I SECTION 1.The legislature finds that Hawaii's coastal waters and coral reefs sustain a way of life by providing fisheries, coastal protection from storms and waves, sustainable ecotourism, recreation, and culture.The people of Hawaii have a responsibility, and the State a public trust duty, to take care of these coastal waters and ecosystems. The legislature further finds that the coral reefs of the world are under mortal stress from anthropogenic climate change.By 2050, nearly all reefs are estimated to be threatened, with seventy-five per cent facing high, very high, or critical threat levels.In West Hawaii, coral cover declined by fifty per cent after coral bleaching in 2014 and 2015, and since then only a fraction of the coral has recovered. Nutrient pollution, sedimentation, and the perturbance of fish and marine invertebrate populations are local stressors which exacerbate the effects of climate change on coral reef communities. Protecting Hawaii's nearshore waters and reefs in this time of change requires action on multiple fronts, including reducing greenhouse gas emissions to zero, sequestering carbon in restored soils and forests, protecting watersheds from erosion, controlling invasive species, and preventing additional non‑native species introductions. Untreated or inadequately treated human wastewater is a source of nutrients to nearshore waters, which can be locally controlled to reduce stress on coral reefs.Responsible wastewater management is also critical for the protection of human health and the safe enjoyment of nearshore waters. The legislature finds that wastewater injection wells and onsite sewage disposal systems, especially cesspools, in coastal areas directly affect our nearshore waters and coral reefs.Research conducted pursuant to Act 125, Session Laws of Hawaii 2017, has shown that nitrogen from human wastewater directly impacts nearshore water quality and is used by invasive algae growing in these waters. Decreasing nutrient flow to groundwater and nearshore waters via individual wastewater onsite sewage disposal systems and municipal sewer-connected wastewater disposal systems can be achieved by encouraging and incentivizing management, education, innovation, and nature-based solutions. The purpose of this Act is toprotect groundwater and nearshore water quality and coral reefs by reducing nutrient pollution from wastewater disposal. PART II SECTION 2. The legislature finds that maintenance of individual wastewater treatment systems is the responsibility of individual homeowners. Irresponsible maintenance practices lead to increased nutrient and bacteria flux to groundwater and nearshore waters. The purpose of this part is to require onsite sewage disposal system servicers to report to the department of health: (1) Any onsite sewage disposal system that receives multiple pump services within a year; and (2) The servicer's service records. SECTION 3 . Chapter 342D , Hawaii Revised Statutes, is amended by adding a new section to part IV to be appropriately designated and to read as follows: " §342D‑ Onsite sewage disposal system servicers; reporting requirements. (a) Every onsite sewage disposal system servicer that provides pump services to an onsite sewage disposal system two or more times within one year shall submit a report to the department with the tax map key number of the onsite sewage disposal system . (b) Every onsite sewage disposal system servicer shall annually submit to the department the servicer's service records, which shall include the following information: (1) The dates the services were provided; (2) The types of services provided; and (3) The tax map key numbers of the onsite sewage disposal systems. (c) For the purposes of this section: " Aerobic treatment unit system" means an individual wastewater system that consists of an aerobic treatment unit tank, aeration device, piping, and a discharge method that is in accordance with rules adopted by the department relating to household aerobic units. "Cesspool" means an individual wastewater system consisting of an excavation in the ground whose depth is greater than its widest surface dimension, which receives untreated wastewater, and retains or is designed to retain the organic matter and solids discharged into it, but permits the liquid to seep through its bottom or sides to gain access to the underground geographic formation. "Onsite sewage disposal system" means any onsite system for the treatment and disposal of domestic sewage, including cesspools, septic systems, and aerobic treatment unit systems. "Onsite sewage disposal system servicer" means any individual, corporation, company, or any other entity or organization that provides services for onsite sewage disposal systems. "Septic system" means an individual wastewater system that typically consists of a septic tank, piping, and a drainage field where there is natural biological decontamination as wastewater discharged into the system is filtered through soil. " PART III SECTION 4. Pursuant to section 342D-72, Hawaii Revised Statutes, before January 1, 2050, every cesspool in the State, excluding cesspools granted exceptions by the director of health, must be: (1) Upgraded or converted to a septic system or aerobic treatment unit system; or (2) Connected to a sewerage system. Successful transition will require early planning for individuals and communities regarding the need and options for cesspool conversions. Additionally, where onsite sewage disposal systems are lawful and appropriate, conducting regular maintenance is critical to reduction of nutrient and bacterial seepage to groundwater and nearshore waters. The legislature finds that the State lacks a residential outreach and engagement effort for affected individuals. The purpose of this part is to commission a comprehensive statewide outreach program by the University of Hawaii sea grant college program, in cooperation and consultation with the department of health, that provides science-based information and understanding of sewage contamination sources in nearshore marine areas; increases understanding of sewage capacity needs; and informs all stakeholders, including the department of health, of appropriate solutions that support converting all cesspools in the State by 2050. SECTION 5. (a) The University of Hawaii sea grant college program, in cooperation and consultation with the department of health, shall develop and conduct a two-year comprehensive statewide outreach program that provides science-based information and understanding of sewage contamination sources in nearshore marine areas; increases understanding of sewage capacity needs; and informs all stakeholders, including the department of health, of appropriate solutions that support converting all cesspools by 2050. (b) The comprehensive statewide outreach program shall have the following objectives: (1) Provide outreach and engagement for residents regarding: (2) Develop a plan for conducting a two-year, statewide, systematic outreach plan focused on providing education and communication about sewage contamination and the need for statewide conversion of cesspools to protect the coastal and nearshore environment; and (3) Conduct a stakeholder needs assessment to identify physical, practical, and financial impediments that may be encountered by land owners who are required to connect pre-existing cesspools to a sewer system or convert cesspools to an individual waste treatment system and recommend solutions to inform the cesspool conversion working group and its finance, technology, and research subgroups about the gaps and sewage capacity needs for the conversion of all cesspools by 2050. (c) The University of Hawaii sea grant college program shall submit a report of its findings and recommendations, including any proposed legislation, to the cesspool conversion working group established pursuant to Act 132, Session Laws of Hawaii 2018, and the legislature by October 1 of every year, with a final report due no later than October 1, 2022. SECTION 6. There is appropriated out of the general revenues of the State of Hawaii the sum of $ or so much thereof as may be necessary for fiscal year 2020-2021 for the University of Hawaii sea grant college program, in cooperation and consultation with the department of health, to carry out the purposes of this part. The sum appropriated shall be expended by the University of Hawaii for the purposes of this part. PART IV SECTION 7. The purpose of this part is to appropriate funds for the University of Hawaii water resources research center, in collaboration with the department of health, to conduct research on the most cost-effective way to upgrade cesspools in the State. SECTION 8. (a) The University of Hawaii water resources research center, in collaboration with the department of health, shall conduct research on wastewater system technologies to determine the most cost-effective way to upgrade cesspools in the State and reduce the impact of cesspools on drinking water and groundwater. (b) The University of Hawaii water resources research center shall submit a report of its findings and recommendations, including any proposed legislation, to the legislature no later than twenty days prior to the convening of the regular session of 2021. SECTION 9. There is appropriated out of the general revenues of the State of Hawaii the sum of $ or so much thereof as may be necessary for fiscal year 2020-2021 for the University of Hawaii water resources research center to conduct research pursuant to section 8. The sum appropriated shall be expended by the University of Hawaii for the purposes of this part. PART V SECTION 10. The legislature finds that the State does not maintain updated records of onsite sewage disposal systems statewide. Understanding the cesspool problem, prioritization of cesspool conversion, and enforcement of the state cesspool ban are reliant upon accurate data regarding the status of cesspools statewide. The purpose of this part is to require and appropriate funds for the cesspool conversion working group to: (1) Compile an updated database of onsite sewage disposal systems statewide; and (2) Submit a report of its findings and recommendations to the department of health and the legislature. SECTION 11. The cesspool conversion working group established by Act 132, Session Laws of Hawaii 2018, shall compile an updated database of onsite sewage disposal systems statewide: (1) Using records from the department of health, onsite sewage disposal system servicers, and the counties; and (2) By conducting homeowner outreach. SECTION 12. The cesspool conversion working group shall submit a report of its findings and recommendations, including any proposed legislation, to the department of health and legislature no later than twenty days prior to the convening of the regular session of 2021. SECTION 13. There is appropriated out of the general revenues of the State of Hawaii the sum of $ or so much thereof as may be necessary for fiscal year 2020-2021 for the cesspool conversion working group to compile an updated database of onsite sewage disposal systems statewide and submit a report to the department of health and legislature. The sum appropriated shall be expended by the department of health for the purposes of this part. PART VI SECTION 14. This Act does not affect rights and duties that matured, penalties that were incurred, and proceedings that were begun before its effective date. SECTION 15. If any provision of this Act, or the application thereof to any person or circumstance, is held invalid, the invalidity does not affect other provisions or applications of the Act that can be given effect without the invalid provision or application, and to this end the provisions of this Act are severable. SECTION 16. New statutory material is underscored. SECTION 17. This Act shall take effect on July 1, 2050. Report Title: Water Quality; Onsite Sewage Disposal Systems; DOH; UH W ater Resources Research Center ; UH Sea Grant College Program; Appropriations Description: Establishes reporting requirements for onsite sewage disposal system (OSDS) servicers.Appropriates funds for UH sea grant college program , in collaboration with DOH,to conduct community outreach regarding OSDS.Appropriates funds for UH water resources research center , in collaboration with DOH,to research the most cost-effective way to upgrade or convert cesspools.Requires and appropriates funds for the cesspool conversion working group to compile an updated database of OSDS statewide.Effective 7/1/2050.(HD1) The summary description of legislation appearing on this page is for informational purposes only and is not legislation or evidence of legislative intent.	https://www.capitol.hawaii.gov/sessions/session2020/bills/HB2196_HD1_.HTM
Molecules \| Free Full-Text \| Synthesis, Spectral Characterization and Biological Activities of Co(II) and Ni(II) Mixed Ligand Complexes 2,4-Dinitrophynylhydrazine and two thiocyanate ions in a (M:L1:L2) 1:2:2 molar ratio was synthesized in the complexes of Co(II) and Ni(II). The prepared compounds were identified through a C.H.N.S. analysis, conductivity measurements, powder X-ray diffraction (PXRD), the infrared spectrum, and a UV-visible spectrum analysis, in addition to the magnetic properties being measured. The measurements of the molar conductance implieda nonelectrolytic nature of compounds Co(II) and Ni(II). The magnetic susceptibility, as well as electronic spectra, represented all the metal complexesthroughoctahedral geometry, respectively. The PXRD patterns suggested that all the complexes were an orthorhombic system with unit cell parameters. The in-vitro biological activity of the ligand and the metal complexes were screened against the Gram-positive and negative pathogenic bacteria Staphylococcus aureus, Bacillus subtilis, Pseudomonas, aeruginosa and Escherichia coli, as well as the fungal species of Aspergillusniger and Candida albicans.Thus, the metal complexes showeda high efficiency of antimicrobial activity compared with the ligand. Furthermore, applications of the ligand, as well as the metal complexes, were tested for in-vitro antioxidant potential in aDPPH assay. The results showed that the activity of the metal complexes with the in-vitro antioxidant was more active than that of 2,4-dinitrophenylhydrazine(DNPH). Synthesis, Spectral Characterization and Biological Activities of Co(II) and Ni(II) Mixed Ligand Complexes by P. Manimaran 1 , S. Balasubramaniyan 1 , Mohammad Azam 2,* , D. Rajadurai 3 , Saud I. Al-Resayes 2 , G. Mathubala 4 , A. Manikandan 4,* , S. Muthupandi 5 , Zishan Tabassum 6 and Imran Khan 7 1 Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia 3 Department of Chemistry, Government Arts College (Autonomous), Karur 639005, India 4 Department of Chemistry, Bharath Institute of Higher Education and Research, Selaiyur, Chennai 600073, India 5 Department of Physics, Loyola College, Affiliated to University of Madras, Chennai 600034, India 6 Department of Chemistry, Rajshree Institute of Management and Technology, Bareilly 243122, India 7 Applied Science Humanities Section, University Polytechnic, Faculty of Engineering and Technology, Aligarh Muslim University, Aligarh 202002, India * Authors to whom correspondence should be addressed. Molecules 2021 , 26 (4), 823; https://doi.org/10.3390/molecules26040823 Received: 22 December 2020 / Revised: 20 January 2021 / Accepted: 25 January 2021 / Published: 5 February 2021 Abstract : 2,4-Dinitrophynylhydrazine and two thiocyanate ions in a (M:L1:L2) 1:2:2 molar ratio was synthesized in the complexes of Co(II) and Ni(II). The prepared compounds were identified through a C.H.N.S. analysis, conductivity measurements, powder X-ray diffraction (PXRD), the infrared spectrum, and a UV-visible spectrum analysis, in addition to the magnetic properties being measured. The measurements of the molar conductance implieda nonelectrolytic nature of compounds Co(II) and Ni(II). The magnetic susceptibility, as well as electronic spectra, represented all the metal complexesthroughoctahedral geometry, respectively. The PXRD patterns suggested that all the complexes were an orthorhombic system with unit cell parameters. The in-vitro biological activity of the ligand and the metal complexes were screened against the Gram-positive and negative pathogenic bacteria Staphylococcus aureus, Bacillus subtilis, Pseudomonas , aeruginosa and Escherichia coli , as well as the fungal species of Aspergillusniger and Candida albicans .Thus, the metal complexes showeda high efficiency of antimicrobial activity compared with the ligand. Furthermore, applications of the ligand, as well as the metal complexes, were tested for in-vitro antioxidant potential in aDPPH assay. The results showed that the activity of the metal complexes with the in-vitro antioxidant was more active than that of 2,4-dinitrophenylhydrazine(DNPH). Keywords: mixed-ligand complexes ; DNPH ; antimicrobial ; DPPH assay 1. Introduction Mixed chelating metal complexes are the focus for lots of researchers, as theyaremore than ever hugely important within the biological organism in pharmacological applications like antibacterial and fungal, anticancer, anti-inflammatory and antitumor [ 1 ]. The coordination chemistry of transition metal ions through different forms of ligands has been improved through the recent developments within the fieldof bioinorganics, as well as medicinal chemistry [ 2 ]; transition metals have a significant role to play in utilizing transition metal complexes as drugs for treatments for many diseases, which is in an important field of research [ 3 ]. As a probe of the biological system, steady and harmless metal complexes among active metal places are valuable [ 4 ]. The environment of the metal center, such as coordination geometry, ligands and, also, donor groups, are the key factors for metalloproteins performing unique physiological functions [ 5 ]. 2,4-Dinitrophenylhydrazine (DNPH) is a vital part of various biological and pharmaceutical applications [ 6 ]. It is an analog of H 2 NNH 2 (hydrazine) and, moreover, an essential class of drugs [ 7 ]. Nitrogen and, furthermore, oxygen are able to be coordinated, which is helpful for bioinorganic processes [ 8 ]. The SCN (thiocyanate) faction can be used as a negative ion; otherwise, one can use mono-dentate chelating coordinates like S and N with a bridging ligand. The high coordination capability of the SCN group has a variety of bonds, respectively [ 9 ]. This current report synthesized the compounds of Co(II)and Ni(II) from DNPH and SCN ions and, furthermore, the physicochemical characterizations, and the goal was to study the biological potential of DNPH among the complexes of Co(II) and Ni(II). 2. Materials and Methods 2.1. Materials All the chemicals were purchased from commercial sources and were used with no further purification process (CoCl 2 ·6H 2 O, NiCl 2 ·6H 2 O and KSCN) from Merck, and 2,4-dinitrophenylhydrazone was obtained from Sigma Aldrich, along with the solvents like DMSO, DMF, acetone, ethanol and methanol, used as AnalaR grade. 2.2. Analytical Characterizations An elemental analysis was performed by using a CHNS analyzer. Conductivity measurements were reported from (Equip–Tronics, eq-661A) a conductivity meter at 30 °C in DMF medium (10 −3 M). The infrared spectrum measured the wavelength from 4000–400 cm −1 .The electronic absorption spectra were carried out on Jasco V-630 optical resolution 1 nm and wavelength ranging from 200–800 nm, and the powder X-ray diffraction (PXRD) patterns were carried out on a Shimadzu. The magnetic properties were measured from the Model MsB-MK1 using Guey’s Balance Magnetic Susceptibility. 2.3. Synthesis of Co(II) and Ni(II) Mixed Ligand Complexes The complexes of Co(II) and Ni(II) were prepared by DMF solution of (20 mM) DNPH with an ethanol solution of metal chloride (10 mM). The above solution was magnetically stirred and refluxed about one hour, as well as adding an addition of 20-mM de-ionized water solution of potassium thiocyanate ( Figure 1 ). The entire solution was refluxed at six hours. Finally, the colored complex was cooled, filtered in addition to washed with EtOH solution and, after that, dried out in anhydrous CaCl 2 vacuum desiccators. 2.4. In-Vitro Antimicrobial Studies DNPH and the complexes of Co(II) and Ni(II) were treated for antimicrobial efficiency via using various species of Gram-positive and, furthermore, Gram-negative pathogenic bacteria and fungi, such as B. subtilis , E. coli , P. aeruginosa , S. aureus , A. niger and C. albicans , using the disc diffusion method. The free ligand, as well as Co(II) and Ni(II) compounds, were dissolved in DMSO. The variations (30, 60 and 90 µg/mL) of the solution were arranged individually. The prepared discs were dipped within a specified variation of free ligand, in addition to the complexes located within petri plates containing a nutrient medium sowed through every bacterial and fungal serum individually. Every plate was incubated for 24 and 48 h for the bacteria, as well as fungi, at 37 °C; furthermore, the zone of inhibition values were noted [ 10 ]. 2.5. In-Vitro Antioxidant (DPPH) Assay DPPH has generally been used to estimate the free radical scavenging ability of different antioxidants. The radical scavenging activity of metal complexes and ligand-tested samples were determined with the (2,2-diphenyl-1-picrylhydrazyl) DPPH technique [ 11 ]. The entire tested samples were prepared in various combinations (50, 100 and 150 µg/mL) of metal complexes, and free ligand-blended with 2-mL MeOH (0.1 mM) solution of the DPPH radical and kept at room temperature for 30 min in a dark place. Then, the decreased absorption was measuring at 517 nm in the UV-visible spectrum. The % of radical scavenging efficiency was considered from the following equation [ 12 ]: DPPH Scavenging ability(%) = Abs control − Abs sample/Abs control × 100 (1) 3. Results and Discussion The physical properties with the analytical data of the metal complexes are summarized in Table 1 . The Co(II) and Ni(II) complexes are stable at room temperature and soluble in DMSO and DMF. The CHNS analysis of the ligand, as well as metal compound, experimental values are in good agreement with the theoretical calculated values with the complex ratio 1:2:2 between the metals and ligand. 3.1. Molar Conductance The molar conductance values of the metal complexes were measured at a 1 × 10 −3 M concentration of DMF solution, and all the complexes showed conductance in the range of 17.86–19.85 Ω −1 cm 2 mol −1 at 37 °C, as shown in Table 1 . The lowest conductivity value indicated a nonelectrolyte nature, and outside their coordination sphere, there is no counter ion present in the complexes [ 13 ]. 3.2. FTIR Spectra Analysis The infrared spectra analyses of ligands 2,4-dinitrophenylhydrazine and thiocyanate and their corresponding coordination compounds ( Figure 2 ) were carried out, and the relevant peaks (cm −1 ) are given in Table 2 . The FTIR spectrum of the ligands (DNPH) and their metal complexes were characterized at bands 3324, 1319 and 920 cm −1 , assigned to ν(NH) amine and aromatic nitro ν(NO), in addition to ν(N–N) hydrazine, respectively, for DNPH [ 14 ]. In the IR spectrum, the complexes showed evidence of ligand bands through suitable shifts due to their complex formations [ 15 ]. The IR spectra of 2,4-dinitrophenyl hydrazine observed sharp peaks at 3324 cm −1 due to the ν(N-H) frequency, which was moved to a lower frequency at 3288–3278 cm −1 for the metal complexes, thus signifying that the amino nitrogen group is coordinated to a metal atom. Further supporting the observed ν(N-N) stretching frequency, it was shifted to a higher wave number in the metal complexes [ 16 ]. The ν(NO) symmetric stretching band was indicated at 1319 cm −1 ; furthermore, these band were shift higher at 53–38 cm −1 , and there was a downward change of the ν(NO 2 ) asym to 15–20 cm −1 in the spectra of the complexes. These findings indicate that the ligands were coordinated with metal ions through the one oxygen of the nitro group [ 17 ]. The new bands in the complexes were about 2072–2095 cm −1 due to the ν(SCN). These results showed that thiocyanate coordinated with the metal ions through the nitrogen atom bonded to NCS in iso-thiocyanate mode [ 18 , 19 , 20 ]. The lower frequency bands appeared in two synthesized complexes at 539–551 cm −1 , in addition to 412–496 cm −1 , which was attributed to the ν(M-O), as well as ν(M-N) bands, correspondingly [ 21 ]. The FTIR spectra results showed that the ligands were coordinated with metal ion via amino N, nitro O and SCN nitrogen atoms engaging coordination sides in the complexes. 3.3. UV-Visible Spectrum and Magnetic Moments The electronic absorption spectrum of DNPH and their Co(II) and Ni(II) complexes in DMF are shown in Figure 3 , which contains the absorption regions, band assignments and the proposed geometry of the complexes given in Table 3 . 2,4-Dinitrophenyl hydrazine exhibits two absorptions at 363 nm and 267 nm, assignable to n→π* and π→π, correspondingly. The Co(II) complex absorption bands at 281, 388 and721 nm are attributed to the π→π, LMCT and 4 T 1g (F)→ 4 T 2g (F) transitions, signifying an octahedral geometry. A measured magnetic property assessment of 5.1 BM may be additional evidence for octahedral geometry [ 22 ]. The Ni(II) complex provides absorption bands at 284, 390 and 444, as well as 724 nm, are attributed to the π→π,LMCT, 3 A 2g (F)→ 3 T 1 g(P) and 3 A 2g (F)→ 3 T 1g (F)transitions, respectively, corresponding to a high spin octahedral geometry. Further confirmation was achieved by the magnetic moment range at 3.2 BM, which is consistent for the suggested octahedral arrangement [ 23 , 24 ]. 3.4. Powder XRD Analysis The powder X-ray diffraction analysis of the Co(II) and Ni(II) complexes are given in Figure 4 . The PXRD pattern of the metal complexes was defined as sharp crystalline peaks. The PXRD pattern of the metal complex lattice parameters were calculated through the assistance of a computer program, XPERT PRO. The metal complexes gave the values of the lattice constants a = 10.82, α = 900, b = 9.24(4), β = 900, c = 6.03(2), γ = 900, V = 65.25 and the crystal system orthorhombic and Bravais-type Primitive (P) for the Co(II) complex. The Ni(II) complex lattice constants are a = 11.14, α = 90°, b = 9.59(4), β = 90°, c = 4.79(2), γ = 90°, V = 511.05 and the crystal system of orthorhombic and Bravais type Primitive (P). The crystallite sizes were calculated for the compounds of Co(II) and Ni(II) using Debye Scherrer’s Equation [ 25 ]: D = 0.9λ/β cosθ (2) where λ = wavelength of the X-ray radiation (Cu Kα = 1.5406 A°), β = (FWHM) full-width half-maximum, θ = diffraction angle and constant as 0.9. The crystallite sizes were around 29.28 and 30.59 nm, respectively. 3.5. Antimicrobial Efficiency The antimicrobial activity of the ligands, in addition to the Co(II) and Ni(II) complexes, against the pathogenic bacteria and fungi activity results are shown in Table 4 , along with Figure 5 The antimicrobial results show that the ligand is fairly active; furthermore, the metal compounds have a better efficiency than the ligand. The Co(II) complex is extremely active against the bacteria and fungi species compared with the Ni(II) complex and free ligand. The toxicity functions of the compounds and ligand can be due to an improvement in the lipophilic nature. The polarity of metal atoms is primarily decreased by the ligand due to the limited distribution of the positive charge through the donor groups and potential delocalization of the π–electron. The ligand also enhances the central metals’ lipophilic natures, which consequently favors permeation through the cell membrane lipid layer [ 26 , 27 , 28 ]. For a raise in the concentrations of the compounds, the activity increases. It is proposed that complexes with antimicrobial potential will also perform in destroying the microorganism or otherwise preventing microbe reproduction by blocking its active sites [ 29 ]. The complexes’ efficiency is arranged as follows: Co(II) > Ni(II) > L. 3.6. Antioxidant Studies (DPPH Assay) The increased antioxidant activity of the complexes is able to be ascribed to an electron withdrawing effect of the metal ions that facilitate letting loose theH + atom to decrease the DPPH radical. Under certain atmospheric conditions, and during normal cellular function in the body, free radicals are generated. Thus, antioxidants play an important role in preserving the human body from the harm of reactive oxygen species [ 30 ]. The antioxidant activities of 2,4-dinitrophenylhydrazine and its Ni(II) and Co(II) compounds were studied with DPPH, as seen in Figure 6 , as well as Table 5 . The Ni(II) complex exhibited strong scavenging efficiency, whereas the Co(II) complex exhibited more moderate activity than the ligand. Compare to the ligand, the higher scavenging behaviors of the Ni(II) complexes can be attributed to the coordination of metal through the ligand [ 31 ]. 4. Conclusions 2,4-Dinitrophenylhydrazine and the thiocyanate complexes of Co(II) and Ni(II) were synthesized and characterized. The C, H, N and S analyses showed that the complexes have a 2:1ratio of ligand to metal. The evidence on the molar conductivity revealed that the compounds are non electrolytic in nature. The octahedral structure for the complexes of Co(II) and Ni(II) was determined based on the results obtained from the UV-visible spectral study and magnetic susceptibility measurements. The powder XRD analysis revealed that the compounds are average crystalline sizes are around 29.28 and 30.59 nm. The in-vitro antibacterial and fungal efficiency pointed out that the complexes of Co(II) and Ni(II) have superior action to DNPH. The in-vitro antioxidant efficiency revealed that both complexes had higher activity than DNPH. Author Contributions Writing—review & editing: M.A., S.I.A.-R., A.M., S.M., Z.T., I.K.; investigation: P.M., G.M.; Data curation: S.B.; funding acquisition: D.R. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Acknowledgments The authors acknowledge the financial support through the Researchers Supporting Project number RSP-2020/147, King Saud University, Riyadh, Saudi Arabia. Conflicts of Interest Authors don’t have any conflict of interests. Sample Availability The sample of compounds are not available from authors. References Alam Siddiki, A.K.M.N.; Islam, S.; Begum, S.; Salam, A. Synthesis, spectral characterization, thermal behavior and biological activities study of ternary metal complexes of alanine and 1, 8-diaminonapthalene with Co(III), Ni(II), Cu(II), Zn(II) and Cd(II). Mater. Today Proc. 2020 . [ Google Scholar ] [ CrossRef ] Hossain, M.S.; Banu, L.A.; E-Zahan, M.K.; Haque, M.M. Synthesis, Characterization and Biological Activity Studies of Mixed Ligand Complexes with Schiff base and 2,2′-Bipyridine. Appl. Sci. Res. Rev. 2019 , 6 , 1–7. [ Google Scholar ] [ CrossRef ] Raman, N.; Sobha, S. 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FTIR (Fourier transform infrared) spectra of ( a ) 2,4-dinitrophenylhydrazine (DNPH), ( b ) the Co(II) complex and ( c ) the Ni(II) complex. Figure 3. UV-visible spectrum of DNPH, along with the Co(II) and Ni(II) complexes. Figure 3. UV-visible spectrum of DNPH, along with the Co(II) and Ni(II) complexes. Figure 4. Powder X-ray diffraction (PXRD) patterns of the ( a ) Co(II) complex and ( b ) Ni(II) complex. Figure 4. Powder X-ray diffraction (PXRD) patterns of the ( a ) Co(II) complex and ( b ) Ni(II) complex. Figure 5. Results of the antimicrobial potential screening for DNPH and its metal complexes. Figure 5. Results of the antimicrobial potential screening for DNPH and its metal complexes. Figure 6. Result of the DPPH radical scavenging abilities. Figure 6. Result of the DPPH radical scavenging abilities. Table 1. Physical data, as well as analytical characterizations, of the metal compounds. Table 1. Physical data, as well as analytical characterizations, of the metal compounds. Complexes M.F MW Color of the Complexes % of Yield Elemental Analysis Found/(Calculated) % Λ m Ω −1 cm 2 mol −1 %C %H %N %S % Metal (Co(DNPH) 2 (SCN) 2 ) CoC 14 H 12 N 10 O 8 S 2 571.36 Blue 69 29.45 2.12 24.52 11.22 10.31 19.85 29.42 2.09 24.48 11.18 10.29 (Ni(DNPH) 2 (SCN) 2 ) NiC 14 H 12 N 10 O 8 S 2 571.12 Green 74 29.44 2.12 24.53 11.23 10.28 17.86 29.37 2.08 24.47 11.22 10.20 Λm—Molar conductivity; M.F—Molecular Formula; MW—Molecular Weight. Table 2. Selected FTIR spectral data of the ligands and their metal complexes (cm −1 ). Table 2. Selected FTIR spectral data of the ligands and their metal complexes (cm −1 ). Compounds ν(N-H) ν(NO 2 )asym ν(NO 2 )asym ν(N-N) ν(SCN) ν(M-O) ν(M-N) DNPH 3324 1516 1319 920 - - - (Co(DNPH) 2 (SCN) 2 ) 3284 1495 1371 969 2094 539 496, 446 (Ni(DNPH) 2 (SCN) 2 ) 3278 1501 1378 978 2098 551 449, 423 Table 3. UV-visible absorption spectral data and magnetic moment values. Table 3. UV-visible absorption spectral data and magnetic moment values. Complex λ max (nm) Band Assignments Geometry Magnetic Moment (B.M) DNPH 267 π–π - - 363 n–π* (Co(DNPH) 2 (SCN) 2 ) 281 π–π* Octahedral 5.1 388 LMCT 721 4T1g(F)–4T2g(F) (Ni(DNPH) 2 (SCN) 2 ) 284 π–π* Octahedral 3.2 390 LMCT 450 3A2g (F)→3T2g (P) 724 3A2g (F)→3T2g (F) LMCT—ligand to metal charge transfer. Table 4. Antimicrobial activities of DNPH and their metal complexes. Table 4. Antimicrobial activities of DNPH and their metal complexes. Organism Name Co(II) Complex Ni(II) Complex 2,4-Dinitrophenyl Hydrazine Test (mm) 30 µg/mL 60 µg/mL 90 µg/mL 30 µg/mL 60 µg/mL 90 µg/mL 30 µg/mL 60 µg/mL 90 µg/mL Bacillus subtilis 10 16 20 9 13 19 - 2 5 Staphylococcus aureus 10 20 24 9 12 15 1 3 6 Pseudomonas aeruginosa - 12 19 - 4 10 - 1 2 Escherichia coli 13 16 18 10 15 20 - - 3 Aspergillusnigre 10 12 19 5 15 20 5 10 12 Candida albicans 13 16 20 10 18 20 - 8 10 Table 5. Percent of radical scavenging abilities of the Co(II) and Ni(II) complexes and DNPH. Table 5. Percent of radical scavenging abilities of the Co(II) and Ni(II) complexes and DNPH. Compounds 150 μg/mL 100 μg/mL 50 μg/mL 2,4-dinitrophenyl hydrazine 59.60 52.24 50.57 Co(II) complex 64.22 58.93 54.15 Ni(II) complex 68.75 63.29 60.54 Manimaran, P.; Balasubramaniyan, S.; Azam, M.; Rajadurai, D.; Al-Resayes, S.I.; Mathubala, G.; Manikandan, A.; Muthupandi, S.; Tabassum, Z.; Khan, I. Synthesis, Spectral Characterization and Biological Activities of Co(II) and Ni(II) Mixed Ligand Complexes. Molecules 2021, 26, 823. https://doi.org/10.3390/molecules26040823 AMA Style Manimaran P, Balasubramaniyan S, Azam M, Rajadurai D, Al-Resayes SI, Mathubala G, Manikandan A, Muthupandi S, Tabassum Z, Khan I. Synthesis, Spectral Characterization and Biological Activities of Co(II) and Ni(II) Mixed Ligand Complexes. Molecules. 2021; 26(4):823. https://doi.org/10.3390/molecules26040823 Chicago/Turabian Style Manimaran, P., S. Balasubramaniyan, Mohammad Azam, D. Rajadurai, Saud I. Al-Resayes, G. Mathubala, A. Manikandan, S. Muthupandi, Zishan Tabassum, and Imran Khan. 2021. "Synthesis, Spectral Characterization and Biological Activities of Co(II) and Ni(II) Mixed Ligand Complexes" Molecules26, no. 4: 823. https://doi.org/10.3390/molecules26040823 Manimaran, P.; Balasubramaniyan, S.; Azam, M.; Rajadurai, D.; Al-Resayes, S.I.; Mathubala, G.; Manikandan, A.; Muthupandi, S.; Tabassum, Z.; Khan, I. Synthesis, Spectral Characterization and Biological Activities of Co(II) and Ni(II) Mixed Ligand Complexes. Molecules 2021, 26, 823. https://doi.org/10.3390/molecules26040823 Manimaran P, Balasubramaniyan S, Azam M, Rajadurai D, Al-Resayes SI, Mathubala G, Manikandan A, Muthupandi S, Tabassum Z, Khan I. Synthesis, Spectral Characterization and Biological Activities of Co(II) and Ni(II) Mixed Ligand Complexes. Molecules. 2021; 26(4):823. https://doi.org/10.3390/molecules26040823 Chicago/Turabian Style	https://www.mdpi.com/1420-3049/26/4/823
NuSTAR results and future plans for magnetar and rotation-powered pulsar observations - CaltechAUTHORS NuSTAR results and future plans for magnetar and rotation-powered pulsar observations An, H.and Bhalerao, V.and Bellm, E. C.and Forster, K.and Grefenstette, B. W.and Harrison, F. A.and Madsen, K. K.and Rana, V. R.and Tendulkar, S.(2014) NuSTAR results and future plans for magnetar and rotation-powered pulsar observations.Astronomische Nachrichten, 335 (3). pp. 280-284. ISSN 0004-6337. doi:10.1002/asna.201312032.https://resolver.caltech.edu/CaltechAUTHORS:20140410-114248478 Abstract The Nuclear Spectroscopic Telescope Array (NuSTAR) is the first focusing hard X-ray mission in orbit and operates in the 3–79 keV range. NuSTAR's sensitivity is roughly two orders of magnitude better than previous missions in this energy band thanks to its superb angular resolution. Since its launch in 2012 June, NuSTAR has performed excellently and observed many interesting sources including four magnetars, two rotation-powered pulsars and the cataclysmic variable AE Aquarii. NuSTAR also discovered 3.76-s pulsations from the transient source SGR J1745–29 recently found by Swift very close to the Galactic center, clearly identifying the source as a transient magnetar. For magnetar 1E 1841–045, we show that the spectrum is well fit by an absorbed blackbody plus broken power-law model with a hard power-law photon index of ∼ 1.3. This is consistent with previous results by INTEGRAL and RXTE. We also find an interesting double-peaked pulse profile in the 25–35 keV band. For AE Aquarii, we show that the spectrum can be described by a multi-temperature thermal model or a thermal plus non-thermal model; a multi-temperature thermal model without a non-thermal component cannot be ruled out. Furthermore, we do not see a spiky pulse profile in the hard X-ray band, as previously reported based on Suzaku observations. For other magnetars and rotation-powered pulsars observed with NuSTAR, data analysis results will be soon available. Item Type: Article Related URLs: URL URL Type Description http://dx.doi.org/10.1002/asna.201312032 DOI Article http://onlinelibrary.wiley.com/doi/10.1002/asna.201312032/abstract Publisher Article http://arxiv.org/abs/1402.1079 arXiv Discussion Paper ORCID: Author ORCID Bhalerao, V. 0000-0002-6112-7609 Bellm, E. C. 0000-0001-8018-5348 Forster, K. 0000-0001-5800-5531 Grefenstette, B. W. 0000-0002-1984-2932 Harrison, F. A. 0000-0003-2992-8024 Madsen, K. K. 0000-0003-1252-4891 Rana, V. R. 0000-0003-1703-8796 Additional Information: © 2014 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim. Received 2013 Dec 20; accepted 2014 Jan 14; Published online 2014 Mar 16. This work was supported under NASA Contract No. NNG08FD60C, and made use of data from the NuSTAR mission, a project led by the California Institute of Technology, managed by the Jet Propulsion Laboratory, and funded by the National Aeronautics and Space Administration. We thank the NuSTAR Operations, Software and Calibration teams for support with the execution and analysis of these observations. This research has made use of the NuSTAR Data Analysis Software (NuSTARDAS) jointly developed by the ASI Science Data Center (ASDC, Italy) and the California Institute of Technology (USA). V.M.K. acknowledges support from an NSERC Discovery Grant, the FQRNT Centre de Recherche Astrophysique du Québec, an R. Howard Webster Foundation Fellowship from the Canadian Institute for Advanced Research (CIFAR), the Canada Research Chairs Program and the Lorne Trottier Chair in Astrophysics and Cosmology. A.M.B. acknowledges the support by NASA grants NNX10AI72G and NNX13AI34G. Part of this work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DEAC52-07NA27344. Group: NuSTAR, Space Radiation Laboratory Funders: Funding Agency Grant Number NASA NNG08FD60C Natural Sciences and Engineering Research Council of Canada (NSERC) UNSPECIFIED Fonds de recherche du Québe-Nature et technologies (FRQ-NT) UNSPECIFIED Canadian Institute for Advanced Research (CIFAR) UNSPECIFIED Canada Research Chairs Program UNSPECIFIED Lorne Trottier Chair in Astrophysics and Cosmology UNSPECIFIED NASA NNX10AI72G NASA NNX13AI34G Department of Energy (DOE) DE-AC52-07NA27344 Subject Keywords: space vehicles; stars: neutron; telescopes; X-rays: stars Other Numbering System: Other Numbering System Name Other Numbering System ID Space Radiation Laboratory 2014-68 Issue or Number: 3 DOI: 10.1002/asna.201312032 Record Number: CaltechAUTHORS:20140410-114248478 Persistent URL: https://resolver.caltech.edu/CaltechAUTHORS:20140410-114248478 Official Citation: An, H., Kaspi, V.M., Archibald, R., Bachetti, M., Bhalerao, V., Bellm, E. C., Beloborodov, A. M., Boggs, S. E., Chakrabarty, D., Christensen, F. E., Craig, W. W., Dufour, F., Forster, K., Gotthelf, E. V., Grefenstette, B. W., Hailey, C. J., Harrison, F. A., Hascoët, R., Kitaguchi, T., Kouveliotou, Ch., Madsen, K. K., Mori, K., Pivovaroff, M. J., Rana, V. R., Stern, D., Tendulkar, S., Tomsick, J. A., Vogel, J. K., Zhang, W. W. and the NuSTAR Team (2014), NuSTAR results and future plans for magnetar and rotation-powered pulsar observations. Astron. Nachr., 335: 280–284. doi: 10.1002/asna.201312032 Usage Policy: No commercial reproduction, distribution, display or performance rights in this work are provided. ID Code: 44857 Collection: CaltechAUTHORS Deposited By: INVALID USER Deposited On: 10 Apr 2014 21:40 Last Modified: 10 Nov 2021 16:57	https://authors.library.caltech.edu/44857/
EHRI - Bundesarchiv, Berlin-Lichterfelde - Items 81 to 100 of 763 The European Holocaust Research Infrastructure Online Portal Show Item Details Archival Descriptions Clear all filters close Filter Results Language of Description German (763) Country Germany (763) Remove Filter close Holding Institution Bundesarchiv, Berlin-Lichterfelde (763) Search items held by Bundesarchiv, Berlin-Lichterfelde... Search search Advanced query tips arrow_drop_down × There are several ways to be more specific in your search query: "Phrase" Search an exact match of your query, e.g. "Member lists" +Phrase Given word has to be in the result, e.g. +Gestapo -Phrase Exclude given word from search, e.g. -Gestapo Use the following syntax to restrict the search to specific fields: field:"phrase" For instance, you can find all descriptions that have the phrase "Auschwitz Birkenau" in their titles by searching for title:"Auschwitz Birkenau". The following fields are currently available: identifier title creator person place subject address Displaying items 81 to 100 of 763 sort Search result ordering Relevance ID/Code Name Recently Updated Detail Country: Germany close Reichsverkehrsministerium Bundesarchiv, Berlin-Lichterfelde R 5 German 1919-1945 15771 AE Schriftgut Updated 3 months ago Eisenbahnabteilungen: Grundlegendes zur Reichsbahn im Rahmen des Staats- und Völkerrechts 1912-1939 (137), Vorgeschichte, Gründung und Entwicklung der Deutschen Reichsbahngesellschaft 1901-1944 (76), Grundsätzliches zur Deutschen Reichsbahn ab 1937, einschließlich des Verwaltungsrats 1920-1946 (133) Allgemeine Verwaltung und Organisation (725): v.a. Beziehungen zu Behörden, Institutionen, Organisationen und Verbänden 1901-1946 (137), Neuerungen, Erfindungen, Patente 1923-1945 (71), Privatbahnen und Kleinbahnen 1883-1945, 1957 (218), Gliederung der Verwaltung 1895-1944 (57), Geschäftsverteil... Wirtschaftsgruppe Sägeindustrie Bundesarchiv, Berlin-Lichterfelde R 13-XXXII German 1937-1946 85 AE Schriftgut Updated 8 years ago Neben wenigen Akten mit Rundschreiben 1937-1946 sind v. a. Betreuerberichte über einzelne holzverarbeitende Firmen 1937-1944 überliefert. Zugeordnet sind 10 Aktenbände Nachkriegsangelegenheiten 1945-1946 Wirtschaftsgruppe Lebensmittelindustrie Bundesarchiv, Berlin-Lichterfelde R 13-XXVI German 1918-1945 602 AE Schriftgut Updated 8 years ago Im Bestand dokumentiert wird die Tätigkeit folgender Fachgruppen: Fachgruppe Lebensmittelindustrie 1934-1945, Fachgruppe Getreidemühlenindustrie (u.a. Unterlagen über ost- und mitteldeutsche Mühlen) 1923-1944, Fachgruppe Fleischwarenindustrie 1938, 1942 (1), Fachgruppe Ölmühlenindustrie 1937, 1939-1945 (102), Reichsverband der deutschen Obst- und Gemüseverwertungsindustrie e.V./ Fachgruppe Obst- und Gemüseverwertungsindustrie 1918, 1921, 1933-1945 Wirtschaftsgruppe Metallindustrie Bundesarchiv, Berlin-Lichterfelde R 13-XXIV German 1942-1945 39 AE Schriftgut Updated 8 years ago Neben Akten der Wirtschaftsgruppe Metallindustrie 1942-1945 ist im wesentlichen die Tätigkeit der Fachgruppe Metallerzeugende Industrie 1937, 1941-1945 und der Fachgruppe Metallhalbzeugindustrie 1941-1945 dokumentiert. SS-Helferinnenschule Oberehnheim Bundesarchiv, Berlin-Lichterfelde NS 32-II German 1942-1945 122 AE Schriftgut Updated 8 years ago Errichtung, Organisation und Entwicklung der SS-Helferinnenschule 1942-1945 (22), Lei‧tung, Führungs- und Aufsichtspersonal, ärztliche Betreuung 1933-1945 (12), Liegenschaften, Inventar und Beschaffungswesen 1942-1945 (14), innerer Dienst, Ausbildungs-, Arbeits- und Dienstpläne 1942-1945 (21), Werbung und Einstellung von SS-Helfe‧rinnen 1942-1945 (11), Anforderungen und Einsätze von SS-Helferinnen 1943-1945 (18), Personalangelegen‧heiten 1942-1945 (24) Trotz seines relativ geringen Umfangs dokumentiert der vorliegende Bestand sehr gut die Geschichte der SS-Helferinnenschule sowie ihre Bezie... Wirtschaftsgruppe der Papier-, Pappen-, Zellstoff- und Holzstofferzeugung Bundesarchiv, Berlin-Lichterfelde R 13-XXVIII German 1935-1945 5 AE Schriftgut Updated 8 years ago Neben Statistischen Jahrbüchern für die Deutsche Papier-, Pappen-, Zellstoff- und Holzstoffindustrie 1937-1944 ist die Satzung der Fachgruppe Holzstofferzeugung 1935 sowie ein band mit Rundschreiben 1944-1945 überliefert. Reichsstelle für Glas, Keramik und Holzverarbeitung Bundesarchiv, Berlin-Lichterfelde R 8-XI German 1932-1973 243 AE Schriftgut Updated 8 years ago Die Masse der Akten hat die Abwicklung des Warenverkehrs mit verschiedenen Staaten zum Inhalt. Eine weitere Gruppe umfasst statistisches Material über die Versorgungslage bei den einzelnenWarengruppen gemäß der Zuständigkeit der Überwachungsstelle für Waren verschiedener Art. Die Unterlagen über die Übewachungs- bzw. Reichsstelle selbst sind recht spärlich und auch die Akten betr. Regelung von Bewirtschaftungs- und Prdoduktionsangelegenheiten, Zulassung von Devisenberatern und Durchführung von Betriebsprüfungen treten mengenmässig kaum in Erscheinung. Wirtschaftsgruppe Luftfahrtindustrie Bundesarchiv, Berlin-Lichterfelde R 13-XXV German 1936-1944 22 AE Schriftgut Updated 8 years ago Die wenigen überlieferten Aktenbände betreffen neben der allgemeinen Geschäftstätigkeit 1936-1944 v.a. Normungsfragen 1938-1943. Darüber hinaus sind dem Bestand drei Handakten des Leiters der Wirtschaftsgruppe Admiral Rudolf Lahs zugeordnet. Wirtschaftsgruppe Kraftstoffindustrie Bundesarchiv, Berlin-Lichterfelde R 13-XXIII German 1936-1944 5 AE Schriftgut Updated 8 years ago Vorhanden sind nur 5 Aktenbände: Rundschreiben 1939, Berichte über Besprechungen 1941, Satzung der Wirtschaftsgruppe 1937, Deutschlands Treibstoff- und Mineralölversorgung (Denkschrift) 1936, Verschiedenes 1942-1944 Konzentrationslager Natzweiler Bundesarchiv, Berlin-Lichterfelde NS 4-NA German 1936-1945 119 AE Schriftgut Updated 6 months ago Neben Akten über die Überstellung und den Arbeitseinsatz der Häftlinge sowie den damit verbundenen organisatorischen Angelegenheiten sind Akten zu den Außenkommandos des Lagers vorhanden. Zum SS-Personal liegen diverse Personalakten von SS-Angehörigen und SS-Helferinnen vor. Darüber hinaus sind Unterlagen über Versetzungen und Kommandierungen vorhanden. Der Verwaltungsschriftwechsel umfasst allgemeine Anordnungen, Kommandantur- und Sonderbefehle sowie Dienstvorschriften. Diverse Akten beinhalten Schriftwechsel betreffend den Unterhalt des Lagers. Häftlinge 1937-1944 (59), SS-Personal 1939-1... Allgemeine SS: SS-Oberabschnitte, SS-Abschnitte und unterstellte Einheiten außerhalb des Gebietes der BRD Bundesarchiv, Berlin-Lichterfelde NS 47 German 1934-1945 56 AE Schriftgut Updated 6 months ago Der vorliegende Bestand dokumentiert anschaulich die Tätigkeiten des RuS-Führers und einiger SS-Pflegestellen im Oberabschnitt "Weichsel" sowie des RuS-Führers Frankreich: An der Art der Bearbeitung von Verlobungs- und Heiratsgesuchen, von Gesuchen um Aufnahme in die SS, in Fragen der (An-) Siedlung von SS-Angehörigen, der "Wiedereindeutschung", Volkszugehörigkeit und der Behandlung von "Mischehen" und unehelichen Kindern wird immer wieder die Rassenideologie der SS deutlich: Streng wurde auf die Einhaltung der "Rassenreinheit" der SS und in Volkszugehörigkeitsfragen auf den "Schutz" des de... Wirtschaftsgruppe Stahl- und Eisenbau Bundesarchiv, Berlin-Lichterfelde R 13-II German 1939-1944 5 AE Schriftgut Updated 8 years ago Statistik, Hollerithlisten, Verwaltungssachen, Gemeinschaftshilfe Wirtschaftsgruppe Druck Bundesarchiv, Berlin-Lichterfelde R 13-XIX German 1944-1945 2 AE Schriftgut Updated 8 years ago Vorhanden sind lediglich zwei Aktenbände zur Organisation sowie zu Ausbildung und Prüfungswesen Konzentrationslager Dachau Bundesarchiv, Berlin-Lichterfelde NS 4-DA German 1909-1945 49 AE Schriftgut Updated 6 months ago Inhaltliche Charakterisierung Neben Aufstellungen von Häftlingen und deren Einsatz sowie deren Bewegungen innerhalb des Lagersystems liegen Unterlagen zum SS-Personal und dessen Beförderung, Ernennung und Kommandierung vor. Personenbezogenes Schriftgut zu einzelnen SS-Angehörigen und Capos sowie zu Ermittlungen aus der Zeit nach Mai 1945 im Zusammenhang mit im Lager Dachau verübten Verbrechen ist ebenfalls im Bestand enthalten. Die Verwaltungsakten betreffen Material-, Verpflegungs- und Bekleidungsbeschaffung. Überliefert sind auch Unterlagen der Zentralbauleitung der Waffen-SS und Polizei ... Reichsfinanzministerium Bundesarchiv, Berlin-Lichterfelde R 2 German 1879-1945 84859 AE Schriftgut Updated 8 years ago Die Überlieferung des RFM deckt mehr oder weniger umfangreich das Gesamtaufgabenspektrum der Behörde mit folgenden Überlieferungsschwerpunkten ab: - Aufstellung des Reichshaushalts, dabei v.a. Akten zur Aufstellung des Haushalts der Fachressorts, zum Heeres-, Marine- und Kolonialetat, zum Schuldenwesen des Reichs sowie zu Reichsbürgschaften, Reichsbeteiligungen, Exportkrediten, zu Banken, Währungs- und Devisenangelegenheiten - Organisations- und Verwaltungsangelegenheiten der Reichsfinanzverwaltung, Liegenschafts- und Reichsbauverwaltung, dabei v.a. Akten zur Unterbringung der Dienststellen... 11. Panzer-Division Bundesarchiv, Berlin-Lichterfelde RH 27-11 German 156 AE8,3 lfm Schriftgut Updated 8 years ago Ia: KTB August 1940 bis Dezember 1943 sowie Zustandsberichte 1943-1945 (in RH 10/149). Ib: KTB Januar bis April 1941und Juni 1941 bis Juli 1943 sowie KTB der Kampfgruppe Eschrich September/November 1944 und Unterlagen für eine Divisionsgeschichte. Ic: TB Januar bis Oktober 1941, Ende Januar bis Dezember 1942 und Februar bis Dezember 1943. IIa: TB Mitte Januar 1942 bis März 1943 und August bis Dezember 1943. Sturmabteilungen der NSDAP Bundesarchiv, Berlin-Lichterfelde NS 23 German 1921-1945 1263 AE Schriftgut Updated 6 months ago Teil 1: 1921-1945 (439): Befehle, Verfügungen, Anordnungen 1927-1940 (71), Verwaltungsangelegenheiten 1931-1945 (208), Rechtsamt o.Dat. (26), Presseangelegenheiten o.Dat. (16), SA-Obergruppen und SA-Grup‧pen o.Dat. (104), Diverses o.Dat. (14) Teil 2: 1931/1933-1935 (15): Chef des Ausbildungswesens 1931/33-1935 (15) Langtext: Die Geschichte der SA wird durch die in NS 23 überlieferten Unterlagen der OSAF nur in sehr geringem Umfang deutlich. Lediglich die Tätigkeit des Führungshauptamtes und des Gerichts- und Rechtsamtes, mit einem Schwerpunkt auf der Zeit nach 1933, sind einigermaßen belegt... Zentralnachweiseamt für Kriegerverluste und Kriegergräber Bundesarchiv, Berlin-Lichterfelde R 80 German 1920-1945 21 AE Schriftgut Updated 8 years ago Maßnahmen zur Erhaltung der deutschen Kriegergräber und Kriegerdenkmäler aus dem Krieg 1870/71 in Frankreich und bei Saarbrücken 1921-1945 (6), Kriegerdenkmäler und Kriegergräber.- Reiseberichte mit Bildern 1925-1936 (10), Personalakten 1933-1945 (4) Konzentrationslager Groß-Rosen Bundesarchiv, Berlin-Lichterfelde NS 4-GR German 1939-1945 21 AE Schriftgut Updated 6 months ago Inhaltliche Charakterisierung Neben Aufstellungen von Häftlingen und deren Bewegungen innerhalb des Lagersystems sowie verschiedenen Meldungen über durchgeführte Exekutionen enthält der Bestand personenbezogenes Schriftgut zu einzelnen Häftlingen. Personalangelegenheiten der SS-Wachmannschaften sind lediglich in drei Aktenbänden überliefert. Die Verwaltungsunterlagen betreffen Bereiche wie Krankenbau, Waffen- und Gerätebestand, Auszeichnungsvorschläge und Briefwechsel der Häftlinge mit ihren Angehörigen. Ferner liegt ein Fotoalbum der Kommandantur vor. Reichspressekammer Bundesarchiv, Berlin-Lichterfelde R 56-IV German 1933-1945 42 AE Schriftgut Updated 6 months ago Die wenigen überlieferten Akten der Reichspresskammer sind kaum aussagekräftig. Mitgliederkarteien und -akten sind von der Reichspressekammer anders als bei den anderen Kammern der reichskulturkammer nicht geführt worden. Die Erfassung der Mitglieder erfolgte durch die "Fachverbände" der Kammer.[1] [1] siehe Vermerk von D. Werner vom 21.12.1973 in 2477-23/23 < 1 2 3 4 5 (current) 6 7 8 9 ... 38 39 > Keep up with EHRI news Subscribe to our mailing list Facebook Twitter English Français Deutsch Polski	https://portal.ehri-project.eu/institutions/de-002429/search?country=de&page=5&sort=detail
Cephalopod International Advisory Council 2006 \| Page 2 \| The Octopus News Magazine Online Certainly wish I could be there (if they'd even let me in :grin:). Have fun, ambassadors of TONMO.com! Course they would Tony! Wish you caould be there... Cephalopod International Advisory Council 2006 \| Page 2 \| The Octopus News Magazine Online TONMO Forums Latest activity New posts Ceph News octobot's News Desk Ask octobot (beta) Articles New articles Latest reviews Author list Series list Photos/Videos New media New comments Supporters Account Upgrades About Us TONMO FAQ Meet the Staff Get More Involved! Advertise With Us TONMOCON Log in Register What's new Latest activity New posts Menu Log in Register Install the app Install The Octopus' Den Cephalopod International Advisory Council 2006 Thread starter marinebio_guy Start date Jul 21, 2005 Prev 1 2 3 4 Next First Prev 2 of 4 Go to page Go Next Last Jean Colossal Squid Registered Joined Nov 19, 2002 Messages 4,217 Oct 5, 2005 #16 tonmo said: Certainly wish I could be there (if they'd even let me in ). Have fun, ambassadors of TONMO.com! Click to expand... Course they would Tony! Wish you caould be there too! and Kat yes I'm assuming the worst too, got my talk halfway ready (that way if I have to change to poster I have the pics etc all ready to go!!) J Reply Melissa Larger Pacific Striped Octopus Registered Joined Apr 3, 2003 Messages 1,136 Oct 8, 2005 #17 Will those of you presenting put up your pictures accompanying your talks or posters on TONMO? Please? Have fun! Melissa Reply Jean Colossal Squid Registered Joined Nov 19, 2002 Messages 4,217 Oct 8, 2005 #18 Melissa said: Will those of you presenting put up your pictures accompanying your talks or posters on TONMO? Please? Have fun! Melissa Click to expand... Will do although at this stage most of mine are drawings and graphs. Main_board Halifax to Hobart Wow.....that's some distance! Christchurch to Melbourne is about 3 hours then a wee wait of about 2-3 hours before the flight to Hobart. Was going to leave from Dunedin but that was going to be nearly $500 more........can't quite figure out why, so have a four hour bus trip to Christchurch first, still 'tis extra time to memorise my talk and to get stressed out!!!! J Reply main_board Vampyroteuthis Registered Joined Feb 5, 2003 Messages 373 Oct 29, 2005 #19 Well, finally registered for the conference! And not a day too soon either for that early cut off of Nov. 1. Feels soooooo good, I'm just soooo excited! Cheers! Reply Jean Colossal Squid Registered Joined Nov 19, 2002 Messages 4,217 Oct 29, 2005 #20 main_board said: Well, finally registered for the conference! And not a day too soon either for that early cut off of Nov. 1. Feels soooooo good, I'm just soooo excited! Cheers! Click to expand... See ya there, just heard I'm talking apparently same talk in 2 different sessions !!!! Aint gonna happen 1 is quite enough!!!!!!!!! Sent my registration off a few weeks ago with a big fat cheque (don't have a credit card .......waaaaaaaaaaaay too dangerous!!!) Cheers J Reply main_board Vampyroteuthis Registered Joined Feb 5, 2003 Messages 373 Oct 30, 2005 #21 Hmmmm, that just might be a little awkward! Good luck with all the preparations. Cheers! Reply monty TONMO Supporter Staff member Registered Joined Mar 8, 2004 Messages 4,883 Oct 30, 2005 #22 main_board said: Hmmmm, that just might be a little awkward! Good luck with all the preparations. Cheers! Click to expand... Did they, in typical conference planning form, schedule the two talks in different rooms at the same time? I hope your talks go well, in any case... Reply Jean Colossal Squid Registered Joined Nov 19, 2002 Messages 4,217 Oct 30, 2005 #23 Rooms, times etc haven't been assigned yet but.........still they are ONLY GETTING ONE TALK!!!!!!!!!!!!! Thanks for the good luck wishes ...I'm gonna need it!!! J Reply DHyslop Architeuthis Registered Joined Dec 22, 2004 Messages 1,713 Oct 30, 2005 #24 Jean. said: .....still they are ONLY GETTING ONE TALK!!!!!!!!!!!!! Click to expand... Oh, come on---it would look great on your CV! Good luck, and I hope it goes better than my Geological Society of America talk last year Dan Reply Jean Colossal Squid Registered Joined Nov 19, 2002 Messages 4,217 Oct 30, 2005 #25 DHyslop said: Oh, come on---it would look great on your CV! Good luck, and I hope it goes better than my Geological Society of America talk last year Dan Click to expand... I hope it goes well too, I've given a presentation nearly every year at the NZ Marine Science Society Conference but that conference generally has no squid biologists at it, (unless Steve and Kat can find the time in their very busy schedules to attend ) so's I don't have to stress too much but a WHOLE conference of ceph people I'm sure your talk was great really...on the whole when i talk to people after their presentations they pick holes in it but the audience usually find nothing wrong!!!!!!! J Reply DHyslop Architeuthis Registered Joined Dec 22, 2004 Messages 1,713 Oct 30, 2005 #26 If you've given regular research talks you probably don't need either cv padding or well wishes I really don't understand how myself or anyone else can be so nervous about public speaking. It is so irrational. I was watching Bill Clinton give an hour-long speech to a college group in Texas today on C-Span. Completely extemporaneous, without any notes or anything. I was in such awe until I realized that I, or anyone else, can do the exact same thing when we're talking to a friend and aren't under pressure. Completely psychological. It reminds me of a bit by Jerry Seinfeld where he's talking about a poll that said people's number two fear is death, and their number one fear is public speaking. The logical conclusion is that if you have to go to a funeral, most people would prefer to be in the casket than to have to give the eulogy! Dan Reply Jean Colossal Squid Registered Joined Nov 19, 2002 Messages 4,217 Oct 31, 2005 #27 DHyslop said: If you've given regular research talks you probably don't need either cv padding or well wishes Click to expand... Oh yes I do every little bit helps!!!! DHyslop said: I really don't understand how myself or anyone else can be so nervous about public speaking. It is so irrational. I was watching Bill Clinton give an hour-long speech to a college group in Texas today on C-Span. Completely extemporaneous, without any notes or anything. I was in such awe until I realized that I, or anyone else, can do the exact same thing when we're talking to a friend and aren't under pressure. Completely psychological. Click to expand... Yup.....still gives me the willies tho'! What's even worse is that I work in a Public Aquarium where I teach and give tours regularly AND I've nearly completed an interpretive guide course but talking about my own research to people in the know still freaks me out (and yes I know I talk myself into it!!!!) DHyslop said: It reminds me of a bit by Jerry Seinfeld where he's talking about a poll that said people's number two fear is death, and their number one fear is public speaking. The logical conclusion is that if you have to go to a funeral, most people would prefer to be in the casket than to have to give the eulogy! Dan Click to expand... Hmmmmmmmm not sure I'd go quite THAT far.......OTOH if the casket was comfy.............. Jean Reply main_board Vampyroteuthis Registered Joined Feb 5, 2003 Messages 373 Dec 29, 2005 #28 Hey Everyone! I have a silly little question here: how formal do you think the dress code is going to be? I'm just an undergrad student, so initially I was assuming that I could get away with jean shorts and t-shirts (except for the more formal functions like reception and poster project presentation), especially considering how hot it's going to be, hopefully. However, after talking to my parents about it they said that in North America showing up in blue denim at any conferece, regardless of temperature, is not acceptable. Generally people down under seem to be a little more relaxed and laid back (at least the kiwi's were) so now I'm really, royally confused. Please advise (hehehe ). Cheers, Your clueless Canuck! Reply DHyslop Architeuthis Registered Joined Dec 22, 2004 Messages 1,713 Dec 29, 2005 #29 I think you could get away with a nice button-up, collared shirt and some khaki pants. Then again I'm a geo guy so I'm used to a little less formal dress code. If you ever go to a paleontology conference, you can tell at first glance who's a geologist and who's a zoologist, because half of the people are wearing blue jeans or khakis, the other half are in suit and tie. You can also get a margarita in every poster session. Dan Reply cuttlegirl Colossal Squid Registered Joined Sep 16, 2005 Messages 4,933 Jan 25, 2006 #30 Good Luck to everyone giving presentations. Wish I could be there... Reply Prev 1 2 3 4 Next First Prev 2 of 4 Go to page Go Next Last	https://tonmo.com/threads/cephalopod-international-advisory-council-2006.4415/page-2
Quantitative EEG Evaluation During Robot-Assisted Foot Movement - [scite report] Supporting: 5, Mentioning: 24 - Passiveand imagined limbmovements induce changes in cerebral oscillatory activity. Central modulatory effects play a role in plastic changes, and are of uttermost importance in rehabilitation. This has extensively been studied for upper limb, but less is known for lower limb. The aim of this study is to investigate the topographical distribution of event-related desynchronization/synchronization(ERD/ERS) and task-relatedcoherence during a robot-assisted and a motor imagery task of lower limb in healthy subjects to inform rehabilitation paradigms. 32-channels electroencephalogram (EEG) was recorded in twenty-one healthy right footed and handed subjects during a robot-assisted single-joint cyclic right ankle movement performed by the BTS ANYMOV robotic hospital bed. Data were acquired with a block protocol for passive and imagined movement at a frequency of 0.2 Hz. ERD/ERS and task related coherence were calculated in alpha1 (8-10 Hz), alpha2 (10.5-12.5 Hz) and beta (13-30 Hz) frequency ranges. During passive movement, alpha2 rhythm desynchronized overC3 and ipsilateral frontal areas (F4, FC2, FC6); betaERD was detected over the bilateral motor areas (Cz, C3, C4). During motor imagery, a significant desynchronization was evident for alpha1 over contralateral sensorimotor cortex (C3), for alpha2 over bilateral motor areas (C3 and C4), and for beta over central scalp areas. Task-related coherence decreased during passive movement in alpha2 band between contralateral central area (C3, CP5, CP1, P3) and ipsilateral frontal area (F8, FC6, T8); beta band coherence decreased between C3-C4 electrodes, and increased between C3-Cz. These data contribute to the understanding of oscillatory activity and functional neuronal interactions during lower limb robot-assisted motor performance. The final output of this line of research is to inform the design and development of neurorehabilitation protocols. Quantitative EEG Evaluation During Robot-Assisted Foot Movement Anna Bosco et al. Abstract: Passiveand imagined limbmovements induce changes in cerebral oscillatory activity. Central modulatory effects play a role in plastic changes, and are of uttermost importance in rehabilitation. This has extensively been studied for upper limb, but less is known for lower limb. The aim of this study is to investigate the topographical distribution of event-related desynchronization/synchronization(ERD/ERS) and task-relatedcoherence during a robot-assisted and a motor imagery task of lower limb in healthy subject… Show more “…This increases the feasibility of utilizing sensorimotor rhythms for the design of endogenous BCIs, which are more beneficial than exogenous BCIs. This finding is consistent with the survey results where the 57% of the selected studies utilizing motor imagery task and ERD is the most common signal that have been used in the selected studies [ 12 , 23 , 24 , 29 , 40 , 42 ] to control the assistive devices as illustrated in Figure 5 b.…” Section : Results supporting confidence: 90% “…Central modulatory influences play an important role in the plasticity change and are utmost significant in rehabilitation [ 63 , 64 ]. Therefore the topological distribution of the ERD/ERS and task-related coherence during exoskeleton assisted and a motor imagery in ankle-foot movements has been investigated in [ 24 ] to give rich information of rehabilitation paradigm. A BTS ANYMOV robotic hospital bed was used to actuate ankle joint movements and 32 EEG were employed to record the brain activity during cyclic right ankle movement.…” Section : Results mentioning confidence: 99% “…Current effort has been developed to integrate two components, combining the ideas of walk training with that of passive joint motion (ANYMOV robotic bed, BTS Bioengineering, Milan, Italy). The compresence of the two training modalities should ideally cover the rehabilitation needs from the very acute phase to successive steps of recovery [ 24 ].…” Section : Introduction mentioning confidence: 99% 2 , Daud 3 et al. 2018 Sensors 68 0 38 0 Electroencephalography (EEG) signals have great impact on the development of assistive rehabilitation devices. These signals are used as a popular tool to investigate the functions and the behavior of the human motion in recent research. The study of EEG-based control of assistive devices is still in early stages. Although the EEG-based control of assistive devices has attracted a considerable level of attention over the last few years, few studies have been carried out to systematically review these studies, as a means of offering researchers and experts a comprehensive summary of the present, state-of-the-art EEG-based control techniques used for assistive technology. Therefore, this research has three main goals. The first aim is to systematically gather, summarize, evaluate and synthesize information regarding the accuracy and the value of previous research published in the literature between 2011 and 2018. The second goal is to extensively report on the holistic, experimental outcomes of this domain in relation to current research. It is systematically performed to provide a wealthy image and grounded evidence of the current state of research covering EEG-based control for assistive rehabilitation devices to all the experts and scientists. The third goal is to recognize the gap of knowledge that demands further investigation and to recommend directions for future research in this area. “…This increases the feasibility of utilizing sensorimotor rhythms for the design of endogenous BCIs, which are more beneficial than exogenous BCIs. This finding is consistent with the survey results where the 57% of the selected studies utilizing motor imagery task and ERD is the most common signal that have been used in the selected studies [ 12 , 23 , 24 , 29 , 40 , 42 ] to control the assistive devices as illustrated in Figure 5 b.…” Section : Results supporting confidence: 90% “…Central modulatory influences play an important role in the plasticity change and are utmost significant in rehabilitation [ 63 , 64 ]. Therefore the topological distribution of the ERD/ERS and task-related coherence during exoskeleton assisted and a motor imagery in ankle-foot movements has been investigated in [ 24 ] to give rich information of rehabilitation paradigm. A BTS ANYMOV robotic hospital bed was used to actuate ankle joint movements and 32 EEG were employed to record the brain activity during cyclic right ankle movement.…” Section : Results mentioning confidence: 99% “…Current effort has been developed to integrate two components, combining the ideas of walk training with that of passive joint motion (ANYMOV robotic bed, BTS Bioengineering, Milan, Italy). The compresence of the two training modalities should ideally cover the rehabilitation needs from the very acute phase to successive steps of recovery [ 24 ].…” Section : Introduction mentioning confidence: 99% , 2 , Daud 3 et al. 2018 Sensors Electroencephalography (EEG) signals have great impact on the development of assistive rehabilitation devices. These signals are used as a popular tool to investigate the functions and the behavior of the human motion in recent research. The study of EEG-based control of assistive devices is still in early stages. Although the EEG-based control of assistive devices has attracted a considerable level of attention over the last few years, few studies have been carried out to systematically review these studies, as a means of offering researchers and experts a comprehensive summary of the present, state-of-the-art EEG-based control techniques used for assistive technology. Therefore, this research has three main goals. The first aim is to systematically gather, summarize, evaluate and synthesize information regarding the accuracy and the value of previous research published in the literature between 2011 and 2018. The second goal is to extensively report on the holistic, experimental outcomes of this domain in relation to current research. It is systematically performed to provide a wealthy image and grounded evidence of the current state of research covering EEG-based control for assistive rehabilitation devices to all the experts and scientists. The third goal is to recognize the gap of knowledge that demands further investigation and to recommend directions for future research in this area. “…In addition, it is possible to use EEG during task performance in an ecological environment. This framework allows exploration of the brain's functional changes and monitoring of brain activity in response to rehabilitation tasks [201] [202] [203] , potentially shedding light on specific brain-behavior relationships.…” et al. 2019 The development of robotic devices for rehabilitation is a fast-growing field. Nowadays, thanks to novel technologies that have improved robots' capabilities and offered more cost-effective solutions, robotic devices are increasingly being employed during clinical practice, with the goal of boosting patients' recovery. Robotic rehabilitation is also widely used in the context of neurological disorders, where it is often provided in a variety of different fashions, depending on the specific function to be restored. Indeed, the effect of robot-aided neurorehabilitation can be maximized when used in combination with a proper training regimen (based on motor control paradigms) or with non-invasive brain machine interfaces. Therapy-induced changes in neural activity and behavioral performance, which may suggest underlying changes in neural plasticity, can be quantified by multimodal assessments of both sensorimotor performance and brain/muscular activity pre/post or during intervention. Here, we provide an overview of the most common robotic devices for upper and lower limb rehabilitation and we describe the aforementioned neurorehabilitation scenarios. We also review assessment techniques for the evaluation of robotic therapy. Additional exploitation of these research areas will highlight the crucial contribution of rehabilitation robotics for promoting recovery and answering questions about reorganization of brain functions in response to disease.In the last decades, innovative robotic technologies have been developed in order to effectively help clinicians during the neurorehabilitation process. The term "robotic technology" in this application domain refers to any mechatronic device with a certain degree of intelligence that can physically intervene on the behavior of the patient, optimizing and speeding up his/her sensorimotor recovery. The two key capabilities of these robots are: (1) Assessing the human sensorimotor function; and (2) re-training the human brain in order to improve the patient's quality of life. However, most of the studies in this field have been focused more on the development of the devices, whereas less effort was made on maximizing their efficacy for promoting recovery. The main challenge consists of designing effective training modalities, supported by appropriate control strategies. Thus, each robotic device supports a pre-defined training modality depending on the low-level control strategy implemented and also on the residual abilities of each patient. Usually, most of the rehabilitation devices implement a passive training modality (robot-driven, position control strategy), where the robot imposes the trajectories, and an active training modality (patient-driven), where the robot modulates its trajectory in response to the subject's intention to move [7,8]. However, among all the different training modalities, the most relevant is the assistive one. Assistive controllers help participants to move their impaired limbs according to the desired postures during grasping, reaching, or walki... “…To the best of our knowledge, this is the first study to demonstrate the effectiveness of sensory stimulation-based CPM-MT system in terms of a control method (asynchronous and synchronous control) and human influence (muscle fatigue). To date, there have been few studies on the modulation of EEG cortical activity during robot-assisted tasks [54, 55] , and no study has evaluated different CPM-MT methods and their effect on muscle fatigue.…” Robotic mirror therapy (MT), which allows movement of the affected limb, is proposed as a more effective method than conventional MT (CMT). To improve the rehabilitation effectiveness of post-stroke patients, we developed a sensory stimulation-based continuous passive motion (CPM)-MT system with two different operating protocols, that is, asynchronous and synchronous modes. To evaluate their effectiveness, we measured brain activation through relative and absolute power spectral density (PSD) changes of electroencephalogram (EEG) mu rhythm in three cases with CMT and CPM-MT with asynchronous and synchronous modes. We also monitored changes in muscle fatigue, which is one of the negative effects of the CPM device, based on median power frequency (MPF) and root mean square (RMS). Relative PSD was most suppressed when subjects used the CPM-MT system under synchronous control: 22.11%, 15.31%, and 16.48% on Cz, C3, and C4, respectively. The absolute average changes in MPF and RMS were 1.59% and 9.78%, respectively, with CPM-MT. Synchronous mode CPM-MT is the most effective method for brain activation, and muscle fatigue caused by the CPM-MT system was negligible. This study suggests the more effective combination rehabilitation system for MT by utilizing CPM and magnetic-based MT task to add action execution and sensory stimulation compared with CMT. method uses voluntary exercise to improve a patient's motivation to rehabilitate [4] and prevents the deterioration of the motor ability of the lesioned brain hemisphere using a visual illusion that bilateral movement has been accomplished [5,6]. However, a major drawback of conventional MT (CMT) is that the paralyzed arm does not move at all during the treatment. Thus, muscle atrophy can be aggravated and the elbow can become stiff. Spasticity and hypertonus are likely to limit the functional use of the paralyzed limb. Additionally, muscle hyperexcitability may lead to secondary complications including contracture, pain, and reduced range of motion. In the long term, these complications may also result in structural changes in connective tissues and muscle fibers [7,8]. In such situations, patients lose their motivation to rehabilitate. In addition, the prevalence of strokes increases in an aging society, and the public healthcare burden of patients who have suffered a stroke increases. The current emphasis on cost reduction in medical services has resulted in reducing the duration of in-patient rehabilitation of post-stroke patients. This results in patients terminating treatment with incomplete recovery. These situations have triggered research on better and cost-efficient methods of treatment for post-stroke patients.To overcome the current limitations of CMT methods, a robotic system that actually moves the affected limb has recently been proposed as an emerging rehabilitative method [9,10]. However, building a new system for only one rehabilitation method, like MT, is difficult to introduce in many hospitals owing to budget and utilization issues. In addition, intro...	https://scite.ai/reports/quantitative-eeg-evaluation-during-robot-assisted-wGRr8l
Rolfes PWM (Pty) Ltd v Golding (3579/2016) [2016] ZAGPPHC 73 (12 February 2016) \| Noteup \| LawCite Rolfes PWM (Pty) Ltd v Golding (3579/2016) [2016] ZAGPPHC 73 (12 February 2016) Download original files PDF format RTF format IN THE HIGH COURT OF SOUTH AFRICA (GAUTENG DIVISION, PRETORIA) Case number: 3579/2016 Date: 12 February 2016 Not reportable Of interest to other judges Revised In the matter between: ROLFES PWM (PTY) LTD APPLICANT And ROBERT WILLIAM GOLDING RESPONDENT JUDGMENT PRETORIUS J. This is an urgent application requesting the court to enforce a restraint of trade agreement as follows: "2. Respondent is restrained from the following activities: 2.1. being interested in as trustee, proprietor, shareholder, member, manager, director, adviser, consultant, employee, financier or agent or for any person or entity which is directly or indirectly engaged in any activity which is similar to or competes with the business of Applicant; 2.2. enticing any of Applicant's customers, principals and suppliers away from it or to terminate its relations with Applicant or to change its contractual arrangements with Applicant; 2.3. encouraging or enticing any emp oyees of Applicant to terminate its employment with Applicant; 2.4. doing any of the acts listed in clause 5 of Annexure "B" to the Founding Affidavit. 3. The aforesaid interdict will be effective for a period of two years commencing on 30 November 2015 within the province of Gauteng." (2) In Sunshine Records (Pty) Ltd v Frohling and Others 1990(4) SA 782 (A) at 794 B-E the court summarised the law applicable in restraint of trades as follows confirming the dictum in Magna Alloys and Research (SA) (Pty) Ltd v Ellis 1984(4) SA 874 A: "For present purposes the effect of this judgment may be summarised as follows (vide at 893 - 4). In determining whether a restriction on the freedom to trade or to practise a profession is enforceable, a court should have regard to two main considerations. The first is that the public interest requires, in general, that parties should comply with their contractual obligations even if these are unreasonable or unfair. The second consideration is that all persons should, in the interests of society, be permitted as far as possible to engage in commerce or the professions or, expressing this differently, that it is detrimental to society if an unreasonable fetter is placed on a person's freedom of trade or to pursue a profession. In applying these two main considerations a courl will obviously have regard to the circumstances of the case before it. In general, however, it will be contrary to the public interest to enforce an unreasonable restriction on a person's freedom to trade." FACTS: (3) From September 2011 until 30 November 2015 the respondent was employed by the applicant as regional manager in Gauteng. On 5 September 2011 the respondent signed a restraint of trade agreement. The respondent took up employment with the applicant's direct competitor, after resigning. On 12 January 2016 the applicant ascertained that the respondent had made a proposal to one of the applicant's customers, namely First National Bank, Fairlands, in regards to an air conditioner for services normally supplied by the applicant. The applicant thereafter launched this application, alleging that the respondent is breaching the restraint of trade. (4) It is common cause that the restraint of trade is only valid for twenty four (24) months and therefore the court is requested to find the application to be urgent. Idid hear the matter as an urgent application. (5) On 12 January 2016 one of applicant's regional managers paid a routine visit to one of the applicant's existing customers, FNB (Fairlands) to which the applicant renders services in relation to its air conditioning system, where he found the respondent's business card lying on the desk of the FNB representative. He was informed that G-Chem, where the respondent is presently employed, had done a representation for the customer and introduced G-Chem as a supplier who could deliver the same services as the applicant. FNB (Fairlands) was one of the customers which respondent attended to whilst working for the applicant and the respondent knows their needs, prices they pay and who to contact. Respondent was, whilst working for the applicant, the face of the applicant who interacted with the clients on a personal level. OPPOSITION: (6) The respondent opposes the application and alleges that the restraint is void due to vagueness in respect of the area of its intended operation; it is limited in its description of the type of business in respect of which it operates and the restraint is unreasonable in that it protects no proper interest and is too wide in respect of its duration the capacities of association with a competitive firm intended to be covered thereby. VAGUENESS: (7) The restraint provides the territory of the restraint as: "...any region in which the Group conducts the Business as at the Termination Date or during the 12 (twelve) month precedent the Termination Date." It is clear that the restraint does not relate to specific defined areas. In the notice of motion the applicant requests the interdict to be operational for two years from 30 November 2015 in the province of Gauteng only, thus defining the area. (8) In National Chemsearch (SA) (Pty) Ltd v Borrowman and Another 1979(3) SA 1092 (T) at 1116 D the Full Bench decided: "The ratio of this approach I shall attempt to formulate as follows: when a restraint according to its terms as agreed upon is found to be unreasonably wide in its scope of operation, the Court can, in a proper case, enforce the restraint partially, by issuing an order incorporating the addition of such limiting words to the restraint as agreed upon as are appropriate to restrict its scope of operation to what is found to be reasonable." (Court's emphasis) (9) In BHT Water Treatments (Pty) Ltd v Leslie 1993(1) SA 47 (W) Marais J found at page 54: "In this case, instead of seeking to defend against attack the prima facie enforceable restraint clause, the applicant has in effect said: 'I seek enforcement of my restraint clause subject to a limitation. To that extent I concede that the original clause was too wide.' This seems to me the only effect of the concession, whether made on the papers or in argument by counsel. In the present case it seems to me that the applicant is saying: 'My original restraint was in principle good and enforceable, save that it is geographically too wide and should be limited to certain territories.' .The applicant, properly making a concession that the restraint is geographically too wide, does not in my view concede that the restraint is otherwise unreasonable, and I am of the view that the onus of showing that enforcement of the cut down restraint is unreasonable, remains on the respondent." (10) I find in the present instance that the above dictum is applicable. The applicant is only requesting a restraint in relation to the Gauteng province. There can thus no longer be any reliance on the scope of the restraint being too vague in relation to the territory. BUSINESS OF THE APPLICANT: (11) "Business" is defined in the agreement as "the business conducted by the Group, namely the business of supplying services, chemicals, equipment into water treatment, personal care and home care industries". The respondent alleges that the business of the applicant in this instance is limited and relates to only two clients. (12) "Prescribed customers" are defined as "any person with whom the Group conducted the Business, or any person with whom the Group held negotiations for the supply of Prescribed Goods or Prescribed Services, within 12 (twelve) months prior to the Termination Date." (Court's emphasis) (13) "Prescribed services" are defined as "the services conducted by the Group, including the business of supplying services, chemicals, equipment into water treatment, personal care and home care industries." (Court's emphasis) (14) The respondent contends that if an end customer is not a player in the "water treatment industry" such a customer will fall outside the definition of "Business" and will thus not be part of the restraint. The definition sets out that the applicant will be "supplying services". (15) According to the respondent the restraint is confined to customers who conduct industries "into water treatment, personal care and home care industries". (16) The applicant contends that the restraint does not only deal with customers "in the water treatment industry", but also with customers who are supplied with services and chemicals relating to water treatment. The applicant's representative set out in the founding affidavit that the main business of the applicant is the supply of "water treatment solutions" to various industries. The applicant explains that, for example, should a client run a cooling tower, the applicant ensures via the treatment that the water used does not corrode a customer's equipment. The applicant conducts site visits on a monthly basis, where the water is tested and the relevant chemicals supplied, as necessary. It is thus clear that the applicant is supplying services as well. (17) The respondent voluntarily agreed to the terms of the restraint agreement. It is common cause between the parties that, at the time of the respondent's resignation, he had paid weekly visits to the applicant's existing customers, which were approximately 150 in total; administered service representatives of the applicant for whom he was responsible and sourcing new customers. To the aforementioned customers the respondent was the face of the applicant, representing the applicant. He had personal contact with the applicant's clients, they knew him as the representative of the applicant and dealt with him on a regular basis. (18) In Rawlins and Another v Caravantruck (Pty) Ltd 1993(1) SA 537 at 542 G-H Nestadt JA found: "Even though the persons to whom an employee sells and whom he canvasses were previously known to him and in this sense 'his customers', he may nevertheless during his employment, and because of it, form an attachment to and acquire an influence over them which he never had before. Where this occurs, what I call the customer goodwill which is created or enhanced, is at least in part an asset of the employer. As such it becomes a trade connection of the employer which is capable of protection by means of a restraint of trade clause." (Court's emphasis) (19) In Rawlins and Another v Caravantruck (Pty) Ltd (supra) it was held: "Much will depend on the duties of the employees; his personality, the frequency and duration of the contact between him and the customers; where such contact takes place, what knowledge he gains of their requirements and business; the general nature of their relationships (including whether an attachment is formed between them, the extent to which customers rely on the employee and how personal their association is)" This decision is applicable in the present situation, as the respondent had intimate knowledge of the business of the clients and interacted with the clients as the face of the applicant. (20) These common cause facts put paid to the respondent's submission that there are only two clients who would be affected, as at the time of respondent's employment with the applicant, the respondent was responsible for 150 customers. I find that the respondent is incorrect when submitting that customers such as FNB (Fairlands) fall ouside the scope of the restraint. I find that the phrase "supplying services etc into (the) water treatment industry" does not mean that it must be a client in the water treatment industry, but that customers who use "water treatment" products are included regardless whether it is such a customer's principle business. It is found that the respondent was known to specific customers, knew the products they needed and the prices that they would pay and knew the price structures of the applicant to quote to the customers. I thus find that the applicant has a proprietary interest. The principles set out in the above dictum are applicable in these circumstances. UNREASONABLENESS: (21) The court has to take cognisance of the fact that the respondent resigned at the same time that his father and uncle had left the company and their restraint had run out. They are now all involved in a new company which is in direct competition with the applicant and the respondent is an employee of the new company. (22) There is no reason given as to why the respondent could not be employed in another province, by the new company. There is no reason for the respondent to be unemployed and economically inactive. He was a highly regarded employee of the applicant, who earned accolades and bonuses as a result of his good work. In Den Braven SA (Pty) Ltd v Pillay and Another 2008(6) SA 229 (D) at paragraph 50 Wallis AJ held: "The proper approach in my view is for the court to ask itself whether the conduct that the applicant seeks to restrain by way of an interdict is conduct that falls within the terms of the restraint agreement and from which the former employee agreed to abstain. If the answer to that question s in the affirmative the court then moves to an analysis of whether it should, in accordance with the principles of public policy, enforce the agreement to that extent by granting relief to the applicant. It has no need in those circumstances to have regard to those portions of the agreement that are more extensive than the relief actually being sought." (Court's emphasis) (23) The respondent's submission that a two year period for the restraint is too long cannot be justified as he had agreed to the restraint for such a period when he signed the agreement. I cannot find that it is against public policy for him to be restrained for a further twenty one and a half months. (24) In BHT Water Treatment (Pty) Ltd v Leslie 1993(1) SA 47 (W) at 57J - 58H it was decided that a prejudice is met where an employee takes up employment with a direct competitor even if the person undertakes not to divulge confidential information to the new employer. No such guarantee was provided by the respondent in the present instance. (25) In Den Braven (supra) it was decided at paragraph 32: "In summary the approach of the Constitutional Court is that contractual obligations are enforceable unless they are contrary to public policy, which is to be discerned from the values embodied in the Constitution and in particular in the Bill of Rights. Where the enforcement of a contractual provision would be unreasonable and unfair in the light of those fundamental values it will be contrary to public policy to enforce the contract or the contractual term in question." And at p253 D-G Wallis AJ found: "The person who sells a business and then seeks to make use of the trade connection that he sold will be interdicted from doing so even in the absence of a restraint of trade agreement. The employee who seeks to tum their employer's confidential information, trade secrets or trade or customer connection to their own account for the benefit of themselves or a competitor of their employer acts in a no less reprehensible fashion and I can think of no good reason why our law should not afford a remedy to a business that seeks protection against this type of unfair competition. Where the business has sought to protect itself by securing a restraint of trade undertaking from the employee there is no reason for the courts or the law to view this with disfavour. It is only where the bounds of public policy are overstepped that the court will withhold its assistance." (Court's emphasis) (26) I cannot find that the dictum in Kelly Group Ltd v Capazorio and Others 2011 JDR 0221 GSJ at 36-41 applicable as the facts in the present matter differ. (27) The respondent has joined a company in direct competition to the applicants business. He voluntarily agreed to the terms of the restraint agreement. The applicant has conceded that the terms of the agreement are too wide in respect of the region or territory and seeks constraint only in respect of Gauteng. I can come to no other conclusion, but that although 24 months may seem too long, the respondent signed the agreement at the time, and never complained that the restraint was too wide. He is only complaining now that the shoe is pinching. In any event two and a half months of the 24 months have already expired and the scope of the restraint has been curtailed to the province of Gauteng only. (28) Therefor I make the following order: 1. The application is urgent in terms of Rule 6(12) and that non compliance with ordinary time periods is condoned. 2. The Respondent is restrained from the following activities: 2.1. being interested in as trustee, proprietor, shareholder, member, manager, director, adviser, consultant, employee, financier or agent or for any person or entity which is directly or indirectly engaged in any activity which is similar to or competes with the business of Applicant; 2.2. enticing any of Applicant's customers, principals and suppliers away from it or to terminate its relations with Applicant or to change its contractual arrangements with Applicant; 2.3. encouraging or enticing any employees of Applicant to terminate its employment with Applicant; 2.4. doing any of the acts listed in clause 5 of Annexure "B" to the Founding Affidavit. 3. The aforesaid interdict will be effective for a period of two years commencing on 30 November 2015 within the province of Gauteng only. 4. The respondent is to pay the costs of this application. ______________________ Judge C Pretorius Case number : 357912016 Matter heard on : 2 February 2016 For the Applicant : Adv. FJ Erasmus Instructed by : VDT Incorporated For the Respondent : Adv. J Blou SC Instructed by : Cyril Ziman & Associates Date of Judgment : 12 February 2016	http://www.saflii.org/za/cases/ZAGPPHC/2016/73.html
Full article: Microbial metabolites as modulators of the infant gut microbiome and host-microbial interactions in early life The development of infant gut microbiome is a pivotal process affecting the ecology and function of the microbiome, as well as host health. While the establishment of the infant microbiome has been... Microbial metabolites as modulators of the infant gut microbiome and host-microbial interactions in early life Henrik M. Roager a Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark Correspondence [email protected] https://orcid.org/0000-0002-2504-8313 View further author information , Catherine Stanton b APC Microbiome Ireland, Teagasc Moorepark Food Research Centre, Fermoy, Co. Cork, Ireland https://orcid.org/0000-0002-6724-7011 View further author information & Lindsay J. Hall c Gut Microbes & Health, Quadram Institute Biosciences, Norwich, UK;d Intestinal Microbiome, School of Life Sciences, ZIEL – Institute for Food & Health, Technical University of Munich, Freising, Germany;e Norwich Medical School, University of East Anglia, Norwich, UK https://orcid.org/0000-0001-8938-5709 View further author information Full Article ABSTRACT The development of infant gut microbiome is a pivotal process affecting the ecology and function of the microbiome, as well as host health. While the establishment of the infant microbiome has been of interest for decades, the focus on gut microbial metabolism and the resulting small molecules (metabolites) has been rather limited. However, technological and computational advances are now enabling researchers to profile the plethora of metabolites in the infant gut, allowing for improved understanding of how gut microbial-derived metabolites drive microbiome community structuring and host-microbial interactions. Here, we review the current knowledge on development of the infant gut microbiota and metabolism within the first year of life, and discuss how these microbial metabolites are key for enhancing our basic understanding of interactions during the early life developmental window. KEYWORDS: Metabolites metabolomics infants microbiota health host diet Introduction A relatively simple microbial community at birth develops into a diverse and complex microbial ecosystem across the early life window Citation 1, which plays a vital role in postnatal maturation and development of the endocrine, nervous and immune systems Citation 2 , Citation 3. The gut microbiome thus has a profound influence on both early and long-term health and development Citation 4 , Citation 5. In addition to influencing development and maturation of the host immune system, the gut microbiota has a number of important functions in the host, including breakdown of ingested complex carbohydrates, protection against pathogenic bacteria and metabolic functions including production of vitamins, short chain fatty acids (SCFAs) and bile acid biotransformation Citation 6. The importance of neonatal bacterial colonization for the growth of a healthy individual is clear and exhibits the power that the microbiome has on its host from an early stage in development. The gut microbiota composition is initially known to be in a state of flux and consequently stabilizes, so that by age 2.5–4 years, it begins to resemble the composition and characteristics of an adult gut Citation 7 , Citation 8. In this early phase, the gut microbiota is more vulnerable to modulation than in the adult state Citation 9, suggesting that the first 1000 days of life is a critical window of opportunity for optimal bacterial colonization. Disruption to microbial development during this period is believed to have long-lasting consequences, impacting on normal immune and neurocognitive development and has been associated with increased risk of developing diseases such as asthma and metabolic syndrome later in life Citation 10 , Citation 11. The gut microbiota may also be modulated at this critical phase in a beneficial manner. Strategies to optimize early microbial acquisition during this key developmental window of opportunity may help to prevent and treat disease. Interventions to modulate the early microbiome include the use of probiotic and prebiotic interventions or combinations of both, as either synbiotics Citation 12or postbiotics Citation 13. The most promising results for probiotics have been seen in the prevention or treatment of diarrhea in children and in necrotizing enterocolitis in preterm infants Citation 14 , Citation 15. Pharmabiotics including microbially produced bacteriocins, bacteriophages and SCFAs have gained interest for potential application for microbiota modulation Citation 16–19. Furthermore, there has been a shift in recent years to expand microbiome research beyond profiling taxonomic composition using 16S rRNA gene sequencing and to focus on gut microbial functionality and activity using whole metagenome sequencing (WMS) and metabolomics. WMS while more costly than 16S rRNA sequencing provides insight on the functions encoded by the genes present in the microbiome. WMS also facilitates community structure to be examined at a far greater and reliable taxonomic resolution beyond genus level to examine species and subspecies Citation 20. In addition, metabolomics is a useful complementary approach to measure metabolites in the gut derived from the diet, host or the microbiota (collectively denoted the gut metabolome) Citation 21. Advances in informatics such as machine learning have also provided superior insight and facilitated meaningful interpretations of functional microbiome research Citation 22 , Citation 23. This review briefly discusses the factors influencing the gut microbiota in early life, summarizes current literature available on the diet-dependent development of the infant gut metabolome, and discusses how microbiota-derived metabolites may be key for early life microbiome and host development. Factors influencing the gut microbiota in early life Non-nutritional factors Delivery mode exerts a significant influence of gut microbiota composition, exposing the infant to various microbes associated with the maternal gut and vaginal tract Citation 24. Passage of the infant through the birth canal exposes it to the mother’s vaginal and fecal bacteria thereby contributing to microbial and metabolic diversity in the infant gut Citation 25. Cesarean section impairs the transfer of certain maternal strains resulting in an infant gut microbiota with increased abundance of potentially pathogenic microbes, and a lack of beneficial taxa such as Bifidobacterium Citation 26. Other factors reported to influence the development of the infant gut microbiome include gestational age, host genetics, feeding regime, geographical location and perinatal antibiotic usage Citation 27 , Citation 28. Gestational age is an important factor in gut microbiota development with preterm birth associated with reduced diversity and delayed colonization with Bifidobacteriumcompared with full-term infants Citation 29. Exposure to antibiotics in early life has been reported to induce an increased abundance of members of the Enterobacteriaceaefamily and decrease in abundance of Bifidobacterium Citation 30 , Citation 31. Antibiotic exposure has also been linked with the development of metabolic and inflammatory diseases later in life Citation 32. In recent years, evidence also supports the existence of a breast milk microbiome, which is a source of beneficial microbes to the infant Citation 27 , Citation 33 , Citation 34. Infants also acquire microbes that colonize their gut from the environment including siblings, pets and the hospital Citation 5 , Citation 28 , Citation 35. Breastmilk Human breast milk can meet all nutritional requirements essential for infant growth, health and development Citation 36. Breast milk contains essential nutrients such as caseins, whey, fatty acids, and lactose as well as micronutrients including Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, calcium and vitamin A Citation 28 , Citation 37. Furthermore, breast milk is a source of an array of bioactive components such as human milk oligosaccharides (HMOs). HMOs consist of > 150 known complex glycans with the most common being 2′-fucosyllactose (2′FL), accounting for 20–30% of all HMOs Citation 37–39. HMOs are not digested in the upper gastrointestinal (GI) tract and are degraded in the colon by specific HMO-degrading bacteria, mostly Bifidobacterium, into metabolites such as acetate and lactate with potential beneficial host health effects Citation 28 , Citation 38. The ability of some species of Bifidobacteriumto efficiently degrade HMOs makes them dominant members of the microbiota of breastfed infants. Host secretor status, based on active or inactive copy of the fucosyltransferase 2 (FUT2) gene, determines a mother’s ability to produce HMOs Citation 40–43. Non-secretors have been associated with reduced Bifidobacteriumand Bacteroidesabundances and lower microbial diversity in their infant’s gut microbiota Citation 44–47. The absence/decrease of 2′FL in non-secretor women has potential implications for infant short and long term health and development Citation 48–50. Formula milk Compositional analysis of the infant gut microbiota has shown altered community structures in formula-fed infants compared to breastfed infants Citation 51 , Citation 52. Higher abundance of potentially pathogenic bacteria such as Enterobacteriaceaeand Clostridium, as well as antimicrobial resistance genes, is observed in formula-fed infants compared to exclusively breastfed infants Citation 8 , Citation 51 , Citation 53 , Citation 54. Conversely, breastmilk feeding is associated with low microbial diversity, dominated by HMO-utilizing Bifidobacteriumspecies and saccharolytic fermentation compared to formula-feeding Citation 27 , Citation 55. Due to formula milk’s higher protein content, formula fed infants may also exhibit a higher degree of proteolytic metabolism in the gut Citation 56 , Citation 57. Proteolytic microbiota-derived metabolites have been linked to detrimental cardiovascular and metabolic health effects in adults Citation 58–61, as discussed in greater details below. Yet, whether changes in colonic fermentation observed in formula fed infants influence the risk of developing diseases later remains unknown. Nonetheless, many infant formulas have in recent years been supplemented with prebiotics in an attempt to mimic health benefits of HMOs in breast milk. Prebiotic supplementation has predominantly consisted of short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS), and HMOs such as 2-fucosyllactose and Lacto-N-neotetraose Citation 62–64. Weaning and beyond During the transition period to solid foods, typically between 4–6 months of age, changes appear in the richness and diversity of the infant gut microbiota. Milk adapted bacterial species such as B. longumsubsp. infantistypically decrease in this period Citation 65. Due to the increased consumption of protein and dietary fibers during this period, microbes capable of digesting more complex nutrients increase in abundance such as Lachnospiraceae, Bacteroidaceaeand Ruminococcaceae Citation 66–68. Microbiota maturation occurs continuously even beyond five years of age where the children have acquired a diverse, stable and adult-like configuration, but with a lower community richness compared to the adult microbiota Citation 69. Malnutrition Food is a major factor shaping the gut microbiota in early life. This is also evident in children who do not receive adequate nutrition during infancy and early childhood. Malnourished infants and children develop an immature gut microbiome Citation 70, which may contribute to impairment of child growth Citation 71 , Citation 72. The disturbance in microbial succession in malnourished children could contribute to lifelong deficits in growth and development as reviewed elsewhere Citation 73. Intriguingly, a recent 3-month-long intervention study showed that a microbiota-directed complementary food prototype in comparison with an existing ready-to-use supplementary food promoted weight gain in children with moderate acute malnutrition between the ages of 12 months and 18 months of age Citation 74. The study suggested that the improved weight gain could be mediated by a more complete repair of the gut microbiota Citation 74. Supporting this hypothesis, a placebo-controlled trial in 2- to 6-month-old undernourished Bangladeshi infants with severe acute malnutrition found that supplementation with a Bifidobacterium longumsubspecies infantisstrain promoted weight gain that was associated with reduced levels of intestinal inflammation markers Citation 75. Globally in 2020, 149 million children under the age of five years were estimated by be stunted Citation 76, emphasizing the need for also understanding the role of the immature gut microbiome in malnourished children. Colonic fermentation and microbial metabolites in early life The transitioning from a sole source of milk to a diverse range of foods Citation 77not only shapes gut microbiome composition Citation 1 , Citation 8 , Citation 78, but also shapes gut microbial metabolism in early life resulting in the generation of a plethora of small molecules (metabolites) (Figure 1). Figure 1.Gut microbiota-derived metabolites in early life. Gut microbial metabolism changes in early life with the progression in early nutrition from breastfeeding to solid foods concurrent with a progression in microbiome and metabolome diversity. During breastfeeding, the dominance of the infant gut by human milk oligosaccharide (HMO) degrading Bifidobacteriumspecies results in high levels of lactate and acetate, as well as in aromatic lactic acids (i.e. phenyllactic acid, 4-hydroxyphenyllactic acid and indolelactic acid). With the progression in diet, the dietary complexity increases and more indigestible proteins and fiber end up in the colon of the child. Consequently, colonic fermentation changes resulting in the formation of short-chain fatty acids (SCFA, i.e. acetate, propionate and butyrate) and gases (i.e. hydrogen and methane). Furthermore, proteins are degraded into amino acids, which are fermented by the resident gut microbes into branched SCFAs (i.e. isobutyrate, isovalerate and 2-methylbutyrate), amines (i.e. histamine, dopamine, tyramine, γ-aminobutyric acid (GABA), tryptamine), as well as aromatic acetic and propionic acids (e.g. indoleacetic acid and indolepropionic acid). Figure 1.Gut microbiota-derived metabolites in early life. Gut microbial metabolism changes in early life with the progression in early nutrition from breastfeeding to solid foods concurrent with a progression in microbiome and metabolome diversity. During breastfeeding, the dominance of the infant gut by human milk oligosaccharide (HMO) degrading Bifidobacteriumspecies results in high levels of lactate and acetate, as well as in aromatic lactic acids (i.e. phenyllactic acid, 4-hydroxyphenyllactic acid and indolelactic acid). With the progression in diet, the dietary complexity increases and more indigestible proteins and fiber end up in the colon of the child. Consequently, colonic fermentation changes resulting in the formation of short-chain fatty acids (SCFA, i.e. acetate, propionate and butyrate) and gases (i.e. hydrogen and methane). Furthermore, proteins are degraded into amino acids, which are fermented by the resident gut microbes into branched SCFAs (i.e. isobutyrate, isovalerate and 2-methylbutyrate), amines (i.e. histamine, dopamine, tyramine, γ-aminobutyric acid (GABA), tryptamine), as well as aromatic acetic and propionic acids (e.g. indoleacetic acid and indolepropionic acid). Colonic fermentation of carbohydrates The most studied microbiota-derived metabolites are the SCFAs. SCFAs are products of colonic fermentation of HMOs, dietary fiber and proteins, and known to affect human metabolism in numerous ways via activation of several host receptors in different organs Citation 79. SCFAs also serve as energy substrates both for the resident gut microbes (as discussed further below), as well as human cells with butyrate being a primary energy substrate for colonocytes Citation 80, and propionate being a substrate for gluconeogenesis in the intestine Citation 81and liver Citation 82 , Citation 83. In adults, the major SCFAs acetate, propionate and butyrate are typically found in a 3:1:1 ratio, whereas succinate and lactate appear as intermediates and therefore do not appear in consistent levels. However, in early life, SCFA profiles change concordant with the child’s progression in dietary and microbiome diversity Citation 84 , Citation 85. During breastfeeding (early phase), the SCFA profile is characterized by low acetate and high succinate, during complementary feeding (middle phase) by high lactate, pyruvate and formate, and after cessation of breastfeeding (late phase) by high propionate and butyrate Citation 84. The high abundances of lactate, pyruvate and formate measured in the infant gut during the early phase reflect a less-developed microbiome since these metabolites, in the context of a developed gut microbiome, typically would have been converted into other metabolites Citation 79 , Citation 86. Compared to non-breast infants, exclusive breastfed children have been reported to have lower absolute concentrations of total SCFAs including acetate, butyrate, propionate, valerate, isobutyrate, and isovalerate, yet higher concentrations of lactate at four months of age Citation 87. Bifidobacteriumare highly abundant in breastfed infants Citation 88due to their ability to metabolize HMOs Citation 89, which results in the production of acetate and lactate Citation 90. Yet, with the cessation of breastfeeding and development of the gut microbiome Citation 1, butyrate production increases in the infant gut Citation 84. Despite the large dynamics in SCFAs observed in early life and their potential importance as signaling molecules, the relationships between SCFAs, the gut microbiome and given carbohydrate substrates are rather limited. Furthermore, with over 200 HMO varieties identified in human milk and with large variations in HMO profiles between mothers and throughout lactation Citation 91 , Citation 92, it also remains to be elucidated how differences in breastmilk HMO profiles affect the infant’s gut microbial metabolism. Colonic fermentation of proteins Studies on gut microbial metabolites in the context of early life have mainly been limited to the study of SCFAs Citation 90 , Citation 93–95. However, given that intake of dietary fiber and proteins increases with the complementary diet Citation 77 , Citation 96, which is associated with increased gut microbial diversity Citation 68and capacity to transport amino acids during infancy Citation 8 , Citation 78, a multitude of microbial-derived metabolites of dietary fiber and proteins Citation 58 , Citation 59 , Citation 97–104are likely to change with this dietary transition. For example, it was recently reported that HMO-degrading Bifidobacteriumspecies convert aromatic amino acids (i.e. tryptophan, phenylalanine and tyrosine) into aromatic lactic acids (i.e. indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) in the infant gut Citation 88. In agreement with breastfed infants being dominated by Bifidobacterium Citation 68, aromatic lactic acids have been found in higher levels in feces of breastfed infants compared to formula-fed infants Citation 85 , Citation 105and weaned infants Citation 88, emphasizing the strong interplay between early life nutrition and specific gut microbes affecting the levels of microbial aromatic amino acid catabolites in early life. Other examples of microbiota-derived metabolites changing in early life are the branched-chain fatty acids (BCFA, i.e. isobutyrate, isovalerate, 2-methylbutyrate). The BCFA reflect increased proteolytic fermentation as they originate from conversion of the branched-chain amino acids valine, leucine and isoleucine Citation 21, which are implicated in insulin resistance Citation 106. The levels of proteins and amino acids could likely play a role in dictating the levels of BCFA, since a study found that breastfed infants had significantly lower levels of fecal BCFAs compared to infants fed two infant formulas with extensively hydrolyzed proteins and free amino acids, respectively, at one and two months of age Citation 107. Infant formula typically contains more protein and lower free amino acids than breast milk Citation 108 , Citation 109, suggesting that more proteins are being fermented in the colon of formula-fed infants. In line herewith, a study in newborn rhesus monkeys found that by reducing the protein content in formula, urinary levels of microbial-derived proteolytic compounds (i.e. 3-indoxylsulfate, 4-hydroxyphenylacetate, and 2-hydroxyisobutyrate) could be reduced Citation 110. Fecal BCFA levels have also been associated with variations in breastmilk lipid and HMO compositions Citation 111. Furthermore, BCFA have been reported to increase in the infant gut over time independent of early feeding (breastfeeding versus formula feeding) Citation 57 , Citation 84 , Citation 93, suggesting that the lack of HMO following a progression toward solid food promotes a shift toward amino acid fermentation in the infant gut. Also biogenic amines (i.e. cadaverine and tyramine) have been reported in higher levels in feces of formula-fed infants compared to breastfed infants Citation 112 , Citation 113. These differences could be due to differences in the gut microbiome composition, as infant formula-associated genera include Streptococcusand Enterococcus Citation 114, which are producers of putrescine, tyramine and cadaverine Citation 115 , Citation 116. Another prevalent commensal in early life as children progress toward a solid diet is Ruminococcus gnavus Citation 117, which is also able to produce tryptamine in vitro Citation 118. However, it remains to be investigated whether R. gnavusindeed produces tryptamine in the infant gut. In fact, many microbial proteolytic-derived metabolites associated with detrimental effects on cardiovascular and metabolic health in adults, such as trimethylamine-N-oxide (TMAO, derivative of carnitine, betaine and choline) Citation 58, imidazole propionate (derivative of histidine) Citation 59, phenylacetylglutamine (derivative of phenylalanine) Citation 60, p-cresol sulfate and indoxyl sulfate (derivatives of tyrosine and tryptophan, respectively) Citation 61, remain understudied in the context of early life. These metabolites would be expected to arise when children transition toward adult-like solid foods. Yet, very few studies have looked into the impact of the complementary diet on the infant gut microbiome Citation 68. Colonic fermentation of lipids and bile acids Dietary fat is also metabolized by microbes in the gastrointestinal tract. Infants are, through breast milk and to some extent formula milk, provided with the essential fatty acids linoleic acid (LA) and alpha-linoleic acid (ALA), as well as the long chain polyunsaturated fatty acids (LC-PUFA): eicosapentaenoic acid (EPA), arachidonic acid (AA) and docosahexaenoic acid (DHA, omega-3 fatty acid) Citation 77. Besides having direct effects on the gut microbiome composition and activity Citation 119, the polyunsaturated fatty acids can be metabolized by colonic microbes into hydroxy fatty acids, oxo fatty acids, conjugated fatty acids, and partially saturated trans-fatty acids as intermediates Citation 120–122. Interestingly, specific Bifidobacteriumstrains have been found to be able to convert LA to conjugated linoleic acid (CLA) Citation 122 , Citation 123, which has been associated with a variety of systemic health promoting effects Citation 124. Although the production and importance of CLA in the infant gut are currently unknown, another LA-derivate measured in feces, 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME) has been suggested to impede immune tolerance in early life Citation 125 , Citation 126. This metabolite was recently reported to be produced by common early-life gut microbiome members, namely B. bifidumand E. faecalisstrains Citation 125. Furthermore, a recent randomized, controlled, clinical trial reported that infants receiving formula milk containing HMOs (i.e. 2-fucosyllactose and LNnT) had reduced fecal levels of two dihydroxy fatty acids (12,13-DiHOME and 9,10-dihydroxy-12Z-octadecenoic acid (9,10-diHOME)) compared to infants receiving control formula milk without HMOs, suggesting that HMO-induced alterations in the microbiome may affect microbial conversion of fatty acids Citation 127. Therefore, more studies are warranted to investigate intestinal fatty acid metabolism in the infant gut, which is likely to depend on the amount of fatty acids ingested, the efficacy of absorption in the small intestine, as well as the individual gut microbiome composition. Upon intake of fat, bile is released into the small intestine to aid digestion of lipids. Bile acids constitute the primary component of bile and is conjugated by glycine (dominant in humans) and taurine, respectively Citation 128. While approximately 95% of the bile acids are reabsorbed in the ileum and returned to the liver via the portal vein, unabsorbed bile acids end up in the colon where they undergo chemical transformations by the microbiota resulting in secondary bile acids Citation 129. Microbial deconjugation of bile acids reduces their reuptake in the small intestine, which affects the pool of bile acids entering the colon Citation 129. Furthermore, microbial modification of bile acids affects their chemical structure leading to altered signaling via host receptors including the nuclear farnesoid X receptor (FXR) and G protein coupled bile acid receptor 1 (TGR5) Citation 128, which may have major impact on host metabolism as discussed elsewhere Citation 130 , Citation 131. Concordant with the succession of the gut microbial community in early life, the intestinal bile acid profiles develop according to both the microbiota-stage and nutritional stage. A longitudinal study with 10 healthy Japanese subjects found that during the first six months of life, infants dominated by Bifidobacteriumspecies had high fecal levels of unconjugated primary bile acids whereas infants dominated by Enterobacteriaceaehad high fecal levels of conjugated primary bile acids Citation 132. Indeed, bile salt hydrolase activity, catalyzing deconjugation of conjugated bile acids, is common in Bifidobacterium Citation 133, suggesting that Bifidobacteriumis a key player deconjugating bile acids during breastfeeding. Yet, as infants progress toward a solid diet, dietary energy intake goes up Citation 77, dietary complexity and gut microbial diversity increase Citation 68. Consequently, both the total excretion of bile acids in the feces as well as the fecal levels of secondary bile acids increase Citation 85 , Citation 132. Furthermore, decreasing level of primary bile acids and an increase of secondary bile acids in feces have consistently been observed after weaning Citation 132 , Citation 134 , Citation 135. Differences in fecal bile acid profiles have also been observed when comparing breastfed and formula-fed infants with breastfed infants showing higher levels of sulfated bile acids and formula fed infants showing higher levels of secondary bile acids Citation 85. Finally, a study in mice has shown that oral administration of bile acids to newborn mice accelerate postnatal microbiome maturation Citation 136, suggesting that the progression in intestinal bile acid profiles during infancy also drives maturation of the postnatal gut microbiome. Microbial metabolites as modulators of the microbiome community structuring Gut microbial conversion of dietary substrates into metabolites represents a potential regulatory mechanism by which specific gut microbes impact the wider gut ecosystem (Figure 2). In particular HMO-derived metabolites produced by primary HMO degraders drive cross-feeding networks that facilities growth of other early life taxa and crucial interspecies interactions Citation 137 , Citation 138. HMOs are poorly digested by the infant but are favored growth substrates for certain Bifidobacteriumspecies and strains that can enzymatically degrade these complex dietary components that include LN(n)T, fucosylated and sialylated structures Citation 139. Along with Bifidobacterium, Bacteroides, Ruminococcusand more recently Akkermansiahave also been shown to degrade these complex carbohydrates, although in most cases this relates to enzymatic cleavage of sugar side chains and correlates with associated mucin degradation pathways Citation 140–142. Certain Bifidobacteriumspecies seem to have limited impact on wider ecosystem structuring due to their ‘selfish’ digestion of HMOs. This is particularly true for B. longumsubsp. infantisstrains where they actively transport (via ABC transporters) and internalize whole (intact) HMOs to perform intracellular breakdown, utilizing the monosaccharide metabolites for their own cellular processes, rather than sharing among other early life microbes Citation 143. Other species such as B. bifidum, Bifidobacterium pseudocatenulatum, B. longumsubsp. longumand B. brevealso carry out extracellular hydrolysis of complex HMOs, and then import and metabolize the resulting mono- and di-saccharides. These strains therefore provide an important keystone function during early life by providing simpler metabolites for cross-feeding Citation 144 , Citation 145. Metabolites that can be used by other secondary degraders include the SCFAs acetate and lactate, formate, succinate, pyruvate, fucose, and 1,2-propanediol (1,2-PD) Citation 84 , Citation 146. Previous work has indicated that within ‘mini’ Bifidobacteriumecosystems (from individual infants), there is often a keystone member that actively breakdown different HMOs, which provides key metabolites such as fucose, galactose, acetate and N-acetylglucosamine then utilized by other non-HMO degrading strains Citation 138. Other work supports this concept, showing that during growth on HMOs, cross-feeding interactions between multiple bifidobacterial strains increase overall cell numbers, which was linked to production of formate, acetate, 1,2-propanediol, and lactate during co-cultivation Citation 147. Most recently, a study has indicated how ‘timing’ of sugars in the infant gut shape the wider Bifidobacteriumecosystem, with B. bifidumand B. longumsubsp. infantisdominating through inhibitory priority effects based on their ability to digest HMOs, whilst B. brevebenefits from facilitative priority effects and dominates by utilizing fucose (aligning with profiles observed in metagenomic datasets) Citation 148. These studies highlight the importance of cross-feeding term ‘syntrophy’ for Bifidobacterium, which has been defined as ‘obligately mutualistic metabolism’ whereby without a complete mini ecosystem all or combinations of strains cannot survive without the other. This collective approach to HMO utilization may indicate additional processes by which multiple Bifidobacteriumspecies and strains dominate the breastfed infant gut, and successfully outcompete other bacterial taxa. Indeed, acetate and lactate production by Bifidobacterium(in response to HMO-metabolism) is associated with lowering intestinal pH, which also correlates with changes in microbial composition, such as reducing levels of potential pathogens like Enterobacteriaceae, thus enhancing colonization resistance in the early life gut Citation 149 , Citation 150. In agreement, in vitroexperiments have found that SCFAs directly inhibit growth of enteric pathogens belonging to the Enterobacteriaceaefamily including Escherichia coli, Klebsiella and Salmonellain a pH-dependent manner Citation 151–153. Microbial metabolites as modulators of the infant gut microbiome and host-microbial interactions in early life Figure 2.Microbial metabolites as modulators of the infant gut microbial ecosystem. An illustration of the ways in which microbial metabolites are thought to impact the development of the gut microbiome ecosystem during infancy. Human milk oligosaccharides (HMOs) of breast milk are likely to enter the distal gut and be degraded by HMO degraders (for example Bifidobacterium Bacteroides, Ruminococcusand Akkermansia). Among the HMO degraders, particular Bifidobacteriumspecies are important as they are specialized in HMO degradation. Some Bifidobacteriumspecies (mainly B. longumsubsp. longum, B. bifidumand B. breve) degrade HMOs extracellular, whereas other Bifidobacteriumspecies (mainly B. longumsubsp. infantis) take up the HMOs via ABC transporters and metabolize them inside the cell. The sharing or lack of sharing of nutrients (both carbon sources and micronutrients) have consequences for cross-feeding and competition in the infant gut microbiome affecting the microbial community structure. As the child transitions from a milk-based diet to a solid food-based diet, the microbiome diversity increases and the cross-feeding networks change. Other primary degraders of dietary fibers (typically belonging to Lachnospiracea, Bacteroideacea, Clostridiacea) take over and replace the Bifidobacteriumspecies. Generation of specific microbial metabolites may be key for colonization resistance toward pathobionts when microbiome diversity is low. The pathobionts may be excluded or kept low in abundance through low intestinal pH (due to short-chain fatty acids, SCFAs), through direct antimicrobial activity such as bacteriocins, which are antimicrobial, or simply through nutrient limitations. Figure 2.Microbial metabolites as modulators of the infant gut microbial ecosystem. An illustration of the ways in which microbial metabolites are thought to impact the development of the gut microbiome ecosystem during infancy. Human milk oligosaccharides (HMOs) of breast milk are likely to enter the distal gut and be degraded by HMO degraders (for example Bifidobacterium Bacteroides, Ruminococcusand Akkermansia). Among the HMO degraders, particular Bifidobacteriumspecies are important as they are specialized in HMO degradation. Some Bifidobacteriumspecies (mainly B. longumsubsp. longum, B. bifidumand B. breve) degrade HMOs extracellular, whereas other Bifidobacteriumspecies (mainly B. longumsubsp. infantis) take up the HMOs via ABC transporters and metabolize them inside the cell. The sharing or lack of sharing of nutrients (both carbon sources and micronutrients) have consequences for cross-feeding and competition in the infant gut microbiome affecting the microbial community structure. As the child transitions from a milk-based diet to a solid food-based diet, the microbiome diversity increases and the cross-feeding networks change. Other primary degraders of dietary fibers (typically belonging to Lachnospiracea, Bacteroideacea, Clostridiacea) take over and replace the Bifidobacteriumspecies. Generation of specific microbial metabolites may be key for colonization resistance toward pathobionts when microbiome diversity is low. The pathobionts may be excluded or kept low in abundance through low intestinal pH (due to short-chain fatty acids, SCFAs), through direct antimicrobial activity such as bacteriocins, which are antimicrobial, or simply through nutrient limitations. Looking beyond Bifidobacterium, HMO-derived metabolites also cross-feed other early life taxa. In vitrostudies have shown that growth of Limosilactobacillus reuteriis enhanced through 1,2-propanediol produced by B. breveUCC2003 Citation 146. There has also been a number of studies exploring the cross-feeding impacts on a range of butyrate-producing bacteria, given their key health-promoting role. Specifically, butyrate-producing bacteria can utilize acetate and lactate, and HMO-derived monosaccharides as carbon sources, which serves to increase their levels in the infant gut. For example, Anaerostipes caccaehas previously shown to only grow in co-culture with B. longumsubsp. infantis, leading butyrate production Citation 154. Additional SCFAs production by Eubacterium halliiin response to (fucosylated) HMO breakdown by B. breveand/or B. longumsubsp. infantisenables utilization of L-fucose (for production of butyrate), and 1,2-PD uptake for propionate production Citation 137, although the latter has yet to be demonstrated in the infant gut. The availability of L-fucose also supports growth of other microbes encoding Fuc catabolic pathways such as B. thetaiotaomicronand A. muciniphila, but these microbes can also cleave fucose from fucosylated HMOs, according to their fucosidase activity Citation 155. Notably, some pathogenic bacteria have evolved strategies to use fucose to their advantage, including Salmonellaand C. jejuni, which is the latter case appears to be enriched in breastfed infants when compared to those on formula Citation 156. Thus, the availability of different metabolites in the gut may both have beneficial and detrimental consequences depending on the ecological circumstances. In some cases there may be competitive interactions via production of metabolites know to inhibit metabolic reactions and growth of other microbiota members e.g. hydrogen sulfide (H 2S), or SCFAs (lowering the pH), or via production of metabolites with direct antimicrobial activity such as bacteriocins. Bacteriocins are ribosomally-synthesized antimicrobial peptides, which are active against other bacteria, and can be either narrow spectrum (i.e. targeting similar species) or broad spectrum (i.e. across diverse genera), with the host bacterium being resistant Citation 157. A number of early life microbiota members, including Bifidobacterium, are known to produce these antimicrobials which may be linked to their ability to modulate the wider microbiota, and also inhibit overgrowth of potentially pathogenic bacteria that would otherwise be harmful to the infant Citation 158. The gene clusters required for biosynthesis appear to be very strain specific; previous work has indicated that the bacteriocin bifidin (produced by Bifidobacterium bifidumNCDC 1452) has activity against a range of Gram positive and Gram negative’s including Escherichia coliand Staphylococcus aureus Citation 158, which are common members of the early life gut microbiota. There are other Bifidobacterium-associated bacteriocins, however these have shown activity against specific food-borne pathogens including Salmonellaspp. and Bacillus cereus, thus may not be so relevant in the context of the first 12 months of life. More recently, Bifidobacterium longumsubsp. infantisLH_664 has been shown to encode and produce a narrow spectrum bacteriocin (putatively named Bifidococcin_664) that whilst not impacting growth of Lactobacillusand Enterococcusstrains, does have discrete activity against a potentially important pathobiont in the (preterm) gut, Clostridium perfringens Citation 159. The ability of these active peptides to target specific bacteria, may be particularly important in the context of early life perturbations (such as preterm birth, C-section and/or antibiotic treatments), when levels of pathobionts may be higher given the absence of these key metabolite/peptide modulating factors that would otherwise be produced by Bifidobacteriumwhich may be depleted in these contexts. However at this stage it is unclear if the dietary (e.g. HMO) milieu in the gut plays a role in shaping the production of these peptides, and further work is required to disentangle these relationships. With the introduction of additional complex dietary components (particularly plant-derived) during weaning there is a significant expansion in cross-feeding networks due to the resultant complex milieu of metabolites produced by primary degraders Citation 144 , Citation 145. This is due to the huge variety of glycoside hydrolases encoded across different taxa (particularly in the Bacteroidesgenus, many of which act as primary degraders) that enables the diverse array of bonds between monosaccharide units to be ‘broken’, thus allowing these simple sugars to enter into different metabolism pathways to provide energy (ATP) for cellular responses and growth Citation 160. Fermentation end products are further metabolized by cross-feeders which often results in the production of SCFAs, with increasing production of butyrate and propionate, in comparison to the acetate dominant SCFA profile observed during exclusive milk-based feeding Citation 161. Additional key components that can be produced as a result of protein fermentation are amino acids, which play a central metabolism (enzyme co-factors) role for many bacteria, driving growth and changes in motility, biofilm formation and virulence factor expression Citation 162. Furthermore, there are strain level differences with respect to B vitamins biosynthesis, which is required by the host, and by other strains unable to de novosynthesize these key metabolites Citation 163. For example, several early life taxa are predicted, and have been experimentally confirmed, to produce vitamin B1 including some Bacteroidesspp., Clostridiumspp., Lactobacillusspp., and Bifidobacteriumspp. Citation 164. These strains are expected to play a key role for other species and strains that lack a vitamin B1 synthesis (e.g. Faecalibacteriumspp.), highlighting the cross-feeding and also competition for this essential metabolite in the infant gut Citation 165. It is clear that this time-period represents a highly dynamic period of ecosystem development, with burgeoning cross-feeding networks being established, and like other underdeveloped ecosystems, may be particularly sensitive to diet-derived perturbations Citation 166. However, clear evidence on the longer-term effects during this time period are required via both longitudinal cohorts and experimental studies. For a comprehensive review of this with a more complex (adult-like) ecosystem see a review by Oliphant and Allen-Verco Citation 161. Finally, the spatial context of these potential metabolite interactions should be considered. Clearly the levels and diffusability of key metabolites would be expected to have the most pronounced impact on ecosystem structure on those microbes in close proximity to each other. However, given the complex ‘geography’ of the gut, including the overall length, mucus layers, and micro-structure e.g crypts, it is likely that the studies undertaken so far may not completely replicate these spatial considerations. Therefore, additional model systems e.g. organoids and mice, may be required to pinpoint relative contributions of microbial metabolites as modulators of the infant gut microbiome. Microbial metabolites as mediators of host-microbial cross talk in early life Given the dynamics of microbial metabolites in the gut and their absorption into the circulation Citation 167, these microbiota-derived molecules not only shape the gut microbiome ecosystem, but also likely play a central role in mediating host-microbial cross-talk in early life as they may communicate with host cells via host receptors in the intestine and distant organs (Figure 3) Citation 21 , Citation 168 , Citation 169. However, only few studies have studied the gut luminal and circulating concentrations of the metabolites in early life. This is an important gap to fill in order to figure out whether concentrations of the metabolites are within the range of the dose-response curve for the particular metabolite on the host receptor. Here we shortly discuss four areas where microbial metabolites may play a vital role in early life (Figure 4). Microbial metabolites as modulators of the infant gut microbiome and host-microbial interactions in early life Figure 3.Dynamics of selected signaling metabolites in the infant gut and their interaction with host receptors. The figure illustrates the change in relative abundances of known key microbiota-derived metabolites generated from saccharolytic Citation 84and proteolytic fermentation Citation 84 , Citation 88as well as from bile acid metabolism Citation 132in the infant gut. The metabolite profiles change as the infant goes from breastfeeding to solid foods concurrent with a maturation of the gut microbiome from a less to a more diverse microbiome. The main host receptor targets for each of the signaling metabolites is indicated to the right. As indicated by the arrows, some metabolites can bind several different host receptors Citation 168. Figure 4.Gut microbiota-derived metabolites as mediators of host-microbial cross-talk in early life. The microbiota-derived metabolites can impact host development in various ways as they activate different host receptors. For example, microbiota-derived metabolites can stimulate the intestinal immune system (affecting release of cytokines), enteroendocrine cells (affecting release of gut hormones), and enterochromaffin cells (affecting release of serotonin). Subsequently, the secreted molecules can affect the intestinal barrier and immune function, the intestinal nervous system with effects on intestinal motility and the gut-brain axis, and potentially the host metabolism and inflammation throughout the body upon absorption and circulation through the portal vein. Figure 4.Gut microbiota-derived metabolites as mediators of host-microbial cross-talk in early life. The microbiota-derived metabolites can impact host development in various ways as they activate different host receptors. For example, microbiota-derived metabolites can stimulate the intestinal immune system (affecting release of cytokines), enteroendocrine cells (affecting release of gut hormones), and enterochromaffin cells (affecting release of serotonin). Subsequently, the secreted molecules can affect the intestinal barrier and immune function, the intestinal nervous system with effects on intestinal motility and the gut-brain axis, and potentially the host metabolism and inflammation throughout the body upon absorption and circulation through the portal vein. Microbial metabolites and intestinal barrier function Although a ‘strong’ barrier is considered essential for host health, during very early life a balance is required; allowing key microbial metabolites to cross and initiate immune programming in the underlying mucosal and at more distal and systemic sites. Butyrate is the main ‘fuel’ used by intestinal epithelial cells (IECs) for growth Citation 170, however concentrations of butyrate are relatively low during milk feeding, but steadily increase across the weaning period and beyond Citation 84, due to the expansion in butyrate producing bacteria given the increasingly complex dietary environment Citation 84. Acetate (and propionate) can be consumed by IECs, however this is a less efficient process than for butyrate. Nevertheless, acetate is also associated with inducing additional anti-inflammatory responses in the gut epithelium such as enhancing tight junction protein expression and anti-inflammatory cytokine production Citation 171. This appears to be mediated through Toll-like receptors (TLRs) and G protein-coupled receptors (GCPRs), including FFA2 pathway stimulation, as defined using KO mouse models. This acetate-ligand interaction can lead to NLRP3 inflammasome activation Citation 172, which also links to a more efficient clearance of enteric pathogens from the gut Citation 173, and enhanced production of sIgA (via Dendritic Cell-B cell activation). Of the other metabolites discussed above, such as B vitamins, it is appreciated these also directly modulate host immune responses, including the epithelial barrier (for a comprehensive overview see Yoshii et al. Citation 174, and there is also work suggesting that bacteriocins may have a dual role, providing direct antimicrobial activity and also promoting immune responses, however this seems to be more with respect to innate immune cells like macrophages Citation 159. Furthermore, aromatic lactic acids could be important in early life since they may modulate immune function via both the aryl hydrocarbon receptor (AhR) and hydroxycarboxylic acid receptor 3 (HCA3) Citation 88 , Citation 175 , Citation 176. During the last decade, tryptophan catabolites have emerged as potential key AhR-ligands playing a role in regulating intestinal barrier and immune function Citation 98. It was recently shown that fecal levels of indolelactic acid were positively correlated with the fecal samples’ ability to activate AhR in an AhR-reporter cell line Citation 88, suggesting that indolelactic acid is a key AhR-ligand in early life. However, it remains to be determined whether indolelactic acid and/or other microbiota-derived AhR ligands indeed play a role for immune barrier development in the context of early life. For all of these studies, it is important to note that most work in this area has concentrated on adult models. Previous work has suggested that microbes (including Bifidobacterium) drive distinct responses in the neonate vs. later life time points Citation 177, thus there is a pressing need to determine how microbial metabolites such as aromatic lactic acids and SCFAs modulate host intestinal responses during the early life developmental window. Microbial metabolites and intestinal motility Stool frequency and consistency vary significantly according to early life nutrition between and within infants during the first year of life Citation 178. Despite this, very little is known about the interplay between the diet, the developing gut microbiota, and the ever-changing bowel habits in early life. Several microbial metabolites, which have been measured in the infant gut, could potentially play a role in affecting gut motility in early life, although this has not yet been investigated. For example, tryptamine has been found to accelerate transit time in vivothrough the 5-HT4 receptor (5-HT4R), a receptor uniquely expressed in the colonic epithelium Citation 118 , Citation 179. Other tryptophan-derived catabolites may also affect intestinal motility via AhR signaling in enteric neurons in the distal gastrointestinal tract Citation 180. Furthermore, SCFAs can stimulate the release of serotonin (5-HT) in enterochromaffin cells by activating GPCRs such as FFA3 (GPR41), FFA2 (GPR43), and HCA2 (GPR109A). Serotonin has multiple paracrine and endocrine roles including promotion of peristalsis via the enteric nervous system Citation 181. Secondary bile acids and SCFAs may also through TGR5 and FFA2/FFA3, respectively, stimulate release of GLP-1 and PYY in enteroendocrine cells and thereby affect colonic motility Citation 182 , Citation 183. Variations in intestinal transit time have been associated with the gut microbiome composition and activity in adults Citation 184. Furthermore, given the large fluctuations and changes in SCFAs, secondary bile acids and proteolytic metabolites during the first year of life, it is possible that the gut microbiome contributes to inter- and intra-individual variations in bowel habits during infancy. Such variations could potentially be linked to common functional gastrointestinal disorders in infants such as infantile colic and functional constipation Citation 185. Microbial metabolites and whole body metabolism SCFAs are proposed to affect whole body metabolism and inflammation upon absorption and circulation in the blood stream to distant organs through interactions with host receptors Citation 169. Furthermore, SCFAs can indirectly affect whole body metabolism by stimulating secretion of gut hormones (e.g. GLP-1 and PYY) in enteroendocrine cells affecting appetite and through stimulation of immune cells that regulate whole body metabolism Citation 79. The high gut luminal levels of SCFAs, lactate, and succinate measured during infancy could possibly be important for recruitment of macrophages and neutrophils acting through FFA2, HCA1, and GPR91, respectively Citation 168. However, in the context of early life, little is known about the role of SCFAs regulating whole body metabolism and inflammation. High fecal levels of formate during early infancy (3–4 months of age) have been associated with lower BMI z-score, whereas high fecal levels of butyrate have been associated with a higher BMI z-score at 3 years of age in Canadian infants Citation 186. Based on these observations one could speculate that the development of the infant gut metabolome from high formate (reflecting a low-diversity microbiome) to high butyrate (reflecting a more diverse microbiome) could play a role in growth trajectories Citation 186. Yet, the timing of the gut metabolome development may be important, since another study found that Danish infants with normal weight gain at nine months of age had significantly higher fecal concentrations of butyrate compared to infants with high weight gain Citation 111. In line with this, both exclusive formula feeding as well as early introduction to solid foods (vs later) in infancy has been associated with altered gut microbiota and increased risk of being overweight in early childhood Citation 52 , Citation 187. Prospective studies focusing on the infant gut metabolome development are warranted to understand whether the gut microbiota via production of metabolites is indeed casually involved in the programming of host metabolism, which may trigger long-lasting physiological effects that promote or prevent diseases. Concluding remarks Together, there is a clear need to uncover and explore microbial metabolites and their interactions with both gut microbes and host cells within early life. These microbial interactions may be pivotal for establishment of the gut microbiome and appropriate cross-talk between gut commensals and host cells with both short- and long-term physiological consequences. Currently, much of the work with regards to microbial metabolites and ecosystem structuring have been done in the context of the adult gut. Furthermore, only few aspects of cross-feeding in the infant gut such as Bifidobacterium-metabolism of HMOs and the generation of SCFAs have been studied. Therefore, prospective infant cohort studies following infants’ progression in diet, concurrent with their progression in gut microbiome composition and activity, are needed to further advance the field. By collecting and analyzing longitudinal fecal samples by untargeted metabolomics, unpreceded insights into known and novel microbial-derived metabolites, as well as their dynamics across and within infants during early life, can be provided Citation 88. Combined with high-resolution microbiome profiling, enabling strain level classification Citation 20, as well as immune cell profiling Citation 176, this may take the field to a whole new level. 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Puthimari Bazar Branch Post Office, Nagaon 26, Assam Puthimari Bazar Post Office, Nagaon Puthimari Bazar post office is located at Puthimari Bazar, Nagaon of Assam 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 Puthimari Bazar PO is782426. This Postoffice falls under Nagaon postal division of the Assam postal circle. The related head P.O. for this branch office is Nagaon head post office and the related sub-post office (S.O.) for this branch office is Kampur post office. Puthimari Bazar 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 Puthimari Bazar. Types of Post Offices Post offices are basically classified into 3 types, namely – Head Post Office, Sub-Post Office including E.D. Sub-Office and Branch Postoffice. Puthimari Bazar 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 Puthimari Bazar Post Office & Its Pin Code Branch Office Information Puthimari Bazar 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 Puthimari Bazar Post Office Recruitment Location Map Contact Details About India Post Puthimari Bazar Post Office & Its Pin Code Often Post Offices are named after the town / village / location they serve. The Puthimari Bazar Post Office has the Postal Index Number or Pin Code 782426. 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. <table><tbody><tr><th> P.O. Name</th><td> Puthimari Bazar PO</td></tr><tr><th> Pincode</th><td> 782 426</td></tr></tbody></table> The first digit of 782426 Pin Code '7' represents the region, to which this Post Office of Puthimari Bazar belongs to. The first two digits of the Pin Code '78' represent the sub region, i.e, Assam. The first 3 digits '782' represent the post-office revenue district, i.e, Nagaon. The last 3 digits, i.e, '426' represent the Puthimari Bazar Delivery Branch Office. Branch Office Information The Puthimari Bazar 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 Nagaon, which falls under Dibrugarh region. The circle name for this PO is Assam and it falls under Nagaon Taluka and Nagaon District. The state in which this Dakghar is situated or located is Assam. The related head postoffice is Nagaon post office and the related sub post office is Kampur post-office. The phone number of Puthimari Bazar post office is unavailable at present. <table><tbody><tr><th> PO Type</th><td> Branch Office</td></tr><tr><th> Delivery Status</th><td> Delivery</td></tr><tr><th> Postal Division</th><td> Nagaon</td></tr><tr><th> Postal Region</th><td> Dibrugarh</td></tr><tr><th> Postal Circle</th><td> Assam</td></tr><tr><th> Town / City / Tehsil / Taluka / Mandal</th><td> Nagaon</td></tr><tr><th> District</th><td> Nagaon</td></tr><tr><th> State</th><td> Assam</td></tr><tr><th> Related Sub PO</th><td> Kampur Sub Office</td></tr><tr><th> Related Head PO</th><td> Nagaon Head Post Office</td></tr></tbody></table> Puthimari Bazar Post Office Services Traditionally the primary function of Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar and nearby localities can avail all the types of mail services. Retail Services Post offices in India serve in various ways and Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar peoples and nearby living people. The premium services provided by Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar 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. <table><tbody><tr><th> Bharatiya Dak Ghar Seva</th><th> Tracking Number Format</th><th> Number of Digits</th></tr><tr><td> Electronic Money Order (eMO)</td><td> 000000000000000000</td><td> 18</td></tr><tr><td> Express Parcel</td><td> XX000000000XX</td><td> 13</td></tr><tr><td> International EMS Artilces to be delivered in India</td><td> EE123456789XX</td><td> 13</td></tr><tr><td> Registered Mail</td><td> RX123456789IN</td><td> 13</td></tr><tr><td> Speed Post (EMS) Domestic</td><td> EE123456789IN</td><td> 13</td></tr></tbody></table> Express Parcel Post In Express Parcel Post, the Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar postal costumer can access services based on – complaint registration, complaint status and guidelines on complaints. <table><tbody><tr><th> ePost Office Website</th><td> www.epostoffice.gov.in</td></tr></tbody></table> Financial Services The customers of Puthimari Bazar can enjoy the various savings schemes available in this post office that prove to be highly beneficial for the people living in Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar 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 09:00 AM or 10:00 AM and the closing time is 06:00 PM or 07:00 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 Puthimari Bazar Branch Post Office from the official resources. India Post Tracking Online tracking of India Post allowed Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar 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 Puthimari Bazar Post Office Recruitment For latest Puthimari Bazar post office recruitment kindly visit www.indiapost.gov.in/recruitment.aspx. Location Map Puthimari Bazar Branch Post Office is located in Puthimari Bazar, Nagaon. 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 Puthimari Bazar Post Office, can be resolved at Puthimari Bazar Branch Post Office. You can send letters to "Postmaster, Puthimari Bazar Branch Post Office, Puthimari Bazar, Nagaon, Assam, India, Pincode: 782 426". The official website of the Berhampur University Sub Office is www.indiapost.gov.in. Puthimari Bazar Branch Office Address: Puthimari Bazar Branch Post Office, Puthimari Bazar, Nagaon, Assam, India Pin Code: 782426 Website: www.indiapost.gov.in About India Post India Post is 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 India with 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. Puthimari Bazar Post Office Summary <table><tbody><tr><th> Dak Ghar Name</th><td> Puthimari Bazar Branch Post Office</td></tr><tr><th> Pincode</th><td> 782426</td></tr><tr><th> Dakghar Type</th><td> Branch Office</td></tr><tr><th> Post Office Delivery Status</th><td> Delivery Branch Office</td></tr><tr><th> Postal Division</th><td> Nagaon</td></tr><tr><th> Postal Region</th><td> Dibrugarh</td></tr><tr><th> Postal Circle</th><td> Assam</td></tr><tr><th> Location</th><td> Puthimari Bazar</td></tr><tr><th> Town / City / Tehsil / Taluka / Mandal</th><td> Nagaon</td></tr><tr><th> District</th><td> Nagaon</td></tr><tr><th> State</th><td> Assam</td></tr><tr><th> Country</th><td> India</td></tr><tr><th> Related Sub Office</th><td> Kampur Sub Office</td></tr><tr><th> Related Head Office</th><td> Nagaon Head Post Office</td></tr><tr><th> Website</th><td> www.indiapost.gov.in</td></tr><tr><th> ePost-office Web Site Address</th><td> www.epostoffice.gov.in</td></tr><tr><th> Speed Post Tracking Website</th><td> www.indiapost.gov.in/speednettracking.aspx</td></tr><tr><th> Recruitment Web Site Address</th><td> www.indiapost.gov.in/recruitment.aspx</td></tr></tbody></table>	https://www.postoffices.co.in/assam-as/puthimari-bazar-nagaon-26/amp/
Experts: Emergency Preparedness Cuts in Budget Deal Threaten U.S. Security — ProPublica The budget deal being finalized by Congress includes significant cuts to federal grants for emergency first responders. Experts say the reductions could place the U.S. at risk during a major disaster. Experts: Emergency Preparedness Cuts in Budget Deal Threaten U.S. Security The budget deal being finalized by Congress includes significant cuts to federal grants for emergency first responders. Experts say the reductions could place the U.S. at risk during a major disaster. The budget agreement being finalized this week by Congress includes cuts that could place the country at increased risk in an emergency such as the one that’s unfolding in Japan, disaster preparedness experts say. They’re particularly troubled by a $786 million cutback in grants from the Federal Emergency Management Agency to support first responders, a 19 percent reduction from the 2010 budget. “The cuts undermine the security of the country, as far as disaster preparedness is concerned,” said Dr. Irwin Redlener, director of the National Center for Disaster Preparedness at Columbia University. “A very significant cutback is really inexplicable given what we’re observing unfold now in Japan.” The FEMA first responder grants have been the primary source of funding for state and local agencies to train for major disasters, according to William Banks, director of the Institute for National Security and Counterterrorism and a Syracuse University law professor. State and local officials are responsible for initiating the critical first response in the U.S. preparedness system, which calls for the lowest possible level of government to manage to an emergency. “States have very little resources for this of their own—they have relied on the federal government from the beginning,” Banks said. “They have essentially been able to stand up their preparedness activities in the last decade on the shoulders of federal support.” The federal government is supposed to step in if a crisis is too big for local responders to handle – but as we reported last week,preparedness plans aren’t always clearabout how and when federal authorities get involved. FEMA did not comment on the cutbacks. Since FEMAadministers grantsfor much of the Homeland Security department, including areas such as port and railroad security, it is still unclear how much of the reductions will affect state and local emergency planning. Thesummary of cutsprovided by the House Appropriations Committee does not specify which FEMA first responder grant programs the $786 million reduction is taken from. A majority staffer with the House Appropriations Committee, speaking on condition of anonymity, confirmed that the cuts come from “FEMA first responder grants.” But the staffer said the assertion that the cuts would threaten national security is unfounded. Several cuts came from programs that weren’t performing well or had failed to spend most of the previous grants they had received, including Port and Transit Security and Emergency Operations Centers, according to information provided by the staffer. The agreement also cut $50 million from FEMA’s National Predisaster Mitigation Fund and $38 million from a fund to modernize flood maps. Redlener, the disaster preparedness expert, said that while the appropriations committee is obligated to ferret out waste, the cuts were reckless and overly broad. “I don’t think anyone proposed these particular cuts based on a finely tuned, nuanced analysis of which programs are working and which aren’t,” Redlener said. “This is much more of a sledgehammer set of reductions within FEMA.” One of Redlener’s greatest concerns is that the budget agreement could indicate the beginning of a trend toward defunding emergency preparedness programs. “These proposals and the bipartisan agreement to move them forward potentially represent where we’re going in future budgets, including 2012,” he said. “If this is the direction we’re going in, I think the country is in for a lot more trouble.”	https://www.propublica.org/article/experts-emergency-preparedness-cuts-in-budget-deal-threaten-us-security
Membrane Vesicles Derived from Gut Microbiota \| Encyclopedia MDPI Encyclopedia is a user-generated content hub aiming to provide a comprehensive record for scientific developments. All content free to post, read, share and reuse. Membrane Vesicles Derived from Gut Microbiota Multidrug-resistant (MDR) superbugs can breach the blood–brain barrier (BBB), leading to a continuous barrage of pro-inflammatory modulators and induction of severe infection-related pathologies, including meningitis and brain abscess. Both broad-spectrum or species-specific antibiotics (β-lactamase inhibitors, polymyxins, vancomycin, meropenem, plazomicin, and sarecycline) and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles have been used to treat these infections. However, new therapeutic platforms with a broad impact that do not exert off-target deleterious effects are needed. Membrane vesicles or extracellular vesicles (EVs) are lipid bilayer-enclosed particles with therapeutic potential owing to their ability to circumvent BBB constraints. Bacteria-derived EVs (bEVs) from gut microbiota are efficient transporters that can penetrate the central nervous system. In fact, bEVs can be remodeled via surface modification and CRISPR/Cas editing and, thus, represent a novel platform for conferring protection against infections breaching the BBB. blood–brain barrier extracellular vesicles gut microbiota 1. Introduction The blood–brain barrier (BBB) plays a central role in the unique and complex microenvironment of the central nervous system (CNS) [ 1 ]. In particular, it restricts the entry of drugs and other exogenous molecules, including host immune cells [ 2 ]and infectious pathogens [ 3 ]. Nevertheless, opportunistic pathogens can occasionally breach the BBB and cause serious illnesses, including meningitis and brain abscess [ 4 ]. Although the occurrence of CNS infection is relatively rare, chronic malignancies can result in serious neurological disorders [ 5 ]. Drug-resistant pathogens, including Acinetobacter baumannii, Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, and Streptococcusspp. can enter via the respiratory tract and mucosa and breach the BBB [ 6 ]. In the BBB, pathogens tightly regulate intrinsic virulence mechanisms via drug-resistance pumps [ 7 ]and biofilm formation [ 8 ]. Acinetobacterspp., Klebsiella, and S. aureusfurther modulate the expression of proinflammatory cytokines [ 9 ]and movement of immune cells, thereby destabilizing the endothelial lining and tight junctions of the BBB [ 10 ]. However, due to the complexity of the brain microenvironment and its associated endothelial tight junctions, transport of effective antimicrobials and therapies is challenging [ 11 ]. In fact, the physiological nature of the CNS environment prevents 90–95% of antimicrobials from progressing toward drug development [ 12 ]. Various nanoparticles (NPs), especially liposomal NPs [ 13 ] [ 14 ] [ 13 , 14 ], and their derivatives (e.g., polysaccharide and polyester NPs) [ 15 ] [ 16 ] [ 15 , 16 ]are considered effective and innovative drugs against pathogens that invade the BBB. However, NP-associated toxicity [ 17 ]and dose-dependent mortality [ 18 ]seriously limit their application. It is, therefore, necessary to consider alternatives, particularly those that can mimic non-immunogenic biological entities [ 19 ]. Membrane vesicles or extracellular vesicles (EVs) play crucial roles in polymicrobial interkingdom communication [ 20 ]. Microbial evolution involves the continuous transfer of metabolites via nanosized vesicles that carry important biomolecules, virulence factors, and membrane receptors of the cells from which they originate [ 21 ]to proximal and distant cells via blood and lymphatic systems. These vesicles range in size from 20 to 400 nm. The release of EVs is a general phenomenon performed by many cell types, including those of eukaryotes, Gram-negative/-positive bacteria, and archaea [ 22 ], as a means of communicating with other cells. In particular, bEVs have been characterized as the delivery vehicles of host–microbe interactions, responsible for the delivery of signaling molecules, such as autoinducers, virulence factors [ 23 ] [ 24 ] [ 23 , 24 ], and antibiotic genes [ 25 ] [ 26 ] [ 25 , 26 ]. In contrast to pathogen–host interactions, mucosal- or gut microbiota-derived bEVs contribute to homeostasis, immune system regulation, bowel movements, and the gut–brain axis [ 27 ]. Based on their immunomodulatory properties, gut microbiota-derived bEVs are currently employed in therapies aimed at promoting both humoral and cell-mediated responses [ 28 ]. Among them, tuning probiotic-derived bEVs, for interactions between interstitial cells and the gut–brain axis, represents a novel strategy for promoting immune responses during infectious disease [ 29 ]. Furthermore, this strategy can benefit from the ease of fermentation culture techniques, potential application of probiotics, and mucoadhesive encapsulation [ 30 ] [ 31 ] [ 30 , 31 ]. Moreover, combining functional biomaterials with active bEVs has the potential to target autoimmune inflammatory dispositions and treat severe chronic infections [ 32 ]. More specifically, beneficial gut microbiota-derived bEVs are a promising tool to regulate the gut–brain axis by reducing inflammation and restoring immunity [ 33 ], creating a benchmark for the targeted delivery of drugs to the CNS. However, currently, most EV-based drugs are derived from eukaryotic systems, including those for cancer [ 34 ], gastric disorders, and polymicrobial infections, due to the various challenges related to bEVs [ 35 ]. Nevertheless, genetically modifying bEVs via surface remodeling [ 36 ]to target neurotransmitters and quorum sensing (QS) inhibitors, and through CRISPR/Cas system-based modifications [ 37 ], has the potential to provide novel noninvasive therapies against BBB infections [ 38 ]. 2. Blood–Brain Barrier (BBB): A Roadblock to Invading Pathogens The endothelial layer of the BBB selectively transports immune cells and other metabolites involved in maintaining the functional stability of the nervous system [ 39 ]. However, during the neonatal period, in some cases, the BBB can shield pathogens, resulting in a breach of the protective layer and subsequent serious disorders and infection [ 40 ]. Endogenous markers, such as pathogen-associated molecular patterns and small molecular motifs conserved within a class of microbes [ 41 ], are recognized by endothelial receptors of the BBB. This recognition results in an immunological burst at the target site [ 42 ]that can breach the endothelial lining. Moreover, the complicated structure of the CNS limits the access of several antimicrobial agents to the nervous system [ 43 ], however, facilitating the transport of lipophilic drugs with a molecular weight <400 Da [ 44 ]that form fewer than eight hydrogen bonds via lipid-mediated free diffusion [ 45 ], into the bloodstream via the transcellular route [ 46 ]. As efficient drugs, antiepileptics (e.g., diazepam and phenytoin) [ 47 ] [ 48 ] [ 47 , 48 ], PLGA-coated nanoparticles, and laser-assisted therapies (e.g., focused ultrasound and interstitial thermal therapy) are commercially available [ 49 ] [ 50 ] [ 49 , 50 ]. However, these therapies do not guarantee the long-term potency of drugs because the microbial flora is constantly evolving, either through horizontal gene transfer or cell-to-cell communication, resulting in reduced susceptibility to certain drugs [ 51 ]. 3. Multidrug-Resistant (MDR) Superbugs: A Prominent Case Involving the BBB Infections caused by MDR superbugs have emerged as a major threat to global health in the post-antibiotic era, especially in the 21st century [ 52 ]. The Centre for Disease Control and World Health Organization have predicted that there will be ~2 million cases of MDR infections and 27,000 related deaths per year by 2050 in Asia, Africa, and North America [ 53 ]. Carbapenem and colistin are the most widely used last-resort antibiotics against bacterial infections [ 54 ]; however, by the late 2000s, drug resistance exhibited an unexpected increase in mortality associated with hospital-acquired infections by 40–60% [ 55 ]. Pan-drug resistant A. baumanniiis routinely reported in patients with meningitis [ 56 ] [ 57 ] [ 58 ] [ 56 , 57 , 58 ]and has acquired resistance to most antibiotic therapies, including colistin and tetracycline [ 59 ] [ 60 ] [ 59 , 60 ]. Although combined treatment with gentamicin and meropenem is efficient, the reduction rate of infection is <17–19% [ 61 ]given that the BBB limits the permeability of drugs and the continuous administration of drugs further increases the probability of resistance [ 62 ] [ 63 ] [ 62 , 63 ]. Moreover, frequently screened drug-resistant pathogens ( A. baumannii [ 64 ]and E. coli [ 65 ]), few routinely screened pathogens ( N. meningitidisand Streptococcusspp.) [ 66 ] [ 67 ] [ 66 , 67 ], other neuroinvasive pathogens ( Haemophilus influenzae) [ 68 ], and Chlamydophila pneumoniae [ 69 ]not only disrupt the tight junctions of the BBB but also induce leakage between tight junctions and vascular endothelial cells [ 70 ]. For example, Gram-positive L. monocytogenes, Staphylococcusspp., and Streptococcus pneumoniaeelevate the levels of proinflammatory cytokines and disrupt the endothelial lining in the CNS [ 71 ], thus creating a path of invasion for opportunistic pathogens. 4. Bacteria-Derived EVs (bEVs): Nanoscale Vesicles bEVs have been studied since the early 1960s when lipid-like structures released from E. coli were discovered as a means to transport secondary metabolites and intrinsic biomolecules to the communicating host [ 72 ] . After the discovery of bEV production from Gram-positive bacteria, such as Bacillus subtilis , Mycobacterium tuberculosis , S. aureus , and Streptococcus spp., bEV release is regarded as a general phenomenon carried out by bacteria that has an important role in cell-to-cell communication and disease progression during gastric cancers and tuberculosis [ 73 , 74 ] . Cell-to-cell communication by bEVs involves internalization via the endothelial layer, micropinocytosis, and endocytosis by utilizing invasion proteins at the host–pathogen interface [ 75 ] . Certain pathways, such as the stress induced network, cause bEVs to function as anti-phagocytosis bodies, evading phagocytosis and weakening the clearing mechanism via the host immune response [ 76 ] . M. tuberculosis is a classic example of pathogen evasion of the innate immune responses; that is, it infects phagocytic and inhibits phagosome maturation. Moreover, Athman et al. [ 77 ] discovered that Mycobacterium bEVs produce lipoglycans and lipoproteins that play an important role in regulating the host immune response and facilitating persistent infection. Further, it was found that S. aureus -derived bEVs contain super-antigens (protein A and lipase) that aid cells in phagocytosis evasion. Meanwhile, a proteomics study [ 78 ] found that immunoglobulin (IgG)-bound lipase and super-antigen (hydrogenated form of squalene; SQA) are presented in bEVs, thus highlighting the potential role of S. aureus in evading anti-phagocytic activity via super-antigens and lipase production. bEVs also have a basic role in exchange of genetic materials (DNA and RNA) through horizontal gene transfer, during which bEVs serve as a means of cell-to-cell communication within the same bacterial species [ 79 ] . Additionally, a study conducted on bEV cargo of A. baumannii reported the presence of a carbapenamse gene ( bla OXA-24 ) that increases the antibiotic susceptibility pattern against β-lactam antibiotics [ 80 ] . Similar studies on bEVs derived from N. gonorrhoeae [ 81 ] and S. aureus [ 82 ] have identified the presence of the outer membrane (OM) protein PorB and alpha toxins that transfer genetic materials, inducing apoptosis and host cell death. bEVs released from the cell envelope of Gram-negative bacteria are so-called outer membrane vesicles (OMVs). The envelope is made up of three layers: the OM, cytoplasmic membrane, and the periplasmic space in between, which contains a layer of peptidoglycan (PG) [ 83 ] . An inside leaflet of phospholipids and an outer leaflet of lipopolysaccharide (LPS; also known as endotoxin) constitute the OM. LPS causes inflammatory responses in host cells [ 84 ] , whereas the OM has a porous structure that aids in waste removal and nutrition uptake, and the peptidoglycan (PG) layer maintains the osmotic pressure of the cell and regulates the hostile environment (antibiotic stress) [ 85 ] . Gram-positive, unlike Gram-negative, bEVs are produced from cytoplasmic constituents via a blebbing mechanism; their genetic composition is comparable to that of Gram-negative bEVs, with the exception of the lipoprotein structure [ 86 ] . Apart from the normal mechanism of blebbing, prophage-encoded endolysins have also facilitated bEV release from Gram-negative and -positive bacteria. Studies on Bacillus spp. and Staphylococcus spp. have revealed that the prophage-encoded endolysin generates holes in the peptidoglycan cell wall, thus highlighting the potential role of these enzymes in bacterial cell wall lysis during mass production of bEVs [ 87 ] [ 88 ] [ 87 , 88 ] . 5. Nanoscale bEVs as Potential Therapeutic Platforms Recently, bioinspired NPs such as host (eukaryotic) EVs (hEV) and bEVs have shown promising effects against chronic infections [ 89 ] [ 90 ] [ 89 , 90 ] . Compared with their nanomaterial counterparts (liposomal NPs), bEVs provide increased drug delivery and efficient antigen-presenting properties [ 91 ] [ 92 ] [ 93 ] [ 91 , 92 , 93 ] . Various microbes including Helicobacter spp., Klebsiella pneumoniae , Lactobacillus spp., P. aeruginosa , S. aureus , and Streptococcus spp. are involved in the transfer of metabolites between species for intracellular communication and are used in novel adjuvant-associated therapeutics as well as nano-sized vaccine delivery platforms for various infections [ 94 ] [ 95 ] [ 94 , 95 ] . hEVs have shown complexity of the yield coefficient, a high production cost, and limited downstream process, all of which limit their biomedical applications [ 96 ] [ 97 ] [ 110 , 111 ] . The continuous evaluation of EVs as potential tools against chronic infection has led to the development of bEVs derived from Clostridium butyricum [ 98 ] [ 112 ] and L. paracasei [ 99 ] [ 113 ] . Given that most chronic illnesses involve ‘dysbiosis’ of the gut microbiota, tuning the absorption capacity and nutrition digestion factors of the microbiome might influence the host–microbe physiological imbalance. 6. Unresolved Issues with Gut Microbiota-Derived bEVs in Modulating the Gut–Brain Axis: Old Is Gold The continuous usage of antibiotics during BBB infections leads to prognosis of early psychosis and neurotoxicity [ 100 ] [ 114 ] . Gut microbiota dysbiosis, a state where the physiological combinations of flora are transformed into pathological combinations [ 101 ] [ 115 ] via continuous antibiotic administration, has been linked to neural abnormalities. This link is via the vagal nerve, which is associated with a lower response of neurotransmitters inducing systemic inflammation in the CNS [ 102 ] [ 116 ] . These features highlight the importance of the gut–brain axis in modulating CNS homeostasis. 6.1. Gut–Brain Axis The term ‘ Gut–Brain axis ’ refers to a bidirectional network that includes multiple connections such as the vagus nerve (nervous control), immune coordination (epithelial and mucosal barrier), and secondary metabolite generation from microbes [ 103 ] [ 117 ] . The complex architecture of the gut–brain axis entails the constant transit of neurotransmitters within the gastrointestinal (GI) tract, which, in turn, modulates the immune system, including macrophages and mast cells [ 104 ] [ 118 ] . These immune cells boost neuron excitability and regulate the host’s behavioral response. A recent study found that gut dysbiosis caused by a broad-spectrum antibiotic during traumatic brain injury (TBI) resulted in increased neuronal loss, suppressed neurogenesis, altered microglia and peripheral immune response, and modulated fear memory response, suggesting a role of gut microbiota in the recovery from TBI [ 105 ] [ 119 ] . 6.2. Gut Microbiota-Derived bEVs vs. Eukaryotic-Derived hEVs (Physiological Counterpart) Generally, the use of hEVs is significantly limited by the yield coefficient and high-throughput screening. In addition, the current scenario for combating antibiotic resistance with chronic illness is not favored by the use of pathogen-derived bEVs, because the sudden release of pro-inflammatory factors by bacteria cannot be controlled [ 106 ] [ 120 ] . In contrast, beneficial gut microbiota have shown the effective immune responses and efficient pathogen inhibition activity [ 107 ] [ 121 ] . Moreover, bEVs from beneficial gut microbiota take a role in triggering inflammatory responses through LPS and lipoteichoic acid [ 108 ] [ 122 ] and can cross the intestinal barrier, and have effective anti-inflammatory properties against chronic infections and gut dysbiosis [ 109 ] [ 123 ] . The physiological features of hEVs differ significantly from gut microbiota-derived bEVs. 6.3. Problems Related to Gut Microbiota-Derived bEVs on BBB-Associated Diseases The ‘dysbiosis’ condition in the gut microbiota environment by antibiotic usage has also shown certain detrimental impacts such as Alzheimer’s disease, autism, and arthritis, all of which clearly demonstrate the mechanistic behavior and coordinated axis of mental health and intestinal mucosa [ 110 ] [ 127 ] . A study by Lee et al. [ 111 ] [ 128 ] showed that the release of bEVs from a gut pathogen Paenalcaligenes hominis , revealed movement of bEVs via the vagus nerve, producing cognitive impairment in the nervous system. Another study using Porphyromonas gingivalis , an oral pathogen, demonstrated the importance of LPS-coated bEVs in the onset of Alzheimer’s disease, emphasizing the role of protease and LPS in triggering the damage of collagen fibers, fibrinogen connective tissues, and induction of proinflammatory mediators in the transfer of bEVs that alter brain cognitive function [ 112 ] [ 129 ] . The main drawback of bEVs derived from the gut microbiota is that they have a negative impact on memory, cognition, and neuroinflammation. Therefore, direct application of such bEVs may have both adverse and beneficial neurologic effects on CNS homeostasis. 6.4. Beneficial Roles of Probiotic-Derived bEVs on Gut–Brain-Axis Control Considering the diverse array of gut microbiota from intestinal niches, probiotics including Bifidobacterium spp. and Lactobacillus spp. have been identified to create neurotransmitters (acetylcholine, gamma-aminobutyric acid (GABA), and serotonin), which continually control CNS homeostasis [ 113 ] [ 114 ] [ 130 , 131 ] . Overall, probiotics not only govern the bidirectional transit of biochemical signals, but also improve the host’s behavioral response such as anxiety [ 115 ] [ 132 ] , depression, and stroke [ 116 ] [ 133 ] . Apart from periodontal and gut pathogens, probiotics such as Lactobacillus spp. have influence on the motor neuron complex (M-N complex). This M-N complex includes the enteric nervous system (endocrine functions and secretion from intestinal mucosa) and the vagus nerve. Lactobacillus spp. normally modulates the neurotransmitter signals via the vagus nerve (intestinal nerve), involving sensory transmission of neuronal signals via the enteric nervous system to the CNS [ 114 ] [ 131 ] . 7. Conclusions The effectiveness of EVs against various infectious pathogens has been highlighted in recent literatures. However, most of them have largely focused on developing therapeutics or drug delivery vehicles by utilizing either NPs or hEVs (exosomes). Although these agents are clinically significant, their utilization is limited by long-term toxicity and the related mortality, low immunogenic response, stability issues, cost of scaling up, fermentation culture conditions, and downstream processing. In contrast to hEVs, only a few FDA-approved therapeutic bEVs are available . This is due to either failed trials or a low therapeutic efficiency. The concept of ‘postbiotics’ has recently been evaluated as a source of nonviable bacterial supplements capable of regulating the gut–brain axis. That means, the use of probiotics alone may be limited in scope; however, it can be enhanced by tuning the active components of postbiotics to initiate the release of probiotics-derived bEVs or -enriched bEVs. Meanwhile, limitations of combining NPs with antimicrobial compounds have hampered their application for the treatment of infections; moreover, this strategy does not address safety issues related to BBB breach. Collectively, the work summarized in this review provides insights into the efficacy of probiotic-derived bEVs and the novel concept of ‘postbiotics’ as a potential tool for the development of therapeutic platforms to overcome drug resistance in pathogens causing neurological disorders.	https://encyclopedia.pub/entry/history/compare_revision/79796
Slideshow: Invicta FC 33 Quick images from Saturday's Invicta FC 33 card. Facebook Twitter Reddit WhatsApp Email Dec 17, 2018 Chantel Coates def. Ashlynn Kleinbeck R1 0:28 via KO (Punch) Invicta FC 33 Credit: Dave Mandel/Invicta FC Chantel Coates def. Ashlynn Kleinbeck R1 0:28 via KO (Punch) Invicta FC 33 Credit: Dave Mandel/Invicta FC Chantel Coates def. Ashlynn Kleinbeck R1 0:28 via KO (Punch) Invicta FC 33 Credit: Dave Mandel/Invicta FC Anastasia Nikolakakos def. Ashley Medina R2 3:26 via TKO (Punches) Invicta FC 33 Credit: Dave Mandel/Invicta FC Anastasia Nikolakakos def. Ashley Medina R2 3:26 via TKO (Punches) Invicta FC 33 Credit: Dave Mandel/Invicta FC Anastasia Nikolakakos def. Ashley Medina R2 3:26 via TKO (Punches) Invicta FC 33 Credit: Dave Mandel/Invicta FC Brittney Victoria Grizelle def. Sarah Kleczka via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Brittney Victoria Grizelle def. Sarah Kleczka via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Brittney Victoria Grizelle def. Sarah Kleczka via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Brittney Victoria Grizelle def. Sarah Kleczka via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Brianna Van Buren def. Jamie Moyle via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Brianna Van Buren def. Jamie Moyle via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Brianna Van Buren def. Jamie Moyle via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Brianna Van Buren def. Jamie Moyle via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Brianna Van Buren def. Jamie Moyle via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Alesha Zappitella def. Amber Brown via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Alesha Zappitella def. Amber Brown via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Alesha Zappitella def. Amber Brown via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Alesha Zappitella def. Amber Brown via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Kay Hansen def. Sharon Jacobson R3 4:47 via Submission (Armbar) Invicta FC 33 Credit: Dave Mandel/Invicta FC Kay Hansen def. Sharon Jacobson R3 4:47 via Submission (Armbar) Invicta FC 33 Credit: Dave Mandel/Invicta FC Kay Hansen def. Sharon Jacobson R3 4:47 via Submission (Armbar) Invicta FC 33 Credit: Dave Mandel/Invicta FC Kay Hansen def. Sharon Jacobson R3 4:47 via Submission (Armbar) Invicta FC 33 Credit: Dave Mandel/Invicta FC Danielle Taylor def. Montserrat Ruiz via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Danielle Taylor def. Montserrat Ruiz via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Danielle Taylor def. Montserrat Ruiz via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Danielle Taylor def. Montserrat Ruiz via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Danielle Taylor def. Montserrat Ruiz via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Danielle Taylor def. Montserrat Ruiz via Unanimous Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Jinh Yu Frey def. Minna Grusander via Split Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Jinh Yu Frey def. Minna Grusander via Split Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Jinh Yu Frey def. Minna Grusander via Split Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Jinh Yu Frey def. Minna Grusander via Split Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Jinh Yu Frey def. Minna Grusander via Split Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC Jinh Yu Frey def. Minna Grusander via Split Decision Invicta FC 33 Credit: Dave Mandel/Invicta FC More info about Invicta FC 33 Subscribe to our Newsletter * indicates required Email Address * Latest News ALL UFC BELLATOR PFL ONE Sean Brady Reveals Septic Bursitis Forced Exit from UFC 290 Josiah Harrell Steps in to Face Jack Della Maddalena at UFC 290 Glover Teixeira Glad to See Alex Pereira Move to LHW: ‘For Him to Drop to 185 is Crazy’ Grant Dawson Confident He Proved Himself with Lopsided Win at UFC on ESPN 48 Sean Strickland Angles for Title Shot: ‘We Need Some Fresh Blood In There’ UFC on ESPN 48 Bonuses: Brener, Kutateladze Win Fight of the Night Sean Brady Reveals Septic Bursitis Forced Exit from UFC 290 Josiah Harrell Steps in to Face Jack Della Maddalena at UFC 290 Glover Teixeira Glad to See Alex Pereira Move to LHW: ‘For Him to Drop to 185 is Crazy’ Grant Dawson Confident He Proved Himself with Lopsided Win at UFC on ESPN 48 Sean Strickland Angles for Title Shot: ‘We Need Some Fresh Blood In There’ UFC on ESPN 48 Bonuses: Brener, Kutateladze Win Fight of the Night 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 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 2023 PFL 6 Play-by-Play, Results & Round Scoring 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! 24% Decently entertaining, but not a big fight or better than other fights on the card. 42% Fairly dull; Magomedov only had a single round of cardio and wasn't a serious foe. 26% It sucked 8% TOTAL: 451 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... 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U.S. Census Bureau QuickFacts: Somerset County, New Jersey; Gloucester County, New Jersey; New Jersey; Middlesex County, New Jersey; Sussex County, New Jersey Frequently requested statistics for: Somerset County, New Jersey; Gloucester County, New Jersey; New Jersey; Middlesex County, New Jersey; Sussex County, New Jersey QuickFacts Somerset County, New Jersey; Gloucester County, New Jersey; New Jersey; Middlesex County, New Jersey; Sussex County, New Jersey QuickFacts provides statistics for all states and counties, and for cities and towns with a population of 5,000 or more. Table <table><tbody><tr><th> All Topics Population Age and Sex Race and Hispanic Origin Population Characteristics Housing Families & Living Arrangements Computer and Internet Use Education Health Economy Transportation Income & Poverty Businesses Geography</th><th> Somerset County, New Jersey</th><th> Gloucester County, New Jersey</th><th> New Jersey</th><th> Middlesex County, New Jersey</th><th> Sussex County, New Jersey</th></tr><tr><td> Population Estimates, July 1, 2022, (V2022)</td><td>  346,875</td><td>  306,601</td><td>  9,261,699</td><td>  861,418</td><td>  146,084</td></tr></tbody></table> People Population Population Estimates, July 1, 2022, (V2022)  346,875  306,601  9,261,699  861,418  146,084 Population estimates base, April 1, 2020, (V2022)  345,356  302,285  9,289,031  863,183  144,231 Population, percent change - April 1, 2020 (estimates base) to July 1, 2022, (V2022)  0.4%  1.4%  -0.3%  -0.2%  1.3% Population, Census, April 1, 2020345,361302,2949,288,994863,162144,221 Population, Census, April 1, 2010323,444288,2888,791,894809,858149,265 Age and Sex Persons under 5 years, percent  4.8%  4.9%  5.6%  5.3%  4.7% Persons under 18 years, percent  20.8%  21.0%  21.5%  21.2%  19.2% Persons 65 years and over, percent  17.3%  17.0%  17.4%  16.3%  19.2% Female persons, percent  50.6%  50.8%  50.7%  50.2%  49.6% Race and Hispanic Origin White alone, percent  65.6%  81.6%  70.7%  57.8%  92.2% Black or African American alone, percent (a)  11.0%  12.1%  15.4%  12.9%  3.3% American Indian and Alaska Native alone, percent (a)  0.4%  0.3%  0.7%  0.8%  0.3% Asian alone, percent (a)  20.7%  3.3%  10.5%  26.1%  2.3% Native Hawaiian and Other Pacific Islander alone, percent (a)  0.1%  0.1%  0.1%  0.1%  0.1% Two or More Races, percent  2.2%  2.5%  2.4%  2.4%  1.8% Hispanic or Latino, percent (b)  16.4%  7.9%  21.9%  23.2%  11.6% White alone, not Hispanic or Latino, percent  51.5%  75.6%  52.9%  38.9%  82.0% Population Characteristics Veterans, 2017-20219,98215,467309,64223,5066,881 Foreign born persons, percent, 2017-202126.5%5.5%22.9%33.4%7.9% Housing Housing units, July 1, 2022, (V2022)133,445117,7993,785,346317,33862,843 Owner-occupied housing unit rate, 2017-202175.5%80.4%63.8%63.9%84.2% Median value of owner-occupied housing units, 2017-2021$444,700$232,800$355,700$362,900$282,700 Median selected monthly owner costs -with a mortgage, 2017-2021$2,890$2,148$2,560$2,586$2,284 Median selected monthly owner costs -without a mortgage, 2017-2021$1,241$946$1,102$1,105$989 Median gross rent, 2017-2021$1,722$1,301$1,436$1,612$1,387 Building permits, 202290782736,9742,474226 Families & Living Arrangements Households, 2017-2021125,363109,2903,397,156299,45555,401 Persons per household, 2017-20212.712.712.662.782.57 Living in same house 1 year ago, percent of persons age 1 year+, 2017-202189.8%89.9%89.7%89.0%92.0% Language other than English spoken at home, percent of persons age 5 years+, 2017-202132.7%9.2%31.9%45.6%10.3% Computer and Internet Use Households with a computer, percent, 2017-202196.6%94.8%93.9%94.6%95.7% Households with a broadband Internet subscription, percent, 2017-202194.4%90.7%89.4%90.6%92.5% Education High school graduate or higher, percent of persons age 25 years+, 2017-202194.3%93.7%90.5%89.9%95.4% Bachelor's degree or higher, percent of persons age 25 years+, 2017-202156.1%34.5%41.5%44.8%38.1% Health With a disability, under age 65 years, percent, 2017-20214.5%8.3%6.6%6.0%7.4% Persons without health insurance, under age 65 years, percent  6.2%  5.7%  8.4%  8.1%  5.7% Economy In civilian labor force, total, percent of population age 16 years+, 2017-202169.2%66.9%65.8%65.7%68.2% In civilian labor force, female, percent of population age 16 years+, 2017-202163.6%62.4%60.8%59.4%64.2% Total accommodation and food services sales, 2017 ($1,000) (c)941,735562,21223,785,0761,790,517274,226 Total health care and social assistance receipts/revenue, 2017 ($1,000) (c)2,963,1621,682,36574,723,3866,618,597662,924 Total transportation and warehousing receipts/revenue, 2017 ($1,000) (c)705,004629,43930,902,5284,487,13676,344 Total retail sales, 2017 ($1,000) (c)6,750,8094,813,242149,171,30014,855,9711,832,807 Total retail sales per capita, 2017 (c)$20,417$16,535$16,783$17,964$12,974 Transportation Mean travel time to work (minutes), workers age 16 years+, 2017-202131.730.031.533.636.9 Income & Poverty Median household income (in 2021 dollars), 2017-2021$121,695$93,208$89,703$96,883$101,645 Per capita income in past 12 months (in 2021 dollars), 2017-2021$61,805$42,742$46,691$43,300$48,744 Persons in poverty, percent  5.5%  7.7%  10.2%  8.0%  6.1% <table> Businesses<tbody><tr><th> Businesses</th><th></th><th></th><th></th><th></th><th></th></tr><tr><td> Total employer establishments, 2021</td><td>9,727</td><td>6,223</td><td>233,950</td><td>21,897</td><td>3,133</td></tr><tr><td> Total employment, 2021</td><td>179,324</td><td>98,293</td><td>3,570,543</td><td>395,031</td><td>29,788</td></tr><tr><td> Total annual payroll, 2021 ($1,000)</td><td>17,314,893</td><td>4,968,486</td><td>256,423,692</td><td>29,193,608</td><td>1,544,718</td></tr><tr><td> Total employment, percent change, 2020-2021</td><td>-5.0%</td><td>-5.5%</td><td>-6.5%</td><td>-4.7%</td><td>-6.5%</td></tr><tr><td> Total nonemployer establishments, 2019</td><td>29,016</td><td>17,578</td><td>762,163</td><td>64,680</td><td>11,486</td></tr><tr><td> All employer firms, Reference year 2017</td><td>8,671</td><td>4,929</td><td>188,322</td><td>18,457</td><td>3,109</td></tr><tr><td> Men-owned employer firms, Reference year 2017</td><td>5,563</td><td>3,001</td><td>123,258</td><td>11,407</td><td>1,998</td></tr><tr><td> Women-owned employer firms, Reference year 2017</td><td>1,383</td><td>919</td><td>35,466</td><td>3,619</td><td>536</td></tr><tr><td> Minority-owned employer firms, Reference year 2017</td><td>2,088</td><td>546</td><td>42,061</td><td>6,860</td><td>366</td></tr><tr><td> Nonminority-owned employer firms, Reference year 2017</td><td>5,538</td><td>3,824</td><td>133,485</td><td>9,835</td><td>2,493</td></tr><tr><td> Veteran-owned employer firms, Reference year 2017</td><td>329</td><td>273</td><td>8,138</td><td> S</td><td> S</td></tr><tr><td> Nonveteran-owned employer firms, Reference year 2017</td><td>7,237</td><td>4,064</td><td>166,931</td><td>15,981</td><td>2,684</td></tr></tbody></table> <table> Geography<tbody><tr><th> Geography</th><th></th><th></th><th></th><th></th><th></th></tr><tr><td> Population per square mile, 2020</td><td>1,144.1</td><td>938.8</td><td>1,263.0</td><td>2,791.4</td><td>278.1</td></tr><tr><td> Population per square mile, 2010</td><td>1,071.7</td><td>895.3</td><td>1,195.5</td><td>2,621.6</td><td>287.6</td></tr><tr><td> Land area in square miles, 2020</td><td>301.87</td><td>322.00</td><td>7,354.76</td><td>309.22</td><td>518.66</td></tr><tr><td> Land area in square miles, 2010</td><td>301.81</td><td>322.01</td><td>7,354.22</td><td>308.91</td><td>519.01</td></tr><tr><td> FIPS Code</td><td>34035</td><td>34015</td><td>34</td><td>34023</td><td>34037</td></tr></tbody></table> Value Notes  Estimates are not comparable to other geographic levels due to methodology differences that may exist between different data sources. 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 the2021 5-year ACS Comparison Guidancepage. 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. FFewer than 25 firms DSuppressed to avoid disclosure of confidential information NData for this geographic area cannot be displayed because the number of sample cases is too small. FNFootnote on this item in place of data XNot applicable SSuppressed; does not meet publication standards NANot available ZValue 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.	https://www.census.gov/quickfacts/fact/table/somersetcountynewjersey,gloucestercountynewjersey,NJ,middlesexcountynewjersey,sussexcountynewjersey/PST045222
WH 2012: The professional left better learn to live with disappointment \| The Hill White House officials do not expect liberal commentators to lessen their criticism of the administration in the coming two years. WH 2012: The professional left better learn to live with disappointment White House officials do not expect liberal commentators who viewPresident Obama as the compromiser-in-chief to lessen their criticismof the administration in the coming two years. In fact, they expect it to get worse. That’s because Obama has shown every indication that he is reading from former President Clinton’s playbook and moving toward the right in the name of bipartisan compromise. And nobody at the White House is pushing back on that description. {mosads}In the days following the Democrats’ November shellacking, Obama has given every indication that he is serious about joining Republicans in their at-least-rhetorical push to cut spending. That continued Tuesday as Obama, after meeting with Democratic and GOP leaders at the White House, said that he is looking for “common ground” with Republicans. Obama made it clear: He favors results to ideological purity, and he expects the same from Republicans. “[Americans] did not vote for unyielding partisanship,” Obama said. “They’re demanding cooperation.” The president even told the GOP that he didn’t do a good enough job of reaching out to it over the past two years. The Republicans did not reciprocate. So is the president “bending” while Republicans show no signs of moving in Obama’s direction? “I’m not sure I call that bending,” White House press secretary Robert Gibbs said. “I call that trying to work together.” While that sounds like the basis for Triangulation 101 and a feel-good Washington story of sacrifice for the common good, all liberals hear is more of Obama giving while Republicans take. And labor unions, the most fundamental and well-organized constituency within the left, were nothing short of furious at Obama’s call for a two-year pay freeze for federal workers this week. AFL-CIO President Richard Trumka said Obama’s move risks “reinforcing the myth, pushed by some for politically convenient but cynical reasons, that America suffers from a federal government comprised of unproductive and overpaid civil servants.” “Nothing could be further from the truth,” Trumka said. If the White House is worried about further angering its base, aides certainly aren’t showing it. White House officials do not take seriously any talk, no matter how preliminary, of a credible primary challenge to the president, and the larger view is that the more Obama is seen as a centrist, the better off he’ll be. Liberals, they think, can shut up and get on board to help Obama paint the portrait of moderation the White House is hoping to have framed before November 2012. “I think of the second Clinton administration, with welfare reform, with balanced budgets, with trade agreements,” McConnell said. “I think we all agree there’s no particular reason why we can’t find areas of agreement and do some important things for the American people over the next two years.” While it turned out well for Clinton, liberals say Obama is missing the point. Democrats didn’t lose because moderates broke for Republicans, lefties say. Democrats lost because liberal independents, the same ones who were chanting, “Yes we can!” in 2008, stayed home in 2010. The kind of energy that swept Obama into the White House will not be replicated during the president’s reelection campaign if liberals feel abandoned by Obama, says the professional left. In other words, the enthusiasm gap that Obama repeatedly dismissed in 2010 could cause him serious heartburn in 2012 even if he doesn’t have to fight another Democrat for the nomination. Stephanie Taylor, co-founder of the Progressive Change Campaign Committee, warned of just that on Tuesday, saying that the midterms should be a “wake-up call” for Obama. “President Obama shouldn’t be worried about criticism from ‘the professional left,’ ” Taylor said. “He should be worried about criticism from millions of former Obama voters who are severely disappointed in him right now. The fact is that many former Obama voters stayed home in 2010, and unless he starts enacting the popular progressive change he campaigned on, they may stay home again in 2012.” If members of the left are holding out hope that Obama will come around to their reading of the midterms, they had better learn to live with disappointment. And Obama had better hope disappointment doesn’t lead to disengagement. Youngman is the White House correspondent for The Hill. Find his column, Obama’s Bid for Reelection, on thehill.com. Tags Mitch McConnell	https://thehill.com/blogs/ballot-box/sam-youngman/76312-wh-2012-the-professional-left-better-learn-to-live-with-disappointment/
Med Lagen som Verktyg \| Independent Living Institute Med Lagen som Verktyg Vi måste lära oss att hävda oss Abidi, Javed . 1999. Vi måste lära oss att hävda oss. Disability Awareness in Action Newsletter, nummer 74, juli 1999. av Javed Abidi, Executive Director, National Centre for Promotion of Employment of Disabled, i Indien In English Artikeln har tidigare publicerats i Disability Awareness in Action Newsletter, nummer 74, juli 1999. Javed Abidis ursprungliga artikel från vilken dessa utdrag tagits publicerades ursprungligen i DeepShitha, Spastics Society of Eastern Indias nyhetsblad i december 1998. We (Disabled People) Must Learn to Exert Ourselves Abidi, Javed . 1999. We (Disabled People) Must Learn to Exert Ourselves. Disability Awareness in Action Newsletter no. 74, July 1999. by Javed Abidi Executive Director, National Centre for Promotion of Employment of Disabled, India På svenska This article appeared in Disability Awareness in Action Newsletter no. 74, July 1999. Javed Abidi's original article, from which these extracts were taken, were originally published in DeepShitha, the journal of the Spastics Society of Eastern India, in December 1998. Is Personal Assistance Relevant for Developing Countries? Dr. Adolf Ratzka . 2006. Is Personal Assistance Relevant for Developing Countries? s Personal Assistance Relevant for Developing Countries? by:Adolf Ratzka, December 2006 <here is a image 3841ec7ca6c9e74d-1a66e207307b4bd5> <here is a image 4480518bb6cf610b-c6cc48e18622d94e See> Curriculum Vitae. A Matter of Perception King, Audrey . 2006. A Matter of Perception. <here is a image 27cf828894dcf3ba-9f7af862cfc81296> Audrey King, M.A., is an internationally known writer, speaker, and advocate on disability issues. A trained rehabilitation psychologist she is the author of two books, Count Me In (1985) and There's Lint in Your Belly Button (1987), both of which focus on integration of persons with disabilities in society. Ms King has been using ventilator, electric wheelchair and personal assistance since 1952. Company Disability Policy Guidelines and Self-assessment Checklist [Anonymous] . 2005. Company Disability Policy Guidelines and Self-assessment Checklist. A company's commitment to diversity in staff, customers or clients is part of its organizational identity. As such it needs to be expressed and displayed in a statement on the company's website. The policy regarding people with disabilities should be a distinct part of the document. This document is also available in PDF format here. Checklist for University Disability Information and Self-assessment questions Independent Living Institute, Sweden . 2005. Checklist for University Disability Information and Self-assessment questions. This document is also available in PDF format here. Your university should have a policy with respect to people with disabilities and information for people with disabilities. Both should be easy to find, informative and accessible. Modelo para una Política Nacional de Asistencia Personal Dr., Ratzka Adolf; . 2004. Modelo para una Política Nacional de Asistencia Personal. LanguageSpanish La política sugerida aquí es diferente, porque está escrita por individuos quienes en sí dependen de la asistencia diaria de otros. El Centro Europeo para la Excelencia en Asistencia Personal (ECEPA) (www.ecepa.org) está formado por ocho organizaciones asociadas 1, en ocho países europeos, que son operadas y controladas por personas con discapacidad y se especializa en brindar y defender los servicios de asistencia personal para personas con discapacidad. Usando nuestra experiencia combinada con las políticas de asistencia personal, se recopiló una lista de características para una política que promueve la autodeterminación y la ciudadanía completa para las personas con discapacidades extensivas. File attachments: <here is a image 99f540ca7e0b7aeb-56dcf9690606b639> POLÍTICA NACIONAL DE ASISTENCIA PERSONAL.pdf English Deutsch Nederlands The Independent Living Movement in the UK Evans, John . 2003. The Independent Living Movement in the UK. John Evans was one of the founders of Project 81 that marked the beginning of the Independent Living Movement in the UK. Since 1996 he has been the chair of the European Network on Independent Living (ENIL). In this document he gives an overview of the origin of the Independent Living Movement in the UK, it's development and evolution, as well as the current situation (2003). What is Independent Living - A Personal Definition Dr., Ratzka Adolf; . 2003. What is Independent Living - A Personal Definition. Dr., Ratzka Adolf; . 2003. Vad är Independent Living - en personlig definition. The Craving of the Benevolent Berg, Susanne . 2003. The Craving of the Benevolent. Berg, Susanne . 2002. Kleinfield, Sonny . 1992. Declaring independence in Berkeley. The Journey from Disability Shame to Disability Pride Stone, Karen . 2000. The Journey from Disability Shame to Disability Pride. ILRU . 1992. Disability issues: organizing community support - Tools for Power ILRU Disability issues: organizing community support - Tools for Power. Stone, Karen . 2001. Ugly. Ugly loved three things in this world: fighting, eating garbage, and shall we say, love. The combination of these things combined with a life spent outside had their effect on Ugly. Developing assistants management skills - Tools for Power Care Support Ideas, HCIL (Hampshire Center for Independent Living) Developing assistants management skills - Tools for Power. With little or no previous experience the disabled person seeking to live independently suddenly finds her/himself thrust into the role of employer. Not surprisingly the effective management skills essential to coping with the day-to-day matter of relating to her/his personal assistant are sometimes absent or under-developed. Power to the people D'Aubin, April . 1992. Power to the people. Power to the people Possibilities of Independent Living of persons with disabilities in Africa Silwimba, Felix . 1992. Possibilities of Independent Living of persons with disabilities in Africa. Possibilities of Independent Living of persons with disabilities in Africa The Strasbourg Resolutions European Network on Independent Living(ENIL) . 1989. The Strasbourg Resolutions. In April 1989, the first European Independent Living Conference was held at the European Parliament in Strasbourg, France. The meeting's theme was Personal Assistant. The conference resulted in the founding of the European Network for Independent Living, ENIL. Here, the resolution adopted at the conference. GAD's Center for Independent Living . 1989. GAD's Center for Independent Living can help. (1993) We have already assisted nearly a dozen people in the employment of their own personal assistants. This really does put you, the disabled person in control. You can decide who to employ, which hours they should work and what they should do. But control brings with it responsibilities and this is where GAD can help. European Network on Independent Living: disability rights Dr. Adolf Ratzka . 1999. European Network on Independent Living: disability rights. <here is a image 9d61582dbcf23d30-a64b9aa5735b69ee> ENIL is the umbrella of individuals and organizations dedicated to promoting Independent Living among persons with disabilities and the general public in Europe. The website for ENIL is now at https://enil.eu/ This page is from 1999. Time Magazine Recognizes Adolf Ratzka as European Visionary [Anonymous] . 1998. Time Magazine Recognizes Adolf Ratzka as European Visionary. Time Magazine. In 1961, German-born teenager Adolf Ratzka was paralyzed by polio. He seemed destined to spend his life in institutions, but at 22 won a scholarship to study in California. The U.S. was then the only country with Photograph of Dr. Adolf Ratzka together with daughter, Katharina.facilities, such as a personal assistant and a car that could be driven by wheelchair-bound people, enabling severely disabled persons to pursue normal academic study. Towards a more helpful society Bang, Marian . 1996. Towards a more helpful society. The world is full of devices that make daily tasks easier. For the disabled, assistive devices make daily tasks possible. Marian Bang spoke to the Disability Action Research Team (DART) who see research into these as far more than just reports on paper. Rather they are a tool for empowering both those with abilities and their care-givers. Introduction to direct payments for personal assistance Dr. Adolf Ratzka . 1996. Introduction to direct payments for personal assistance. Presentation given at the HELIOS Study Visit on Independent Living and Personal Assistance in Stockholm, June 7-9, 1996. Supporting families in keeping disabled family members at home: Swedish policy instruments Dr. Adolf Ratzka . 1995. Supporting families in keeping disabled family members at home: Swedish policy instruments. In most countries the importance of the family as a form of social insurance is declining. As the extended family gradually disappears with industrialization and the labor market's demands on geographical mobility, as divorce rates go up and single parents become increasingly common, the ability of the family to provide mutual aid in everyday life is diminishing. One of the results is that families have fewer resources left for members with special needs such as disabled children or old parents. If there is no place for these groups in the family, where can they turn to? What is your personal definition of Independent Living? Dr., Ratzka Adolf; . 1992. What is your personal definition of Independent Living? Personal accounts What is your personal definition of Independent Living? It is the ability to live independently and productively in the community and to live with the same freedom of choice as a non-disabled person. So it's not that you are living on your own but that you control where you live and have the same range of choices as a non-disabled person. (Jill Weiss) Personal assistance in Germany, overview and external links Independent Living Institute . 2014. Personal assistance in Germany, overview and external links. Around 2000 people have personal assistance financed through personal budgets in Germany. Germany has a population of 80 million so 2000 PA users are not very many. Links: The ANEDcountry report on the implementation of policies supporting independent living for disabled people for Germany. Personal assistance in Norway, overview and external links Independent Living Institute . 2014. Personal assistance in Norway, overview and external links. There are 3000 people getting personal assistance in Norway (2012 total population 5 million). Figures from ENIL state an average of 47 hours per week for members of one cooperative assistance provider (2013). http://lovdata.no/dokument/NL/lov/2014-06-20-41 (The legal amendment granting right to personal assistance) http://www.regjeringen.no/nb/dep/hod/dok/regpubl/prop/2013-2014/Prop-86-L-20132014.html?id=758644 (proposition for changes to the law) Personal assistance in Belgium, overview and external links Independent Living Institute . 2014. Personal assistance in Belgium, overview and external links. According to theENIL Personal Assistance Tables for Belgiumthere were 2112 PAB (personal assistance budget) users in Flanders (nov 2012) and 250 PAB users in Wallonia. 6000 more people are waiting for a personal assistance budget. Belgium has a population of 11 million people. Personal assistance in Ireland, overview and external links . 2014. There is personal assistance in Ireland (population 6.3 million) and theDisability Federation of Irelandhas in 2014 written a report:Access to Life: Personal Assistant Services in Ireland and Independent Living by People with Physical and Sensory Disabilities.	https://www.independentliving.org/mlsv/sv/docs4/sv/docs4/dpi022000sv.html?page=22
Calvin's Commentaries, Vol. 5: Harmony of the Law, Part III: The Law: The Second Table: Ceremonial Supplements Calvin's Commentaries, Vol 5: Harmony of the Law, Part III, full text etext at sacred-texts.com Calvin's Commentaries, Vol. 5: Harmony of the Law, Part III , tr. by John King, [1847-50], at sacred-texts.com The Ceremonial Supplements of the Sixth Commandment Deuteronomy 21 Deuteronomy 21:1-9 1.If onebe found slain in the land which the Lord thy God giveth thee to possess it, lying in the field, andit be not known who hath slain him; 1.Quum inventum fuerit cadaver hominis occisi in terra quam Jehova Deus tuus dabit tibi ut possideas eam, prostratum in agro, nec cognitum fuerit quis percusserit eum: 2.Then thy elders and thy judges shall come forth, and they shall measure unto the cities which areround about him that is slain. 2.Tunc egredientur seniores tui, et judices tui, et metientur usque ad civitates quae sunt in circuitibus cadaveris hominis illius occisi. 3.And it shall be, thatthe city which isnext unto the slain man, even the elders of that city shall take an heifer, which hath not been wrought with, and which hath not drawn in the yoke; 3.Et seniores urbis, propinquioris urbis illi cadaveri occiso, capient vitulam de armento qua nemo usus fuerit, et quae non traxerit jugum. 4.And the elders of that city shall bring down the heifer unto a rough valley, which is neither card nor sown, and shall strike off the heifer’s neck there in the valley: 4.Et adducent seniores ejus urbis vitulam ad vallem asperare, quae nunquam fuerit arata, neque seminata, et praecident cervicem vitulae illic in valle. 5.And the priests, the sons of Levi, shall come near; (for them the Lord thy God hath chosen to minister unto him, and to bless in the name of the Lord;) and by their word shall every controversy and every stroke be tried 5.Et accedent sacerdotes filii Levi (eos enim elegit Jehova Deus tuus ut ministrent ipsi, et ad benedicendum in nomine Jehovae: et juxta quorum sermonem erit omnis lis atque omnis plaga.) 6.And all the elders of that city, that arenext unto the slain man, shall wash their hands over the heifer that is beheaded in the valley: 6.Et omnes seniores ejus urbis ubi accesserint ad cadaver hominis occisi, lavabunt manus suas super vitulam percussam in valle. 7.And they shall answer and say, Our hands have not shed this blood, neither have our eyes seen it. 7.Et testificabuntur, ac dicent, Manus nostrae non effuderunt sanguinem istum, neque oculi nostri viderunt. 8.Be merciful, O Lord, unto thy people Israel, whom thou hast redeemed, and lay not innocent blood unto thy people of Israel’s charge. And the blood shall be forgiven them. 8.Expia populum tuum Israel quem redemisti Jehova, et ne imputes sanguinem innocentem in medio populi tui Israel: et expiabitur ab eis sanguis. 9.So shalt thou put away the guilt ofinnocent blood from among you, when thou shalt do that which isright in the sight of the Lord. 9.Tu autem auferes sanguinem innocentem e medio tui, quum feceris quod rectum est in oculis Jehovae. 1. If one be found slain in the land . This Supplement: is of a mixed character, relating partly to the civil, and partly to the criminal law. We are informed by it how precious to God is the life of man; for, if a murder had been committed by some unknown person, He requires an expiation to be made, whereby the neighboring cities should purge themselves from the pollution of the crime. Whence it appears that the earth is so polluted by human blood, that those who encourage murder by impunity, implicate themselves in the guilt. The question here is as to a secret crime, the guilt of which attaches to the neighboring cities, until, by the institution of a diligent inquiry, they can testify that the author is not discovered; how much less excusable, then, will they be, if they allow a murderer to escape with impunity? The rite prescribed is, that the elders of the nearest city should take a heifer which had not drawn in a yoke, and bring it into a stony and barren valley, cut off its neck with the assistance of the priests, wash their hands, and bear witness that their hands as well as their eyes are pure, as not being cognizant of the criminal. God chose a heifer that had not born a yoke, in order that the satisfaction made by innocent blood might be represented in a more lively manner; whilst it was to be killed in a desert place, that the pollution might be removed from the cultivated lands. For, if the blood of the heifer had been shed in the middle of the market-place of the city, or in any inhabited spot, the familiarity with the sight of blood would have hardened their minds in inhumanity. For the purpose, therefore, of awakening horror, it was drawn out into a solitary and uncultivated spot, that they might be thus accustomed to detest cruelty. But although, properly speaking, this was not a sacrifice which could be offered nowhere except in the sanctuary, still it nearly approached to the nature of a sacrifice, because the Levites were in attendance, and a solemn deprecation was made; nevertheless, they were not only employed as ministers of the altar, but also as judges, for their office is expressed in the words, that they were “chosen to minister to God, to bless the people, and to pronounce sentence as to every stroke.” 6. And all the elders of that city . The washing of their hands had the effect of stirring them up the more, so that they should not inconsiderately protest in that solemn rite that they were pure and guiltless; for it was just as if they had presented the corpse of the dead mall before God, and had stood themselves opposite to it to purge away the crime. At the same time, also, they ask for pardon, because it might have been through their carelessness that the man was smitten; and again, since, by the sacrilege of Achan alone the whole people were contaminated, it was to be feared lest the vengeance of God should extend more widely on account of the offense committed. And thus they were again taught how greatly God abominates murders, when the people pray that they may be pardoned for the crime of another, as if, by the very looking upon it, they had contracted guilt. God at length declares that He will not impute it to them, when they have duly performed this rite of expiation; not because the heifer was the price of satisfaction to propitiate God, but because in this way they humbly reconciled themselves to Him, and shut the door against murders for the time to come. On this account it is said — “Thou shalt put away the blood from among you;” for if the murder be passed over without observation, there remains a blot upon the people, and the earth itself, in a manner, stinks before God. Deuteronomy 12 Deut. 12:15,16,20-25 15.Notwithstanding thou mayest kill and eat flesh in all thy gates, whatsoever thy soul lusteth after, according to the blessing of the Lord thy God which he hath given thee: the unclean and the clean may eat thereof, as of the roe-buck, and as of the hart. 15.Pro omni desiderio animae tuae mactabis, et comedes carnes secundum benedictionem Jehovae Dei tui, quam dederit tibi intra omnes portas tuas: immundus et mundus comedet eas, sicut capream et cervum. 16.Only ye shall not eat the blood; ye shall pour it upon the earth as water. 16.Tantummodo sanguinem non comedetis, super terram effundetis illum instar aquae. 20.When the Lord thy God shall enlarge thy border, as he hath promised thee, and thou shalt say, I will eat flesh, (because thy soul longeth to eat flesh,) thou mayest eat flesh, whatsoever thy soul lusteth after. 20.Quum dilataverit Jehova Deus tuus terminum tuum, quemadmodum loquutus est tibi, et dixeris, Comedam carnem, quod concupiscat anima tua vesci carnibus: juxta omne desiderium animae tuae comedes carnes. 21.If the place which the Lord thy God hath chosen to put his name there be too far from thee, then thou shalt kill of thy herd, and of thy flock, which the Lord hath given thee, as I have commanded thee, and thou shalt eat in thy gates whatsoever thy soul lusteth after. 21.Quum longinquus a te fuerit locus quem elegerit Jehova Deus tuus ut ponat nomen suum ibi, mactabis de bobus tuis et de pecudibus tuis quas dederit Jehova tibi: quemadmodum praecepi tibi, et vesceris in portis tuis secundum omne desiderium animae tuae. 22.Even as the roe-buck and the hart is eaten, so thou shalt eat them; the unclean and the clean shall eat of them alike. 22.Certe quemadmodum comeditur caprea et cervus, sic comedes illas: immundus pariter et mundus vescentur illis. 23.Only be sure that thou eat not the blood: for the blood is the life; and thou mayest not eat the life with the flesh. 23.Tantum roborare ut non comedas sanguinem: quia sanguis est anima, et non comedes animam una cum carne. 24.Thou shalt not eat it; thou shalt pour it upon the earth as water. 24.Non comedes illum, sed in terram effundes illum instar aquae. 25.Thou shalt not eat it; that it may go well with thee, and with thy children after thee, when thou shalt do that whichis right in the sight of the Lord. 25.Non vesceris illo, ut bene sit tibi, et filiis tuis post te, quum feceris quod rectum est in oculis Jehovae. Leviticus 7 Leviticus 7:26-27 26.Moreover, ye shall eat no manner of blood, whether it beof fowl or of beast, in any of your dwellings. 26.Nullum sanguinem comedetis in cunctis habitationibus vestris, tam de avibus quam de jumentis. 27.Whatsoever soul it bethat eateth any manner of blood, even that soul shall be cut off from his people. 27.Omnis anima quae comederit ullum sanguinem, excidetur anima illa e populis suis. Leviticus 19 Leviticus 19:26 26.Ye shall not eat anythingwith the blood. 26.Non comedetis cum sanguine. Deuteronomy 12:15 . Notwithstanding thou mayest kill . What precedes I have introduced in its proper place, viz., that they should not kill the sacrifices anywhere but in the sanctuary, of which there was only one in Judea. Here the permission to eat meat is given, provided that they do not offer the animals to God, but eat of them as of wild beasts. By way of example, two kinds are mentioned, the roe-buck and the hart, of which no offering was made. They are, therefore, freely allowed to eat meat wheresoever they pleased, with this exception, that they should not taste the blood; for, although this was observed by their forefathers before the giving of the Law, God ratifies it anew when He would gather a peculiar people to Himself. We know that immediately after the deluge, Noah and his posterity were commanded to abstain from blood; but, inasmuch as the greater part of mankind soon degenerated, it is probable that all nations neglected God’s command, and permitted to themselves a universal license on this point; and it is even questionable whether this observance, which was everywhere fallen into desuetude, prevailed among the family of Shem. Certainly it may be conjectured from the renewed promulgation of the law, that it was altogether obsolete; at any rate, God would have His chosen people distinguished by this mark of separation from heathen nations. The reason of the prohibition which is now mentioned had already been declared, 18 viz., because the blood is the seat of life. But although it, was allowable to kill an animal for food, yet, was it a useful restraint to prevent inhumanity, that they should not touch the blood; for if they abstained from the blood of beasts, much more necessary was it to spare human blood. After God, therefore, has forbidden blood to be eaten, He immediately proceeds to speak of men themselves: “Whose sheddeth man’s blood, by man shall his blood be shed: for in the image of God made he man.” 19 ( Ge 9:4-6 .) Hence I have deemed it appropriate to annex all the passages in which God commands the people to abstain from blood, to the Sixth Commandment. In itself, indeed, the eating of blood was a thing of no great importance: since, therefore, God so often inculcates a point of so little weight, it may be inferred that the law has some further object. To this may be added the severity of the punishment, for surely it was not a crime worthy of death to taste the blood of some little bird; and hence, also, it is manifested that the prohibition had another meaning, viz., that cruelty might be abhorred. And the words of Moses show that the eating of blood is not forbidden because it infected man with its uncleanness, but that they might account the life of man to be precious; for it is said, “the blood is the life,” which, in the opinion of Augustine, 20 is equivalent to its being “the sign of life;“ but Moses rather means that animal life is contained in the blood. Wherefore, blood, which represents the life, was not interdicted without reason, nor was it only sinful to eat the blood by itself, but also together with the flesh, as is expressly declared both in Deuteronomy and in the last passage from Leviticus. 23. Only be 21 sure that thou eat not . It is not without cause that he earnestly exhorts them to inflexible firmness, because it was both a matter trifling in appearance, and its observation troublesome, whilst it was easy to decline from it on account of the universal example of the Gentiles. For if they considered within themselves that it contributed not to holiness that they should not touch blood, hence a snare to indulgence might easily have arisen. Leviticus 17 Leviticus 17:10-14 10. And whatsoever man there beof the house of Israel, or of the strangers that sojourn among you, that eateth any manner of blood; I will even set my face against that soul that eateth blood, and will cut him off from among his people. 10.Quicunque e domo Israel, et e peregrinis qui peregrinantur in medio eorum, comederit ullum sanguinem, ponam faciem meam in animam quae comederit sanguinem, et excidam eam e medio populi sui. 11. For the life of the flesh isin the blood; and I have given it to you upon the altar, to make an atonement for your souls: for it isthe blood thatmaketh an atonement for the soul. 11.Quia anima carnis in sanguine est: ego autem dedi illum vobis super altare ad expiandum animus vestras, quia sanguis animam expiabit. 12. Therefore I said unto the children of Israel, No soul of you shall eat blood, neither shall any stranger that sojourneth among you eat blood. 12.Ideo dixi filiis Israel, Nulla anima ex vobis comedet sanguinem, et peregrinus qui pregrinatur in medio vestri non comedet sanguinem. 13. And whatsoever man there beof the children of Israel, or of the strangers that sojourn among you, which hunteth and catcheth any beast or fowl that may be eaten; he shall even pour out the blood thereof, and cover it with dust. 13.Et quicunque e filiis Israel, et e peregrinis qui peregrinantur in medio eorum, venatus fuerit venationem bestiae vel avis quae comeditur, effundet sanguinem ejus et cooperiet pulvere. 14. For it isthe life of all flesh; the blood of it isfor the life thereof: therefore I said unto the children of Israel, Ye shall eat the blood of no manner of flesh: for the life of all flesh isthe blood thereof; whosoever eateth it shall be cut off. 14.Quia anima cujusque carnis, sanguis ejus est in anima: dixique filiis Israel, Sanguinem cujuscunque carnis non comedetis, quia anima cujusque carnis est sanguis ejus: quicunque comederit illum, excidetur. 10. And whatsoever make there be of the house of Israel . God here not only condemns to death whosoever shall have polluted themselves by eating of blood, but declares that He will Himself take vengeance on them, though they may escape from the hands of the judges; for He not only prescribes to the judges what it is right for them to do, but asserts for Himself the office of inflicting the punishment. For, if we consider the intention of the Law, is there anything to surprise us in this; for although it be not consistent that the blood of a brute should be compensated for by the death of a man, still we must remember that this mode of instruction 22 was necessary for a rude people, lest they should speedily lapse into barbarism. But, lest they should complain that no use remained for the blood, He reminds them that since it was given for atonement, they would be very ungrateful if they were not content with so great a blessing; and surely, since it was the price they were to pay for appeasing God, this was an employment of it far to be preferred to food. If, then, they desired to exchange into ordinary food the blood, which was destined to the altar for the reconciliation of God, Moses indirectly reproves their ingratitude; for when God took away the right of eating it, He left them something better, which should have abundantly satisfied them. But we have elsewhere 23 seen in what manner blood atones for souls, i e ., in a sacramental manner, upon which it must be observed that what properly belongs to Christ is thus transferred by metonomy to figures and symbols, yet in such a way that the similitude should neither be empty nor inefficacious; for in so far as the fathers apprehended Christ in the external sacrifices , atonement was truly exhibited in them. In this passage also, I do not understand “the strangers” to be all such visitors as may have journeyed amongst them on matters of business, but those who had devoted themselves to the worship of God; for many foreigners, abandoning their superstitions, were circumcised, and it behooved that such as these should be expressly laid under the bonds of the Law, lest, if it had not referred to them, they should have withdrawn themselves from obeying it. This point must, therefore, be briefly adverted to, lest we should suppose that heathen sojourners were prohibited from the eating of blood, whereas they were allowed to buy for food 24 even flesh that had been torn by beasts. Since, however, the Patriarchs before the Law had abstained from blood, and its prohibition had no reference to the First Table or the legal service, hence it came to pass that when the Apostles abrogated the ceremonial law, they did not dare to allow immediately the free eating of blood, lest great scandal should arise from this new and unwonted thing. ( Ac 15:20 .) Wherefore, lest so trifling a matter should cause deadly schisms in the Churches, they commanded the Gentiles not to eat of blood; adding as the reason, that those who were accustomed to read the writings of Moses, would be disturbed at this innovation; yet this was only observed for a short period, as we gather from Paul. 25 It was, not without superstition and misplaced zeal;. retained by some even to the days of Tertullian. Footnotes 18 See on Leviticus 3:17 , vol. 2, p. 335, whence, however, he refers to Genesis 9:4 . C. Society’s edition, vol. 1, p. 293. 19 Lat . “Qui effuderit sanguinem hominis in homine;” he who shall have shed the blood of man in man. — Vide C . in loco . 20 Quaest. in Leviticum, 57 Section 2. “Illud appellatur anima, quod significat animam.” — Edit . Benedict . tom . 3, p. 1 pag. 516. 21 Lat ., “Roberare.” Margin, A . V ., “ Heb ., Be strong.” 22 “Hanc paedagogiam .” — Lat . “Ceste doctrine puerile.” — Fr . 23 See onExodus 12:21, antevol. 1 p. 221. 24 See on Deuteronomy 14:21 , ante vol. 2, p. 69. 25 There is no reference here in the Latin, but the Fr . is, “comme il se peut recueillir par ce que Sainct Paul en escrit aux Corinthiens;” as may be gathered from what St. Paul writes respecting it to the Corinthians. In C .’ s Commentary on the Acts, 15:28, he says, “We know that this law was foredone by Paul, so soon as the tumult and contention was once ended, when he teacheth that nothing is unclean, ( Ro 14:14 ,)and when he granteth liberty to eat all manner of meats, yea, even such as were sacrificed to idols. ( 1Co 10:25 .)” — C . Society ’ s edit ., vol. 2, p. 79. Tertullian, Apol ., cap . 9, speaks as follows; “Erubescat error vester Christianis, qui ne animalium quidem sanguinem in epulis esculentas habemus, qui propterea quoque suffocatis et morticinis abstinemus, ne quo modo sanguine contaminemur, vel intra viscera sepulto.” See Bingham, book 17 ch. 5 sec. 20 “But on the other hand, because it was the custom of the Catholic Church, almost to the time of St. Austin, to abstain from eating of blood, in compliance with the rule given by the Apostles to the Gentile converts; therefore, by the most ancient laws of the Church, all clergymen were obliged to abstain from it under pain of degradation. This is evident from the Apostolical Canons, and those of Gangra, and the second Council of Orleans, and the Council of Trullo. But as this was looked upon by some only as a temporary injunction, so it appears from St. Austin that it was of no force in the African Church. (Contra Faust., lib. 32, c. 13.) He that would see more about it may consult Curcellaeus, who has written a large dissertation upon the subject.” Next: Political Supplements	https://www.sacred-texts.com/chr/calvin/cc05/cc05011.htm
NATO - Opinion: ''NATO: Defending against Ballistic Missile Attack'' - Speech by NATO Secretary General Anders Fogh Rasmussen at the Royal United Services Institute in London, 15-Jun.-2011 ''NATO: Defending against Ballistic Missile Attack'' Speech by NATO Secretary General Anders Fogh Rasmussen at the Royal United Services Institute in London Russian Ukrainian Professor Clarke, Ladies and Gentlemen, This annual conference has become the point of reference for discussion on missile defence. It brings together experts from a wide range of countries, from governments, and from industry. And I want to thank you for inviting me to contribute to your discussion. Missile defence is particularly important for our Alliance. And it has the potential to fundamentally change how NATO works with other nations to build lasting security and stability. Last November, at the NATO Summit in Lisbon, we agreed to develop a missile defence capability. We also invited Russia to cooperate with us. Those decisions were the culmination of over 8 years of discussions. And they initiated a major Alliance programme of work. This work has two parallel tracks – one that is purely internal, and one that is external with Russia. And work is progressing on both. In my remarks today, I want to answer three questions. WHY do we need missile defence? WHY do we need transatlantic cooperation to make it work? And WHY do we want to cooperate with Russia? Let me start with WHY we need it. As we sit here discussing missile defence, some people elsewhere in the world are discussing missile attack. Over 30 states either already have, or are developing, missile technology. These missiles can be fitted with conventional warheads, or with weapons of mass destruction. Some of them can already reach parts of NATO territory. Others can threaten NATO interests. And all the time, technology is advancing. Ranges are increasing. Accuracy and payloads are increasing. And the number of countries with a proven capability is increasing. We cannot ignore these trends. We cannot afford to have even one of our cities hit. We cannot take the risk of doing nothing. Missile threats are real. And our defence must be real. NATO is responsible for the defence and protection of our territory and the 900 million people who live on it. This is our raison d’être. And this is why we have to take action. We need to demonstrate our determination to defend and protect our citizens. To defend and protect our territory. And to defend and protect our forces. At the same time, this will demonstrate that we will not be coerced or intimidated by proliferation programmes. This is why NATO needs missile defence. It is why we agreed that missile defence is a core element of our collective defence. And it is why we have decided to develop a missile defence capability to protect NATO European populations, territory, and forces. This leads to my second point. WHY is transatlantic cooperation necessary to protect NATO European Allies? Building effective missile defence is challenging. But it can be done. We are already building a NATO system to protect deployed troops from missile attack. It is tried and tested technology. And we have already demonstrated that it works. We have agreed to expand the capability of this system, so it can also protect NATO European populations and territory. We will do this in stages. This staged approach means we can include the latest technical developments. We can adapt to an evolving threat. And we can ensure we stay at least one step ahead. The United States has decided to do it on a multilateral basis, in NATO. It will share its capability with Allies, to help protect them too. And it will share the decision making with Allies, so they are involved in choosing the right responses. At a time when some are voicing concerns that the United States is disengaging from Europe, this contribution to missile defence is an extremely strong signal of America’s continuing commitment to our continent. It was warmly welcomed by all Allies. And the first elements will deploy to Europe later this year. But the United States’ contribution on its own is not enough. To be effective in protecting all European Allied territory, the American assets need to be accompanied by other nations’ missile defence sensors and interceptors. Seven European Allies 1already contribute their national missile defence systems for the protection of Allied forces. We now need European Allies to contribute to territorial missile defence too. And all these national elements need to be integrated into a single NATO network. This is the essence of NATO missile defence for Europe. It is all about bringing Allies’ individual contributions together into one unified system. It is a strong signal that Europe and North America are committed to transatlantic security. It will bind them closer together. And it will make our Alliance even stronger. Our goal is to have an interim capability by the time of our Summit next year. At the same time, it achieves economies of scale. It offers far better protection than if Allies deployed their assets on a purely national basis. And it perfectly illustrates the benefits of what I call “Smart Defence”. In times of economic difficulty, the “Smart Defence” approach means we can do together what we cannot do alone. It allows us to deliver better security for all. Not by spending more money. But by spending more time and effort on multinational cooperation and coordination. NATO provides the coherence. And it ensures that Allies can plug their own capabilities into a common system. Missile defence for Europe also underlines why NATO’s transatlantic role will continue to be critical for our security. We will coordinate the contributions of Allies from both sides of the Atlantic. We will provide the glue to hold everything together with our command and control system. And we will provide the political consultation and decision-making framework for collective defence. Now let me turn to my third point. WHY do we want to cooperate with Russia? Large parts of Russia, and many Russian citizens, face a missile threat too. And NATO is convinced that cooperating with Russia on missile defence is in the interest of all of us – NATO Allies, and Russia. It makes sense politically. It makes sense practically. And it makes sense militarily. What does NOT make sense, is for Russia to talk about spending billions of roubles on a new offensive system to target the West. This type of rhetoric is unnecessary. This type of thinking is out of date. This type of investment is a waste of money. Because, we are not a threat to Russia. We will not attack Russia. We will not undermine the security of Russia. The threats to Russia come from elsewhere. And our invitation to cooperate on missile defence is proof of that. So where are we on our cooperation? From the beginning, the Allied position has been very clear. We are not talking about a single system. We have taken a decision to build an Allied system. That is a reality. And that will not change. What we are talking about is synergy between our NATO system and a Russian system. The reason for this is simple. NATO has collective defence obligations which bind all Allies. And our territorial missile defence system will be part of our collective defence framework. We cannot outsource our collective defence obligations to non-NATO members. And actually I am equally convinced that Russia would not want to give up any of its sovereignty either. Last week, in Brussels, NATO and Russian Defence Ministers discussed the next steps in our missile defence cooperation. We all understand that the foundation for our cooperation must be confidence and trust. Russia says it wants guarantees. We can give these by agreeing that our systems will not undermine the strategic balance. That they will strengthen each others security – and not weaken it. But I remain convinced that the best guarantee for Russia is to be part of the process. And to be connected to the system. We should focus on actual cooperation, not abstract questions. This is the best way to enhance transparency and confidence. And it builds up the mutual trust that is necessary to take the key decisions we need to take. We have already made good progress in a number of areas. Including on the basis of Russian ideas for joint centres. For example, we could envisage setting up a joint centre where we could look at the ballistic missile threat together, share early warning data, exchange information and share assessments. We could also envisage setting up a joint centre where we could coordinate our responses. And let me emphasise the word coordinate . It would allow us to ensure we select the best and most appropriate response. This is the very reason why cooperation between NATO and Russia is important. Because it can lead to a more effective missile defence capability for both of us. But it can lead to so much more too. Missile defence cooperation can create a virtuous cycle. It can help us to build the confidence and trust to tackle some of the more difficult issues in our relationship. It provides a unique opportunity for us to build greater security and stability across the entire Euro-Atlantic area. And it could lead to a sea-change in the way we look at our relations. That is a political goal worth working hard for. And by taking the political decision to trust each other, it’s a goal we can achieve. Ladies and gentlemen, I know that many of you here today are intimately involved in delivering NATO’s missile defence capability. And I would like to thank you for your work. And please keep up your efforts. Because with your help, we can achieve our goal of an interim NATO capability at our Summit next year. And I hope we can announce closer cooperation with Russia too. That would be progress well worth celebrating. An effective missile defence is a vital capability for the Alliance. It reinforces our transatlantic solidarity. It provides an opportunity for us to work more closely with Russia. And it could be a real game-changer in the way NATO and Russia deliver Euro-Atlantic security. We could build security with each other, rather than against each other. Our past was divided through fear and suspicion. Our future can be shared through cooperation and confidence. Thank you. 1. France, Germany, Greece, Italy, Netherlands, Poland and Spain. From the event High resolution photos Secretary General in London: Missile Defence - A Critical Capability 16 Jun. 2011 ''NATO: Defending against Ballistic Missile Attack'' - Speech by NATO Secretary General Anders Fogh Rasmussen at the Royal United Services Institute in London 15 Jun. 2011 NATO Secretary General and Prime Minister Cameron exchange views on Libya and Afghanistan 15 Jun. 2011 Topics	https://www.nato.int/cps/en/natohq/opinions_75473.htm
Roles of the Fast-Releasing and the Slowly Releasing Vesicles in Synaptic Transmission at the Calyx of Held \| Journal of Neuroscience Roles of the Fast-Releasing and the Slowly Releasing Vesicles in Synaptic Transmission at the Calyx of Held Abstract In the calyx of Held, fast and slow components of neurotransmitter release can be distinguished during a step depolarization. The two components show different sensitivity to molecular/pharmacological manipulations. Here, their roles during a high-frequency train of action potential (AP)-like stimuli were examined by using both deconvolution of EPSCs and presynaptic capacitance measurements. During a 100 Hz train of AP-like stimuli, synchronous release showed a pronounced depression within the 20 stimuli. Asynchronous release persisted during the train, was variable in its amount, and was more prominent during a 300 Hz train. We have shown previously that slowly releasing vesicles were recruited faster than fast-releasing vesicles after depletion. By further slowing recovery of the fast-releasing vesicles by inhibiting calmodulin-dependent processes (Sakaba and Neher, 2001b), the slowly releasing vesicles were isolated during recovery from vesicle depletion. When a high-frequency train was applied, the isolated slowly releasing vesicles were released predominantly asynchronously. In contrast, synchronous release was mediated mainly by the fast-releasing vesicles. The results suggest that fast-releasing vesicles contribute mainly to synchronous release and that depletion of fast-releasing vesicles shape the synaptic depression of the synchronous phase of EPSCs, whereas slowly releasing vesicles are released mainly asynchronously during high-frequency stimulation. The latter is less subject to depression presumably because of a rapid vesicular recruitment process, which is a characteristic of this component. synaptic transmission synaptic vesicle release synaptic plasticity exocytosis presynaptic synaptic Introduction In neuroendocrine cells and some synapses, distinct kinetic components of release were observed when intracellular Ca 2+was elevated in a step-like manner by a step depolarization or Ca 2+uncaging (Neher and Zucker, 1993;Thomas et al., 1993;von Gersdorff and Matthews, 1994;Moser and Beutner, 2000;Thoreson et al., 2004). This led to the hypothesis that several distinct pools of vesicles exist in these preparations. Some kinetic components have been selectively eliminated by knockout of presynaptic proteins, disruption of protein–protein interaction, and pharmacological tools, indicating differences in the release processes and locations with respect to presynaptic Ca 2+channels (Martin, 2003). Although vesicle pools can be separated most easily when the presynaptic Ca 2+concentration is elevated continuously and in a step-like manner, it is unclear how these distinct pools of vesicles are released under more physiological conditions, especially during bursts of action potentials (APs) in spiking neurons. APs create only brief millisecond-long Ca 2+transients that may contribute to the release from vesicle pools in complex ways. Nevertheless, several physiological studies have indicated different release kinetics among synaptic vesicles during APs. Quantal analysis as well as the use of MK-801 [(+)-5-methyl-10,11-dihydro-5 H-dibenzo [a,d] cyclohepten-5,10-imine maleate] has suggested that release probability of synaptic vesicles is not uniform (Walmsely et al., 1988;Hessler et al., 1993;Rosenmund et al., 1993;Dobrunz and Stevens, 1997). It has also been suggested that a simple vesicle pool depletion model cannot explain the time course of synaptic depression during repetitive stimulation (Betz, 1970;Christensen and Martin, 1970;Kusano and Landau, 1975;Dittman and Regehr, 1998;Wu and Borst, 1999;Rosenmund et al., 2002).Moulder and Mennerick (2004)showed that repetitive stimulation of synapses did not deplete all of the releasable vesicles, suggesting that some synaptic vesicles were reluctant for release. Other studies suggested that different sets of vesicles mediate synchronous/asynchronous release evoked by APs. For example, synchronous and asynchronous releases are affected differently by deletion of synaptotagmin (Littleton et al., 1993;Geppert et al., 1994;Nishiki and Augustine, 2004) and disruption of SNARE proteins (Gansel et al., 1987;Molgo et al., 1989;Schoch et al., 2001). The calyx of Held is a large presynaptic terminal in the auditory brainstem with many active zones, and simultaneous presynaptic and postsynaptic patch clamp allows detailed analysis of transmitter release kinetics (Forsythe, 1994;Borst et al., 1995;von Gersdorff and Borst, 2002). Two sets of readily releasable vesicles (termed fast-releasing and slowly releasing vesicles here) can be distinguished that are distinct with respect to their release probability and speed of recruitment (Wu and Borst, 1999;Sakaba and Neher, 2001b). This study addresses how fast-releasing and slowly releasing vesicles are used during a high-frequency train of AP-like stimuli. Only frequencies as high as 300 Hz depleted both types of vesicles in the steady state. The results also show that the fast-releasing vesicles are released synchronously early during the train, whereas the slowly releasing vesicles are released asynchronously during the stimulation. Materials and Methods Transverse brainstem slices (150–200 μm thick) were prepared from 8- to 11- d-old Wistar rats (Forsythe, 1994;Borst et al., 1995) according to institute guidelines. The standard extracellular solution contained (in m m) 125 NaCl, 2.5 KCl, 2 CaCl 2, 1 MgCl 2, 25 glucose, 25 NaHCO 3, 1.25 NaH 2PO 4, 0.4 ascorbic acid, 3 myo-inositol, and 2 Na-pyruvate (pH 7.4, gassed with 95% O 2/5% CO 2). Experiments were performed at room temperature. During recordings, 1 μ mTTX, 10 m mTEA-Cl, and 50 μ m d-AP-5 were added to isolate presynaptic Ca 2+currents and postsynaptic AMPA receptor-mediated EPSCs. Cyclothiazide (100 μ m) and kynurenic acid (1 m m) were added to block desensitization and possible saturation of AMPA receptors and also to avoid voltage-clamp errors. A calyx of Held and the postsynaptic medial nucleus of the trapezoid body principal neuron were simultaneously whole-cell clamped at −80 mV with an EPC9/2 amplifier (HEKA Elektronik, Lambrecht/Pfalz, Germany). The presynaptic patch pipette (3–5 MΩ) solution contained (in m m) 135 Cs-gluconate, 20 TEA-Cl, 10 HEPES, 5 Na 2-phosphocreatine, 4 MgATP, 0.3 GTP, and 0.05 EGTA, pH 7.2. In some experiments, the calmodulin binding domain (CaM kinase II 290-309; 20 μ m) was added to the presynaptic pipette solution. The presynaptic series resistance (5–20 MΩ) was compensated by 30–90%. The postsynaptic pipette (2–3.5 MΩ) contained the same solution as the presynaptic pipette, except that the EGTA concentration was increased to 5 m m. The postsynaptic series resistance (3–8 MΩ) was electrically compensated by the amplifier such that the uncompensated resistance was <3 MΩ. The remaining resistance was further compensated off-line. Presynaptic capacitance measurements were performed using an EPC/9 amplifier and the Sine+DC technique (Lindau and Neher, 1988;Sun and Wu, 2001;Yamashita et al., 2005). A sine wave (30 mV in amplitude, 1000 Hz) was superimposed onto a holding potential of −80 mV. Measurements were accepted when the presynaptic series resistance was <20 MΩ. TTX was obtained from Alomone Laboratories (Jerusalem, Israel). Cyclothiazide, kynurenic acid, and d-AP-5 were obtained from Tocris (Biotrend, Köln, Germany). The calmodulin binding domain peptide was from Calbiochem (Schwalbach, Germany). Cyclothiazide was dissolved in DMSO, and the final concentration in the extracellular solution was 0.1%. Quantal release rates were estimated by the deconvolution method, adapted for the calyx of Held (Neher and Sakaba, 2001a). This method assumes that the total EPSC can be separated into a residual current component because of delayed clearance of glutamate in the synaptic cleft and a current component evoked by quantal release events. By combining deconvolution with fluctuation analysis, we have shown previously that this method is valid in the presence of cyclothiazide and kynurenic acid, which block desensitization and possible saturation of the postsynaptic AMPA receptors (Neher and Sakaba, 2001a). Quantal release rates, as determined by deconvolution, were integrated to obtain cumulative release, as displayed in the figures. Variance analysis was performed to estimate quantal amplitudes and release rates as has been described previously (Neher and Sakaba, 2001a). Trains (300 Hz) of AP-like stimuli were applied with intertrain intervals of >30 s. More than five trains were applied to each presynaptic terminal. For the variance calculation, the differences between two subsequent traces were used. These differences were further filtered to extract fluctuation associated with quantal events. All values are expressed as mean ± SEM. Results In this study, the roles of kinetically distinct vesicle pools during a high-frequency train of AP-like stimuli were examined. The presynaptic patch pipette contained a low Ca 2+buffer (0.05 m mEGTA), and the extracellular solution contained cyclothiazide and kynurenic acid to prevent postsynaptic AMPA receptor desensitization and saturation (Neher and Sakaba, 2001a;Joshi and Wang, 2002;Scheuss et al., 2002;Taschenberger et al., 2002). InFigure 1 A, the presynaptic terminal was depolarized to +40 mV for 1 ms to mimic an AP. Such an AP-like stimulus elicited a presynaptic Ca 2+tail current (Fig. 1 A, I pre) and induced a Ca 2+influx of 1.09 ± 0.13 pC ( n= 6 cells; range, 1–1.5 pC). This was only slightly larger than that induced by a single AP in a previous study [1 pC (Borst and Sakmann, 1998)]. EPSCs were evoked in response to the presynaptic Ca 2+influx and had an amplitude of 2.82 ± 1.06 nA ( n= 6). Considering that kynurenic acid blocks EPSC amplitudes by ∼50% (Neher and Sakaba, 2001a;Scheuss et al., 2002), the (corrected) amplitude is comparable to that evoked by a single AP in an unclamped terminal (3–10 nA) (Borst et al., 1995;Schneggenburger et al., 1999;Scheuss et al., 2002;Taschenberger et al., 2002). The deconvolution method was used to estimate quantal release rates (Neher and Sakaba, 2001a). The peak amplitude of the release rate was estimated to be 342 ± 138 vesicles ms −1, and the decline in the release rate after the peak could be fitted by a single exponential with a time constant of 347 ± 28 μs. The dotted gray line inFigure 1 Ashows the time point of 1.05 ms after the peak release rate (three times the decay constant) in which synchronous release declined completely. To quantify the amounts of synchronous and asynchronous release, the period between the two pulses (from immediately after the end of one voltage pulse to the next one) was separated into two segments (separated by dotted line inFig. 1 A), and the mean asynchronous release rate was determined from the number of release events that occurred during the second segment (after the dotted line). Then synchronous release was estimated from the first segment, by subtracting the mean asynchronous release rate observed during the second segment from the release rate during the first segment. Figure 1. Synaptic response to a 100 Hz train of AP-like stimuli at the calyx of Held. A, A single 1 ms depolarizing pulse to +40 mV was applied to the presynaptic terminal (AP-like stimulus) to elicit a Ca 2+current ( I pre). An EPSC was evoked in response to Ca 2+influx. Quantal release rates (rel. rate) were estimated using the deconvolution method. The amount of release before and after the dotted line was termed as synchronous and asynchronous release, respectively. B, The same cell pair as in A. A 100 Hz train of AP-like stimuli was applied, which was followed by a step-depolarizing pulse (prepulse to +70 mV for 2 ms, followed by repolarization to 0 mV for 50 ms). The dotted line in the EPSC trace indicates the residual current component attributable to delayed clearance of glutamate as modeled by the deconvolution method (residual current) (Neher and Sakaba, 2001a). The cumulative amount of release was obtained by integrating release rates from the deconvolution method. Filled circles in the cumulative release plot indicate cumulative amount of synchronous release during the train. C, The same cell pair as in A, and a single step-depolarizing pulse (prepulse to +70 mV, followed by repolarization to 0 mV for 50 ms) was applied to the presynaptic terminal. In cumulative release traces, the black trace indicates an original cumulative release. The gray trace indicates the cumulative release that is corrected by the recruitment of new vesicles after depletion (Sakaba and Neher, 2001a). D, Cumulative release traces during a step-depolarizing pulse with (B) and without (C) a preceding 100 Hz train (black traces). The difference between the two traces is shown as a gray trace and was used to estimate how many fast-releasing and slowly releasing vesicles had been released during a 100 Hz train by fitting the time course. It has been shown that inactivation of presynaptic Ca 2+channels might contribute to synaptic depression during low-frequency stimulation by APs (Xu and Wu, 2005) (but seeTakahashi et al., 2000). In this study, analysis was restricted to synaptic responses during high-frequency stimulation (≥100 Hz), in which presynaptic Ca 2+currents show little inactivation and depletion of releasable vesicles is the determining factor for synaptic depression (Wu and Borst, 1999).Figure 1 Bshows the response to a 100 Hz train of AP-like stimuli. The presynaptic Ca 2+currents (Fig. 1 B, I pre) showed an initial facilitation (the second pulse elicited 106.5 ± 2.0% of the first one; n= 6) with subsequent stimuli maintaining the slight enhancement (the last pulse elicited 108.3 ± 2.1%). EPSCs showed initial facilitation, followed by a strong depression (Fig. 1 B, EPSC). The cumulative amount of release was estimated by integrating the quantal release rates obtained by the deconvolution method (Fig. 1 B, bottom). During the train, 3297 ± 634 vesicles were released, on average ( n= 6), with 2208 ± 468 vesicles released synchronously according to the above criterion. The amount of synchronous release was comparable to AP-evoked release in previous studies (Scheuss et al., 2002;Taschenberger et al., 2002). The fraction of synchronous release to total release varied among different cell pairs (50–80% of total) (compareFigs. 1 B,3 C). When fitted by a single exponential, cumulative synchronous release had a time constant of 8.7 ± 1.3 AP-like stimuli. At the end of the train, a step depolarization (a prepulse to +70 mV for 2 ms, followed by a repolarization to 0 mV for 50 ms) was applied to deplete all releasable vesicles. In total (train plus depleting pulse), 4631 ± 810 vesicles were released, indicating that 50–80% of the total releasable vesicles were released during the train. Figure 1 Cshows the responses obtained when a step depolarization was applied to the presynaptic terminal (prepulse to +70 mV for 2 ms, followed by repolarization to 0 mV for 50 ms). Cumulative release during the depolarizing pulse (Fig. 1 C, solid trace) shows a bi-exponential time course. The sustained phase of release late during the presynaptic depolarization was presumably attributable to the recruitment of synaptic vesicles. It has been shown that the recruitment of synaptic vesicles has a time constant of 100–300 ms (Wu and Borst, 1999;Sakaba and Neher, 2001b). When the effect of recruitment was corrected (Sakaba and Neher, 2001b), the slow component saturated earlier during the depolarizing pulse (Fig. 1 C, gray trace). In the example trace, the cumulative release could be fitted by a double exponential with time constants of 1.02 ms (53% of the total fit, 1525 vesicles) and 9.17 ms (932 vesicles). On average, the cumulative release was fitted by a double exponential with time constants of 2.1 ± 0.48 ms (61 ± 9% of the total fit, ranging from 45 to 100%) and 18.2 ± 4.9 ms. The time constant of the slow component of release was variable with 0.05 m mEGTA in the presynaptic pipette, and cumulative release was best fitted by a single exponential in some cases. This is because of overlapping facilitation of the slow component of release, which was caused by accumulation of residual Ca 2+concentration during a prolonged depolarization (Wu and Borst, 1999;Sakaba and Neher, 2001a). Separation of the two components is much easier when a higher concentration of EGTA is added to the presynaptic pipette, with two components having time constants of 2–3 ms (50% of the total fit, fast-releasing vesicles) and 20–30 ms (slowly releasing vesicles), respectively (Sakaba and Neher, 2001a). If a single pool of vesicles is responsible for transmitter release at the calyx of Held, a single exponential release time course with a longer time constant should be observed at higher concentrations of EGTA, but this was not the case. The amount of release during a step depolarization was reduced to 43 ± 13% (29–63%) when a 100 Hz train preceded a step depolarization (Fig. 1 D; alsoFig. 1, compare B, C). In four of six cell pairs, the two components of release during the control depolarizing pulse (without a preceding 100 Hz train) were well separated even in a low Ca 2+-buffering condition (Fig. 1 D, control). In these cases, cumulative release during the control depolarization (a total of 3071 ± 624 vesicles) was fitted by a double exponential with time constants of 1.45 ± 0.31 ms (55 ± 8% of the total fit, ≈1700 vesicles) and 14.8 ± 4.4 ms (≈1400 vesicles). To learn how many fast-releasing and slowly releasing vesicles contributed to the synaptic response during a 100 Hz train, the cumulative release during a step depolarization both with (Fig. 1 D, with train) and without (Fig. 1 D, control) a preceding 100 Hz train was compared. By subtracting the cumulative release after a 100 Hz train from that during the control depolarization (Fig. 1 D, gray trace, difference), a 100 Hz train was estimated to have consumed 2107 ± 460 vesicles, and the difference (Fig. 1 D, gray trace) could be fitted by a double exponential with time constants of 1.0 ± 0.20 ms (63 ± 7.3% of the total fit, ≈1300 vesicles) and 15.8 ± 3.8 ms (≈800 vesicles) (Fig. 1 D, gray trace). Thus, ∼80% (1300 of 1700) of the fast-releasing and 60% (800 of 1400) of the slowly releasing vesicles must have released during a train. However, this approach does have a limitation, because a preceding 100 Hz train may have accumulated presynaptic residual Ca 2+concentration and accelerated the time course of release in the following pulse by facilitation (Wu and Borst, 1999;Sakaba and Neher, 2001a). Therefore, an alternative method was developed to estimate the contributions of fast-releasing and slowly releasing vesicles during a high-frequency train (seeFig. 3). Correlation between presynaptic capacitance jumps and cumulative release estimated by the deconvolution method The deconvolution method is based on the accurate estimation of the current component because of delayed clearance of glutamate (Neher and Sakaba, 2001a) (Fig. 1 B, dotted trace). Thus, it is possible that the estimate of release (especially asynchronous release) might be inaccurate. Although fluctuation analysis has confirmed release rates estimated from the deconvolution method (Neher and Sakaba, 2001a,b), another independent estimate of release is important. To this end, the deconvolution method was combined with presynaptic capacitance measurements, which should reflect the amount of exocytosis (Fig. 2) (Neher and Marty, 1982;Lindau and Neher, 1988;Sun and Wu, 2001). The time course of exocytosis during the depolarizing pulse cannot be measured by the capacitance measurement because of large conductance changes. So, the number of stimuli (1–20) was varied to estimate the amount of release during an AP train (Fig. 2 A–D).Figure 2 Ashows traces of presynaptic and postsynaptic currents during a 100 Hz train of 20 AP-like stimuli.Figure 2 Bshows the capacitance changes associated with this stimulation. After the train, presynaptic membrane capacitance was increased (Fig. 2 B, C m). The rapid capacitance decay (time course of 0.5 s after the stimulus train) associated with conductance changes (Fig. 2 B, G m) does not reflect the release of neurotransmitter, because botulinum toxins, which blocked EPSCs effectively (Sakaba et al., 2005;Yamashita et al., 2005), did not block this component (Yamashita et al., 2005). Indeed, the rapid decay remained after infusion of botulinum toxins that blocked postsynaptic currents ( n= 3 cell pairs). After this initial decay, capacitance decayed within 10–30 s (depending on the stimulation strength) and presumably reflects endocytosis (data not shown) (Sun et al., 2002;Yamashita et al., 2005). Thus, the plateau after the rapid decay was used to obtain the amplitude of the capacitance jump because of the presynaptic stimulation (Fig. 2 B, gray line).Figure 2, Cand D, shows cumulative release and capacitance traces, respectively, which were obtained by a different number of AP-like stimuli. When comparing the amount of cumulative release estimated by the deconvolution method to the amplitude of capacitance jump, the relationship between the two was linear (Fig. 2 E) (correlation coefficient of 0.97 ± 0.01 from n= 7 cell pairs), suggesting that the deconvolution method is consistent with capacitance measurements. The slope of the relationship inFigure 2 Esuggests that release of a single vesicle adds a capacitance of 80 ± 12 aF. The values were variable (42–110 aF) but overlapped with the previous estimate (55 aF) (Sun et al., 2002). The results from presynaptic capacitance measurements support the idea that the deconvolution method gives a valid estimate of release during presynaptic stimulation. Figure 2. Correlation between the amounts of cumulative release and presynaptic capacitance responses. A, A 100 Hz train of AP-like stimuli was applied, and presynaptic calcium currents and EPSCs are shown. The dotted line in the EPSC trace indicates the current component attributable to delayed clearance of glutamate. B, Presynaptic capacitance ( C m), conductance ( G m), and series conductance ( G s) values before and after a 100 Hz train of AP-like stimuli as shown in A. C, Cumulative amounts of release estimated by the deconvolution method. The number of AP-like stimuli was varied from 1 to 20. The same cell pair as in Aand Bis shown. D, The same cell pair, but presynaptic capacitance changes in response to the trains are shown. The cross symbol indicates where the amplitude of capacitance increase relative to baseline was measured. E, Correlation between the amount of cumulative release and the capacitance jump elicited by a train, obtained from Cand D. Roles of the fast-releasing and the slowly releasing synaptic vesicles during a 100 Hz train of AP-like stimuli It has been shown previously that 0.5 m mEGTA clearly separates the release of fast-releasing and the slowly releasing synaptic vesicles during a step depolarization (Sakaba and Neher, 2001a,b). On the other hand, this concentration of EGTA may slow down not only the slow component but also, to some extent, the fast component of release. In addition, the concentration of endogenous Ca 2+buffer is supposed to be much lower than 0.5 m mEGTA at postnatal days 8–10 (Borst et al., 1995;Borst and Sakmann, 1996). Furthermore, APs create only brief millisecond-long Ca 2+transients that may contribute to the release from both vesicle pools in quite complex ways, particularly when trains of APs are applied. To separate the two components of release during the AP-like stimulus train with low Ca 2+buffering, and under more physiological conditions, known differences between the time courses of recovery associated with the two components were used (Wu and Borst, 1999;Sakaba and Neher, 2001b). When Ca 2+/calmodulin-dependent recovery of the fast-releasing vesicles (fast component of release) is blocked (Sakaba and Neher, 2001b), the slowly releasing vesicles (slow component of release) recover much faster (within 200 ms) than the fast-releasing vesicles (several seconds). In this condition, only slowly releasing vesicles should be available for release 500 ms after depletion of both the fast-releasing and the slowly releasing vesicles. At the same time, the interstimulus interval of 500 ms is long enough, such that the slowly releasing vesicles recover completely, whereas the fast-releasing vesicles remain depleted. Based on this idea, two trains of AP-like stimuli (100 Hz for 200 ms) were applied with an interval of 500 ms, and the responses between the two trains were compared (Fig. 3 A). At the end of each train, a step depolarization (a prepulse to +70 mV for 2 ms, followed by a repolarization to 0 mV for 50 ms) was applied to deplete all releasable vesicles. Ca 2+-dependent recruitment of the fast-releasing vesicles was blocked by 20 μ mcalmodulin binding domain peptide (CaM kinase II 290-309) in the presynaptic patch pipette. Consistent with a previous study (Sakaba and Neher, 2001b), recovery of the fast-releasing vesicles, measured with a pair of step depolarizations separated by an interval of 500 ms, was only 6 ± 6% ( n= 3 cell pairs) when 0.5 m mEGTA and 20 μ mcalmodulin binding domain peptide were included in the presynaptic patch pipette. Download figure Open in new tab Figure 3. Release of the fast-releasing and the slowly releasing vesicles during a 100 Hz train of AP-like stimuli. A, Similar toFigure 1, but a 100 Hz train (for 200 ms) was applied twice with an interval of 500 ms in the presence of the calmodulin inhibitor peptide (calmodulin binding domain, 20 μ m). The duration of the AP-like stimulus was 1 and 1.5 ms, in the first (left) and the second (right) stimulation protocol, respectively. After a train, a step-depolarizing pulse (prepulse to +70 mV for 2 ms, followed by repolarization to 0 mV for 50 ms) was applied to deplete the remaining pool of releasable vesicles. Dotted lines in the EPSC traces indicate the current component mediated by delayed clearance of glutamate. The left and right panels use the same scale bars (right), except in the insets. The inset in the left panel shows release rates evoked by the first AP-like stimulus (gray) and the average release rates of the last five AP-like stimuli (black) during the first train. Bi, Superimposed traces of presynaptic calcium currents during the first (gray) and the second (black) trains. Only the responses to the first AP-like stimulus are shown. Bii, Average amount of presynaptic Ca 2+influx in response to a single AP-like stimulus during the first and the second trains. Biii, Total amount of presynaptic Ca 2+influx during the first and the second trains. C, Cumulative amounts of release during the first and the second trains (solid traces). By subtracting the cumulative release during the second train (slowly releasing vesicles only) from that during the first train, the release time course of the fast-releasing vesicles was estimated (open circles). The amount of synchronous release (synch. rel.) during the first train is shown as filled circles. The amount of synchronous release during the second train is shown as filled triangles. Presynaptic Ca 2+currents showed initial facilitation (105.7 ± 0.9% on the second pulse) and little inactivation during a 100 Hz train (Fig. 3 A, left) (99.5 ± 1.1% at the last stimulation; n= 6 cell pairs). With an interval of 500 ms, the same stimulation protocol was applied again (Fig. 3 A, right). Because presynaptic Ca 2+currents inactivate slightly during the second train (Forsythe et al., 1998), the duration of each AP-like stimulus was prolonged to 1.5 ms to adjust the amount of presynaptic Ca 2+influx between the two trains (Fig. 3 B). As has been shown inFigure 1, the first pulse train evoked phasic EPSCs that usually showed evidence of depression around the 10th stimulation. The inset inFigure 3 Ashows release rates evoked by the first AP-like stimulus (gray) and the average release rates of the last five stimuli (black), showing more asynchronous release later during the train. The first train released 3372 ± 713 vesicles, of which 1619 ± 362 vesicles were released synchronously ( n= 6 cell pairs) (Figs. 3 C, filled circles,4). A subsequent step depolarization released additional synaptic vesicles, with 4523 ± 838 vesicles being released in total (Fig. 4, train+pulse). Thus, a pool of releasable vesicles was not emptied during the train. Figure 4. The amount of fast-releasing vesicles during a 100 Hz train of AP-like stimuli. From the left, the amount of synchronous release, the amount contributed by fast-releasing vesicles, the total amount of release during the first 100 Hz train, and the total amounts of release including those during a depleting pulse are shown. Data were obtained by using the stimulation protocol shown inFigure 3.The average data are from n= 6 cell pairs. Error bars indicate SEM. The second train (Fig. 3 A, right) produced much less synchronous release. On average, 1632 ± 310 vesicles were released during the second train, of which only 252 ± 38 vesicles were released synchronously (Fig. 3 C, filled triangles). In total, 2309 ± 431 vesicles were released during the second stimulation protocol (train plus depleting pulse). Assuming that all vesicles released during the second stimulation protocol are the slowly releasing ones, 69 ± 3% of the total slowly releasing vesicles (train plus depleting pulse) were released during the second train. This fraction was comparable to that estimated using the method ofFigure 1 C(∼60%). By comparing cumulative release obtained during the first and the second trains (Fig. 3 C), the number of fast-releasing vesicles released during a 100 Hz train was estimated. Specifically, the cumulative release during the second stimulation protocol was subtracted from that during the first stimulation protocol to estimate the release time course of fast-releasing vesicles (Fig. 3 C, open circles). This assumes that the second train releases only slowly releasing vesicles and that these are equal in number to those slow ones released during the first train. With this approach, 1770 ± 400 fast-releasing vesicles were estimated to be released during a 100 Hz train (Figs. 3 C, open circles,4). This number was similar to that of synchronous release during the first train (1619 ± 362 vesicles) (Figs. 3 C, filled circles,4). By also comparing responses obtained with the first and the second depleting step depolarizations, 2313 ± 453 fast-releasing vesicles were released in total (train plus depleting pulse), indicating that 75 ± 3% of the total fast-releasing vesicles were released during a train. This fraction was comparable to that estimated using the method ofFigure 1 C(80%). Release time courses of synchronous release and fast-releasing vesicles during a 100 Hz train were best described by single exponentials with time constants of 7.5 ± 0.9 and 8.5 ± 1.1 AP-like stimuli, respectively. Similar time courses and amounts of release (Fig. 4) suggest that fast-releasing vesicles are mainly responsible for synchronous release. At the same time, these data also suggest that most of the asynchronous release during application of a high-frequency train is mediated by the slowly releasing vesicles. Roles of the fast-releasing and the slowly releasing vesicles during a 300 Hz train of AP-like stimuli A 100 Hz stimulation caused variable amounts of asynchronous release (Figs. 1 ⇑ ⇑–4). Higher-frequency stimulation (300 Hz) would lead to elevated Ca 2+concentrations and elicit more asynchronous release. InFigure 5, a 300 Hz train of AP-like stimuli (1 ms depolarization to +40 mV) was applied for 100 ms (Fig. 5). A 300 Hz train was strong enough to deplete most of the releasable vesicles, which was confirmed by a subsequent depleting pulse (prepulse to +70 mV for 2 ms, followed by repolarization to 0 mV for 20 ms) (Fig. 5). Specifically, the 300 Hz train and the depleting pulse released 3169 ± 519 and 295 ± 43 vesicles, respectively ( n= 8). Therefore, both fast-releasing and slowly releasing vesicles were mostly depleted during a train, as has been shown previously for the case of APs byWu and Borst (1999). Figure 5. Synaptic response to a 300 Hz train of AP-like stimuli. AP-like stimuli were applied 30 times to the presynaptic terminal at a frequency of 300 Hz. After the train, a single step-depolarizing pulse (prepulse to +70 mV for 2 ms, followed by repolarization to 0 mV for 20 ms) was applied to release remaining releasable vesicles. The same stimulation protocol as shown inFigure 3was used in the presence of a calmodulin blocker to examine roles of the two sets of vesicles during a 300 Hz train of AP-like stimuli.Figure 6 Ashows an example of two 300 Hz trains. On average, the first 300 Hz train released 2204 ± 215 vesicles in total ( n= 7 cell pairs) (Fig. 7). In the case ofFigure 6 A, synchronous EPSCs showed strong depression within the 10th stimulation, whereas asynchronous release persisted later during the train (Fig. 6 A, left, inset). Correspondingly, cumulative release did not increase in a step-like manner in response to individual pulses later during the train. Rather, a continuous almost linearly increasing cumulative release was observed (Fig. 6 C, uppermost trace and inset), suggesting copious asynchronous release. Download figure Figure 6. Release of the fast-releasing and the slow releasing vesicles during a 300 Hz train of AP-like stimuli. A, The same asFigure 3, but a 300 Hz train (for 100 ms) was applied twice with an interval of 500 ms in the presence of the calmodulin inhibitor peptide. From the top, presynaptic calcium currents ( I Ca), EPSCs, and release rates are shown. The left and right panels use the same scale bars. The expanded EPSC trace (left) and release rates (right) later during the train (time period indicated by a bar in the EPSC trace) are shown as an inset. The dotted line in the expanded release trace indicates a release rate of 0. Bi, Superimposed traces of presynaptic calcium currents during the first and the second trains. Only the responses to the first AP-like stimulus were shown. Bii, Average amount of presynaptic Ca 2+influx in response to a single AP-like stimulus during the first and the second trains. Biii, Total amount of presynaptic Ca 2+influx during the first and the second trains. C, Cumulative amounts of release during the first and the second trains (solid traces). By subtracting the cumulative release during the second train from that during the first train, the release time course of the fast-releasing vesicles was estimated (open circles), assuming that only the slowly releasing vesicles were isolated during the second train. The amount of synchronous release during the first train is shown as filled circles. The expanded cumulative release time course during the first train is shown as an inset. Figure 7. The amount of fast-releasing vesicles during a 300 Hz train of AP-like stimuli. From the left, the amount of synchronous release, the amount contributed by the fast-releasing vesicles, and the total amount of release during a train are shown. Data were obtained by using the stimulation protocol shown inFigure 6.The average data are from n= 9 cell pairs. Error bars indicate SEM. The amount of synchronous and asynchronous release was determined by using the same method shown inFigures 1 ⇑ ⇑–4. The amount of synchronous release during the train was 835 ± 85 vesicles (Figs. 6 C, filled circles,7), which was similar to that of fast-releasing vesicles (976 ± 119 vesicles) (Figs. 6 C, open circles,7). Furthermore, synchronous release has a time course (time constant of 10.7 ± 1.7 AP-like stimuli when fitted by a single exponential) similar to the release of fast-releasing vesicles (time constant of 9.3 ± 0.9 AP-like stimuli). To obtain an independent estimation of the release rates late during the train (50–100 ms), an ensemble variance analysis was combined (Neher and Sakaba, 2001a). In seven cell pairs, a 300 Hz train was repeated more than five times, and quantal size was estimated to be 18.6 ± 1.8 pA; this is similar to the value reported in the presence of cyclothiazide and kynurenic acid (15 pA) (Neher and Sakaba, 2001a;Scheuss et al., 2002). The release rate from the variance analysis was estimated to be 6.1 ± 1.1 vesicles/ms, similar to the value estimated from the deconvolution method (6.3 ± 1.1 vesicles/ms). From the experiment shown inFigure 6, it is concluded that synchronous release at 300 Hz is primarily carried by fast-releasing vesicles. In addition, asynchronous release is mediated by the slowly releasing vesicles. These conclusions are the same as those obtained using a 100 Hz train (Figs. 1 ⇑ ⇑–4). Although a 300 Hz train depletes most of the rapid-releasing and the slowly releasing vesicles (Fig. 5), a 100 Hz train depletes 75–80% and 50–70% of the fast-releasing and the slowly releasing vesicles, respectively (Figs. 1 C,3) Discussion In this study, the roles of two kinetically distinct pools of vesicles in synaptic transmission at the calyx of Held were examined, and it was shown that the fast-releasing vesicles mainly contributed to synchronous release, whereas the slowly releasing vesicles mainly contributed to asynchronous release occurring during a high-frequency train of AP-like stimuli (Figs. 3 ⇑ ⇑ ⇑–7). Synchronous release underwent rapid depression, whereas asynchronous release persisted throughout the train (Figs. 3,6). The estimation of transmitter release is based on the deconvolution method (Neher and Sakaba, 2001a), which involves a model of delayed glutamate clearance from the synaptic cleft. An accurate estimation of release rates was especially difficult when release rates were low and a significant current component attributable to delayed clearance of glutamate was seen. Nevertheless, other observations supported the notion that asynchronous release occurred during a high-frequency train of AP-like stimuli. The amplitude of the presynaptic capacitance response observed after an AP train had a linear relationship to the cumulative amount of release obtained by the deconvolution method (Fig. 2). Different types of fluctuation analysis confirmed the release rates estimated from the deconvolution method (Neher and Sakaba, 2001a,b;Scheuss et al., 2002). Furthermore, variance analysis of the late phase of EPSCs attained during a 300 Hz train of AP-like stimuli gave estimates of release rates similar to those obtained from the deconvolution method (this study). Variance analysis also showed that quantal amplitudes stayed constant during a high-frequency train. It is interesting to note that short-term synaptic depression accompanies decrease in quantal sizes, which is not attributable to postsynaptic mechanisms at hippocampal synapses (Chen et al., 2004). Asynchronous release during high-frequency stimulation was mainly mediated by the slowly releasing synaptic vesicles (the slow component of release) observed with a step depolarization (Figs. 3 ⇑ ⇑ ⇑–7). Asynchronous release termed here is vesicle release that takes place after synchronous release decays fully and before the next stimulation. It is therefore different from delayed release, which was elicited for a prolonged period after (high-frequency) stimulation (in the order of hundreds of milliseconds to seconds) (Midlei and Thies, 1971;Rahamimoff and Yaari, 1973;Zengel and Magleby, 1981;Zucker and Lara-Estralla, 1983;Atluri and Regehr, 1998). It is possible that the slowly releasing vesicles contribute to synchronous release, although the contribution must be relatively small. In the experiment shown inFigure 3 C, 20% of the total release during the second stimulation (≈200 vesicles) occurred synchronously. Recovery of the fast-releasing vesicles has a time constant of 5 s in the presence of a calmodulin blocker (Sakaba and Neher, 2001b), so a 500 ms interval should have allowed recovery of 10% of the fast-releasing component (≈100–150 vesicles), which can be released synchronously. The remaining 50–100 vesicles may then originate from the slowly releasing pool. Thus, any claim that synchronous release is mediated solely by the fast-releasing vesicles would be an over-simplification. Furthermore, given that replenishment rates of slowly releasing vesicles are quite high and release probability is low, slowly releasing vesicles may especially contribute to the steady-state postsynaptic responses during repetitive stimulation. Synaptic responses under a long-lasting train of APs are difficult to study, because other factors such as presynaptic Ca 2+channel inactivation may contribute to synaptic depression (Forsythe et al., 1998;Xu and Wu, 2005) (but seeTakahashi et al., 2000). Furthermore, when the intervals between stimulations are increased, calmodulin-independent recovery of the fast-releasing vesicles (time constant of 4–6 s) contributes more significantly to the synaptic responses. Then the analysis used inFigures 3 ⇑ ⇑ ⇑–7cannot be adopted because I will violate the underlying assumption that recovery of the fast-releasing vesicles is minor. Selective block of the fast-releasing and the slowly releasing components of release at resting conditions will be helpful. We have shown before that recruitment of slowly releasing vesicles is much faster than that of fast-releasing vesicles (Wu and Borst, 1999;Sakaba and Neher, 2001b). Moreover, recovery of the fast-releasing vesicles was retarded, when recovery of the slowly releasing vesicles was slowed by disruption of actin polymerization or depletion of ATP in the presynaptic terminal (Sakaba and Neher, 2003). These observations led to the working hypothesis that the fast-releasing vesicles are derived from maturation from the slowly releasing synaptic vesicles (Wu and Borst, 1999;Sakaba and Neher, 2003). At the calyx of Held, the recruitment rate of the slowly releasing vesicles is 10 vesicles ms −1(Neher and Sakaba, 2001b), which persists even during a 500 ms step depolarization (our unpublished observation). Consistent with this, optical measurements at the calyx of Held synapse using FM1-43 have demonstrated a large reserve pool of vesicles, which is 10 times larger than the releasable pool of vesicles (the fast-releasing and the slowly releasing vesicles combined). This pool recycles with a time course of minutes (de Lange et al., 2003). An asynchronous release rate of six vesicles ms −1was observed during a 300 Hz train (Fig. 6), which was similar or below the recruitment rate of slowly releasing vesicles. This means that newly recruited synaptic vesicles are released as asynchronous release during a high-frequency train of AP-like stimuli once most of the releasable vesicles have been depleted. Under the working hypothesis of vesicle maturation, it is also expected that synchronous release remains depressed as long as the slowly releasing vesicle pool is not refilled. In this respect, it is possible that ongoing asynchronous release causes further depression of the synchronous release component, as has been shown byOtsu et al. (2004). It is also possible that asynchronous release can access both immediately and readily releasable pools of synaptic vesicles, depending on the stimulation patterns, regulation of Ca 2+buffering, and extrusion in the presynaptic terminal as proposed byHagler and Goda (2001). Possible cross talk of the two vesicle pools needs future systematic study under a wider range of physiological conditions. The present study has demonstrated that different release kinetics arises from physically distinct pools of synaptic vesicles. The importance of the work is that we can predict changes in synchronous/asynchronous release from effects that neuromodulators, deletion/mutation of synaptic proteins, or various stimulus patterns have on one of the two pools. However, inference in the reverse sequence, from a change in synchronous/asynchronous release to change in vesicle pools is more difficult, although this might be more relevant for the study of most synapses. Other factors, such as changes in AP waveforms, inactivation and facilitation of Ca 2+channels, and regulation of presynaptic Ca 2+concentration in the presynaptic terminal, may also contribute to observed changes and confound their interpretation. Furthermore, because of such factors, it is not necessarily the easiest task to determine physically distinct vesicle pools based on the time course of synaptic depression (Elmqvist and Quastel, 1965;Schneggenburger et al., 1999). The approach shown here is limited to a few preparations, in which vesicle pools can be directly measured, but it may be helpful for the formulation of reasonable models in small synapses, which are not accessible by conventional methods. Specifically, the observation here may have an implication for the synapses where asynchronous release is copious and increases during a high-frequency stimulation (Vincient and Marty, 1996;Lu and Trussell, 2000;Hefft and Jonas, 2005). Although this may be explained by differences in regulation of presynaptic Ca 2+concentration and Ca 2+sensitivity of transmitter release (Millar et al., 2005), an alternative explanation could be that the ratio of the fast-releasing and the slowly releasing vesicles differs among synapses. Footnotes Received January 14, 2006. Revision received April 18, 2006. Accepted April 18, 2006. This work was supported by the Deutsche Forschungsgemeinschaft Center for Molecular Physiology of Brain (Göttingen, Germany). I am grateful to Dr. Erwin Neher for most valuable discussion and comments throughout this work. I also thank Ruth Heidelberger, Matthew Holt, Nobutake Hosoi, Ralf Schneggenburger, Holger Taschenberger, and two anonymous reviewers for helpful comments on this manuscript. Correspondence should be addressed to Takeshi Sakaba, Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Am Fassberg11, D-37077 Göttingen, Germany. Email: tsakaba{at}gwdg.de References Atluri PP, Regehr WG (1998) Delayed release of neurotransmitter release from cerebellar granule cells. J Neurosci 18 : 8214 –8227. Betz WJ (1970) Depression of transmitter release at neuromuscular junction of frog. J Physiol (Lond) 206 : 629 –644. 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Decision on the Report of the Commission on the Situation in the Middle East and Palestine - AfricanLII Decision on the Report of the Commission on the Situation in the Middle East and Palestine Document detail Jurisdiction African Regional Bodies · African Union (AU) Citation EX.CL/Dec.838(XXV) Copy Regional Body Executive Council of the African Union Date 24 June 2014 Language English Type Statement Download Download DOCX (17.5 KB) Download PDF DECISION ON THE REPORT OF THE COMMISSION ON THE SITUATION IN THE MIDDLE EAST AND PALESTINE Doc. EX.CL/848(XXV) The Executive Council, 1. TAKES NOTEof the Report on the Situation in the Middle East and Palestine, and RECALLSall resolutions and decisions of the Organization of African Unity/African Union on the Situation in Palestine towards achieving lasting peace and security in the Middle East; 2. REAFFIRMSits full support to the Palestinian people in their quest for the restoration of their legitimate rights to establish an independent State coexisting peacefully with the State of Israel; 3. REITERATESits support for the peaceful resolution of the Arab-Israeli conflict in accordance with the principles of international law and all relevant United Nations resolutions; and EXPRESSESsupport for the two-state solution; 5. CONDEMNS: i) The continued occupation of Palestinian lands and the Judaization campaign aimed at changing all Islamic and Christian features of the Holy City and reducing the Palestinian population to the fullest extent through the confiscation of their lands and the destruction of their homes, a sectarian concept which undermines the foundation of the peace process; ii) The Israelis violations and continuation of the excavations in the city of Quds El-Sharif (Jerusalem) and its environs aiming at changing the culture and historical monuments of the city, which could end any chance of achieving the two-state solution; iii) The Israeli practices against the Palestinian prisoners and detainees, which are contrary to the international law and international humanitarian law, and CALLS ONthe Israeli government to release all Palestinian and Arab political prisoners and detainees in the Israeli jails EQUALLY DEMANDSthat Israel refrains from arbitrary arrests of Palestinians including children and women which is an act of violation of international laws and human rights norms including the Geneva Convention on the Rights of Women and Children; iv) The continuation of the Israeli government in expanding its settlements in the Palestinian territories occupied since 1967 in violation of international norms and standards, and CALLS FORthe immediate cession of these illegal acts. 6. CALLS ONthe international community to exert pressure on Israel to stop all settlement activities, release Palestinian prisoners in Israeli jails and support the efforts of the Palestine for membership in international agencies and to join international conventions and protocols; 7. REJECTSthe land and sea blockage imposed on the Gaza Strip, which led to the deterioration of the economic and humanitarian situation, and DEMANDSan immediate lifting of all restrictions on Gaza Strip; 8. COMMENDSthe reconciliation between Fatah and Hamas, as well as the establishment of the Government; 9. REQUESTS: i) Member States to boycott goods and products that are produced and exported from the settlements in the Palestinian territories including East Jerusalem; ii) The United Nations and the Quartet to move immediately to shoulder their responsibilities and pressure Israel to commit to the process of serious peace process negotiations; iii) Member States to continue to support the Palestinian people in their struggle to establish a sovereign state over its national territory with Quds El-Sharif (Jerusalem) as its capital. 10. REAFFIRMSthe right of the Palestinian people to establish their own Palestinian Independent State with Quds El-Sharif (Jerusalem) as its capital on its borders of June 1967, and supports the Palestinian approach to obtain full membership of the State of Palestine at the United Nations; 11. URGESthe UN Security Council to shoulder its responsibilities in maintaining international peace and security, and to take the necessary steps to resolve the Arab-Israeli conflict in all its aspects, to achieve a just, comprehensive and lasting peace in the region based on the principle of two-state solution, according to the 1967 borders, and apply the provisions of relevant international law and previous decisions of the Council in this regard; 12. REITERATESthat a just, comprehensive and lasting peace in the Middle East, demands a full withdrawal of Israel from the occupied Arab and Palestinian territories to the line of June 1967, including the Syrian Golan Heights and territories still occupied in southern Lebanon; 13. EXPRESSES ITS FULL SUPPORTfor the position of solidarity with Palestine adopted by the Conference of Non-Aligned States held in Algiers Algeria in May 2014.	https://africanlii.org/akn/aa-au/statement/decision/AU-EC/2014/838/eng@2014-06-24
(PDF) A selective small-molecule inhibitor of c-Met suppresses keloid fibroblast growth in vitro and in a mouse model PDF \| Keloids, tumor-like lesions that result from excessive scar formation, have no definitive treatment modality. Activation of... \| Find, read and cite all the research you need on ResearchGate Article PDF Available A selective small-molecule inhibitor of c-Met suppresses keloid fibroblast growth in vitro and in a mouse model <here is a image 5b953947246f28db-2d3ed4ede3997359> March 2021 Scientific Reports11(1) DOI: 10.1038/s41598-021-84982-4 License CC BY 4.0 Authors: <here is a image f2f62089ad6ff61c-d19572ff1996375a> Min-Ha Choi Min-Ha Choi <here is a image f2f62089ad6ff61c-d19572ff1996375a> Jinhyun Kim Jinhyun Kim <here is a image f2f62089ad6ff61c-d19572ff1996375a> Jeong Hyun Ha Jeong Hyun Ha <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ji Ung Park Seoul National University Hospital Abstract and Figures Keloids, tumor-like lesions that result from excessive scar formation, have no definitive treatment modality. Activation of c-mesenchymal-epithelial transition factor (c-Met) promotes cell proliferation and survival. Selective c-Met inhibitors, such as PHA-665752, may attenuate the activity of keloid fibroblasts and reduce keloid formation. Here, we aimed to evaluate the effect of PHA-665752, a second-generation selective small-molecule inhibitor of c-Met, on human keloid fibroblasts in vitro and in a mouse model. We performed in vitro cytotoxicity assays, scratch tests, western blotting, and immunofluorescence on human keloid fibroblasts. We also injected human fibroblasts into severe combined immunodeficient mice and measured the degree of nodule formation and skin histologic characteristics. We found that keloid fibroblast migration was inhibited by PHA-665752. Inhibitor treatment was also associated with lower expression of members of the hepatocyte growth factor/c-Met pathway, and lower fibroblast activity and collagen synthesis. In the in vivo experiments, PHA-665752—treated mice had lower nodule volumes and weights, accompanied by less inflammatory cell infiltration and collagen deposition, than those in control mice. These findings showed that although an in vivo model may not accurately represent the pathophysiology of human keloid development, PHA-665752 suppressed keloid fibroblast activity by inhibiting the c-Met—related tyrosine kinase pathway. <here is a image 52ae8e091b723ac2-a3586943b8250a34> Clinical and histological features of human keloids. (a) A human keloid from a human ear. (b) Intralesional excisions were histopathologically characterized by MT staining (Original magnification: 100 × , scale bar = 100 µm). (c) Immunohistochemical staining of c-Met in human keloid tissue (Original magnification: 100 × , scale bar = 100 µm). (d) Protein expression of c-Met and p-c-Met in human keloid-derived fibroblast and normal fibroblast. Full-length blot images are presented in Supplementary Fig. 2a. (e) Cell viability and cytotoxicity of PHA-665752 in the CCK-8 analysis (represents p < 0.005, represents p < 0.0001). KF Keloid fibroblast, NF Normal fibroblast, OD Optical density. … <here is a image 45137a80741bfa24-351fdb1a23a227dd> Inhibition of the HGF/c-Met signaling pathway in keloid fibroblasts treated with PHA-665752. (a) Western blot of expression of p-c-Met, p-mTOR, and p-p44/42 MAPK in keloid fibroblasts treated with the indicated concentration of PHA-665752. Full-length blot images are presented in Supplementary Fig. 3a. (b) Relative protein levels (represents p < 0.05, represents p < 0.005). … <here is a image 9c3947ace274301a-e044f3fc722e2dc8> PHA-665752 inhibits the migration of human keloid-derived fibroblasts. (a) Keloid fibroblasts were grown to confluence on 24-well plates and treated with 3 different concentrations of PHA-665752 for 24 h (Original magnification: 100 × , Scale bar = 100 µm). (b) Quantitative analysis of wound closure (represents p < 0.005). … <here is a image daf1386ee01e1562-6482c9fe5c9ce03d> Effects of PHA-665752 on collagen accumulation and ECM synthesis. (a) Western blot analysis of the expression of α-SMA, MMP2, MMP9, and TIMP2 in keloid fibroblasts treated with PHA-665752. Full-length blot images are presented in Supplementary Fig. 4a. (b) The relative protein levels of α-SMA, TIMP2, MMP2, and MMP9 (represents p < 0.05, represents p < 0.005). (c) Immunofluorescence for COL I and COL III. Nuclei were stained with DAPI (blue) (original magnification: 200 × , scale bar = 50 μm). (d) Fluorescence intensity of COL I and COL III (represents p < 0.005). Cont, control. … <here is a image 5a1c51004bc9585e-f29286771deae0a8> Histological and immunohistochemical images of the nodules formed by human keloid fibroblasts in SCID mice 7 days after PHA-665752 treatment. (a) Nodules were harvested from mice treated with DMSO or PHA-665752. (b) Representative H&E staining, MT staining, and immunohistochemistry for the expression of p-c-Met, VEGF, α-SMA, vimentin, MMP2, MMP9, COL I, and COL III in the nodules. The arrows (individual cells) and star (most cells) represent positive (brown) expression. (Original magnification: 400 × , scale bar = 50 μm). … Figures - available from: Scientific Reports  www.nature.com/scientificreports A selective small‑molecule inhibitor of c‑Met suppresses keloid broblast growth in vitro and in a mouse model Min‑Ha Choi 1,2, Jinhyun Kim 1,2,Jeong Hyun Ha 1& Ji‑Ung Park 1 Keloids, tumor‑like lesions that result from excessive scar formation, have no denitivetreatment modality.Activation of c‑mesenchymal‑epithelial transition factor (c‑Met) promotes cell proliferation and survival. Selective c‑Met inhibitors, suchas PHA‑665752, may attenuate the activity of keloid broblasts and reduce keloid formation. Here, we aimed to evaluate theeect of PHA‑665752, a second‑generation selective small‑molecule inhibitor of c‑Met, on human keloid broblasts in vitro and in a mouse model. We performed in vitro cytotoxicity assays, scratchtests, western blotting, and immunouorescence on human keloid broblasts.We also injected human broblasts into severe combined immunodecient mice and measured the degree of nodule formation and skin histologic characteristics. We found that keloid broblast migration was inhibited by PHA‑665752. Inhibitor treatment was also associated with lower expression of members of the hepatocyte growth factor/c‑ Met pathway, and lower broblast activity and collagen synthesis.In the in vivo experiments, PHA‑ 665752—treated mice had lower nodule volumes and weights, accompanied by less inammatorycell inltration and collagen deposition, than those in control mice.These ndings showed that although an in vivo model may not accurately represent the pathophysiology of humankeloid development, PHA‑665752 suppressed keloid broblast activity by inhibiting the c‑Met—related tyrosine kinase pathway. Abbreviations A/AAntibiotic–antimycoticsolution α-SMAAlpha smooth muscle actin BSABovine serum albumin CCK-8Cell counting kit-8 c-MetC-mesenchymal-epithelial transition factor DMEMDulbecco’s modied Eagle’s medium FBSFetal bovine serum ECMExtracellularmatrix ERKExtracellular signal-regulated kinases HGFHepatocyte growth factor PVDFPolyvinylideneuoride HRPHorseradishperoxidase MAPKMitogen-activated protein kinase MMPMatrixmetalloproteinase MTMasson’strichrome mTORMammalian target of rapamycin PI3KPhosphatidylinositol3-kinase SCIDSevere combined immunodecient TGF-βTransforming growth factor-β TIMPTissue inhibitorof metalloproteinase VEGFVascular endothelial growth factor OPEN  Department of Plastic and Reconstructive Surgery,Seoul National University Boramae Hospital, Seoul National   These authors  *  Content courtesy of Springer Nature, terms of use apply. Rights reserved Vol:.(1234567890) www.nature.com/scientificreports/ Keloid scars are benign but locally aggressive broproliferative growths formed during cutaneous healing aer injury 1 ,2 . e lesions can form on any area of skin, and may cause pain and functional impairment. In most cases, the aected sites are aesthetically disguring; keloids can cause emotional distress and mental health problems, such as self-image deterioration. Historically, surgical excision has been the main method to remove keloids. However, keloid recurrence and unsuccessful therapy have prompted the use of other treatment modalities. Intralesional corticosteroid injection improves scar appearance by reducing collagen synthesis, but can produce unsatisfactory results due to skin atrophy andtelangiectasia 3 . Adjuvant radiation therapy is associated with organ brosis and the potential for malignant transformation. Moreover, medications such as interferons, tacrolimus, and 5-uorouracil have been considered for keloid treatment, but they remain experimental in this context. us, there is no single successful therapeutic regimen for the treatment of keloid scars with a low recurrence rate. e development of a better treatment protocol would dramatically benet individuals withkeloids 4 , 5 . e etiology of keloid formation is incompletely understood. Although the mechanism is unclear, genetic predisposition plays arole 6 . Keloid formation is associated with altered growth factor regulation and subsequent abnormal collagen production. According to previous studies, transforming growth factor beta (TGF-β), insulin- like growth factor I, and interleukins are overexpressed in keloidtissues 4 – 9 . Vascular endothelial growth factor (VEGF) expression is also elevated in keloid tissues and appears to promote keloidgrowth 3 , 8 . c-mesenchymal-epithelial transition factor (c-Met) is a transmembrane tyrosine kinase that acts as a receptor for hepatocyte growth factor (HGF). e HGF/c-Met pathway activates the downstream extracellular signal- regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) pathway, eventually driving cell proliferation andmotility 8 , 10 . c-Met and HGF are dysregulated in cancer cells, and they are believed to contribute to tumor invasion, making the pathway an attractive candidate for targeted cancertherapy 7 ,9 , 11 . Phosphorylated c-Met also plays a role in keloidpathogenesis 12 – 14 . Selective small-molecule inhibitors of c-Met inhibit angiogenesis and tumorigenicity, and have cytoreductiveeects, in cancer models. erefore, agents blocking the c-Met pathway are attractive candidates for the treatment of keloid scars. SU-11274, a rst-generation c-Met inhibitor, suppressed keloid broblast proliferation, motility, and viability, but was unsuitable for clinicalapplication 7 , 13 . PHA-665752, a second-generation selective small-molecule inhibitor of c-Met, has more than 50-fold greater selectivity for c-Met than that of other tyrosine and serine/threoninekinases 14 . It has better potency than that of SU-11274 and its eectiveness has been investigated in cancer studies, making it a better candidate for invivostudies 15 ,16 . In this study, we describe the eects of the selective small-molecule c-Met inhibitor PHA-665752 on keloid tissues invitro and invivo. Results Expression of c‑Metin keloids. We conrmed the activation of c-Met in human keloid tissue and human keloid-derived broblasts using intralesional keloid excision samples harvested from patients (Fig. 1a). Masson’s trichrome (MT) staining revealed that collagen brils were randomly distributed in the samples, and mainly located in the dermal aspect (Fig. 1b). We also found that c-Met was expressed in keloid tissue (Fig. 1c), and phosphorylated c-Met (p-c-Met) expression was higher in keloid broblasts than that in normal broblasts (Fig. 1 d). e viability of keloid broblasts was signicantly lower aer treatment with 2, 4, 6, 8, and 10μM PHA- 665752 than that of control-treated keloid broblasts. e half maximal inhibitory concentration of PHA665752 for keloid broblasts was approximately 7.9μM (Fig. 1e). Theeectsof PHA‑665752 on HGF/c‑Metsignaling in keloids. Cells were treated with increas- ing doses (0, 2, 4, and 8μM) of PHA-665752 for 24h (Fig. 2a). e level of p-c-Met was signicantly lower in cells treated with 4μM and 8μM PHA-665752 (0.28±0.14 and 0.12±0.08, respectively) than that in controls (0.71±0.30). e percentage of cells expressing phosphorylated mammalian target of rapamycin (mTOR) was more than 3.2 times lower in cells treated with 8μM PHA-665752 (0.19± 0.08) than that in controls (0.62± 0.32). Similarly, the expression of phosphorylated p44/42 MAPK was lower in cells treated with 8μM PHA-665752 (0.22±0.14) than that in controls (0.49±0.18) (Fig. 2b). Keloid broblast migration assayafter treatmentwith PHA‑665752. e cells treated with 2, 4, and 8μM PHA-665752 showed less migratory ability aer 24h than that in the untreated cells (Fig. 3a). In the scratch assay, we observed signicantly larger gaps between cells in cultures treated with 2, 4, and 8μM PHA- 665752 (57.95%± 9.58%, 72.21%± 5.86%, and 114.69%±6.27%, respectively) than that between cells in the con- trol culture (23.91%± 18.5%) (Fig. 3b). Eectof PHA‑665752 on collagenaccumulation‑relatedextracellularmatrix components in keloids. e cells treated with 0, 2, 4, and 8μM PHA-665752 for 24h (Fig. 4a). Alpha smooth muscle actin (α -SMA) expression levels were 2.5 times lower in cells treated with 8μM PHA-665752 (0.36± 0.37) than those in the controls (0.92±0.17). Tissue inhibitor of metalloproteinase 2 (TIMP2) expression levels were 1.9 times lower in cells treated with 8μM PHA-665752 (0.41±0.24) than those in the controls (0.79±0.14). In contrast, the expression level of metalloproteinase (MMP) 2 was signicantly higher aer treatment with 8μM PHA-665752 (0.97±0.35) than that in the controls (0.35±0.12). MMP9 expression levels were also elevated aer treatment with 2, 4, and 8μM of PHA-665752 (0.71±0.2, 0.89 ±0.29, and 1.06 ±0.3, respectively) compared with those in the control group (0.34± 0.14) (Fig. 4b). Immunouorescence revealed lower collagen type I and type III expres- sion in cells treated with 8μM PHA665752 (22.78%±10.5%, and 49.03%± 7.87% lower, respectively) than that in controls (Fig. 4c,d). Content courtesy of Springer Nature, terms of use apply. Rights reserved Scientic Reports \| (2021) 11:5468 \|  www.nature.com/scientificreports/ Eects ofPHA‑665752 ina human keloid broblast‑derivedSCID mouse modelof nodule formation. On day 7, the SCID mouse group treated with PHA-665752 had an average nodule volume of 12.07 ± 5.18mm 3 , whereas the group treated with 2% DMSO had an average nodule volume of 30.16±8.51 mm 3 . PHA-665752 markedly suppressed nodule volume compared with 2% DMSO (Fig. 5a and Supplemental Fig.1a). e average nodule weight was 2.3 times lower in the PHA-665752–injected group (0.01±0.00g) than that in the 2% DMSO-injected group (0.03± 0.02g) (Supplemental Fig.1b). Seven days aer PHA-665752 injec- tion, the PHA-665752 group had signicantly fewer inammatory cells per 0.1mm 2 (15.75±5.32) than those in the 2% DMSO group (30±1.83 cells) (Fig. 5b and Supplemental Fig.1c). MT staining revealed signicantly lower collagen content in the PHA-665752–treated group (37.13%±6.12%) than that in the 2% DMSO-treated group (69.01% ± 10.6%)(Fig. 5 b and Supplemental Fig.1d). We observed signicantly more cells expressing Figure1. Clinical and histological features of human keloids. ( a ) A human keloid from a human ear. ( b ) Intralesional excisions were histopathologically characterized by MT staining (Original magnication: 100× , scale bar = 100µm). ( c ) Immunohistochemical staining of c-Met in human keloid tissue (Original magnication: 100 × , scale bar = 100µm). ( d ) Protein expression of c-Met and p-c-Met in human keloid-derived broblast and normal broblast. Full-length blot images are presented in Supplementary Fig.2a. ( e) Cell viability and cytotoxicity of PHA-665752 in the CCK-8 analysis (represents p < 0.005, represents p< 0.0001). KFKeloid broblast, NF Normal broblast, OD Optical density. Content courtesy of Springer Nature, terms of use apply. Rights reserved  Vol:.(1234567890) Scientic Reports \| (2021) 11:5468 \|  www.nature.com/scientificreports/ Figure2. Inhibition of the HGF/c-Met signaling pathway in keloid broblasts treated with PHA-665752. ( a ) Western blot of expression of p-c-Met, p-mTOR, and p-p44/42 MAPK in keloid broblasts treated with the indicated concentration of PHA-665752. Full-length blot images are presented in Supplementary Fig.3a. ( b ) Relative protein levels (represents p < 0.05, represents p< 0.005). Figure3. PHA-665752 inhibits the migration of human keloid-derived broblasts. ( a) Keloid broblasts were grown to conuence on 24-well plates and treated with 3 dierent concentrations of PHA-665752 for 24h (Original magnication: 100×, Scale bar=100µm). ( b) Quantitative analysis of wound closure (represents p < 0.005). Content courtesy of Springer Nature, terms of use apply. Rights reserved  Vol.:(0123456789) Scientic Reports \| (2021) 11:5468 \|  www.nature.com/scientificreports/ p-c-Met, VEGF, α-SMA, vimentin, collagen type I, and collagen type III in the 2% DMSO group (7.24%±3.29%, 45.7% ± 9.88%,27.87% ± 10.21%,59.42% ± 8.51%,47.12% ± 10.59%,and27.03% ± 10.87%,respectively)than those in the PHA-665752 group (1.14% ± 0.46%, 41.43% ± 5.4%, 17.2% ± 3.8%, 51.33% ± 7.45%, 21.99% ± 7.09%, and 8.58%±5.21%, respectively). MMP2 and MMP9 were expressed in lower percentages of cells in the 2% DMSO-treated group (41.41%±6.05% and 43.61%±11.83%, respectively) than those in the PHA-665752– treated group (57.26%± 12.48% and 63.32%± 12.54%, respectively) (Fig. 5b and Supplemental Fig.1e). Discussion We observed increased collagen synthesis and overexpression of c-Met in keloid specimens, consistent with the results of previous studies. Upon treatment with PHA-665752, we observed lower keloid broblast viability than that in untreated samples. PHA-665752 functions by inhibiting HGF-stimulated c-Met autophosphorylation and the constitutivephosphorylation of downstream mediators of the HGF/c-Met pathway in multiple tumor celllines 14 . ese results suggest that PHA-665752 is a potent inhibitor of c-Met activity in keloid scars and interferes with the downstream HGF/c-Metpathway 14 . scratch test demonstrated that PHA-665752 inhibited Figure4. Eects of PHA-665752 on collagen accumulation and ECM synthesis. ( a) Western blot analysis of the expression of α-SMA, MMP2, MMP9, and TIMP2 in keloid broblasts treated with PHA-665752. Full-length blot images are presented in Supplementary Fig.4a. ( b) e relative protein levels of α-SMA, TIMP2, MMP2, and MMP9 (represents p < 0.05, represents p< 0.005). ( c) Immunouorescence for COL I and COL III. Nuclei were stained with DAPI (blue) (original magnication: 200×, scale bar=50μm). ( d) Fluorescence intensity of COL I and COL III (*represents p < 0.005). Cont, control. Content courtesy of Springer Nature, terms of use apply. Rights reserved  Vol:.(1234567890) Scientic Reports \| (2021) 11:5468 \|  www.nature.com/scientificreports/ keloid broblast migration. Since broblast migration is known to be mediated by TGF-β activation, our ndings are consistent with a previous study that suggested PHA-665752has an inhibitory eect on TGF-βsignaling 17 . Aer we determined the inhibitory eects of PHA-665752 on broblast survival, proliferation, and migration, we examined its eects on the expression of proteins that are involved in the formation of keloid scars. TIMP2 is an endogenous inhibitor of MMPs. High levels of TIMP2lead to accumulation of the extracellular matrix (ECM), whereas low levels of TIMP lead to matrix proteolysis We found higher levels of MMPs and a lower TIMP2-to-β-actin ratio in cells treated with PHA-665752 than those in control cells. Although MMPs can be elevated during the wound-healingprocess 18 , concurrent MMP elevation and TIMP suppression suggest that PHA-665752 enhances MMP expression, resulting in less ECM accumulation. Consistent with this interpreta - tion, the c-Met inhibitor also suppressed collagen synthesis. Figure5. Histological and immunohistochemical images of the nodules formed by human keloid broblasts in SCID mice 7days aer PHA-665752 treatment. ( a) Nodules were harvested from mice treated with DMSO or PHA-665752. ( b) Representative H&E staining, MT staining, and immunohistochemistry for the expression of p-c-Met, VEGF, α-SMA, vimentin, MMP2, MMP9, COL I, and COL III in the nodules. e arrows (individual cells) and star (most cells) represent positive (brown) expression. (Original magnication: 400×, scale bar = 50μm). Content courtesy of Springer Nature, terms of use apply. Rights reserved  Vol.:(0123456789) Scientic Reports \| (2021) 11:5468 \|  www.nature.com/scientificreports/ Given that keloids occur exclusively in humans, animal models have been dicult to develop and are rarely used 19 . We used the keloid animal model that was introduced by Fujiwara etal., who implanted keloid broblasts into the dorsal skin of SCIDmice 20 . We found that nodule size in both the PHA-665752 injection and DMSO groups decreased over time; nodule volume decreased more quickly in the inhibitor group. Although it is unclear why the keloid nodules decreased in size even in the untreated group, it might have been caused by a natural regression, as keloids occur exclusively in humans. is phenomenon was also observed in the study by Fujiwara etal., but it is not typically observed in human keloid tissues. Keloid regression contributes to the diculty of producing animal keloid models and implies that the treatment response may dier from a potential clinical response. However, the weights of the harvested nodules diered between the treatment and control groups, which suggested that PHA-665752 antagonized keloid tissue formation or maintenance. Our study has several limitations. First, the invivo model does not accurately represent keloid pathogenesis. Second, although the site of origin may aect keloid tissue responses to PHA-665752, we did not analyze our results based on tissue origin. Finally, more keloid tissue samples would have contributed to a moregeneraliz - able, reliable result. Conclusion PHA-665752, a selective small-molecule inhibitor of c-Met, may be an alternative treatment modality that eec - tively reduces the proliferation of keloids. In the future, additional experimental research and clinical trials will be needed to test the safety and eectiveness of c-Met inhibitors for the treatmentof keloid scars. A combination therapy comprising PHA-665752 with other eective keloid treatment modalities may improve patient outcomes. Methods Ethicalapproval. e study has been reviewed and approved by Boramae Hospital Institutional Review Board in compliance with Helsinki Declaration and Integrated Addendum to ICH: Guideline for Good Clinical Practice (ICH-GCP) (approval no. 26-2017-20). Samples of human keloid tissue were obtained from patients who provided informed consent prior to conducting this study according to the guidelines of the Ethics Com- mittee. Humankeloid‑derivedbroblastcell cultures. Keloid tissues were obtained from six patients who underwent excision surgery at Seoul National University Boramae Hospital. e keloid tissues were washed three times with Dulbecco’s phosphate-buered saline with 1% antibiotic–antimycotic solution (A/A; Welgene, Gyeongsangbuk-do, Republic of Korea) and cut into 3-mm-thick pieces. Subsequently, the tissues were digested with 5mg/ml dispase (Roche, Basel, Switzerland) for 4h at 37°C. e dermis and epidermis were separated, cut into 1-mm-thick pieces, and digested to a single-cell suspension with 3mg/ml collagenase type I (ermo Fisher, Waltham, MA, USA). e cells were growth in Dulbecco’s modied Eagle’s medium (DMEM; Biowest, Nuaillé, France) containing 10% fetal bovine serum (FBS; Biowest, France) and 1% A/A in a humidied incuba- tor with 5%CO 2 at 37°C. Cells from passage 3 to 5 were used for experiments. Cell viability analysis. Cell viability was measured using Cell Counting Kit-8 (CCK-8; Dojindo Laborato- ries, Kumamoto, Japan). Keloid broblasts (1.0×10 4 cells/well) were cultured in triplicate in DMEM containing 10% FBS and 1% A/A in 96-well plates. e cells were treated with PHA-665752 (0.1, 0.2, 0.4, 0.8, 1, 2, 4, 6, 8, and 10μM; Selleckchem, Houston, TX, USA) for 24h. en, a mixture of CCK-8 solution (10 μL) and DMEM (90 μL) was added to each well, and the plates were incubated for 1h in an incubator at 37°C in 5%CO 2 . e absorbance of each well was measured at a wavelength of 450nm with a SpectraMax ABS (Molecular Devices, San Jose, CA, USA). In vitrowestern blot analysis. Human keloid broblasts were lysed with radioimmunoprecipitation assay buer (ermo Fisher, Waltham, MA, USA), and the protein concentration was measured using a BCA Protein Assay Kit (ermo Fisher, Waltham, MA, USA). Equal amounts of protein were loaded on 8% and 12% sodium dodecyl sulfate–polyacrylamide gels and, aer electrophoresis, transferred to polyvinylidene uo- ride (PVDF) membranes (Millipore, Boston, MA, USA). Aer the PVDF membranes were blocked with 5% bovine serum albumin (BSA) in Tris-buered saline containing TWEEN Registered 20, they were incubated overnight at 4°C with primary antibodies diluted in blocking buer: phospho-c-Met (Tyr1234/1235, 1:1,000), c-Met (N-terminal, 1:1,000), phospho-mTOR (p-mTOR; Ser2448, 1:1,000), mTOR (7C10, 1:1,000), phospho- p44/42 MAPK (p-p44/42 MAPK; r202/Tyr204, 1:1,000), p44/42 MAPK (Erk1/2, 1:1,000), ɑ-SMA (1:1,000), MMP2 (1:1,000), MMP9 (1:1,000), TIMP2 (3A4, 1:1,000) and β-actin (1:5,000). en, the membranes were incubated for 1h at room temperature with horseradish peroxidase (HRP)-conjugated secondary antibodies: goat anti-rabbit IgG HRP (1:5,000) and goat anti-mouse IgG HRP (1:5,000). Protein bands were detected by chemiluminescence using a SuperSignal ECL kit (ermo Fisher, Waltham, MA, USA) and visualized using an ImageQuant LAS 4000 (GE Healthcare Life Science, Marlborough, MA, USA). Immunouorescence. All samples were xed in 4% paraformaldehyde overnight, permeabilized with 100% methanol for 2min, and blocked in 5% BSA for 1h at room temperature. Samples were incubated with primary antibodies against collagen I (Col I, 1:1,000) and collagen III (Col III, 1:1,000) diluted in a blocking buer overnight at 4°C. e samples were then stained with secondary antibodies (Alexa Fluor Registered 594 goat anti-mouse IgG [1:200] and Alexa Fluor Registered 488 goat anti-rabbit IgG [1:200]) for 1h, and nuclei were stained with 1μg/ml NucBlue Live Cell Stain ReadyProbes reagent (ermo Fisher, Waltham, MA, USA) Content courtesy of Springer Nature, terms of use apply. Rights reserved  Vol:.(1234567890) Scientic Reports \| (2021) 11:5468 \|  www.nature.com/scientificreports/ for 20min. e samples were scanned using uorescence inverted microscopy (Leica Microsystems, Wetzlar, Germany). Fluorescence intensity was measured using ImageJ 1.36b imaging soware (National Institutes of Health, Bethesda, MD, USA). Migration assay. Human keloid broblasts (2.0×10 4) were seeded in a 24-well plate. Aer the cells attached to the plate, we created a straight-line scratch in each well using a 1-ml pipette tip. e cells were then treated with PHA-665752 (0, 2, 4, and 8μM) in DMEM containing 2% FBS and 1% A/A for 24h. Images of the wound gap area at the initial time (0h) and 24h aer the scratching were captured under an inverted uorescence microscope (Leica Microsystems, Wetzlar, Germany). e area of the gap created by the scratch was calculated using ImageJ soware and then compared to the size of the initial gap. Experimental animals. e animal study was approved by the Institutional Animal Care and Use Com- mittee of the Seoul National University Boramae Hospital (approval no. 2019–0031). Male NOD.CB17-Prkdc scid/J (SCID) mice (5weeks old, body weight: 22.58±0.91g) were purchased from Charles River Japan (Yoko- hama, Japan). All animal experimental procedures were performed in accordance with ARRIVEguidelines 21 and the Seoul National University Hospital Institutional Animal Care and Use Committee guidelines. Nodule formation by cultured human keloid broblasts in SCID mice. All experiments were per- formed under aseptic conditions. Under anesthesia using isourane, we removed the dorsal surface hair from 6 SCID mice and marked the middle line, and then subcutaneously injected 150 μL human keloid broblasts (5.0 ×10 8 cells) through a 1-ml syringe (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) with a 26-gauge needle. ese cells were obtained from six patients who underwent excision surgery at in our hospi- tal. e cells were cultured 1cm away from the le and right sides of the most prominent region of the mouse backs. Aer nodules formed on the backs of the mice, we injected the le nodules with 2% dimethyl sulfoxide (DMSO; control) and the right nodules with PHA-665752 (16.5μg/100 μL). e nodules were measured every 2 to 3days with calipers, and nodule volume was calculated using the equation: Nodule volume=1/2×A×B 2 , where A=length in millimeters and B=width inmillimeters 15 . On day 14 aer broblast injection, to harvest the nodules, the surrounding skin was carefully separated used forceps and a blade, and only the nodules were collected and weighed. In vivo histological analysis and immunohistochemistry. e nodules were harvested 14days aer the initial cell injection, and then xed in 4% paraformaldehyde for 24h at 4°C, washed with water for at least 4h, and nally embedded in paran. e paran sections(4µm thick) were stained with hematoxylin and eosin (H&E, ab245880, Abcam, Cambridge, UK) and MT (TRM-2, ScyTek, Logan, Utah, USA) stain, according to the manufacturers’ guidelines. e cellularity in the H&E-stained sections(400×magnication) and collagen density in the MT-stained sections(400×magnication) were conrmed for each section using an Olympus BX53 microscope (Olympus Corporation, Shinjuku, Japan); we acquired screenshots of three microscopic elds (right, center, and le). e number of inammatory cells per unit area (0.1mm 2 ) was calculated using the Olympus cellSens standard imaging soware. e optical density of collagen was measured using ImageJ 1.36b. Immunohistochemical analysis was performed using the avidin–biotin complex method. Briey, sections were deparanized and incubated with trypsin enzymatic antigen retrieval solution (ab970; Abcam, Cambridge, UK) for 30min at 37°C. Sections were incubated overnight at 4°C with primary antibodies: p-c-Met (1:20), VEGF (1:50), α-SMA (1:300), vimentin (1:400), MMP2 (1:200), MMP9 (1:50), Col I (1:500), and Col III (1:200). Aer washing three times with Tris-buered saline containing 0.025% Triton X-100, the sections were incubated with secondary antibodies for 30min at room temperature. Images (right, center, and le) were captured with an Olympus BX53 microscope. e optical density of each image was quantied using ImageJ 1.36b imaging soware. Antibodies. e following primary antibodies were used for western blotting, immunouorescence, and immunohistochemical analysis: p-c-Met (#3077; Cell Signaling Technology, Danvers, MA, USA), c-Met (ab51067; Abcam, Cambridge, UK), p-mTOR (#2971; Cell Signaling Technology), mTOR (#2983; Cell Signaling Technology), p-p44/42 MAPK (#9101; Cell Signaling Technology), p44/42 MAPK (#9102; Cell Signaling Tech- nology), α-SMA (14,395-1-AP; Proteintech, Rosemont, IL, USA), MMP2 (10,373-2-AP; Proteintech), MMP9 (10,375-2-AP; Proteintech), TIMP2 (sc-21735; Santa Cruz Biotechnology, Dallas, Texas, USA), COL I (immuno- uorescence: ab6308; Abcam; immunohistochemistry: LS-C343921; LSBio, Seattle, WA, USA), COL III (immu- nouorescence: ab7778; Abcam; immunohistochemistry: LS-C413514; LSBio), β-actin (sc-47778; Santa Cruz Biotechnology), VEGF (sc-57496; Santa Cruz Biotechnology), and vimentin (ab92547; Abcam). e follow- ing secondary antibodies were used: anti-rabbit IgG HRP (western blotting: #7074; Cell Signaling Technology: immunouorescence: R37117; ermo Fisher, Waltham, MA, USA; immunohistochemistry: PK-4001; Vector Laboratories, Burlingame, CA, USA) and goat anti-mouse IgG HRP (western blotting: ADI-SAB-100; Enzo Life Science, Farmingdale, NY, USA; immunouorescence: A11005; ermo Fisher; immunohistochemistry: PK-4002; Vector Laboratories). Statistical analysis. In vitro experimental results are reported as the mean value± standard deviation of at least 3 independent experiments. For invivo experiments, all values are reported as the mean±standard error of analysis of variance. A pvalue less than 0.05 was considered as statistically signicant. 1. Bran, G. M. et al.Keloids: current concepts of pathogenesis (review). Int. J. Mol. Med. 24 (3), 283–293 (2009). 2. Ogawa, R. Keloid and hypertrophic scars are the result of chronic inammation in the reticular dermis. Int. J. Mol. Sci. 18 (3), 606 (2017). 3.Perdanasari, A. T. et al.Recent developments in the use of intralesional injections keloid treatment. Arch. Plast. Surg. 41 (6), 620 (2014). 4. Choi, J. et al.Regulation of transforming growth factor β1, platelet-derived growth factor, and basic broblast growth factor by silicone gel sheeting in early-stage scarring. Arch. Plast. Surg. 42 (1), 20 (2015). 5.LaRanger, R. et al.Analysis of keloid response to 5-uorouracil treatment and long-term prevention of keloid recurrence. Plast. Reconstr. Surg. 143 (2), 490 (2019). 6. Shih, B. & Bayat, A. Genetics of keloid scarring. Arch. Dermatol. Res. 302 (5), 319–339 (2010). 7. Jin, Z. Increased c-Met phosphorylation is related to keloid pathogenesis: implications for the biological behaviour of keloid broblasts. Pathology 46 (1), 25–31 (2014). 8. Wang, Q. et al.Integrin β1 in adipose-derived stem cells accelerates wound healing via activating PI3K/AKT pathway. Tissue Eng. Regen. Med. 17 (2), 183–192 (2020). 9. You, H. et al.c-Met represents a potential therapeutic target for personalized treatment in hepatocellular carcinoma. Hepatology 54 (3), 879–889 (2011). 10.Naldini, L. et al. Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto- oncogene c-MET. Oncogene 6 (4), 501–504 (1991). 11. Kim, H. J. et al.c-MET as a potential therapeutic target in ovarian clear cell carcinoma. Sci. Rep. 6 , 38502 (2016). 12. Danilkovitch-Miagkova, A. & Zbar, B. Dysregulation of Met receptor tyrosine kinase activity in invasive tumors. J. Clin. Investig. 109 (7), 863–867 (2002). 13.Kucerova, L. et al. Tyrosine kinase inhibitor SU11274 increased tumorigenicity and enriched for melanoma-initiating cells by bioenergetic modulation. BMC Cancer 16 (1), 308 (2016). 14. Christensen, J. G. et al.A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes invitro and exhibits cytoreductive antitumor activity invivo. Can. Res. 63 (21), 7345–7355 (2003). 15.Kanaji, N. et al. Hepatocyte growth factor produced in lung broblasts enhances non-small cell lung cancer cell survival and tumor progression. Respir. Res. 18 (1), 118 (2017). 16. Shin, J. Y. et al.A comparison of the eectiveness of triamcinolone and radiation therapy for ear keloids aer surgical excision: a systematic review and meta-analysis. Plast. Reconstr. Surg. 137 (6), 1718–1725 (2016). 17. Gardner, J. & Ghorpade, A. Tissue inhibitor of metalloproteinase (TIMP)-1: the TIMPed balance of matrix metalloproteinases in the central nervous system. J. Neurosci. Res. 74 (6), 801–806 (2003). 18. Armstrong, D. G. & Jude, E. B. e role of matrix metalloproteinases in wound healing. J. Am. Podiatr. Med. Assoc. 92 (1), 12–18 (2002). 19.Polo, M. et al. An invivo model of human proliferative scar. J. Surg. Res. 74 (2), 187–195 (1998). 20. Fujiwara, M., Muragaki, Y. & Ooshima, A. Upregulation of transforming growth factor-beta1 and vascular endothelial growth factor in cultured keloid broblasts: relevance to angiogenic activity. Arch. Dermatol. Res 297 (4), 161–169 (2005). Abstract Background : Breast cancer stem cells (BCSCs) have a critical role in progression of breast cancer by inducing angiogenesis. Several therapeutic strategies have been designed for the treatment of breast cancer by specifically preventing angiogenesis. But there is a dearth of study regarding the treatment procedure which can specifically target and kill the BCSCs and cause lesser harm to healthy cells of the body. A plant-based bioactive compound Quinacrine (QC) specifically kills cancer stem cells (CSCs) without harming healthy cells and also inhibits cancer angiogenesis but the detailed mechanistic study of its anti-CSCs and anti-angiogenic activity is yet to explore. Hypothesis : Earlier report showed that both cMET and ABCG2 play an essential role in cancer angiogenesis. Both are present on the cell surface of CSCs and share an identical ATP-binding domain. Interestingly, QC a plant based and bioactive compound which was found to inhibit the function of CSCs marker cMET and ABCG2. These relevant evidence led us to hypothesize that cMET and ABCG2 may interact with each other and induce the production of angiogenic factors, resulting in activation of cancer angiogenesis and QC might disrupt the interaction between them to stop this phenomena. Methods : Co-immunoprecipitation assay, immunofluorescence assay, and western blotting were performed by using ex vivo patient-derived breast cancer-stem-cells (PDBCSCs) and human umbilical vein endothelial cells (HUVECs). In silico study was carried out to check the interaction between cMET and ABCG2 in presence or absence of QC. Tube formation assay using HUVECs and in ovo Chorioallantoic membrane (CAM) assay using chick fertilized eggs were performed to monitor angiogenesis. In vivo patient-derived xenograft (PDX) mice model was used to validate in silico and ex vivo results. Results : Data revealed that in a hypoxic tumor microenvironment (TME), cMET and ABCG2 interact with each other and upregulate HIF-1α/VEGF-A axis to induce breast cancer angiogenesis. In silico and ex vivo study showed that QC disrupted the interaction between cMET and ABCG2 to inhibit the angiogenic response in endothelial cells by reducing the secretion of VEGF-A from PDBCSCs within the TME. Knockdown of cMET, ABCG2 or both, significantly downregulated the expression of HIF-1α and reduced the secretion of pro-angiogenic factor VEGF-A in the TME of PDBCSCs. Additionally, when PDBCSCs were treated with QC, similar experimental results were obtained. Conclusion : In silico, in ovo, ex vivo and in vivo data confirmed that QC inhibited the HIF-1α/VEGF-A mediated angiogenesis in breast cancer by disrupting the interaction between cMET and ABCG2. Background: Keloid, an aggressive fibroproliferative disease of the skin, is usually caused by infectious skin diseases, burns, and trauma. Objective: This study aimed to assess the effect of SPARC on the keloid pathogenesis. Methods: In normal skin and keloid scar tissues, changes in SPARC expression were analysed by qRT-PCR, western blotting, and immunohistochemistry. Keloid fibroblasts were isolated from human keloid tissue. GSEA was performed to investigate the signalling pathways related to SPARC. Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine, transwell assay, and scratching assays were used to assess fibroblast proliferation and migration. Changes in α-SMA, fibronectin, collagen I, and collagen III levels were examined in fibroblasts by western blotting. Results: SPARC expression was upregulated in keloid scar tissues. In fibroblasts, cell proliferation, migration, collagen production, and extracellular matrix (ECM) synthesis were promoted by SPARC overexpression, whereas SPARC knockdown resulted a converse result. GSEA showed that SPARC regulates the p53 pathway. In keloid scar tissues, there was a negative correlation between SPARC and p53 expression. p53 expression was decreased by SPARC overexpression, whereas SPARC knockdown increased p53 expression. Furthermore, the effects of SPARC on the fibroblast phenotype were reversed by p53 overexpression. Conclusions: Fibroblast proliferation, migration, and ECM synthesis were promoted by SPARC overexpression, which was achieved by regulating the p53 pathway. Our findings provide new therapeutic targets for keloids.	https://www.researchgate.net/publication/349920688_A_selective_small-molecule_inhibitor_of_c-Met_suppresses_keloid_fibroblast_growth_in_vitro_and_in_a_mouse_model
Patient-relevant needs and treatment goals in nail psoriasis \| Request PDF Request PDF \| Patient-relevant needs and treatment goals in nail psoriasis \| Purpose: Patient-centered health care implies that medical decisions are made jointly by physician and patient, based on patient needs. Aims were... \| Find, read and cite all the research you need on ResearchGate Patient-relevant needs and treatment goals in nail psoriasis Quality of Life Research 25(5) DOI: 10.1007/s11136-015-1136-y Authors: A Costanzo E Dauden Generalitat de Catalunya Show all 13 authors Hide Abstract and Figures Purpose: Patient-centered health care implies that medical decisions are made jointly by physician and patient, based on patient needs. Aims were to (a) identify treatment goals for a new questionnaire on patient needs and benefits in nail psoriasis treatment; (b) analyze the importance of treatment goals in patients with nail psoriasis in general and in defined subgroups; and (c) determine the association between overall treatment goal importance and quality of life. Methods: The study comprised the following steps: qualitative survey on needs and burdens in 120 patients; development of items by an interdisciplinary expert group; item testing in 55 patients in four countries; revision of the questionnaire and assessment in 203 patients in six countries (Germany, Denmark, Italy, Spain, USA, Japan). The percentage of patients rating the goals as 'quite/very important' was compared between various patient subgroups. Results: Based on 692 free-text statements, 26 items were developed which were reduced to 24 items after pilot testing. Each of these treatment goals applied to the majority of patients in the multi-center study. Goal importance increased with severity of nail psoriasis, but not with age or disease duration. Manual dexterity and social interaction were of particular importance. Goal importance and quality of life were associated, but not redundant (r = 0.612, p < 0.001). Conclusions: Patients with nail psoriasis have manifold and specific treatment goals. Goal importance is a construct different from disease-specific quality of life and should be assessed separately. The new questionnaire can support goal setting in clinical practice. Percentage of patients rating the treatment goals as ‘quite’ or ‘very important’ in the Patient Needs Questionnaire (n = 201; sorted by importance; item numbers relate to position within the questionnaire; item wording was abbreviated for this figure) … Scatter plot on overall treatment goal importance (NAPPA-PBI, Patient Needs Questionnaire) and nail-psoriasis-related quality of life (NAPPA-QoL) (n = 201; solid line: regression line; dotted line: diagonal) … Figures - available from: Quality of Life Research Discover the world's research 25+ million members 160+ million publication pages 2.3+ billion citations Patient-relevant needs and treatment goals in nail psoriasis C. Blome 1 • A. Costanzo 2 • E. Dauden 3 • C. Ferrandiz 4 • G. Girolomoni 5 • R. Gniadecki 6 • L. Iversen 7 • A. Menter 8 • K. Michaelis-Wittern 9 • A. Morita 10 • H. Nakagawa 11 • K. Reich 12 • M. Augustin 1 Accepted: 19 September 2015 / Published online: 3 October 2015  Springer International Publishing Switzerland 2015 Abstract Purpose Patient-centered health care implies that medical decisions are made jointly by physician and patient , based on patient needs. Aims were to (a) identify treatment goals for a new questionnaire on patient needs and beneﬁts in nail psoriasis treatment; (b) analyze the importance of treatment goals in patients with nail psoriasis in general and in deﬁned subgroups; and (c) determine the association between overall treatment goal importance and quality of life. Methods The study comprised the following steps: qual- itative survey on needs and burdens in 120 patients; development of items by an interdisciplinary expert group; item testing in 55 patients in four countries; revision of the questionnaire and assessment in 203 patients in six coun- tries (Germany, Denmark, Italy, Spain, USA, Japan). The percentage of patients rating the goals as ‘quite/very important’ was compared between various patient subgroups. Results Based on 692 free-text statements, 26 items were developed which were reduced to 24 items after pilot testing. Each of these treatment goals applied to the majority of patients in the multi-center study. Goal importance increased with severity of nail psorias is, but not with age or disease duration. Manual dexterity and social interaction were of particular importance. Goal importance and quality of life were associated, but not redundant ( r = 0.612, p \ 0.001). Conclusions Patients with nail psoriasis have manifold and speciﬁc treatment goals. Goal importance is a construct different from disease-speciﬁc quality of life and should be assessed separately. The new questionnaire can support goal setting in clinical practice. & C. Blome [email protected] 1 Institute for Health Services Research in Dermatology and Nursing (IVDP), German Center of Health Services Research in Dermatology (CVderm), University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany 2 Dermatology Unit, NESMOS Department, Department of Dermatology, University of Rome ‘Tor Vergata’, Rome, Italy 3 Department of Dermatology, Hospital Universitario de la Princesa, Madrid, Spain 4 Servicio de Dermatologı ´ a, Hospital Universitari Germans Trias i Pujol, Universitat Auto ` noma de Barcelona, Barcelona, Spain 5 Clinica Dermatologica, Universita ` di Verona, Verona, Italy 6 Bispebjerg Hospital, University of Copenhagen, Copenhagen NV, Denmark 7 Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark 8 Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA 9 SCIderm GmbH, Hamburg, Germany 10 Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 11 Department of Dermatology, The Jikei University, School of Medicine, Tokyo, Japan 12 Dermatologikum Hamburg, Hamburg, Germany 123 Qual Life Res (2016) 25:1179–1188 DOI 10.1007/s11136-015-1136-y Content courtesy of Springer Nature, terms of use apply. Rights reserved. ... Further signs include leukonychia, onychodystrophy, splinter hemorrhages, and oil drops. Nail psoriasis (NPso) comes with considerable patient burden over and above impairments due to other psoriasis symptoms [2, 7, 8]. Firstly, NPso is highly visible, especially when the fingers are affected, resulting in perceptions of stigma, self-consciousness, and social problems. ... ... This instrument assesses the importance of specific treatment goals from the perspective of patients with NPso, and also evaluates the extent to which these goals have been achieved by NPso treatment. The weighted global score indicates the treatment benefit as perceived by the individual patient, which can complement the data on HRQoL improvement as treatment needs can differ widely from one patient to another [7] . ... Nail Psoriasis and Quality-of-Life Measurement in Clinical Trials: Call for the Use of Nail-Specific Instruments Nail involvement is frequent in people with psoriasis. It can considerably impair health-related quality of life (HRQoL) beyond the impairments due to other psoriasis symptoms, for example, because patients feel ashamed of visible nail defects or because of the functional impairment in manual activities and walking. In clinical trials on nail psoriasis, it is therefore crucial to assess whether the treatment reduces HRQoL impairments that are specific to nail psoriasis. For this purpose, two validated patient questionnaires are available, the Nail Psoriasis Quality of Life Scale (NPQ10) and the Nail Assessment in Psoriasis and Psoriatic Arthritis–Quality of Life (NAPPA-QOL). The ten-item NPQ10 has the advantage of being short and thus quick to administer. The 20-item NAPPA-QOL, in contrast, assesses the different dimensions of HRQoL which is considered a multi-dimensional construct. Yet most randomized controlled trials on nail psoriasis do not evaluate HRQoL improvement. If they do, a number of different instruments are used, most of which are not nail specific. This makes comparison of trial outcomes difficult. Harmonizing the measurement of HRQoL in future clinical trials on nail psoriasis would improve comparability across studies and would also enhance the reliability of meta-analyses. ... In patients with moderate to severe psoriasis and/or nail psoriasis, a wide range of personal treatment goals have already been explored by using the Patient Needs Questionnaire (PNQ) as part of the Patient Benefit Index (PBI) [7] [8] [9][10]. Patient needs in psoriasis patients with sustained controlled disease activity, on the other hand, have rarely been studied. ... ... Since treatment goals differ per patient, individual treatment could be optimized by actively inquiring about the patient's personal treatment goals. As goal importance is a distinct concept from qualityof-life measurements, addressing both these two items could improve the quality of care [8] . ... Unmet Personal Patient Needs in Psoriasis Patients with Low Disease Activity on Adalimumab, Etanercept or Ustekinumab Article Full-text available Mar 2021 M. E. van Muijen Selma Atalay L.J. van Vugt Elke M G J de Jong Background Personal treatment goals have been systematically investigated in psoriasis patients with active but not in controlled disease.Objectives To explore patient needs in psoriasis patients with controlled disease due to biologic therapy with adalimumab, etanercept or ustekinumab.Methods Treatment needs in patients on adalimumab, etanercept or ustekinumab with a stable low disease activity for ≥ 6 months and preferably a Psoriasis Area and Severity Index (PASI) < 5, were explored with the Patient Needs Questionnaire (PNQ). Goal importance was expressed as overall mean importance score, percentage of patients that reported a goal to be quite/very important, and per PNQ subscale. Data were analysed separately for treatment, gender, age group (< 50 vs. ≥ 50 years), biologic naivety and willingness to participate in a pragmatic dose-reduction strategy.ResultsSixty-five patients were included. ‘To be free of itching’, ‘to be healed of all skin defects’ and ‘to have confidence in the therapy’ were rated quite/very important in 78.5% of the patients, followed by ‘to have no fear the disease will progress’ (75.4%) and ‘to get better skin quickly’ (75.4%). Goals related to the subscale ‘confidence in healing’ were still of high importance in controlled disease. Least importance was attributed towards social goals. For female patients, it was significantly more important than for males to ‘feel less depressed’ and ‘be comfortable showing yourself more in public’.Conclusions Psoriasis patients with controlled disease still report substantial treatment needs, with high importance ascribed to confidence in healing. To apply personalized medicine, treatment needs should be explored on an individual level. ... This could be facilitated with a goal-oriented treatment approach as has been established in other fields like psoriasis. 20, 21 In the latter, a consensus on treatment goals was established 22,23 and tools for better identification of needs, goals and benefits were consented. 19,24,25 The principle of goal attainment scaling as used in the Patient Benefit Index (PBI) is to define patients' treatment goals before therapy and evaluate achievement in the course of therapy. ... Development of a Specific Variant of Patient Benefit Index (PBI) Assessing Patient Needs, Goals and Benefits in Rosacea Treatment Article Full-text available Jun 2023 Matthias Augustin Rachel Sommer Christine Blome Anna Langenbruch Introduction: Evaluation of patient-reported outcomes including health-related quality of life (HRQoL) and perceived benefits from treatment has become a fundamental component of medical decision-making. Standardized evaluation of treatment benefits in rosacea based on patient preferences is still lacking. Objective: Development and validation of an instrument for recording patient-defined benefits in rosacea therapy based on the Patient Benefit Index (PBI) methodology. Patients and methods: In an open survey of n = 50 patients, potential benefits of therapy from the patient's perspective were examined. The generated item pool was combined with pre-existing PBI items for other skin conditions and reviewed by an expert panel of dermatologists, psychologists and patients. Items were condensed to n = 25 and converted into a Likert-scaled questionnaire. The validity and feasibility of the resulting Patient Benefit Index for rosacea (PBI-RO) were tested on individuals with rosacea recruited from a German rosacea patient organization. Results: N = 446 patients with rosacea completed the PBI-RO. The internal consistencies measured by Cronbach's alpha were high (Patient Needs Questionnaire [PNQ] 0.94). Mean PBI-RO was 1.9 ± 1.2 (scale from 0 = no benefit to 4 = maximum benefit), 23.5% of the patients experienced a PBI-RO < 1 (no clinically relevant benefit). The PBI-RO correlated with HRQoL, health state, current extent of rosacea lesions and treatment satisfaction. The highest correlation was found between PBI-RO and satisfaction with previous treatment (r = -0.59, p < 0.001); correlation with the extent of rosacea lesions was low (r = 0.16, p < 0.001). Conclusion: The PBI-RO shows satisfying internal consistency and construct validity. It offers the option of a patient-weighted evaluation of the therapeutic benefit of rosacea therapy and may add to more stringent goal orientation in therapy. ... 36 This is particularly important in sensitive conditions such as nail and anogenital affections. [37] [38][39] Well-being in psoriasis: clinical goals Insights on the well-being of the patients are based on the patient's view of their condition, and this concept is increasingly being embraced as a more comprehensive outcome in line with a holistic view and people-centred perspective, but still undervalued in traditional PROs. Well-being is a holistic multifaceted concept that in a study context describes 'to what extent patients will get their healthy lives back', where mental, physical and social functioning are interdependent. ... Patient-reported well-being in value-based care using tildrakizumab in a real-world setting: protocol of a multinational, phase IV, 1-cohort prospective observational study (the POSITIVE study) Article Full-text available Feb 2023 Matthias Augustin Rachel Sommer Esteban Daudén Ulrich Mrowietz Introduction Psoriasis is a chronic inflammatory skin disease that negatively impacts the quality of life of patients and their families. However, the most commonly used decision-making tools in psoriasis, Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA) and Dermatology Life Quality Index (DLQI), do not fully capture the impact of psoriasis on patients’ lives. In contrast, the well-established 5-item WHO Well-being Index (WHO-5) assesses the subjective psychological well-being of patients. Moreover, while drug innovations became available for psoriasis, data on the impact of these therapies on patients’ lives and their closest environment (family, physicians) are limited. This study will assess the effect of tildrakizumab, an interleukin-23p19 inhibitor, on the overall well-being of patients with moderate-to-severe psoriasis. Moreover, the long-term benefit of tildrakizumab on physicians' satisfaction and partners' lives of patients with psoriasis will be evaluated. Methods and analysis This non-interventional, prospective, observational, real-world evidence study will involve multiple sites in Europe and approximately 500 adults with moderate-to-severe psoriasis treated with tildrakizumab. Each patient will be followed for 24 months. The primary endpoint is well-being measured by the WHO-5 questionnaire. Key secondary endpoints include Physician’s Satisfaction and partner’s quality of life (FamilyPso). Other endpoints will evaluate skin-generic quality of life (DLQI-R), Treatment Satisfaction Questionnaire for Medication (TSQM-9), Treatment-related Patient Benefit Index ‘Standard’, 10 items (PBI-S-10) and work productivity and activity impairment due to psoriasis (WPAI:PSO). Statistical analyses will be based on observed cases. Multiple imputations will be performed as a sensitivity analysis, and adverse events will be reported. Ethics and dissemination The study will be conducted according to the protocol, which received ethics committee approval and applicable regulatory requirements of each participating country. The results will be disseminated through scientific publications and congress presentations. Trail registration number ClinicalTrials.gov Identifier: NCT04823247 (Pre-results) View ... The importance of the treatment objectives in PsO can be measured using the Patient Needs Questionnaire (PNQ), the first part of the Patient Benefit Index (PBI), where the patients rate the importance of each goal on a five-point Likert scale (or choose ''does not apply to me'') from a list of 25 different treatment goals [15]. Treatment goals using the PNQ as part of the PBI have been explored in patients with moderate-to-severe PsO, and/or nail PsO in European studies [10,16, 17] . However, assessment of patient treatment goals in PsO using the PNQ has not been studied in the USA. ... Treatment Goals for Psoriasis as Measured by Patient Benefit Index: Results of a National Psoriasis Foundation Survey Article Full-text available Apr 2022 April Armstrong Emily Edson-Heredia Baojin Zhu Stacy R Smith Introduction: This cross-sectional survey was conducted with National Psoriasis Foundation (NPF) to capture treatment perspectives and expectations in patients with psoriasis (PsO) using Patient Needs Questionnaire (PNQ) of Patient Benefit Index (PBI). Methods: Adult participants with self-reported diagnosis of PsO responded to the PNQ portion of PBI by indicating how much they valued different treatment attributes. All the treatment goals were captured on a five-point Likert scale (0 = "Not important", 4 = "Very important"). Treatment goals were obtained for overall population and subgroups based on severity of disease Patient Global Assessment (PGA), age, gender, and Dermatology Life Quality Index (DLQI) total score. All data were expressed as mean and standard deviation [SD]. Results: A total of 1200 participants completed the survey (mean age 51.5 years). Top treatment goal in the overall population was "to have confidence in the therapy" (3.46 [1.01]). Unique to the higher severity subgroup (PGA ≥ 3), "to find a clear diagnosis and therapy" was a top five goal and "to get better skin quickly" was for those with lesser severity (PGA < 3). "To be free of itching" (3.36 [0.99]) was the unique goal in the < 40 age group whereas it was "to get better skin quickly" (3.27 [1.12]) in the ≥ 40 group. In women and men, "to be free of itching" (3.38 [1.13]) and "to get better skin quickly" (3.20 [1.09]) were top five goals, respectively. Patients with ≥ 10 DLQI scores expressed higher treatment goal "to regain control of the disease" (3.66 [0.67]) compared to those with ≤ 10 DLQI scores who expressed "to have confidence in the therapy" (3.40 [1.11]) as the topmost treatment goal. Conclusion: Our results suggest that in patients with PsO, treatment preferences can vary with different characteristics such as age, severity, and gender as measured by using PNQ. Further exploration of this data will help inform treatment decisions and optimize patient outcomes. ... N ail psoriasis is an embarrassing condition with a high unmet medical need (1) . Its negative impact regard ing healthrelated quality of life and impaired ability to perform daily activities are known (2). ... Efficacy of Biologics Targeting Tumour Necrosis Factor-alpha, Interleukin-17 -12/23, -23 and Small Molecules Targeting JAK and PDE4 in the Treatment of Nail Psoriasis: A Network Meta-analysis Article Full-text available Sep 2020 Júlia Szebényi Noémi Gede Peter Hegyi Rolland Gyulai The comparative efficacy of registered anti-psoriatic biologics and small molecules in treating nail symptoms has not been systematically evaluated. The aim of this study was to perform a network meta-analysis to determine the efficacy of biologics and small mole-cules in nail psoriasis. A Bayesian network meta- analysis of 17 randomized clinical trials (a total of 6,053 nail psoriatic patients) was performed, comparing the short-term (week 10-16) efficacy of biologics and small molecules in the treatment of nail psoriasis. All active treatments were found to be superior to place-bo. Ixekizumab 80 mg every 4 weeks (Nail Psoriasis Severity Index (NAPSI) % improvement, Surface Under the Cumulative Ranking (SUCRA)=0.92) and etanercept 50 mg twice weekly (probability of achiev-ing NAPSI 50, SUCRA=0.82) proved the best short-term treatment options. However, efficacy end-points in psoriasis trials were not optimized for nail assessment, and outcome parameters were highly heterogeneous, limiting comparability. In conclusion, outcome parameters and efficacy endpoints of nail psoriasis trials should be harmonized. ... Most of the reviewed studies, however, had outcomes that, while not directly related to SDM, appeared to be consequential to the presence or absence of SDM, often with an affective-cognitive focus. These outcomes include adherence [33,43,45,46], patient satisfaction [30,31,40], relationship [35,38,39,41,48], need [28,32, 36, 39,44], and knowledge [26,29,34]. This is in line with another review on SDM and patient outcomes [58], which found that affective-cognitive outcomes were assessed most often and were primarily based on patient reports of satisfaction, decisional conflict, or other perceptions immediately after an interaction with a clinician. ... Shared Decision Making in Psoriasis: A Systematic Review of Quantitative and Qualitative Studies Article Oct 2018 Marie H Larsen Kåre Birger Hagen Anne-Lene Krogstad Astrid Klopstad Wahl Background Patients with psoriasis face numerous treatment and self-management decisions. Shared decision making is a novel approach where patients’ preferences and values are considered in cooperation with healthcare professionals before making treatment decisions. Objective The objective of this systematic review was to explore what is illuminated in psoriasis research regarding shared decision making, and to estimate the effects of shared decision-making interventions in this context. Methods Qualitative, quantitative, and mixed-methods studies were eligible for inclusion. We searched six electronic databases up to January 2018. Two reviewers independently applied inclusion and quality criteria. The SPIDER framework was used to identify eligibility criteria for study inclusion. Narrative and thematic syntheses were utilized to identify prominent themes emerging from the data. Results A total of 23 studies were included in the review. Of these, we included 18 studies (19 papers) to describe what was illuminated with regard to shared decision making in psoriasis research. Four major themes emerged: interpersonal communication; exchange of competence and knowledge; different world view; and involvement and preference, organized under two analytical themes; “Co-creation of decisions” and “Organization of treatment and treatment needs”. For shared decision-making effects, we included four controlled studies. These varied in scope and interventional length and showed limited use of shared decision making-specific outcome measures, reflecting the early stage of the literature. Because of study heterogeneity, a meta-synthesis was not justified. Conclusions There appears to be a need to strengthen the relationship between medical doctors and patients with psoriasis. The evident lack of knowledge about each other’s competence and the lack of self-efficacy for both patients and providers challenges the basic principles of shared decision making. The effects of shared decision making in psoriasis are inconclusive, and more research appears necessary to determine the possible benefits of shared decision-making interventions. Updates in treatment and impact of nail psoriasis Article May 2023 Expet Rev Clin Immunol Matilde Iorizzo Antonella Tosti Introduction: Nail psoriasis is an inflammatory disorder without a potential scarring outcome, but the nail signs, even the milder ones, can cause discomfort to patients and severely affect their quality of life. Nail psoriasis may be associated with psoriatic arthritis and when it starts during infancy, it may be a predictor of a more severe disease course in adulthood. All these issues contribute to the high economic burden of psoriasis. Areas covered: Nail psoriasis is notoriously difficult to treat, even though new treatments are in continuous development. This paper provides an update on new treatments and address the current gaps in care of nail psoriasis. Expert opinion: A better understanding of the disease pathogenesis and more "real-life"studies will definitely be helpful to improve treatment results. A lower level of heterogeneity should be advisable among trials when evaluating nail psoriasis. Moreover, the relationship between nail psoriasis and psoriatic arthritis should be the focus of unbiased studies in order to better define the real risk that nail psoriasis patients have to develop arthritis. Outcome domains and measures for pain in psoriasis used in registered trials: analysis of studies on ClinicalTrials.gov Jun 2021 Ana Sanader Vučemilović Livia Puljak Aim: Psoriasis includes unpleasant symptoms such as pain. This study aimed to investigate whether clinical trials have domains related to pain in their study designs. Materials and methods: We analyzed all clinical trials about interventions for psoriasis treatment registered on ClinicalTrials.gov and the frequency of pain-related outcomes. Results: Our analysis included 1033 registered clinical trials. They had 1329 primary outcomes and 5457 secondary outcomes. The pain was used in six (0.6%) protocols as a primary outcome and 68 (6.5%) protocols as a secondary outcome. Conclusion: Pain as an outcome was used in few registered clinical trial protocols for the treatment of psoriatic conditions. Future studies should investigate why the trialists do not include pain among primary or secondary outcomes. Treatment goals in psoriasis from a patient perspective: a qualitative study Nov 2018 Tessa A. Kouwenhoven Jeroen A.M. van der Ploeg Peter van de Kerkhof Background: Psoriasis is a chronic inflammatory skin disorder with marked impact on quality of life. In view of the well-recognized need to integrate the patient perspective in psoriasis care, treatment goals which originate entirely from the experiences of the patients are of utmost importance. Objective: To explore treatment goals in patients with psoriasis that originate entirely from the patient perspective. Methods: Data was generated using face-to-face in-depth interviews with 15 Dutch psoriasis patients, which were analysed using template analysis resulting in 2 first-level, 10 second-level and 14 third-level themes. Results: A wide variety of treatment goals was reported. Almost all patients reported their ‘ultimate’ treatment goal would be achieving total skin clearance. Barriers in achieving treatment goals included the fact that psoriasis is a chronic disease with no cure available, lack of effectiveness of current treatment options and side effects of treatments of which the treatment effect does not compensate. Conclusion: There is a great variety and inter-individual difference in treatment goals. Therefore, we recommend to define individualized patient-defined treatment goals, as every patient with psoriasis requires a tailor made treatment program. Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR) Drug survival reflects a drug's effectiveness, safety and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (BADBIR). The survival rates of the first course of biologics for 3523 biologic-naïve patients with chronic plaque psoriasis were compared using survival analysis techniques, and predictors of discontinuation analysed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1879), etanercept (n=1098), infliximab (n=96) and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed female gender (HR 1.22; 95% CI:1.09,1.37), being a current smoker (HR 1.19; 95% CI:1.03,1.38), and a higher baseline DLQI (HR1.01; 95% CI:1.00,1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI:0.71,0.96) was a predictor for drug survival. As compared to adalimumab, patients on etanercept (HR 1.63; 95% CI:1.45,1.84) or infliximab (HR 1.56; 95%CI:1.16,2.09) were more likely to discontinue therapy, whilst patients on ustekinumab were more likely to persist (HR 0.48; 95% CI:0.37,0.62). After accounting for relevant covariates, ustekinumab had the highest first course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.Journal of Investigative Dermatology accepted article preview online, 08 June 2015. doi:10.1038/jid.2015.208. Patient-centered medicine. A professional evolution German psoriasis registry PsoBest: Objectives, methodology and baseline data The German psoriasis registry PsoBest records the long-term efficacy, safety, patient benefit and treatment regimens of psoriasis. Patients with moderate or severe psoriasis are included in PsoBest when treatment with a conventional systemic agent or biologic is started for the first time. Observation time is five years. Standardized physician and patient case report forms are obtained every three to six months. Baseline data of patients included by 31 December 2012 are presented and compared to the national health care study PsoHealth 2007 (n = 2,009). 602 dermatology practices and clinics have been registered and 199 have recruited n = 2,556 patients (63 % by practices, 37 % by clinics). Initially, n = 808 received biologics (316 adalimumab, 34 efalizumab, 209 etanercept, 75 infliximab, 22 golimumab, 152 ustekinumab) and n = 1,651 conventional systemic therapy (928 fumaric acid esters, 518 methotrexate, 161 cyclosporine A, 191 other drugs or UV treatment). Compared to PsoHealth, patients in PsoBest had on average a higher disease severity (PASI 14.7 vs. 10.1; DLQI 11.0 vs. 7.5; EQ-5D VAS 54.0 vs. 64.5), shorter disease duration (18.2 vs. 21.3 yrs.), lower age (47.3 vs. 51.5), higher rates of psoriatic arthritis (20.5 vs. 19.1 %) and nail psoriasis (55.0 vs. 35.6 %). On average patients receiving biologics were younger, more often male and had higher disease severity and comorbidity. Patients in PsoBest represent patients with a high burden of disease. A 10-year trend of insomnia prevalence in the adult Norwegian population Evaluation of Patient-relevant Outcomes of Lymphedema and Lipedema Treatment: Development and Validation of a New Benefit Tool Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA): Development and Validation of a Tool for Assessment of Nail Psoriasis Outcomes. Christine Blome Existing tools for nail psoriasis (NPso) are complex and may not adequately measure outcomes that are important to patients. We developed and validated a new tool, the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA), with 3 components: a questionnaire assessing quality of life (NAPPA-QoL), a 2-part questionnaire assessing patient-relevant treatment benefits (NAPPA-PBI), and a clinical assessment of NPso severity (NAPPA-CLIN). Development of the questionnaires involved multiple steps: 1) collection of items about NPso-related impairments and treatment goals; 2) selection of 48 items by an expert panel, including patients; 3) translation into 8 languages; 4) feasibility testing; and 5) longitudinal validation in 6 countries. Patients found the questionnaires clear (84%) and comprehensible (95.0%). NAPPA-QoL and NAPPA-PBI scores correlated moderately with clinical outcomes (eg, Nail Psoriasis Severity Index [NAPSI]) and markedly with other QoL questionnaires (eg, EQ-5D(™) ). Both questionnaires were sensitive to change. Internal consistency was good (Cronbach's α ≥0.88 for all scales). The NAPPA-CLIN, a brief version of NAPSI that involves assessment of only 4 digits rather than all 20 digits, was found to correlate highly with total NAPSI score (r=0.97; P<0.001). Overall, the 3-component NAPPA tool is a valid, reliable, and practical instrument to assess patient-relevant NPso outcomes. This article is protected by copyright. All rights reserved. Epidemiologie der Psoriasis in Deutschland-Auswertung von Sekundärdaten einer gesetzlichen Krankenversicherung Ziel: Zur Epidemiologie der Psoriasis liegen bisher in Deutschland kaum bevölkerungsbezogene Daten vor. Studienziel war die Abschätzung der Psoriasis-Prävalenz für die Gesamtbevölkerung sowie für versorgungsrelevante Subgruppen. Als weitere epidemiologische Parameter wurden die regionale Verteilung sowie der Schweregrad der Psoriasis erfasst. Methode: Auf der Basis von Routinedaten einer gesetzlichen Krankenversicherung wurde eine Sekundärdatenanalyse durchgeführt. Die Prävalenzen wurden für eine geschlossene Versichertenkohorte für das Jahr 2005 berechnet, wobei als Definitionskriterium für das Vorliegen der Erkrankung mindestens eine Psoriasis-Diagnose nach ICD-10 anlässlich einer ambulanten oder stationären Behandlung oder eines AU-Falls im Jahr 2005 galt. Ergebnisse: Von den 1 344 071 durchgängig Versicherten lag für 33 981 eine Psoriasis-Diagnose vor. Die Ein-Jahres-Prävalenz beträgt damit 2,53%. Bis zum Alter von 80 Jahren stieg die Prävalenzrate mit dem Alter kontinuierlich an, die höchsten Raten fanden sich in den Altersgruppen zwischen 50 und 79 Jahren (3,99–4,18%). Für Kinder und Jugendliche unter 20 Jahren lag die Erkrankungshäufigkeit bei 0,73%. 8,2% aller Erkrankten erhielten eine Therapie, die auf eine mittelschwere bis schwere Verlaufsform hinweist. Die Verteilung der Psoriasis-Prävalenz zeigte auf der Basis 1-stelliger Postleitzahlen (PLZ) regionale Unterschiede von 2,17% im Süden (PLZ 7 und 8) bis 2,78% im Westen (PLZ 5) und Norden (PLZ 2). Schlussfolgerung: Bezieht man die hier ermittelte Prävalenzrate von 2,5% auf die Gesamtbevölkerung, werden in Deutschland ca. 2 Millionen Menschen aufgrund einer Psoriasis ärztlich behandelt. Routinedaten einer gesetzlichen Krankenversicherung sind eine geeignete und relevante Datenquelle zur Erfassung der Behandlungsprävalenz chronischer Krankheiten in der Bevölkerung.	https://www.researchgate.net/publication/282766322_Patient-relevant_needs_and_treatment_goals_in_nail_psoriasis
Therapy with a Free-Standing Robotic Exoskeleton in People with Advanced Multiple Sclerosis: A Feasibility Study Background: Evidence for the use of lower limb robotic exoskeletons for people with advanced multiple sclerosis is in its early stages, and to date there have been no published studies into the use of free-standing exoskeletons in this population. Objective: This study aimed to determine the feasibility of a course of therapy in a free-standing robotic exoskeleton with people with advanced multiple sclerosis. Methods: Following a 12 week wait list control period participants with advanced multiple sclerosis (Kurtzke Expanded Disability Status Scale score of ≥6.0) completed 12 weeks of twice weekly therapy in a free-standing robotic exoskeleton. A battery of assessments was performed at participant enrolment including motor function, balance, strength, independence and health-related quality of life, commencement and conclusion of the intervention phase, and at 12 weeks follow-up. Results: Ten participants were eligible to participate in the study, with eight completing the full duration of the study; two dropped out due to an exacerbation of their condition, unrelated to the intervention. A lack of symptom stability in the control phase made interpretation of outcomes difficult. Participants who completed the intervention demonstrated high acceptance and tolerance of the intervention. No adverse events occurred. Health-related quality of life improved within six weeks of commencing the intervention and was sustained. No other outcomes showed any consistent changes. Conclusion: Therapy with a free-standing robotic exoskeleton is acceptable to people with advanced multiple sclerosis and can improve healthrelated quality of life, however clinical feasibility of this intervention is limited at this time. Research Article - (2023) Volume 10, Issue 1 Therapy with a Free-Standing Robotic Exoskeleton in People with Advanced Multiple Sclerosis: A Feasibility Study Nicola Postol * , Jessica Grissell , Caitlyn McHugh , Andrew Bivard Neil Spratt and Jodie Marquez * Correspondence: Nicola Postol, School of Health Sciences, University of Newcastle, Australia, Email: Author information Abstract Background:Evidence for the use of lower limb robotic exoskeletons for people with advancedmultiple sclerosisis in its early stages, and to date there have been no published studies into the use of free-standing exoskeletons in this population. Objective:This study aimed to determine the feasibility of a course of therapy in a free-standing robotic exoskeleton with people with advanced multiple sclerosis. Methods:Following a 12 week wait list control period participants with advancedmultiple sclerosis(Kurtzke Expanded Disability Status Scale score of ≥6.0) completed 12 weeks of twice weekly therapy in a free-standing robotic exoskeleton. A battery of assessments was performed at participant enrolment including motor function, balance, strength, independence and health-related quality of life, commencement and conclusion of the intervention phase, and at 12 weeks follow-up. Results:Ten participants were eligible to participate in the study, with eight completing the full duration of the study; two dropped out due to an exacerbation of their condition, unrelated to the intervention. A lack of symptom stability in the control phase made interpretation of outcomes difficult. Participants who completed the intervention demonstrated high acceptance and tolerance of the intervention. No adverse events occurred. Health-related quality of life improved within six weeks of commencing the intervention and was sustained. No other outcomes showed any consistent changes. Conclusion:Therapy with a free-standing robotic exoskeleton is acceptable to people with advancedmultiple sclerosisand can improve healthrelated quality of life, however clinical feasibility of this intervention is limited at this time. Keywords Multiple sclerosis • Lower limb • Robotic exoskeleton • Neuro-rehabilitation Introduction Multiple sclerosis (MS) is the most common non-traumatic cause of disability in younger people in the world affecting around 2.8 million people [1,2]. It has recently been shown that those with a Kurtzke Expanded Disability Status Scale (EDSS) score of less than 6.0, i.e. not dependent on a mobility aid, can benefit from physical rehabilitation, with exercise improving walking ability and decreasing the impact on health related quality of life (QoL) [3-5]. Approximately 41% of people with MS have difficulty with independent ambulation [6]. Weightbearing exercise is an important component of the management of condition progression and secondary complications throughout the disease course, and evidence is emerging of the benefits for people with more advanced MS [7]. However, once a person with MS is having difficulty walking, the need for mobility aids, environmental adaptations and healthcare support, can limit access to exercise in weightbearing [8]. Robotic technologies may offer solutions to address some of these barriers to treatment. Robotic technologies with therapeutic applications have been developing rapidly in the last two decades with devices such as the Lokomat ®(Hocoma, Zurich, Switzerland) [9], an exoskeleton combined with bodyweight-supported treadmill training, and the Gait Trainer GTII ®(Reha-Stim, Berlin, Germany) [10], an end-effector device, which combines bodyweight-supported training with a closed chain stepping device. These devices can achieve 10-20 times more steps in a treatment session, therefore providing greater treatment intensity than conventional therapy [11]. A 2020 systematic review which included 10 studies using both the Lokomat ®and the Gait Trainer GTII ®, with participants with an EDSS between 5.5-7.5, showed superiority over conventional therapy for fatigue, spasticity and global mobility, for those with severe disability [12]. This superiority was not demonstrated when a subgroup analysis of only studies using the Lokomat ®was conducted, suggesting more benefit from the Gait Trainer GTII ®. Neither device showed superiority over conventional training at three month follow up. The use of treadmill-based and end-effector robotic a technology has also been shown to be safe, feasible and acceptable to patients [12-14]. However, a lack of consistently improved outcomes for patients compared with conventional therapy, a lack of visuo-spatial variability in training, and a focus on gait over all other functional exercise, has led to the development of overground lower limb robotic exoskeletons with potential application in people with MS [15,16]. The development of overground exoskeletons in the last ten years has provided a way to exercise in supported weightbearing, whilst in varying locations. This offers the opportunity to practice a gross motor task in different contexts, a key principle of neuro-rehabilitation [17]. Lower body exoskeletons such as the ReWalk, ExoAtlet and Ekso, and single joint devices such as Keeogo, have been investigated with MS populations [18-21]. Evidence of the potential benefit of these devices is emerging for outcomes such as walking speed and distance, endurance and stair climbing and QoL [19,21-24]. Whilst these studies are generally positive, one study found that two thirds of participants did not tolerate the treatment and another reported skin irritations [21]. Furthermore, all these devices require the user to support themselves using upper limb support through a walking aid, which precludes many people [25]. A free-standing device may offer additional opportunity to a greater portion of the population. To date there has been limited research into the use of free-standing exoskeletons in the rehabilitation of those with MS. Currently there is only device which can support the user without the need for walking aids, the REX (Rex Bionics, Auckland, New Zealand) [26]. The only published research into therapy with this device in the MS population found that participants did not significantly increase their VO2 during a session of exercise in this device, and there was no change in this after 12 weeks of twice weekly robotic therapy, suggesting no effect on cardiovascular fitness [27]. A 2021 study found that a course of 12 weeks of therapy in the device with people with spinal cord injury was safe and acceptable, but that a small cohort of appropriate participants limited clinical feasibility [28]. A 2021 study of people with stroke found some benefit to levels of independence in activities of daily living after 12 weeks of therapy with the device [29]. To date no study has investigated the potential benefit to rehabilitation outcomes for people with MS after therapy with a free-standing exoskeleton. Given the numerous differences in features between free standing, mobility aid supported, and over-treadmill robotic devices, it is unreasonable to extrapolate the findings from previous research to free-standing devices. It is speculated that each type of device may have application in different sub-groups of the population. For example, it is surmised that free-standing exoskeletons would have higher clinical relevance in those with severe mobility impairment. Evaluate the feasibility of delivering a course of therapy using a free-standing overground robotic exoskeleton in people with severe mobility impairment due to MS (i.e., EDSS≥6). Determine any potential health related benefits of therapy using a freestanding overground robotic exoskeleton in people with severe mobility impairment due to MS. Methods Design This 12-week pre-post intervention trial required participants to attend the University of Newcastle, Australia for twice weekly therapy in a free-standing lower limb robotic exoskeleton. A 12-week waitlist control phase was used to establish the level of symptom stability of each participant prior to the intervention. A 12- week follow-up determined whether any health-related benefits of the therapy were maintained upon completion of the intervention. Participants were screened for cognitive capacity to give consent, and written informed consent was obtained from all eligible participants prior to their involvement in the study. Participants continued routine activities and therapy for the duration of the study. Outcome measures were assessed upon enrolment into the study (week 0), at baseline (week 12), mid intervention (week 18), post intervention (week 24), and follow up (week 36). Ethics approval was granted by the Hunter New England Human Research Ethics Committee and co-registered with the University of Newcastle. This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617001316392). This manuscript was written in accordance with STROBE reporting guidelines. Participants As this was a pilot study, a convenience sample was recruited between November 2017 and June 2019. Data collection was completed in February 2020. Potential participants were identified by staff at the specialised Hunter New England MS clinic based on the following inclusion criteria 1) a diagnosis of MS with a score of ≥6 on the EDSS indicating severe mobility impairment with reliance on a mobility aid or other people for upright activities, 2) resident of the Hunter region, 3) over the age of 18 years, 4) discharged from inpatient rehabilitation services. Exclusion criteria were: 1) weight and height outside the range of 40-100kg and 4'8-6'4" (criteria set by the robotic manufacturer), 2) pregnancy, 3) unstable or severe cardiac or respiratory conditions, 4) recent fractures in lower limbs/pelvis/spine, 5) significant cognitive impairment (<19 on the Montreal cognitive assessment (MoCA)), 6) any medical condition which limits the ability to exercise in an upright position [30]. Equipment The REX (Rex Bionics, Auckland, NZ) is a free-standing lower limb robotic exoskeleton, classified as a class one medical device by the Therapeutic Goods Administration of Australia. It has actuated hips, knees and ankles, and does not require the user to support themselves with a walking aid. Movement is controlled via a joystick on the right arm of the device, by a physiotherapist trained in its operation. The device can walk on flat surfaces at a speed of 0.5m/s, and complete a range of exercises including sit to stand, squats, lunges and sidesteps [26,31]. Intervention Participants completed two sessions of exercise therapy per week for 12 weeks, with each session consisting of up to half an hour of individualised weight bearing therapy in the exoskeleton, as tolerated by the participant, prescribed and administered by a REX accredited physiotherapist. Participants were also provided with a home exercise program relevant to their treatment, which was updated throughout the trial as required. Outcome measures On initial assessment, medical screening was completed to determine eligibility for the study. Standard demographic information and MS status (including EDSS) were also collected. Leg measurements were taken so that the robotic device could be individually fitted. These data were not reassessed. The primary outcome measure of interest was motor function as measured by items 1-5 of the motor assessment scale (MAS), with a score of 30/30 indicating maximum function [32]. A battery of secondary outcome measures was used to identify other potential health related benefits of this intervention. Balance was measured using the functional reach (FR) [33]. The five times sit to stand test (FTSST) was used to measure functional lower limb strength, along with dynamometer measurements of both quadriceps and grip strength [34]. Lean body mass was measured using the Biodynamic BIA 450 bioimpedance analyser (Washington state, USA) and reported as a percentage of total body mass. Functional independence was measured using the Barthel index (BI) where 100 indicates full independence [35,36]. Spasticity of the hamstrings, quadriceps and gastrocnemius muscles was measured with the Tardieu scale [37]. Fatigue was assessed out of 42 using the fatigue assessment scale (FAS), where a score of zero indicates no fatigue [38]. Health related QoL was evaluated on the short form 8 (SF-8) which is scored out of 50, with zero indicating full QoL. Mood was assessed using the hospital anxiety and depression scale (HADS) [39,40]. Anxiety and depression are each scored out of 21, with the total out of 42. Zero indicates no anxiety or depression. This research team designed a survey with a series of 16 Likert style questions to gauge the acceptability of exercising with this device. Five domains covered safety (three questions), likeability (four questions), comfort (five questions), usability (three questions), and desire to continue using the device (one question). Each question was scored out of five, with a maximum total score of 80 indicating high acceptance of the intervention. Two open ended questions asked participants’ most liked and disliked features of this intervention. Data analysis Descriptive statistics, including medians and interquartile ranges (IQR), were calculated for demographic data. Outcome data that were collected bilaterally (FR, strength and spasticity) were reported as the average of both sides. Friedman’s test was used to evaluate differences between outcome scores across the phases of the study. All analyses were conducted on an intention to treat basis, with missing data conservatively imputed using the last observation carried forward method. Results Participants Sixteen participants were referred and assessed for eligibility, with ten meeting the enrollment criteria. The primary reason for ineligibility was not meeting the sizing criteria of the device (n =4). Two participants left the study during the intervention phase, both due to a worsening of their condition unrelated to the intervention. The remaining eight participants completed all 24 intervention sessions in a median of 12.5 weeks (IQR: 12, 13). Variation in the time to complete the intervention was due to researcher and participant illness, and device malfunction.Figure 1for flow of participants through the study. No adverse events were observed or reported throughout the duration of the study. Figure 1.Flow of participants through the study. The median age of participants was 53, with a median time since diagnosis of 27 years. All except one participant had secondary progressive MS, and the median EDSS score was 6.5, indicating a need for bilateral support for mobility over short distances.Table 1for participant demographic data. Table 1:Participant demographic data. Participant Sex Age Time since diagnosis (years) MS type Level of disability (EDSS) Mobility status Enrolment motor assessment scale score (/30) 1 M 50 5.5 PP 6 Stick 28 2 F 52 27 SP 6.5 Frame and assist 18 3 M 42 17 SP 6.5 Frame and assist 20 4* M 54 30 SP 6 Stick 25 5 F 72 44 SP 6.5 Frame and supervision 19 6 F 57 27 SP 6.5 Transfers only 21 7 F 40 17 SP 7 Transfers only 10 8 F 59 31 SP 6.5 Frame 22 9 M 47 16 SP 6.5 Frame 24 10* F 69 31 SP 6.5 Frame 25 Median (IQR) 53 (47.75, 58.5) 27 (17, 30.75) 6.5 (6.5, 6.5) 21.5 (19.25, 24.75) Legend: * - denotes dropouts, IQR – interquartile range, M – male, F – female, MS – multiple sclerosis, PP – primary progressive, SP – secondary progressive, EDSS – Kurtzke expanded disability status scale Primary outcome – function Participants had a median baseline MAS score of 21.5 (IQR: 19.25, 24.75). Between phases differences were not significant (Table 2). Table 2:Results for physical outcomes. Enrolment (0 weeks) Pre-intervention (12 weeks) Mid-intervention (18 weeks) Post-intervention (24 weeks) Follow up (36 weeks) Analysis Outcome Median (IQR) Median (IQR) Median (IQR) Median (IQR) Median (IQR) Q statistic p value Motor assessment scale ( n=10 ) 21.5 (19.25, 24.75) 18 (15.25, 26) 20.5 (17.5, 23) 20 (15.25, 24) 20 (15, 25) 1.86 0.76 Functional reach (cm) ( n=10 ) 6.6 (0, 16) 6 (0, 21.4) 12 (0, 19.6) 12 (0, 19.6) 10.5 (0, 21.5) 5.18 0.27 Five times sit to stand test (secs) ( n=8 ) 22.52 (17.3, 37.8) 23.7 (15.4, 27.9) 20.1 (18, 34.2) 22.7 (16.1, 32.2) 17.5 (16.1, 30.5) 1.37 0.85 Strength: Grip (kgs) ( n=10 ) 20.5 (18, 23) 23.5 (16, 28) 21.8 (17.5, 27) 21.5 (17, 32) 21.8 (17.5, 24) 4.86 0.30 Strength: Quadriceps (kgs) ( n=10 ) 22.5 (14, 33) 23.5 (14, 33) 24 (13, 36) 21.8 (10, 35) 24.3 (14, 31) 0.34 0.99 Tardieu: Hamstrings (◦) ( n=10 ) 0 (0, 0) 0 (0, 0) 0 (0, 0) 0 (0, 0) 0 (0, 0) 8.00 0.09 Tardieu: Quadriceps (◦) ( n=10 ) 0 (0, 0) 0 (0, 0) 0 (0, 0) 0 (0, 0) 0 (0, 0) 8.92 0.06 Tardieu: Gastrocnemius (◦) ( n=10 ) 0 (0, 0) 0 (0, 0) 0 (0, 0) 0 (0, 0) 0 (0, 0) 1.33 0.86 % of lean body mass ( n=10 ) 70.5 (66.7, 81.6) 72.8 (69.7, 83.7) 72.5 (64.2, 83.7) 72.3 (68.2, 83.7) 71.3 (65.5, 83.6 9.13 0.058 Legend: IQR – interquartile range Five times sit to stand test could not be completed by two participants Additional physical outcomes There were no consistent changes in FR FTSST, grip and quadriceps strength, spasticity or percentage of lean body mass throughout the study (Table 2). Other health related outcomes A statistically significant difference in health related QoL was found, with the largest change in the first six weeks of the intervention (median improvement of -3.5, IQR: -4, -1, p = 0.01). Results for fatigue, mood and independence were not statistically significant and showed no clear trends, with inconsistency between participants across time (Table 3). Table 3:Results for additional health related outcomes. Enrolment (0 weeks) Pre-intervention (12 weeks) Mid-intervention (18 weeks) Post-intervention (24 weeks) Follow up (36 weeks) Analysis Outcome ( n=10 ) Median (IQR) Median (IQR) Median (IQR) Median (IQR) Median (IQR) Q statistic P value Fatigue assessment scale 25.5 (21.5, 31.25) 26 (23, 28) 22 (17.75, 26) 21 (20, 25.25) 22 (18.5, 25.75) 7.45 0.11 SF8 18.5 (17, 19) 19 (17.3, 22.3) 16.5 (14.5, 19.5) 18 (15.3, 19.8) 16.5 (15.3, 19.3) 2.5 0.01 Hospital anxiety and depression scale 6.5 (5.3, 9.5) 7.5 (3, 9.8) 4 (4, 8) 9 (4.8, 13) 5.5 (3.3, 9)77.5 4.09 0.39 Barthel index 77.5 (70, 92.5) 75 (71.3, 85) 75 (66.3, 83.8) 75 (75, 83.8) 80 (67.5, 87.5) 5.54 0.24 Legend: IQR – interquartile range, - statistically significant Survey Responses to the closed survey questions were favourable throughout the study, with a median total of all scores of at least 70/80 at all timepoints. The domains of comfort and usability scored the lowest. The most liked features of the device can be grouped into two categories: physical or therapeutic benefits, and emotional and experiential benefits. “ I can move and stand up without having to hold onto anything”, and experiencing “ exercises[participant] can’t do otherwise” were some positive comments. The least liked features related to the logistics of transferring in and out of the device, the device design, and one participant commented that they “ sometimes felt like the device was doing all the work” (Tables 4and5). Table 4:Participant perceptions of the intervention. Pre-intervention (12 weeks) Mid-intervention (18 weeks) Post-intervention (24 weeks) Follow up (36 weeks) n=10 n=10 Median (IQR) Median (IQR) Median (IQR) Median (IQR) Perceived Safety /15 14 (13.25, 15) 15 (15, 15) 15 (15, 15) 15 (14.25, 15) Likeability /20 18.5 (17.25, 19) 20 (18.25, 20) 20 (19, 20) 20 (19, 20) Comfort /25 19.5 (18.25, 21) 20.5 (19.25, 23) 22.5 (21, 24.75) 22 (20.5, 24) Usability /15 12.5 (12, 14) 14 (11.25, 15) 13.5 (12, 15) 14.5 (11.5, 15) Continue use /5 5 (5, 5) 5 (5, 5) 5 (5, 5) 5 (4.25, 5) Total score /80 70.5 (67, 71.75) 75.5 (63, 77.75) 75.5 (70.5, 78.25) 74 (69, 78) Each question scored out of 5; perceived safety – 3 questions, likeability – 4 questions, comfort – 5 questions, usability – 3 questions, continue to use – 1 question Table 5:Open ended survey questions. n=10 “Liked” “Disliked” 1. Physical/therapeutic benefits: a) Standing b) Therapeutic benefit a) Stood for over 5 minutes Ability to stand (n=3) I can move and stand up without having to hold onto anything Standing rather than sitting Felt so tall Standing up straight Being vertical and able to exercise in standing b) Working muscles otherwise can’t Believe it’s toning muscle and increasing strength Exercise can’t do otherwise Felt like a workout Felt like I’d done something Made muscles work which hadn’t in years Muscle soreness from activity Exercise without having to sit down and rest Experience sensation of walking Good stretch 1. Logistics: a) Transfers in and out b) Device design c) Study limitations a) Awkward to get into it Anxiety about needing toilet and being stuck in the device Time it took to get in b) Cumbersome Slow Arms banging the device during upper limb exercises c) When the trial finished 2. Emotional and experiential benefits: a) Feeling of safety b) Feeling of freedom c) Sense of participation in a novel, enjoyable intervention a) Felt safe Ability to move around without having to hold onto stuff Confident in standing as not worried about falling b) Freeing Freedom of standing up c) Gives me something constructive to do Participation The research Trying something new Enjoyed it 2. Therapeutic aspects: Sometimes felt like the device is doing all the work Muscle soreness (delayed onset) like going to the gym Comments from the post-intervention and follow up assessments combined Discussion The high completion rate of the intervention, absence of adverse events, along with positive responses to the survey questions, indicate that this treatment modality is acceptable to people with severe mobility impairment because of MS. However, the lack of change for physical and health related outcomes throughout the study, cast doubt on the clinical feasibility of this intervention. Of the range of outcomes measured, only health related quality of life revealed a statistically significant between phase differences. Our study revealed that this overground robotic therapy is acceptable to participants. A previous study evaluating the perceptions of robotic therapy in people with MS where participants reported high usability and perceived achievement of goals and improved QoL, concluded that this type of intervention can be useful for motivation and commitment to therapy [14]. Those who participated in our study had high compliance and reported positively about their experience. However, recruitment was low with only 16 participants referred over a two year period and of these only eight completed the intervention. As referral was made through a secondary provider, it is possible participants were not all identified, but as this was supplemented by strong local media interest in the study, and local therapist awareness, we can presume participant numbers would not have changed significantly with different recruitment strategies. Therefore, eligibility for this type of therapy appears to limit the clinical relevance of wide scale implementation, and our research does not support the notion that freestanding exoskeletons offer greater clinical feasibility than devices requiring upper limb support. There was no consistent change in motor function over the course of the study. This is a unique study investigating a range of outcomes rather than just gait parameters, which other studies have focused on [19,21-23,25]. We are therefore unable to compare our findings for motor function with other studies. We chose not to evaluate gait parameters, as they were not expected to change in people already dependent on mobility aids or unable to walk. The measure of motor function used in this study has not been validated for people with MS, however the multiple sclerosis functional composite uses the 10m walk test to evaluate lower limb function, which is not appropriate with people with an EDSS of ≥6.0 [41]. Similarly, no benefits were revealed for the remaining physical outcome measures. It is possible that a higher dosage and/or intensity of intervention may have led to more positive changes. Our participants completed 30 minutes of exercise in standing, twice a week, for 12 weeks. This pragmatic dosage was chosen based on what could be realistically offered in the clinical setting. A previous study investigating the use of high intensity therapy (60 minutes, three times a week for three weeks) delivered using a mobility aid supported robotic device (Ekso) reported improved gait speed [22]. Future studies investigating dose parameters are required to ensure the full potential of these devices is explored. This study showed an improvement in health related QoL in the first six weeks of the intervention. With low QoL commonly reported amongst those with MS, this finding merits further exploration [6]. A 2017 robotics study of six people with MS found improved QoL and mental health in almost all participants, which was maintained at three month follow up [23]. Similar results were found in a 2020 case study but with small sample sizes, these results lack external validity [24]. This study did not find a change in levels of independence, which is in contrast to a recent study using a mobility aid supported robotic device (ExoAtlet), however the change they found of 0.26 on the EDSS is unlikely to be clinically relevant as it would not represent a change in level of ability [3,19]. The results for other health related outcomes showed no trends. Future studies with increased dose parameters should still include these types of measures, in order to fully evaluate the potential impact of this intervention on the lives of people with MS. We evaluated a range of physical and health related outcomes which is a strength of this study, as MS is a multifaceted condition with many symptoms which impact QoL [5]. This study had a control phase to determine condition stability, as it can be difficult to evaluate rehabilitation outcomes for people with MS due to the condition’s fluctuating and degenerative nature. However, with changes found during the control phase in most outcomes, and wide IQRs, our participants did not have symptom stability. This makes interpretation of the results difficult, which is further compounded by a small sample size, both of which are considerations for future research with the MS population. Conclusion This study has shown that therapy with a free-standing overground robotic exoskeleton can improve health related QoL and is highly acceptable to participants, results which provide some support for therapy with a free-standing robotic exoskeleton. However, clinical feasibility may be limited by a small proportion of people with MS being eligible for participation. Few studies evaluate options for physical activity in those with severe mobility impairment as a result of MS, and as the disease progresses, these options are warranted to mitigate the secondary complications of inactivity and immobility. Further research with a powered sample is indicated to further explore the potential benefits of this type of intervention. Acknowledgement This research team would like to acknowledge and thank the Australian Institute of Neuro-rehabilitation, for loaning the REX for the duration of the study. Data Availability Data can be accessed by contacting the corresponding author. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflicts of Interest The Authors declare that there is no conflict of interest. References Kobelt, Gisela, Alan Thompson, Jenny Berg and Mia Gannedahl, et al. "New insights into the burden and costs of multiple sclerosis in Europe." Mult Scler 23 (2017): 1123-1136. Google Scholar, Crossref, Indexed at King 3rd, R. "Atlas of MS." Mult Scler Int Federation (2020). Kurtzke, John F. "Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS)." 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(PDF) Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy PDF \| Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical... \| Find, read and cite all the research you need on ResearchGate Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy March 2021 Polymers13(6):923 DOI: 10.3390/polym13060923 License CC BY 4.0 Authors: <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Shadab Md International Medical University (IMU) <here is a image f2f62089ad6ff61c-d19572ff1996375a> Nabil A. Alhakamy Nabil A. Alhakamy <here is a image 174dca3f21c4ab2c-cc64842abac6b6bd> Hibah Aldawsari King Abdulaziz University <here is a image 94395e9819293245-300b610e6620416a> Mohammad Husain Jamia Millia Islamia Abstract and Figures Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of −27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ± 6.0 and 79.43 ± 12.43 µg/cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer. <here is a image ec7586345e51bcd1-999fe010431e2fbe> Response surface morphological plots indicating the comparative effects of independent variables, i.e., Phospholipid conc. (mg); Cholesterol conc. (mg); and Glycerol conc. (% w/v) on (A) Vesicles size, (B) % Entrapment efficiency and (C) Flux of PLM. … <here is a image fdb7ce61363ad235-22625ac82cf56da8> Optimized PLM-loaded glycerosomes (A) average vesicle size (B) zeta potential and (C) transmission electron micrograph. … <here is a image 0ec2d4f2415c5ad1-d76629e81c6ad8fc> Percent drug release of PLM from PLM-loaded glycerosomes, CLs and PLM suspension in PBS of pH 4.5 (A) and 7.4 (B), respectively. … <here is a image b7b78c97ce373cb7-cbc869be191129bf> (A) Represents skin permeation studies in which flux of PLM suspension, CL gel and GM-loaded gel were compared and (B) The amount of drug retained in stratum corneum, epidermis and dermis from free PLM, CL gel, and GM-loaded gel, respectively. Data expressed as mean ± SD (n = 3) (* p ≤ 0.05, ** p ≤ 0.01). … <here is a image bbfb5b777b7e78fb-9ab75d69e699b887> +7 Confocal laser microscopy of (A-D) Rhodamine B solution and (E-H) Rhodamine B-loaded glycerosome, scale bar = 250 µm. … Figures - available via license: Creative Commons Attribution 4.0 International Available via license: CC BY 4.0 polymers Article Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy Shadab Md 1,2, , Nabil A. Alhakamy 1,2, Hibah M. Aldawsari 1,2, Mohammad Husain 3, Nazia Khan 4, Mohamed A. Alfaleh 1,5, Hani Z. Asfour 6, Yassine Riadi 7, Anwar L. Bilgrami 8and Md Habban Akhter 9,    Citation: Md, S.; Alhakamy, N.A.; Aldawsari, H.M.; Husain, M.; Khan, N.; Alfaleh, M.A.; Asfour, H.Z.; Riadi, Y.; Bilgrami, A.L.; Akhter, M.H. Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy. Polymers 2021 , 13, 923. https://doi.org/10.3390/ polym13060923 Academic Editor: Christian Wiraja Received: 27 February 2021 Accepted: 15 March 2021 Published: 17 March 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional afﬁl- iations. Copyright: © 2021 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/). 1 Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; [email protected] (N.A.A.); [email protected] (H.M.A.); [email protected] (M.A.A.) 2 Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia 3 Department of Biotechnology, Jamia Millia Islamia (Central University), New Delhi 110025, India; [email protected] 4 Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India; [email protected] 5 Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia 6 Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; [email protected] 7 Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; [email protected] 8 Department of Entomology, Rutgers University, New Brunswick, NJ 08901, USA; [email protected] 9 Faculty of Pharmacy, DIT University, Dehradun 248009, India * Correspondence: [email protected] (S.M.); [email protected] (M.H.A.) Abstract: Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo . However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efﬁcacy against skin cancer.The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities.The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of − 27 ± 5.12 mV and entrapment efﬁciency of 76.42 ± 9.98%.The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion ﬂuxes of CL gel and GM-loaded gel were 23.31 ± 6.0 and 79.43 ± 12.43 µ g/cm 2 /h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed signiﬁcantly ( p< 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension.Thus, ﬁndings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer. Keywords: Box–Behnken design; confocal microscopy; liposome; gel; plumbagin; skin cancer 1. Introduction Cancer as a life-threatening disease is increasing in prevalence worldwide. It caused an estimated 9.6 million deaths in 2018 with an anticipated mortality of 16.4 million by Polymers 2021 , 13 , 923. https://doi.org/10.3390/polym13060923https://www.mdpi.com/journal/polymers 1 ].Skin cancer is a complex and common malignancy, spreading worldwide with alarming mortality statistics.The common skin cancers are classiﬁed as non-melanoma and melanoma skin cancer. The non-melanoma skin cancer represented by basal cell carcinoma, and squamous cell carcinoma. The skin cancer eruption leads to deformation of skin cells and may result in systemic migration and metastases if not diagnosed promptly [ 2 ]. The pathogenesis of skin cancer is multi-factorial, but the prevalent risk factor is long exposure to carcinogenic and inﬂammatory agent. Indeed, the long exposure to UV radiation (UVA and UVB) also leads to the development of skin cancer due to impairment of genetic material, activating tumor promoter genes, inﬂammation and oxidative stress [ 3 – 5 ]. The current therapeutic approach involves the application of chemotherapy,radiotherapy and surgery. Skin provides a large surface area for the topical delivery of a vast number of ther- apeutic formulations.To overcome this barrier, several strategies have been developed. The strategies include polymeric, organic, and inorganic nanoparticles, liposomes, nio- somes, carbon tubes, micelles, and quantum dots including, ultrasound-assisted delivery, iontophoresis and electroporation [ 6 – 9 ]. The drug-loaded nanocarrier passively accumu- lated neighboring to tumor tissues due to poor lymphatic drainage and vacularization. It provides sustained and local drug delivery to the tumor microenvironment as desirable for treatment of cancer cells. For potential eradication and signiﬁcant apoptosis of tumor cells, long exposure of therapeutics in speciﬁc area of skin is preferably required [ 4 , 10 ]. Conventional liposomes as a vesicular drug delivery system lack the ability to provide sufﬁcient drug release and deeper penetration across the skin, thereby limiting their thera- peutic efﬁcacy.This major drawback led to research of novel vesicular carriers resulting in modiﬁcation of composition of liposomes to increase drug delivery and efﬁcacy [ 11]. In this context, some authors modiﬁed the composition of specially designed vesicular carriers to enhance the permeation and penetration into the deeper layers of skin. Thus, novel, modiﬁed vesicular carriers so-called ultradeformable or elastic liposomes such as transferosome, ethosomes, niosomes, and invasomes have been successfully evaluated and introduced in drug delivery applications [ 12]. Ethosomes, when administered, fuse with the cutaneous layer of skin due to the inter- action of ethanol with skin lipid. The permeation of drug is enhanced into the epidermal layer of skin owing to elastic deformation process [ 13 ]. However, the alcoholic interaction with lipid molecules of skin leads to decreased transition temperature in stratum corneum. It further leads to phase separation and crystal-phase transformation of solid and liquid lipids. Apart from these, the alcoholic content in ethosome causes skin irritation.On the contrary, GM causes no harm and is completely accepted after topical application [ 14 , 15 ]. Furthermore, >20% glycerol stabilizes the GM vesicle system.The high viscosity and hygroscopic nature improve ﬂexibility and ﬂuidity of the lipid bilayer. This nature allows GM to squeeze through topical barrier resulting in higher drug release and improved permeation and efﬁcacy when used topically or transdermally [ 16]. Engineered hydrogel mimics the extra cellular matrix of the epidermal tissue of skin due to better structural and mechanical strength. The nanosized hydrogel as polymeric 3D dimensional network in aqueous dispersion is formed by hydrophilic polymer chains that are chemically or physically cross connected [ 17 ].Gels are intelligently explored in active/passive cancer targeting due to their tailor surface, tunable size, ease of preparation and high encapsulation. It is prominently internalized in the target cells, prevents accumu- lation in the non-target tissues, minimize side effects and reduce therapeutic dose [ 18]. (5-hydroxy-2-methyl-1, 4-naphthoquinone) extracted from root of plant Plumbago zey- lanica having a number of potential therapeutic effects like anti-malarial, anti-microbial [ 19 ] and anti-inﬂammatory effects [ 10 , 20 ].In a number of cancers, including liver, breast, esoph- agus, colon, prostate, brain, and lung cancer, plumbagin have shown in vitro / in vivo anti-proliferative and chemo-preventive effects [ 10 , 20 , 21 ].The tumor inhibitory mecha- nism of plumbagin is based on several molecular signaling pathways which are crucial in cell proliferation, invasion, survival and metastasis. It suppresses these major signal trans- Polymers 2021 , 13 , 9233 of 19 duction pathways STAT3, mTOR/AKT, and NF- κ B which plays pivotal role in the growth, development and progress of cancer. Plumbagin retarded UV-ray induced carcinoma in squamous region of skin in mice [ 22 – 24 ]. The activation of STAT3 signal pathway is associ- ated 70% case of melanoma cancer [ 25 ]. Plumbagin also suppresses hyper-pigmentation of skin by inhibiting an α -melanocyte-stimulating hormone and inhibited tyrosinase activity in B16-F10 melanoma cells [ 26 ].Ti and coworkers also reported that plumbagin do not induce cytotoxicity in normal lens epithelial cells (B3) and normal human keratinocytes (HaCaT) cells at lower concentration (1–5 µ M) suggesting plumbagin is safe for skin application [ 26]. The term “glycerosome” was ﬁrst acquainted by Manca and associates for topical delivery of diclofenac. It is a versatile drug delivery carrier system which is a modiﬁcation of liposomes. They are small or large unilamellar or multilamellar lipid vesicles composed of phospholipids, water, and varying concentrations of glycerol (preferably 20 to 30% w / v). Additionally, they are nontoxic and accepted for topical application [ 16 , 27 ]. The lipid layer in GM is more ﬂexible and possess high ﬂuidity suitable for topical and transdermal drug delivery. The glycerol in these vesicles improves deformability index and thus increases skin permeation and penetration of therapeutics.Cholesterol enhances the stability of GM as well as maintains the lipid membrane integrity by causing barrier to the aqueous phase. When GM dispersed in aqueous phase, phospholipid rapidly arranges themselves as bi-layer vesicles [ 28, 29]. The present study involves the optimization and formulation of PLM-loaded GM using Box–Behnken Design.The independent variables were phospholipid, cholesterol, and glycerol concentration while the dependent variables were vesicle size, entrapment efﬁciency and drug permeation/ﬂux of PLM, respectively.The optimized formulation was characterized for its size, charge and morphology, texture, drug permeation/ﬂux, drug release, permeation, and retention.Additionally, characterizations based on cyto- toxicity were also evaluated. During the study it was speculated that incorporating PLM into GM could enhance drug loading and entrapment with improved aqueous solubility, thereby prolonging systemic availability in sustained-release manner; a combination of all these properties would consequently increase the therapeutic efﬁcacy of PLM and reduce untoward effects. 2. Materials and Methods 2.1. Materials PLM, glycerol, rhodamine B and cholesterol were purchased from Sigma-Aldrich (St. Louis, MO, USA). Phospholipid 90 G was procured by Phospholipid GmbH, Germany. The in vitro cell line B16-F10 cells were obtained from National Centre for Cell Science (NCCS) (Pune, India). Dulbecco’s modiﬁed Eagle’s medium (DMEM), antibiotics, Foetal Bovine Serum, and MTT reagent were purchased from Gibco (Gaithersburg, MD, USA). Analytical grade was used for HPLC water, solvents and chemicals used in the analysis. 2.2. Design and Development of Nanosystem Preparation of PLM-Loaded Nanosystems The PLM-loaded CLs were developed by thin ﬁlm hydration technique [ 27 , 30 ]. A weighted amount of PLM (5 mg/mL) was dissolved in chloroform containing ~1% of ethanol along with phospholipid (15.0 mg/mL) and cholesterol (4.0 mg/mL) in a round- bottom ﬂask and mechanically stirred at 40 ◦ C for 1 h.Under reduced pressure, the mixture was evaporated using a rotary evaporator (Buchi Labortechnik AG, New Castle, MA, USA), resulting formation of transparent lipid ﬁlm around the round bottom ﬂask, and traces of solvent were extracted overnight under vacuum.Further, the lipid ﬁlm was dried and hydrated at pH 7.4 for 1 h in phosphate buffer saline (PBS) for PLM-loaded CLs. Subsequently, the ﬁlm suspension was probe sonicated (Hielscher Ultrasonics, Berlin, Germany) for 1.5 min at 90% amplitude and ultracentrifuged at 7500 × g for 10 min at 4 ◦ C to get rid of unentrapped drug excess in solvent and lyophilized for future application. For Polymers 2021 , 13 , 9234 of 19 PLM-loaded GMs, the obtained lipid ﬁlms were hydrated with glycerol–water mixture (30% w / v glycerol) in two successions followed by mechanical agitation for 1 h at 40 ◦ C. Finally, the vesicle dispersions were sonicated for half cycle, i.e., 60 s with 3 s layoff period for every 5 s. The developed formulation centrifuged at 7500 × g for 10 min at 4 ◦ C to move out unentrapped drug excess, and lyophized for further use. 2.3. Box–Behnken Design Box–Behnken Design Expert (Design-Expert VR Software Version 10, State-Ease Inc., Minneapolis, MN, USA) software was used for optimization of PLM-loaded GMs and CLs [ 13 , 31 , 32 ].Based on the design expert software, 17 total runs were generated with 3-level and 3-factor experimental model for optimization of the GMs formulation.The independent and dependent variables are shown in Table 1. Among the various models like 2FI, cubic, linear, andquadratic, the best ﬁt model was analyzed according to ANOVA for statistical design. The signiﬁcant F-value,low PRESS value, lack of ﬁt ( p> 0.05) determined the best ﬁtting model. Table 1. Box–Behnken design experimental dependent and independent variables with levels (low, medium and high) employed in the fabrication of PLM-loaded GMs. Independent Variables Level Used Low ( −1)Medium (0)High (+1) X 1 : Phospholipid conc. (mg)1522.530 X 2 :Cholesterol(mg)1 2.5 4 X 3 :Glycerol10 20 30 Dependent variables Y 1 : Vesicles size (nm)Minimize Y 2 : Entrapment efﬁciency (%)Maximize Y 3 : Drug permeation/Flux ( µ g/cm 2 /h) Maximize 2.4. Characterization of Nanosystem Dispersion 2.4.1. Particle size, Zeta Potential and Morphological Analysis The Zetasizer-ZSP (Malvern Instruments, Worcestershire, UK) work on the dynamic light scattering was used to evaluate the vesicle size, polydispersity index (PDI) and zeta potential of optimized PLM-loaded CLs, PLM-loaded GMs and rhodamine-loaded glyc- erosome. The formulations were diluted with deionized water and analysed in triplicate ( n = 3). The actual size of PLM-loaded GM and CL and were measured by transmission electron microscopy (TEM, JEOL JEM1010, Tokyo, Japan).The drug-loaded GMs and CLs sample (1 mg/mL) was diluted in deionized water. The sample volume of 10 µ L was then applied on carbon-coated copper grid.The extra water over copper grid was bumped off and dried. It was then negatively stained with 1% phosphotungstic acid and tested at 10–100-fold enlargements operating at an accelerating voltage of 80 kV under the TEM. 2.4.2. Entrapment Efﬁciency and Drug Loading The entrapped amount of PLM in GMs, CLs and ﬂuorescent dye in glycerosome before lyophilization was estimated by high-speed centrifugation system at 7500 × g for 10 min at 4 ◦ C [ 33 , 34 ].After centrifugation, the clear aliquot was removed, ﬁltered and PLM content was analyzed by HPLC analysis.In brief, the separation of analyte using HPLC system (Shimadzu, Japan) was achieved on Agilent C 18 column of dimension 5 µ m, 250 mm ×4.5 mm i.d.The other components of HPLC system were quaternary LC-10 AVP pumps, SPD-10AVP HPLC UV-detector.PLM was estimated at a wavelength of 265 nm in binary mobile phase comprised of methanol and sodium dihydrogen phosphate phase (9:1 v / v ) using calibration curve [ 35 ]. The calibration curve was constructed in the Polymers 2021 , 13 , 9235 of 19 linearity range of 1–10 µ g/mL. The entrapment efﬁciency of the optimized formulation was calculated by using formula.The obtained numeric for the calibration curve was Y = 0.096 X + 0.021 with regression coefﬁcient value (R 2= 0.998). % Entrapment efﬁciency = Drug content (A −B)/Total amount of drug ×100 % Drug loading = Drug content (A −B)/Total weight of glycerosome ×100 where A is the total amount of drug and B is the amount of drug analyzed in the super natant using HPLC [ 34]. 2.4.3. In Vitro Drug Release and Kinetic Studies In vitro drug release study was performed in PBS with an acidic pH 4.5 and PBS pH 7.4.The acidic range is the pH of the skin and pH at the tumor site [ 36 ].The analysis was carried out using dialysis bag techniques. The weighed amount of PLM-loaded GMs, CLs and PLM suspension were placed on the dialysis membrane (MWCO, 12000 Da, Sigma-Aldrich, St.Louis,MO, USA) and immersed in a beaker ﬁlled with 100 mL of PBS solution. The beaker placed in a thermostatically controlled shaking water bath at a temperature 37 ± 0.5 ◦ C and release of the drug from formulation was examined at the mentioned pH values separately. At regular intervals of time (0, 1, 2, 4, 6, 8 & 12 h), 3 mL of PBS was withdrawn and was reinstated with the same amount of fresh PBS to maintain sink condition.The samples were analyzed using HPLC. In release kinetic study, drug release proﬁle from formulation was ﬁtted into zero order, ﬁrst order, Korsmeyer–Peppas, Higuchi, and Hixson-Crowell kinetic models and the best one was discriminated based on the correlation coefﬁcient (R 2~1) value. 2.5. Encapsulation of the Nanosystem into a Preformed Gels The gel base was prepared as the method described in our earlier work [ 13 ]. 1.0% w / w carbopol 934 was continuously stirred for 2 h using magnetic bead in 10 mL of distilled water separately for both PLM-loaded GMs and CLs.Accordingly, propylene glycol, methyl paraben, and triethanolamine were added with uninterrupted stirring until a transparent gel formed. The PLM-loaded GMs and CLs were injected continuously with stirring into the corresponding pre-formed gel base and labeled them as GM-loaded gel and CL gel. The gel texture analyzer was used to measure the texture of developed gels (TA.XT Plus Texture Analyzer, Stable Micro Systems Ltd., Surrey, UK). The spreadability of gels were measured by placing 500 mg of both CLs and GM gels separately in-between the glass slides upto a diameter of 2 cm. Thereafter, the 0.5 kg of weight was placed on the upper glass slide for the duration of 5 min and gels spreading were determined. 2.6. Skin Permeation Studies of GM-Loaded Gels The experiments were performed using fabricated Franz diffusion cell with an effective surface area of diffusion 0.750 cm 2 . The dorsal surface of rat skin was excised with fatty layers removed surgically, washed with alcohol and temporary stored at − 80 ◦ C. Before commencing the permeation study, the stored rat skin was equilibrated in PBS for 2 h at room temperature. The Franz diffusion cells decorated the skin specimenssecurely between donor and receptor compartments with the stratum corneum (SC) side facing the donor compartment.Prior to the study, receptor compartment was ﬁlled with 7.5 mL of PBS solution and stirred continuously with a small magnetic bead at 500 rpm, maintained at a temperature of 37 ± 0.5 ◦ C. GM-loaded gels, CL gels, PLM suspension (each 1 mL) were placed onto the surface of skin and atregular intervals of time, i.e., 0, 1, 2, 3, 4, 6, 8, 12, 14, 16, 20 and 24 h, 1 mL of solution was withdrawn from the receiving compartment and same amount was replaced with fresh solution. The drug content was analyzed by HPLC analysis. Polymers 2021 , 13 , 9236 of 19 2.7. Drug Retention Study of GM-Loaded Gels For drug retention study, the mounted skin was removed from Franz diffusion cell, washed, cleaned for adhered drug particles and further subjected to tape stripping tech- nique for removal of SC from dermal layer using scotch crystal tape [ 37 ]. Furthermore, the epidermis was separated from dermis by applying surgical sterile scalpel. The tissue protein extracting reagent (T-PER) solution in the ratio of tissue:T-PER (1:10 w / v) was applied for ameliorating extraction capacity from skin and probe sonicated for 5 min. Henceforth, the tap strips, dermis and epidermis were transferred into methanol, well sonicated to extract the drug and subsequently analyzed by HPLC. 2.8. Confocal Microscopy of Rhodamine B-Loaded GM To validate the drug release and distribution from GMs formulation into different layer of skin, confocal microscopy was performed which required entrapment of rhodamine B ﬂuorescent dye into glycerosome instead of drug.GMs were loaded with 0.02% w / v ﬂuorescent dye instead of drug in the preparation of GM by thin ﬁlm hydration technique and applied onto the skin. In this experiment, processed animal skin was mounted on the Franz diffusion cell of which stratum corneum of skin was facing to donor compartment. The rhodamine B-loaded GMs (1 mL) was transferred on the donor compartment and release of probe dye in the receptor was checked for the same duration as performed in skin permeation study. The receptor compartment was ﬁlled with 6 mL of PBS, pH 7.4 and the temperature of medium in the diffusion cell was asserted at 32 ± 0.5 ◦ C. Post completion of study, skin was gently wiped with deionized water (HPLC grade) and mounted on the glass slide with a drop of glycerin and observed under confocal microscope with excitation ( λ ex) and emission wavelength ( λ em) was set at 540 nm and 630 nm applying argon laser beam and 65 ×objective lens (EC-Plan Neoﬂuar 65 ×/01.40 Oil DICM27). The distribution and penetration depth of rhodamine B dye into the different layers of skin from GM compared with rhodamine B solution. The z-axis of confocal microscope optically analyzes the ﬂuorescent permeation through the skin layers. 2.9. Cytotoxicity Assessment The cell viability assessment of GM-loaded gels, CL gels, equivalent dose of PLM suspension, blank GMs and blank CLs were performed using MTT assay in murine melanoma cell lines (B16-F10). The mature cells were seeded in 96 well plates (cell density, 5000 cells/well) in 100 µ L of Dulbecco’s Modiﬁed Eagle’s Medium (DMEM) culture media to allow cell adherence. Subsequently, the cells were incubated in humidiﬁed chamber at 37 ◦ C with 100% relative humidity furnished with 5% CO 2 .At the end of 24 h, culture medium was discarded and treated with varying concentrations of 2.5, 5, 7.5, 10 µ M of PLM suspension, CL, and GM-loaded gels.Untreated cells were cultured in complete media and considered as control which is 100% cell viable. Accompanied by 24, 48 and 72 h of treatment, 250 µ L of MTT reagent was added into well plate and humidiﬁed for 2 h. Further, 150 µ L of DMSO was added to dissolve formazan crystals (indicating purple colour) as a means of counting viable cells. The absorbance of the specimen on plates was examined on Microplate Reader (BioTek Synergy HT) at 550 nm and % cell viability was determined [ 38]. 2.10. In Vitro Radical Scavenging Assay The DPPH (2, 2-diphenyl-1-picryl-hydrazyl) radical scavenging power of PLM in optimized GM-loaded gels was determined in accordance with the developed protocol [ 39 ]. The GM-loaded gels (100 µ L) and PLM suspension (100 µ L) were mixed with 3.9 mL of 0.025% DPPH solution with vigorous shaking, incubated for 30 min at 28 ◦ C and quantiﬁed by UV-spectrophotometry at 517 nm.The free radical scavenging power of optimized GM-loaded gels was estimated corresponding to reduced optical density with control and served as an indication of free radical scavenging power of the formulation. The reduced Polymers 2021 , 13 , 9237 of 19 DPPH concentration was measured by plotting calibration curve of Trolox as standard and the antioxidant power was assessed in TEAC as µg Trolox equivalent/g of sample. 2.11. Statistical Analysis The data analysis was performed using analysis of variance (ANOVA) followed by Tukey Kramer analysis for multiple comparison among the groups using GraphPad Prism 7.00 software. Student’s t -test was used as comparison between two groups.The level of signiﬁcance was considered when p< 0.05. 3. Results and Discussions 3.1. Optimization of PLM-Loaded GM by Statistical Design Response surface morphology is extensively employed for the optimization of nanofor- mulation.Among the various statistical experimental designs, Box–Behnken design is an efﬁcient optimization technique used frequently for comparison with conventional optimization procedures. It is largely explored owing to lesser number of experiments and evaluation in optimum time period.The independent variables and their impact on the response used herein for the optimization and development process were based on the signiﬁcant preliminary observation. It has been shown that glycerol 10% or lesser produced vesicles with reduced ﬂexibility, prompt deformation and may have lower skin penetration. As the concentration of glycerol increases in the formulation, the increasing elasticity of vesicles were observed and at 30% glycerol concentration the GM were more elastic and resisted deformation. At this concentration glycerol may act as edge activator at phospholipid bilayer [ 40 ]. The glycerol content in the GM formulation makes the preparation irritant free on topical application as caused by ethanol in ethosome lipid formulation. The cholesterol in GM formulation is added to ameliorate stability in lipid bilayer, for modifying the surface charge and prevention of vesicle aggregation [ 16 ].The experimental runs with % compositions of individual components and their responses are recorded in Table 2. Table 2. Formulations with composition of individual independent variables and observe responses of PLM-loaded glycerosome in Box–Behnken design. Formulation No Independent VariablesObserve Responses X 1 (mg) X 2 (% w/ v ) X 3 (% w/ v ) Y 1 (nm) Y 2 (%) Y 3 FL122.502.5020.00160.00 ± 16.3074.00 ± 3.2069.00 ±6.80 FL222.502.5020.00167.00 ± 17.1073.00 ± 5.3073.00 ±6.10 FL315.002.5010.0096.00 ± 9.4063.00 ± 7.5044.00 ±4.30 FL422.502.5020.00163.00 ± 15.2077.00 ± 8.6072.00 ±6.50 FL530.002.5030.00190.00 ± 18.3084.00 ± 9.1084.00 ±9.90 FL630.004.0020.00200.00 ± 18.4082.00 ± 8.6080.00 ±8.60 FL715.002.5030.0088.00 ± 6.6068.00 ± 7.4074.00 ±5.80 FL830.002.5010.00182.00 ± 14.4065.00 ± 6.6050.00 ±4.60 FL922.501.0010.00150.00 ± 12.7061.00 ± 6.9047.00 ±4.60 FL1022.501.0030.00152.00 ± 10.5071.00 ± 7.4077.00 ±8.60 FL1122.504.0010.00172.00 ± 16.8059.00 ± 4.2054.00 ±5.90 FL1230.001.0020.00180.00 ± 15.0078.00 ± 9.5076.00 ±9.50 FL1322.504.0030.00176.00 ± 16.8080.00 ± 7.8085.00 ±9.90 FL1415.001.0020.0082.23 ± 4.7067.00 ± 7.6067.00 ±6.70 FL1515.004.0020.00115.00 ± 8.5073.00 ± 6.8068.00 ±7.90 FL1622.502.5020.00157.00 ± 10.8078.00 ± 7.3078.00 ±8.80 FL1722.502.5020.00161.00 ± 13.5075.30 ± 9.2072.00 ±8.30 X 1 : Phospholipid (mg); X 2 : Cholesterol (% w / v ); X 3 : Glycerol (% w / v ); Y 1 : Vesicles size (nm); Y 2 : Entrapment efﬁciency (%); Y 3: Drug diffusion Flux ( µ g/cm 2/h). Polymers 2021 , 13 , 9238 of 19 The dependent variables were subjected to numerical models ﬁt analysis, for their individual, interaction and quadratic effects.The different models, i.e., cubic, linear, 2FI and quadratic models, the best ﬁtted model was found to be quadratic model. The optimum value of different responses vesicle size, entrapment efﬁciency, and ﬂux were recorded on the criteria of desirability.The regression analysis of responses, vesicle size (Y 1 ), entrapment efﬁciency (Y 2) and ﬂux (Y 3) for ﬁtting to quadratic model are expressed in Table 3. The 3-D response surface curve showing relative effects of independent variables on responses Y 1 , Y 2 and Y 3 are established in Figure 1 A–C. The statistical plot expressing the correlation between actual vs. predicted value for the responses and their residual plot are indicated in Figure 2 A–F. Figure 1. Response surface morphological plots indicating the comparative effects of independent variables, i.e., Phospho- lipid conc. (mg); Cholesterol conc.(mg); and Glycerol conc. (% w / v) on ( A ) Vesicles size, ( B ) % Entrapment efﬁciency and ( C ) Flux of PLM. Polymers 2021 , 13 , 9239 of 19 Figure 2. The linear correlation plots ( A , C , E ) between predicted vs.observed values and cor- responding residual plots ( B , D , F ) for responses vesicle size, entrapment efﬁciency, and ﬂux of plumbagin (PLM). Table 3. Regression analysis summary for various responses Y 1, Y 2, and Y 3. Response Surface Quadratic ModelR-SquaredAdj R-SquaredPred R-SquaredAdeq PrecisionPRESS% CVMeanSD Response 1 (y 1 )0.99660.99230.985148.695302.25 2.05 152.47 3.13 Response 2 (y 2 )0.97190.93580.829417.237150.612.60 72.25 1.88 Response 3 (y 3 )0.97670.94670.868918.105334.874.24 68.82 2.92 Vesicle size ( Y 1 ) = 161.60 + 46.25 × X 1 +12.25 × X 2 + 0.75 ×X 3 − 3.00 × X 1 ×X 2 + 4.00 ×X 1 × X 3 + 0.50 ×X 2 × X 3 −20.30 × X 1 2 + 3.20 × X 2 2 − 2.30 × X 3 2 EE ( Y 2 ) = 75.46 + 4.75 ×X 1 + 2.13 ×X 2 + 6.88 × X 3 −0.50 × X 1 ×X 2 + 3.50 × X 1 ×X 3 + 2.75 ×X 2 ×X 3 + 0.89 ×X 1 2 − 1.36 × X 2 2 − 6.35 ×X 3 2 Flux = 72.80 + 4.63 × X 1 + 2.50 ×X 2 + 15.63 × X 3 +0.75 × X 1 × X 2 +1.00 × X 1 × X 3 + 0.25 × X 2 ×X 3 − 1.40 ×X 1 2 +1.35 × X 2 2 − 8.40 × X 3 2 3.1.1. Impact of Independent Variables on Vesicle Size (Y 1) The impact of phospholipid concentration, cholesterol and glycerol concentration on vesicle size could be explicated by quadratic polynomial equation as shown in Table 3 . It was worth noting that the Model F-value of 360.55 implicated that the model was signiﬁcant. Polymers 2021 , 13 , 92310 of 19 The “Lack of Fit F-value” of 0.94 implies it was insigniﬁcant.The “Pred R 2 ” of 0.99 is in reasonable agreement with the “Adj R2” of 0.99 as shown in Table 3. The phospholipid concentration had signiﬁcant positive impact on vesicles size of GMs (p < 0.05).The vesicles size analysis of developed formulation revealed the size ranges from 82.23 ± 4.78 nm to 200 ± 18.40 nm.At low concentrations, the observed vesicle sizes were 82.23 ± 4.78 nm and upon increasing the phospholid concentration to 22.5 mg, the maximum increase in vesicle size was 176 ± 16.80 nm (FL13).Further increase in phospholipid concentration to 30 mg led to maximum increase in vesicle size to 200.00 ± 18.40 nm (FL6), as shown in Table 2. The result was observed similar of prior reported method [ 13]. The cholesterol concentration had positive impact on vesicles size of GMs.The increasing cholesterol concentration from 1.5 to 4.0% w / vled to an increase in vesicle size. Although, at same concentration of cholesterol, substantial decrease in vesicle size was observed as in FL14 formulation which could be due to combined effect of phospholipid and glycerol concentrations Table 2. The glycerol concentration had less positive impact on the vesicle size.The formulation FL8 had vesicle size of 182 ± 14.40 nm at 10% w / v. Likewise, formulation FL9 and FL11 of same glycerol concentration (10% w / v) had vesicle size of 150 ± 12.70 and 172 ± 16.80 nm , respectively.In spite of the aforementioned result, small vesicle size of 96 ± 9.40 nm was observed in formulation FL3 at 10% w / vof glycerol concentration which could be due to combined impact of phospholipid and cholesterol concentrations.At 20% w / v of glycerol concentration FL1, FL2, FL4 and FL17 had vesicle size of 160 ± 16.00 nm, 167 ± 17.10 nm , 163 ±	https://www.researchgate.net/publication/350141311_Plumbagin-Loaded_Glycerosome_Gel_as_Topical_Delivery_System_for_Skin_Cancer_Therapy
Bond Characteristics of CFRP Rod Panels Adhered to Concrete under Bending Effects \| Request PDF Request PDF \| Bond Characteristics of CFRP Rod Panels Adhered to Concrete under Bending Effects \| Carbon fiber–reinforced polymer (CFRP) rod panels (CRPs) comprising small-diameter rods at a spacing larger than rod diameter are emerging as an... \| Find, read and cite all the research you need on ResearchGate Bond Characteristics of CFRP Rod Panels Adhered to Concrete under Bending Effects Journal of Composites for Construction23(1) DOI: 10.1061/(ASCE)CC.1943-5614.0000909 Abstract Carbon fiber–reinforced polymer (CFRP) rod panels (CRPs) comprising small-diameter rods at a spacing larger than rod diameter are emerging as an effective adhesively bonded system for retrofit applications. They offer the advantage of a better bond than equivalent CFRP conventional plates due to the increased surface area of the rods. This study aims at characterizing the flexural bond properties of CRPs using the notched concrete beam test specified by the current standard. CRPs with 2-mm rod diameter were used. Rod spacing-to-diameter ratio (S=D) was varied from 3 to 6. CRP width-to-beam width ratio bf=bc was varied from 0.17 to 0.5. The bond length was varied from 25 to 200 mm on one side of the notch. While debonding failure consistently governed, a development length of 80 mm was found, beyond which insignificant change in ultimate load was noticed. The average bond strength was determined to be 5.1 MPa. It was found that the stress in the individual rods at ultimate load increased from 33% to 53% of their ultimate tensile strength as the S=D ratio increased from 3 to 6. A bilinear bond-slip relation was also established for this system. ... 1(d), 2(a)); however, the rods are fully embedded in adhesive, which also resembles NSM reinforcement. Several advantages have been reported for CRPs compared with EBR including: increased bond resistance due to full embedment and using small circular rods, hence increasing FRP area in contact with adhesive [13]; ease of application by using short-length panels (typically 1.22 m) connected by a finger joint, instead of continuous (full-length) plates [2]; possible multi-stage application by stopping work at any panel, leaving the finger joint area uncovered with adhesive, and resuming work at another time, which minimizes disruption of structural function, especially in highway bridge rehabilitation [12][13] [14] . ... ... Several studies were performed on CRP, and confirmed its effectiveness. In Jawdhari et al. [13, 14] , bond properties of CRPs were determined through direct shear tests and notched beam flexure tests, respectively. Peiris and Harik [12] established the development length for CRPs with steel substrate. ... ... The bond tests, comprising 44 specimens, were carried out using the small beam test (Fig. 2). Multiple research studies [14, [27][28] and engineering standards, such as ASTM [29] and ACI 440 [30], recommend the small beam test because of its simplicity, and ability to facilitate statistical validation and results' comparison and interpretation [27]. The beam has a cross-section of 102x102 mm and a length of 356 mm, and features a 3 mmwide and 51 mm-deep (half-depth) mid-span notch, which was created in this study by a saw cut. ... Bond between CFRP rod panels and concrete using cementitious mortar Nov 2019 CONSTR BUILD MATER <here is a image f4f685ea7051bcb8-0cae7208c664fa6e> Akram Jawdhari <here is a image ebf7edc1703bad55-6423d3910b04cada> Amir Fam <here is a image b3be0d545641ccd5-e79b16a026cd8954> Issam E. Harik Carbon-FRP rod panels (CRPs), generated from small diameter rods mounted on a fiberglass mesh, are becoming a viable retrofit option. The gaps between rods enable full encapsulation by adhesive, thereby enhancing bond to existing concrete members, compared to flat plates. Existing studies focused on epoxy adhesive. In this study, 44 notched-beam bond tests, were carried out to investigate the effectiveness of cementitious mortar in bonding CRP to concrete and to examine the effects of a number of material and geometric parameters, comparing CRP to flat plates and mortar to epoxy. Results showed that the mortar was able to achieve a comparable ultimate load (Pult.), 86% that of epoxy, and a much more ductile failure by gradual rod slippage from the mortar. Compared to an equivalent CFRP plate, Pult. of CRP was 1.17 and 7 times, respectively, for epoxy and cementitious mortar. Brittle debonding failure dominated in CRP with epoxy and in CFRP plate with both epoxy and mortar. Pult was found to vary linearly with the bond length of CRP, up to a development length of 125 mm. A value of 460 kN/m can be assumed for bond strength. Rod axial stress (rf) increased by 42%, when CRP panel-to-concrete width (bf /bc) ratio increased from 0.25 to 0.5; decreased linearly by 13% when rod spacing-to-diameter (S/D) ratio increased from 3 to 8; decreased by 76% when rod diameter D increased from 2 to 4 mm. Sand coating the smooth rod resulted in a 45% increase in rf of the 4 mm rods but not the 2 mm rods, although failure shifted from gradual slippage to sudden debonding. ... Fiber-reinforced polymers (FRP) are widely used for the strengthening of reinforced concrete (RC) members due to their various advantages, where they have superb mechanical and physical properties [1][2][3]. In practice, RC beams can be strengthened by using two wellknown systems such as near-surface mounted (NSM) FRP or externally bonded (EB) FRP [4, 5] . These FRP reinforcement in form of bars or plates are bonded to concrete by using special FRP epoxy resin systems [6][7][8][9]. ... Ultimate behavior of RC beams strengthened in flexure using FRP material ENG STRUCT <here is a image 3469a5994b3521c8-f4322a55f87dfe48> Bouzid Haytham <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Rabia Benferhat <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hassaine Daouadji Tahar The present paper investigates the ultimate flexural behavior of strengthened reinforced concrete (RC) beams with Externally Bonded (EB) or Near-Surface Mounted (NSM) Fiber-Reinforced Polymers (FRP) reinforcement. For the purpose of predicting the ultimate loads and deflections of strengthened RC beams, numerical and analytical models were developed. Both models were developed for strengthened RC beams that fail in flexure by FRP rupture. First, an analytical model was developed based on the moment-area theorem and the equilibrium of internal forces. Second, based on the finite element (FE) method, an 3D numerical model was developed using Cast3M software, version 21. The reliability of the numerical model was tested against the analytical and experimental results collected from previous research. The selected RC beams were made with Normal-Strength (NS) and High-Strength Concrete (HSC). The comparison showed that the numerical model has an excellent performance in predicting the load-deflection response until failure. Moreover, the beam damage obtained from the numerical modeling agreed with the experimental results. Finally, a numerical comparative study between EB and NSM systems was conducted. The comparison showed the effectiveness of the NSM system in terms of strength and ductility. Further, the analysis of stress and strain showed that NSM system reduces the stresses and strains in concrete and steel reinforcement and prevents cracks propagation. ... 24 Collectively, a number of parameters can affect the failure mode of FRP-strengthened RC beams, such as concrete strength, FRP bond length, FRP axial stiffness, FRP-toconcrete width ratio, resin bond strength and bond stiffness. [25] [26] [27][28][29][30] Numerically, the bond behaviour between the FRP and the concrete substrate can be simulated by two methods. In the first, the interface between the FRP region and the concrete substrate is modelled as a perfect bond (no slip is allowed between the concrete region and the composite materials). ... Development of a local bond shear stress-slip model of RC beams externally strengthened with FRP materials <here is a image 5582e31fe2629a7e-2012adb4d84ec0fc> Farid Bouziadi <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Abdelkader Haddi <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Touhami Tahenni <here is a image e1fa5aa0b64de5e0-33089145e9dbcdf1> Sofiane Amziane This paper presents an analysis of the numerical investigation of RC beams, strengthened with CFRP and tested in flexure, using the ANSYS © numerical analysis code. In the first part of this paper, finite-element models of RC beams (control and CFRP-strengthened), subjected to four-point bending, are developed based on experimental tests as reported in the literature. Then, a 3D nonlinear finite-element analysis (NLFEAs) with perfect bonding, along with 12 cohesive zone material (CZM) models proposed by researchers in literature, are explored to simulate the behaviour of CFRP-strengthened RC beams. In the second part of this work, the compressive strength of the concrete and the elastic modulus of the epoxy resin are examined to study their effect on the same CFRP-strengthened RC beam. On the basis of those two studies, a bilinear CZM model is modified to predict the behaviour of RC beams strengthened with FRP materials, and interfacial shear debonding phenomena. The modified CZM model is verified against a database of experimental results that includes 23 RC beams, strengthened with FRP tested in flexure, with different concrete compressive strength, FRP modulus of elasticity and resin elastic modulus. The experimental and predicted ultimate loads are compared to verify the accuracy of the modified CZM model. The level of fitness between the modified CZM model and experimental results is elaborated with statistical metrics such as integral of the absolute error (IAE), root mean square error (RMSE) and coefficient of determination (R ² ). The results show good agreement between the experimental and predicted ultimate loads. ... Based on the concept of strip panels, IM CFRP rod panels have been developed and deployed for strengthening reinforced concrete (RC) and prestressed concrete (PC) bridge beams Harik 2018b, c, 2019). Several studies (Jawdhari et al. 2018b;Jawdhari and Harik 2018) evaluated the experimental and numerical behavior of RC beams strengthened with IM CFRP rod panels, while others (Jawdhari et al. 2017(Jawdhari et al. , 2018a (Jawdhari et al. , 2019 examined the panels' bond strength. ... Evaluation of Spliced UHM CFRP Strip Panels for Strengthening Steel Beams J COMPOS CONSTR <here is a image f4f685ea7051bcb8-0cae7208c664fa6e> Akram Jawdhari <here is a image d2f75e6ba90fd300-7816340ecc47bcd4> Abheetha Peiris <here is a image ebf7edc1703bad55-6423d3910b04cada> Amir Fam <here is a image b3be0d545641ccd5-e79b16a026cd8954> Issam E. Harik ... Numerous FE models in the literature on concrete structures were strengthened by TRMs/ NSM FRP rod panels (Awani et al., 2016;Azadeh and Mohannad, 2022;Elsanadedy et al., 2013; Jawdhari et al., 2019; Jawdhari and Fam, 2020;Kadhim et al., 2021). Based on available literature (Koutas and Bournas, 2017), reinforced concrete slabs have been modelled using the finite element method (Kadhim et al., 2022). ... Finite element modelling of reinforced concrete one-way slabs strengthened using basalt textile reinforced mortars Dec 2022 <here is a image 0c8e7684f6774c34-6957ebb7c325fcf4> Naveen Revanna <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Charles K.S. Moy Purpose This paper employs a textile reinforcement strain comparison to study the response of Textile Reinforced Mortars (TRM) strengthened reinforced concrete one-way slab members in flexure using the finite element method. Basalt TRM (BTRM) is a relatively new composite in structural strengthening applications. Experimental data on BTRMs are limited in the literature and numerical analyses can help further the understanding of this composite. With this notion, Abaqus finite element software is utilised to create a numerical method to capture the mechanical response of strengthened slab members instead of time-consuming laboratory experiments. Design/methodology/approach A numerical method is developed and validated using existing experimental data set on one-way slabs strengthened using Basalt TRMs from the literature. An explicit solver is utilised to analyse the finite element model created using calibrated Concrete Damage Plasticity (CDP) parameters according to the experimental requirements. The generated model is applied to extract load, deflection and rebar strains sustained by strengthened reinforced concrete slabs as observed from the experimental reference chosen. The applicability of the developed model was studied beyond parametric studies by comparing the generated finite element tensile strain by the textile fibre with available formulae. Findings CDP calibration done has shown its adaptability. The predicted results in the form of load versus deflection, tensile and compressive damage patterns from the numerical analysis showed good agreement with the experimental data. A parametric study on various concrete strength, textile spacing and TRM bond length obtained shows TRM’s advantages and its favourability for external strengthening applications. A set of five formulae considered to predict the experimental strain showed varied accuracy. Originality/value The developed numerical model considers strain sustained by the textile fibre to make results more robust and reliable. The obtained strain from the numerical study showed good agreement with the experiment results. ... CRPs with 2-mm rod diameters with different spacing to diameter ratios with different boding lengths were used in their work to find the optimum debonding length and the average bond stress. Furthermore, a bilinear bond-slip relation was also established for the CRPs [50] . In 2020, in an experimental work, Jawdhari et al. investigated the effectiveness of cementitious mortar for bonding Carbon-FRP rod panels (CRP) to concrete by performing 44 notched-beam bond tests. ... FRP Sheet/jacket System as an Alternative Method for Splicing Prestressed-precast Concrete Piles Jun 2022 <here is a image af57dd1b17b5044e-74b6d298921d25b2> Seyed Saman Khedmatgozar Dolati <here is a image eea6545081fb1e88-aef3be3212d8ee00> Armin Mehrabi Prestressed precast concrete pile (PPCP) is the most common type of pile currently practiced for establishing bridge foundations because it provides for a rapid, economical, and durable method of construction. For various reasons, including unpredictable soil conditions and shipping as well as transportation limitations, it is preferable or imperative to cast PPCPs with shorter lengths and connect them at the site to achieve longer lengths. Accordingly, various splice systems have been implemented over the decades for connecting PPCPs. However, current splice methods have shortcomings that have limited their applications. This study briefly reviews the limitations of the existing pile splices and introduces a novel method for splicing prestressed precast concrete piles. The proposed splice system utilizes Fiber Reinforced Polymer (FRP) sheets to provide the required strength. The performance of the proposed splice system in developing the required capacity has been investigated according to both ACI 318–14 and FDOT Standard Design Specifications. To demonstrate the effectiveness and constructability of the proposed system, the proposed splice has been designed for an 18-inch (457 mm) square PPCP according to a procedure consistent with ACI 440.2R-17. The results show that this system is effective and can meet all the requirements set forward by the design specifications. The major contribution of this study is the development of a new splicing method that is applicable to both unforeseen and preplanned situations, and offers an economical, corrosion-resistant, and rapid alternative advantageous to other available splicing methods. The new splice is especially valuable for unforeseen conditions where other splice systems fail to provide the required capacity. As important as its novelty, the proposed splice can be designed according to well-established and validated design codes making the need for experimental verification trivial. ... Longer exposure durations resulted in reductions in the bond strength with the highest reduction belonging to the lowest temperature of conditioning. In an attempt to investigate the bond behavior of CRP's in concrete, Jawdhari et al. [30] tested notched beam specimens with different ratios of bar spacing to bar diameter. The bonding length of CRP to concrete was kept constant in one half of the notched beam while this length was changed in the other half to determine the embedment length. ... Estimation of the FRP-Concrete Bond Strength with Code Formulations and Machine Learning Algorithms Apr 2021 COMPOS STRUCT <here is a image 36c3f270f9b4e298-98a8ed679475b7eb> Boğaçhan Başaran <here is a image b6f9965217c262a0-fe765e3477461757> Ilker Kalkan <here is a image 5926153797a41681-f46ee8b0e4dd1b36> Erhan Bergil <here is a image 5859dbb848cdf047-b7b9283aac72af9d> Erdal Erdal The present study pertains to the bond strength and development length of FRP bars embedded in concrete. The experimental results in the literature were compared to the analytical estimates from the equations of different international codes and machine learning techniques, i.e. Gaussian Process Regression, Artificial Neural Networks, Support Vector Machines Regression, Regression Tree and Multiple Linear Regression. The comparison was realized for four different experimental methods, i.e. hinged beam, beam-end, spliced beam and pull-out, to specify the analytical equation or method with the highest agreement with the test results for each method. GPR method was found to provide the highest accuracy with a mean value of 0.95 and a standard deviation of 0.14 for the predicted-to-experimental bond strength ratio. Based on coefficient of determination, Root Mean Square Error and Mean Absolute Percentage Error statistical criteria, GRP method was followed by ANN, MLR and SVMR based on the agreement with the experimental results. Among the code equations, the bond strength equation of the ACI 440.1R-15 code resulted in highest agreement with experimental results, but the predicted values remained on the over-conservative side. The other code formulations were established to yield to estimates, nearly constant for varying test parameters and highly conservative. RC beams strengthened in shear with FRP-Reinforced UHPC overlay: An experimental and numerical study May 2023 <here is a image 5bbba6c3613f153f-294d6d57cc206915> Wissam Nadir <here is a image 083e690fb49c139b-e1d0373389f78f7a> Majid M. A. Kadhim <here is a image f4f685ea7051bcb8-0cae7208c664fa6e> Akram Jawdhari <here is a image 17ec71768eb02c4c-d5f633a321a3a230> Ali Majdi In this study, a hybrid strengthening technique consisting of ultra-high performance concrete (UHPC) overlay reinforced by fiber reinforced polymer (FRP) bars is proposed to strengthen reinforced concrete (RC) beams in shear. Eleven beams, five of which are physical samples tested under static load, and the other six are virtual ones derived from a robust finite element (FE) analysis, are used to assess the effectiveness of this retrofitting technique. Several parameters are examined, namely overlay thickness, overlay configuration (continuous vs. discontinuous), FRP reinforcement ratio in the overlay, and type of FRP rebar (Glass-FRP vs. Carbon-FRP). Results showed that the system was very effective in increasing the beam capacity (Pu) and altering the failure mode from shear to flexure. Increasing the overlay thickness (toverlay) from 0 to 30 mm for plain and FRP-reinforced overlays results in a significant increase in Pu of 76–117%, compared to the control beam. Using discontinuous UHPC strips, although does not alter the shear failure, results in 89% increase in Pu. Reinforcing the overlay with GFRP and CFRP bars results in reducing the overlay thickness needed to shift the failure mode from shear to flexure. The energy absorption index, which is a measure of ductility, of the strengthened specimens was 4.0 to 6.9 times that of the control beam. FRP bars resulted in 11–25% increase in energy absorption compared to plain overlays, with GFRP showing more ductility than CFRP. An analytical procedure is also included and used to predict Pu from modifying existing code equations to include the contribution of UHPC overlay to shear. Systematic calibration procedure for CFRP sheets and rods strengthened RC T-beams by using RBSM Aug 2022 MECH ADV MATER STRUC <here is a image f5bdceddbf1f8d3e-862648309dd6a256> Joko Purnomo Aylie Han Rito Yamakawa <here is a image 2610e59becd63060-d9716c546c6561c4> Buntara Sthenly Gan In this study, a nonlinear 2D rigid body spring model (RBSM) was developed to verify the experimental works of Carbon Fiber Reinforced Polymer (CFRP) sheets and rods strengthened reinforced concrete (RC) T-shape beam (RC T-beam) section under a combination of bending and shearing loads. Modified Mohr–Coulomb criteria were adopted for modeling the plastic damage of concrete material. The orthotropic smeared layers representing the steel and CFRP materials were laminated on the concrete surface to model the reinforcing steel bars, stirrup steel, and CFRP sheets and rods. A mechanical behavior-based approach to fit the experimental results was discussed using the numerical results at each calibration stage. This study shows how the gradient of compressive and ultimate tensile strength of concrete affects the initial flexure behavior of the load-displacement curve of an RC T-beam. In contrast with finite element modeling, the RBSM can exhibit the crack propagation processes of element separation during the simulation. The calibrations showed the agreement of the models used in predicting the flexural behavior, ultimate load, and strengthening effects of the CFRP sheets and rods to the RC T-beam under bending loads. A systematic calibration procedure combined with the recommended use of energy-based criteria to evaluate the results of calibrated load-displacement curve was proposed. Analytical and Parametric Studies on Flexural Performance of Reinforced Concrete Beams Strengthened by Fiber-Reinforced Geopolymer Composites May 2022 ACI STRUCT J <here is a image 056ed2ac918fda16-c022b25573c5255e> Ernesto Guades <here is a image 4aae2c4ddf786c73-ecd27fe7a0478d63> Henrik Stang Analysis and design of two-way slabs strengthened in flexure with FRCM Apr 2022 ENG STRUCT <here is a image 083e690fb49c139b-e1d0373389f78f7a> Majid M. A. Kadhim <here is a image f4f685ea7051bcb8-0cae7208c664fa6e> Akram Jawdhari <here is a image dbbd4d18246e6ec2-92b98d327c373459> Ali Hadi Adheem <here is a image ebf7edc1703bad55-6423d3910b04cada> Amir Fam Fabric reinforced cementitious mortar (FRCM), an emerging sustainable retrofit technique, has seen very limited research and applications on two-way reinforced concrete (RC) slabs. In this study, a three-dimensional finite element (FE) model is developed for FRCM-strengthened slabs, incorporating concrete nonlinearity, cracking, debonding and rupture. After validation with experimental results from literature, an extensive parametric study was performed, examining the effects of FRCM coverage area as a ratio of the width of FRCM reinforcement (wFRCM)-to-span (S); the use of discontinuous FRCM strips; internal steel reinforcement ratio (ρs); compressive strength of concrete (f ′c); and aspect ratio of slab (α). The study showed that ultimate strength (Pu) increases sharply by 84% as (wFRCM/S) increased from zero to 0.25, then only by 19% from (wFRCM/S) of 0.25 to 1.0. In general, Pu increased with f′c and ρs but was not affected by α. Two existing models were evaluated and found to be unconservative or insensitive to key parameters. A regression analysis was performed on data from the parametric study, resulting in two expressions for the FRCM effective strain (εfe) and much better predictions for Pu. Factors influencing strength loss of glass‐fiber‐reinforced composite bars in highly alkaline environment of concrete Article Jan 2022 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Roz-Ud-Din Nassar Gustavo D. Dominguez <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Parviz Soroushian Nastran Abdol Steel corrosion is a significant problem of concrete‐based infrastructure, and it increases the repair costs of the damage to structures. Glass‐fiber‐reinforced polymer (GFRP) composite bars are corrosion‐proof and exhibit relatively higher strength than ordinary steel reinforcement. However, GFRP bars degrade when exposed to the highly alkaline environment of concrete over extended periods. This study focuses on the effect of the high alkalinity of concrete on the tensile strengths of several types of GFRP bars. Different accelerated aging techniques were employed to evaluate the effects of GFRP characteristics (fiber volume fraction, matrix composition, bar diameter, and presence of protective coating) on the alkali resistance. The test results indicated that the alkali attack significantly decreased the tensile strength of GFRP, increasing with age. The alkali resistance of the GFRP bars increased up to a fiber volume fraction of 50% but decreased when the fiber volume fraction increased to 60% and above. The effects of protective coating on alkali resistance were generally positive but not consistent, and the effects of the matrix type and bar diameter on the alkali resistance of GFRP bars were insignificant. Accelerated aging did not change the bond strength but altered the failure mechanism associated with the bond failure of the specimens. A nonlinear analytical model for predicting bond behavior of FRP-to-concrete/steel substrate joints subjected to temperature variations Article Feb 2022 CONSTR BUILD MATER <here is a image 8a260e1128d080c5-4c0965d804b5845f> Kun Dong <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jianwen Hao Peng Li Caiqun Zhong The effective interfacial stress transfer mechanism plays an important role in the mechanical performance of externally bonded fiber reinforced polymer (FRP) strengthened structures. Therefore, a profound understanding of the effect of temperature variation on the bond behavior of FRP-to-concrete/steel joints is helpful to improve the engineering specification of FRP strengthening technology. This paper presented a new analytical approach aimed at predicting the bond and debonding behavior of FRP-to-concrete/steel bonded joints under thermal loading. The proposed analytical solutions were derived based on an exponential temperature-dependent bond-slip model, and these solutions had a rather good prediction accuracy compared with the experimental and finite element numerical results. Some discussions about the bond behavior under temperature variations were carried out with an example. Results of this study showed that with the increase of bond length, there existed an upper limit value for the failure temperature variation, as well as for the maximum FRP stress. Temperature-dependent bond-slip relation was shown to have a great effect on the distribution of FRP stress and interfacial bond stress, especially on the temperature variation–free end slip response. Experimental verification of 2- and 3-D numerical models for bond-slip behavior of CFRP-concrete Article Full-text available Mar 2021 CONSTR BUILD MATER <here is a image 411d5c20eb0a03e8-5ba4ec92847d6a5c> Faisal Mukhtar <here is a image 0fd24df895d3a5f3-fe557cfc39c83532> Mohammed Shehadah This paper studies the bond performance between fiber-reinforced polymer (FRP) and concrete using two variations of the double shear lap test setups. Experimental tests were conducted followed by a series of finite element simulations using cohesive zone model. The experiment utilized an improved double-pull shear setup with the tests conducted on specimens of varying FRP-concrete bond lengths. The numerical simulations were carried out for the improved as well as the traditional setups using two converged meshes with both 2- and 3-D spatial idealizations to study their relative performance. The results are discussed in light of the damage mechanism, load-displacement, strain and stress distribution, bond-slip behavior, and fracture energy. The tested specimens show no effect of bond length variation on the FRP-concrete interfacial strength so long as the bond length exceeds the effective bond length – Only the case of bond length lower than the effective bond length shows otherwise. The study also succeeds in validating the 2- and 3-D numerical simulations using the experiments in both the two cases of spatial idealizations and the two types of test setups in terms of strain and stress distributions, bond-slip curve, and fracture energy. However, while the 3-D models succeed in capturing the failure load accurately, the 2-D models fail to do so. Evidence of similar performance between the improved double shear test and traditional double shear test setups reaffirms the fact that the former could be used to replace the latter. Finite Element Modeling for Debonding of FRP-to-Concrete Interfaces Subjected to Mixed-Mode Loading Article Full-text available This paper presents finite element (FE) modeling of the debonding behavior of fiber reinforced polymer (FRP)-to-concrete interfaces subject to mixed-mode loading, which is realized through a peeling test of FRP composites externally bonded onto a concrete substrate. A cohesive zone model (CZM) is implemented into the FE model to represent the behavior of the FRP-to-concrete interface. Two element schemes (orthotropic plane stress element and beam element) were employed to simulate the behavior of FRP composite plate in the peeling test. The orthotropic plane stress element scheme, bearing a clear physical background and with an easy definition of the material property parameters following the composite mechanics, is found to be superior to the beam element scheme, and thus is utilized to conduct parametric studies. The influences of the peeling angle, the interfacial parameters (i.e., the configuration of the cohesive zone models, the interfacial damage initiation law (DIL), the interfacial damage evolution law (DEL), the coupling of mode-I and mode-II components), on the mixed-mode failure of the FRP-concrete-interface are carefully investigated. The results showed that the mode I component plays a critical role in the debonding failure of FRP-to-concrete interfaces even when the peeling angle is very small. The failure of FRP-to-concrete interface transits promptly from a mode II-dominated one to a mode I-dominated one when the peeling angle increases to a relatively small value (e.g., 4 degree) and subsequently the peeling force (i.e., the debonding strength of FRP) decreases dramatically. Such mixity of the mode I and mode II components should be appropriately considered for refining the analysis of FRP-strengthened RC beams and the FRP debonding strength design, for which a pure mode II interfacial failure was usually assumed. Effective bond length of externally bonded FRP sheets Conference Paper Full-text available Strengthening and repair of concrete structures using externally bonded fiber reinforced polymer (FRP) composite sheets has been popular around the world during the last two decades. However, premature failure due to debonding of the FRP is one of the important issues remaining to be resolved. Numerous research studies have dealt with the debonding problem in terms of bond strength, bond stress-slip relationship, effective bond length, and the interfacial fracture energy, however, determination of the effective bond length is still not completely understood. This paper summarizes previous work on effective bond length and proposes a new relationship for effective bond length with FRP stiffness based on existing experimental data collected in this study. BEHAVIOR OF RC BEAMS STRENGTHENED IN FLEXURE WITH SPLICED CFRP ROD PANELS Thesis Full-text available FRP laminates and fabrics, used as an externally bonded reinforcement (EBR) to strengthen or repair concrete members, have proven to be an economical retrofitting method. However, when used to strengthen long-span members or members with limited access, the labor and equipment demands may negate the benefits of using continuous EBR FRP. Recently, CFRP rod panels (CRPs) have been developed and deployed to overcome the aforementioned limitations. Each CRP is made of several small diameter CFRP rods placed at discrete spacing. To fulfill the strengthening length, CRP’s are spliced together and made continuous by means of overlaps (or finger joints). In this doctoral dissertation, the effectiveness of spliced CRPs as flexural strengthening reinforcement for RC members was investigated by experimental, analytical and numerical methods. The experimental research includes laboratory tests on (1) RC beams under four-point bending and (2) double-lap shear concrete specimens. The first set of tests examines the behavior of concrete members strengthened with spliced CRPs. Several beams were fabricated and tested, including: (a) unstrengthened, (b) strengthened with spliced CRPs, (c) strengthened with full-length CRPs, and (d) strengthened with full-length and spliced CFRP laminates. The double-lap shear tests serve to characterize the development length and bond strength of two commonly used CRPs. Several small-scale CRPs, with variable bond lengths, were tested to arrive to an accurate estimation of development length and bond strength. Several other specimens were additionally tested to preliminarily examine the effects of bond width and rod spacing. A 3D nonlinear finite element simulation was utilized to further study the response of CRP strengthened RC beams, by extracting essential data, that couldn’t be measured in the experimental tests. Additionally, analytical tools were added to investigate the behavior of tested bond and beam specimens. The first tool complements the double-lap shear tests, and provides mathematical terms for important characteristics of the CRP/concrete bond interface. The second tool investigates concrete cover separation failure, which was observed in the beam testing, for RC beams strengthened with full-length and spliced CRPs. Development of Standard Bond Capacity Test for FRP Bonded to Concrete Conference Paper Full-text available Efforts are underway to develop standardised tests to assess the bond capacity of FRP bonded to a concrete substrate. While several bond test configurations have been proposed and some standard tests have been promulgated, many use difficult-to-handle specimens or require relatively complex test apparatuses. This paper focuses on a simple beam-bending bond test based on concrete modulus of rupture (MOR) tests, which are simple to conduct and familiar to most in the anticipated community of users. This study addresses the following parameters that must be properly accounted for in the development of such a standard test: a) specimen size; b) ratio of FRP width-to-beam width; and c) ratio FRP-to-concrete modulus. Furthermore, the study contrasts simplified and rigorous methods of calculating internal specimen forces with measured in situ stresses in order to validate assumptions necessary in developing a standard test method. Bond between near-surface mounted fiber-reinforced polymer rods and concrete in structural strengthening Article Full-text available The use of Near Surface Mounted (NSM) Fiber Reinforced Polymer (FRP) rods is a promising technology for increasing flexural and shear strength of deficient reinforced concrete (RC) members. As this technology emerges, the structural behavior of RC elements strengthened with NSM FRP rods needs to be fully characterized, and bond is the first issue to be addressed. Bond is of primary importance since it is the means for the transfer of stress between the concrete and the FRP reinforcement in order to develop composite action. The objective of this research program was to investigate bond between NSM FRP rods and concrete. Some of the factors expected to affect bond performance were addressed, namely: bonded length, diameter of the rod, type of FRP material, surface configuration of the rod, size of the groove. Results are presented and discussed in this paper. Use of Externally Bonded FRP Systems for Rehabilitation of Bridges in Western Canada Article Full-text available Synopsis: Since its inception in 1995, the ISIS Canada research network has developed design procedures and innovative techniques for the rehabilitation and repair of existing concrete structures using fiber reinforced polymer (FRP) materials. In co-operation with various industrial partners, ISIS Canada has conducted many field application projects, successfully transferring ISIS technology into practice in the field. This paper provides a review of four recent field applications in Western Canada, utilizing externally bonded FRP for the repair and strengthening of bridges. The projects include flexural strengthening of a bridge deck under lateral bending, shear strengthening of I-shaped AASHTO girders for two bridges, and the repair and strengthening of concrete corbels supporting a single girder pedestrian bridge. Some construction costs and the time required to complete each project are presented, as well as practical details specific to each application.	https://www.researchgate.net/publication/329328065_Bond_Characteristics_of_CFRP_Rod_Panels_Adhered_to_Concrete_under_Bending_Effects
Northern Ireland Assembly Committee for Culture, Arts and Leisure Minutes of Evidence 04.12.08 Welcome to the Northern Ireland Assembly web site, which was set up to inform interested viewers of the day-to-day business and historical background of devolved Government in Northern Ireland. COMMITTEE FOR CULTURE, ARTS AND LEISURE OFFICIAL REPORT (Hansard) Gaeltacht Quarter 4 December 2008 Members present for all or part of the proceedings: Mr Barry McElduff (Chairperson) Mr Dominic Bradley Mr Francie Brolly The Lord Browne Mr Kieran McCarthy Mr Raymond McCartney Mr Nelson McCausland Mr McNarry Mr Pat Ramsey Mr Ken Robinson Mr Jim Shannon Witnesses: Mr Donal Moran ) Ms Colette Quinn ) The Department of Culture, Arts and Leisure Ms Linda Wilson ) The Chairperson (Mr McElduff): I wish to draw Members’ attention to the departmental briefing on the Gaeltacht Quarter, which is contained in members’ packs. I welcome Linda Wilson, Donal Moran and Colette Quinn and invite you to make your presentation. Ms L Wilson (Department of Culture, Arts and Leisure): Thank you for giving us the opportunity to provide a short update on progress on the Gaeltacht Quarter. I will briefly cover a few points about the history of the Gaeltacht Quarter development company, the Farset Way project and the capital project, An Cultúrlann. In May 2002, the joint West Belfast and Greater Shankill Task Force report made some recommendations aimed at tackling unemployment and social deprivation in west Belfast and the greater Shankill area. One of the recommendations related to the establishment of a Gaeltacht Quarter in west Belfast. The establishment of a Gaeltacht Quarter development board would develop the cultural cluster in west Belfast into a designated Gaeltacht Quarter, with its physical hub on the Falls Road, but with the Irish language at its heart. The board would steer the initiative, bringing together language, arts, crafts, creative industries, businesses and education to drive economic development, tourism and regeneration. DCAL was designated as the lead Department for the work, primarily because of its language remit. In November 2003, a Gaeltacht Quarter shadow board was established to act as a body that would agree on the best delivery vehicle to give effect to the commitments. The shadow board was established with representation from the local community and business sector, the Department for Social Development, Invest NI and DCAL. The Department commissioned the necessary business case and economic appraisal, which enabled funding of just under £1 million, £538,000 of which was secured from the integrated development fund for the capital development or refurbishment project at An Cultúrlann. DCAL also commissioned Clive Dutton, who is a recognised urban regeneration expert, to produce a report to examine and make recommendations on the way forward for the Gaeltacht Quarter in relation to the management and governance arrangements. A key recommendation arising from Dutton related to the establishment of a mini urban regeneration company. That led to the establishment of the Gaeltacht Quarter Development Company — An Cheathrú Gaeltachta Teo. It began operations in July 2007, and it has been allocated almost £500,000 of integrated development funding over three years. The model of an urban regeneration company gave rise to the creation of a steering group, and that was realigned from the previous shadow board. The steering group involves representatives from central Government, local government, public services in the area and local community and business interests. The aim of the steering group is to facilitate and support the development of the Gaeltacht Quarter by providing advice and guidance to the development company, and to act as a catalyst to help to realise the concept of the Gaeltacht Quarter. In October 2008, the development company tendered for consultants to provide key documents to enable the Gaeltacht Quarter to be developed further in line with previous recommendations. Those recommendations include a baseline study to help to understand the key linguistic and cultural aspects of the area, as well as assessing the position regarding activities such as tourism, educational and vocational activities, etc. They also include a development plan for the quarter, which sets out the vision’s strategic objectives and priorities; a marketing plan, which is based on existing opportunities in the Gaeltacht Quarter and those that are proposed in the development plan; and a strategic and business plan for the area. Consultants have been asked to develop a bilingual two-to-five-year plan for the quarter, which should include proposals for the optimum and legal basis for An Ceathrú Gaeltachta Teo. The tender was awarded to Deloitte consultants. Work on that is under way. For the project to be sustainable in the medium to long term, the development company must attract the interest of and substantial funding from the private sector. An additional project that has been identified as relevant to the Gaeltacht Quarter is the Farset Way project, which is an attempt to re-establish a relationship between the area and Divis Mountain. That is being progressed. In 2006, a capital project to develop and re-establish the Irish language cultural centre at An Cultúrlann was allocated £538,000 from the integrated development fund to support the development of new exhibition space and eight new business units. In May 2005, the estimated cost of the project was £508,000. Since October 2006, the project has been progressed by a project team that involves DFP, DCAL, and a representative from the Arts Council. A design team has been appointed to finalise plans and to oversee the tender for contactors to complete capital works. As the design has become more refined, the cost of projects has escalated significantly. Following the tender process, the most economically advantageous tender that was received was £697,700. As that figure was significantly above the available budget, the project could not proceed. Ways to enable the project to proceed are being considered. A revised business case is currently in the early stages of development. Estimated costs are around £2 million, which will require the involvement of additional funds. Several organisations have expressed interest in the enhanced project: the Department for Social Development; the International Fund for Ireland; the Northern Ireland Tourist Board; and the Arts Council — subject, of course, to normal approvals from DCAL and DFP. Overall, the successful delivery of the Gaeltacht Quarter is relevant to delivering DCAL and wider Government objectives for economic growth, employment and regeneration, as well as delivering a key recommendation from the west Belfast/greater Shankill task force. Considerable work remains to be done. However, progress has been made to establish a Gaeltacht Quarter development company and steering group. Work that Deloitte consultants undertake to complete a baseline study and development plan is a key element of the project. We will continue to work in partnership with the development company and other key stakeholders to endeavour to progress the concept. Thank you. Mr D Bradley: Thank you very much for your presentation, Linda. In your briefing, you mentioned that £538,000 was allocated to the An Cultúrlann development from the integrated development fund. Is that money still available to the project? Ms L Wilson: In principle, yes. Of the £538,000 that was allocated, £35,000 has been spent on the design development process to date, which leaves a balance of £503,000. The IDF was wound up in March 2008. The decision was made centrally to bring the fund to an end. DCAL can confirm that it could make the funding available from its capital line until 31 March 2009. If funding is needed in 2009-10 — which is realistic, given the project’s state of play — we will try our best to make it available, subject to — Mr D Bradley: Is the money available to the Department? Ms L Wilson: We would have to try to find it in the Department’s resources. Mr D Bradley; Where is the money that had been allocated? Ms L Wilson: We had to surrender it. The IDF was an additional allocation to Departments. It was taken back. Mr D Bradley: So you were given money for the project, but you gave it back before the project was completed? Ms L Wilson: The Department had no choice. A decision was taken centrally, and the money was taken back. Mr D Bradley: On what basis? Ms L Wilson: On the basis that the integrated development fund was being wound up. Mr D Bradley: Surely that money was already committed to a project? Ms L Wilson: It was, but it was not spent within the originally anticipated timeframe. That is the key issue. Mr D Bradley: Therefore, the core funding — that £538,000 at the centre of the cocktail of funding from DSD, the International Fund for Ireland, NITB and the Arts Council — is now in doubt? Ms L Wilson: I would not go as far as saying that it is in doubt; DCAL remains committed to the project. I can firmly state that the Department will make efforts to find the money in this financial year from our capital allocation. Thereafter, we will certainly be bidding for funds from DFP. Mr D Bradley: Surely one of the key elements in constructing a cocktail of funding is to have the central core funding in place, and that core funding would then attract other funding, from other sources? If there is no guarantee that that funding is available, it will be very difficult to attract other sources of funding for the project. Ms L Wilson: The funding is available in this financial year, and the Department remains committed, in principle, to that funding. However, we are not into next year’s budget yet and I cannot pre-empt ministerial decisions or allocations. The Department will endeavour to find the funding and will lodge a bid with DFP for those funds at the next appropriate opportunity. It is very much an issue of timing. Mr McCartney: I thank the witnesses for their presentation. At point 14 of the briefing, you name a number of organisations that have expressed an interest in the enhanced project. Will you outline what you mean by “interest”? Ms L Wilson: The Department’s understanding is that DSD may contribute £255,000 to the modernisation fund for the capital project at the An Cultúrlann building. Furthermore, the IFI may contribute £607,000, and the Tourist Board £281,000. Mr McCartney: There was reference made to a report from Deloitte and a revised business case. Are those separate from the funding that you have outlined? Ms L Wilson: Yes, those are separate. Mr McCartney: Is there a timeline as to when they will be completed? Ms L Wilson: The business case is currently being worked on — Mr Donal Moran (Department of Culture, Arts and Leisure): We are working very closely with An Cultúrlann and the consultants who are examining that at the moment. It is being led by DSD, so that Department is setting the time frame. DCAL has provided substantive comments on the initial draft of the report. However, it is up to the consultants and An Cultúrlann to address those issues and then re-engage with us and the other potential sources of funding. Mr McCartney: Will the timeline ensure that all the moneys — such as those provided through the integrated fund — are not lost? Mr Moran: With the indicative timeline that the Department is currently working to, I would hope to have something on those issues by the end of January 2009. Mr McCartney: Obviously, I welcome the commitments made by the Department to steer the project through. Thank you. Mr McCausland: Is the Farset Way project being taken forward by the development company? Ms L Wilson:Yes. Mr McCausland: What stage has that project reached? I have heard it mentioned on a couple of occasions, but I have yet to see any reports on it. Ms Colette Quinn (Department of Culture, Arts and Leisure): The Department will provide the Committee with a written update on the project. Mr McCausland: That is fine. My second question relates to the capital project at An Cultúrlann. My understanding is that the current building is owned by the Springfield Charitable Association. If an extension is built under the capital project, who would then own that? Mr Moran: There are a number of issues that the Department has addressed in relation to the initial business case, and one of those relates to the lease on the building. An Cultúrlann must address those issues before we move to the next stage of business case approval. Mr McCausland: As regards funding for the extension, no matter whatever happens to the current building, the extension would be the property of the company that owns An Cultúrlann. Mr Moran: I do not know the legal position. Mr McCausland: Can you come back to the Committee on that point? Obviously, if you are supporting the extension, you recognise the value of having cultural centres. I am comparing that with the extensive funding for An Gaeláras in Londonderry. Do you see that as confirming the value and validity of the arguments put forward by the Ulster-Scots community at a conference that you attended at Templepatrick recently, where they said that there should be several cultural centres as part of an overarching Ulster-Scots Academy? The value in tourism, cultural and social development has been acknowledged in principle for An Cultúrlann. Would the same arguments be valid in the other case? Ms L Wilson: An Cultúrlann is a specific project in a specific area. A similar case could be made, subject to the interest of other players, for Ulster Scots. However, how many such centres might be viable is a different question. I do not see that there is any barrier, in principle, to a similar initiative if the conditions were right and if other stakeholders were interested in providing the support. Mr McCausland: I was interested in the broad principles of the value of such centres for tourism, culture and social development. Ms L Wilson: I will be able to better answer that when I see the outcome of the Deloitte assignment, which involves a baseline study and a development and marketing plan for that area. There would be parallels and lessons to be learned. Mr McCausland: Deloitte has so many plans. Ms Wilson: Deloitte is carrying out a series of studies for the Gaeltacht Quarter, including a baseline study and a development plan. Mr McCausland: When will that be available? Ms L Wilson: It will be available between March and May 2009. Mr McCausland: Folk from Forbairt Feirste came to the Committee to discuss the Gaeltacht Quarter. We asked them about the difficulty that had arisen with Belfast City Council, which had been asked about the possibility of erecting Irish-language signage in the city cemetery, on the basis that it was within the Gaeltacht Quarter, and I said that the Royal Victoria Hospital and other institutions were in the same area, which had a regional, rather than a local, role. How does the Department envisage that issue being addressed? Ms L Wilson: The Gaeltacht Quarter is about development; its role is not to acquire or impose signage. There is no compulsion on any individual or organisation based in, or using, the Gaeltacht Quarter to communicate in oral or written Irish or to provide public signage in Irish. The Gaeltacht Quarter is very much about regeneration, and the proposal that it should be an urban regeneration company suggests an underlying principle, rather than just the cultural elements involved. It would be using the culture to deliver regeneration. Mr McCausland: That is certainly true for the Gaeltacht Quarter. However, the cultural centre has been there for a long time — even before the Gaeltacht Quarter appeared. Ms L Wilson:Yes. Mr McCarthy: I am a wee bit concerned about the response that you gave to Mr McCausland. We are trying to create a shared future in this place. The Gaeltacht Quarter, which is a joint West Belfast/Greater Shankill Task Force project, is open to the whole community. Mr McCausland’s question about planting something else in another area to satisfy the Ulster-Scots community would be an extension of the division that we have had in this place for far too long. Would it not be better for everyone to come together centrally, rather than to have further division to placate different sections of the community? The Chairperson: I presume that some of those questions are political in nature. We are dealing with a particular application or business case for a Gaeltacht Quarter. Ms L Wilson: That is a point for wider debate. The recommendation is merely one that the joint task force made about Gaeltacht quarter. Mr McCarthy: Yes, but your answer to Nelson’s question was that the Department would be prepared to support a facility somewhere else that is specifically for a particular community. I believe that we should try to embrace all our communities. I am not au fait with the joint task force, but it seems to bring in all the communities in that area. The Chairperson: We will leave it at that. Kieran, you have made your statement, and that is fine. Mr K Robinson: I will again turn to history. My grandfather lived in the area of Farset Way, and my father was born there, so I have a passing interest in it. What are the physical boundaries of the Irish-speaking quarter? There was talk about the shared vision, and I am not looking at the matter from either Nelson or Kieran’s viewpoint. However, if, as has been mentioned, Irish street signs are to appear in areas that are currently shared — areas through which many people pass to use health services, and so on — will some people feel excluded because they are not comfortable with those signs and that general ambience? Finally, where will the Farset River corridor start? How far up the river and the hillside will it run? Ms L Wilson: One of the recommendations is that the precise area needed to be agreed. At the moment, we have a working definition, but we do not have an absolute, precise definition. Mr K Robinson: What part of the Gaeltacht Quarter would be closest to the city centre? Ms L Wilson: Divis Street . The Chairperson: Raymond, you think it is Castle Street? Mr McCartney: I think that Castle Street was mentioned in the presentation. Ms L Wilson: Mr Robinson mentioned signage. Mr K Robinson: Sorry — are we accepting Raymond’s definition that the nearest point is Castle Street? I think that we should be accurate. Ms L Wilson: I have quite a lengthy definition in front of me, but, as I said, I do not think that it is the final, agreed definition that is being used for the purposes of the study. It mentions an area bounded at the western edge by Kennedy Way and the Monagh Bypass, continuing on to the northern boundary at a line following the Upper Springfield and Springfield Roads on both sides as far as Springfield Park, and continuing on one side on the country-bound lane only until the junction of Lanark Way. It then follows the peace line to connect with the start of its eastern boundary at Divis Street/John Street boundary, and from there to a southern boundary line running from Durham Street/Grosvenor Road on one side of the road on its city-bound lane only until Grosvenor Road’s junction with the M1 motorway. It then follows the city-bound lane of the motorway as far as the junction to Kennedy Way. We might need to walk that. [Laughter.] That is the working boundary outline. Mr K Robinson: That is very helpful. What about the boundaries of the Farset Way project? Ms L Wilson: I do not have the details on that. We will cover that matter in our response. Roads signage is essentially a matter for DRD. Mr K Robinson: I am concerned about the shared vision aspect — the fact that if signs in Irish start to appear at some point in the future, that could cause certain people unease. The Chairperson: I thank members and the officials, Linda, Colette and Donal, for their attendance. Feedback Search	https://archive.niassembly.gov.uk/culture/2007mandate/moe/2008/081204.htm
UK promotes City as center for global Islamic finance. - Free Online Library Free Online Library: UK promotes City as center for global Islamic finance. by " Arab News (Jeddah, Saudi Arabia)" ; News, opinion and commentary General interest Islamic banking UK promotes City as center for global Islamic finance. MLA style: "UK promotes City as center for global Islamic finance.." The Free Library . 2009 Al Bawaba (Middle East) Ltd. 28 May. 2023 https://www.thefreelibrary.com/UK+promotes+City+as+center+for+global+Islamic+finance.-a0198518948 Chicago style: The Free Library . S.v. UK promotes City as center for global Islamic finance.." Retrieved May 28 2023 from https://www.thefreelibrary.com/UK+promotes+City+as+center+for+global+Islamic+finance.-a0198518948 APA style: UK promotes City as center for global Islamic finance.. (n.d.) >The Free Library. (2014). Retrieved May 28 2023 from https://www.thefreelibrary.com/UK+promotes+City+as+center+for+global+Islamic+finance.-a0198518948 Byline: Mushtak Parker LONDON: The Islamic Sukuk market received a potentially major boost in the UK budget 2009 announced by Chancellor of the Exchequer Alistair Darling in the House of Commons last week. The chancellor confirmed in his budget statement three further measures on alternative finance instruments (the euphemism for Islamic finance referred to in the UK legislation) as part of the ongoing drive to promote the UK as a center for Islamic finance. The measures are aimed at anyone (institution) wishing to obtain finance by issuing Alternative Finance Investment Bonds (AFIBs) (the UK euphemism for Sukuk) using land assets as securities under the arrangements for issuing the bonds in the United Kingdom. They include: (a) provision of relief from stamp duty land tax (SDLT) in respect of transactions undertaken as part of the issue of alternative finance property investment bonds; (b) provision of relief from tax on capital gains in respect of transfers of land to and from Sukuk issuance vehicles; and (c) ensuring that the person obtaining the financing will continue to be entitled to claim capital allowances while the land is held by the Sukuk issuance vehicle. It is a stated ambition of the Labour government to further promote the City of London as a center for global Islamic finance, trade and investment and to create a level playing field between conventional and equivalent Islamic financial products. According to the budget statement, "Legislation will be introduced in Finance Bill 2009 to provide relief from the provisions of SDLT and the Taxation of Chargeable Gains Act 1992 for persons wishing to raise finance by using land assets in the United Kingdom. Further legislation will also set out the capital allowances consequences of the SDLT and capital gains measures." The measures, according to the UK Treasury, will take effect on or after the date that Finance Bill 2009 receives royal assent. The chancellor first outlined the intention of the UK government to introduce legislation to provide relief from stamp duty land tax for alternative finance investment bonds in the Pre-Budget Report (PBR) in November 2008. This despite a disappointing concurrent announcement that the UK Treasury would not be issuing a debut sovereign Sukuk in the wholesale sterling market at the present time. According to Treasury Minister Ian Pearson, "the government is committed to promoting the City of London as a center for global Islamic finance and to working toward a level playing field between conventional and alternative financing instrument. New legislation will be introduced in the Finance Bill 2009 to provide relief from stamp duty land tax for alternative finance investment bonds. And in conjunction with the FSA, the government will examine the regulatory treatment of Sukuk (alternative finance investment bonds) in the UK and will consult on this issue in the near future." The announcement has been welcomed by the Islamic finance market in the City and beyond. Angela Savin, senior tax associate at City law firm, Norton Rose LLP, stressed that "for the last few years, HM Revenue & Customs (HMRC) have been very receptive to representations made for the tax treatment of Islamic finance to be no more onerous than conventional finance. These changes should ensure that there are now no UK tax obstacles to issuing Sukuk backed by UK land." Norton Rose, which is one of the top international law firms servicing the global Islamic finance industry, is confident that the UK "tax changes will give a considerable boost to the UK Islamic finance initiative and ensure that in these difficult times alternative sources of finance will be available in the UK." Foreign bankers such as Nazmi Camalxaman, general manager of CIMB Group's London branch, welcomed the move and stressed the importance of the UK issuing a Sukuk. "The market is waiting for the debut UK sovereign Sukuk issuance, because it will set the benchmark especially of other potential originators in the developed countries and in the EU, and start a nascent Euro-Sukuk market." CIMB would also like the UK government to be more proactive and follow in the footsteps of the World Bank, the International Finance Corporation and the Islamic Development Bank (IDB) to issue a Malaysian ringgit-denominated Sukuk "because there is high demand for such AAA-rated issuances in Malaysia." Richard Thomas, CEO of Global Securities House (UK) and chairman of Gatehouse Bank, is confident that the UK sovereign Sukuk is "work in progress." He stressed the fact that Whitehall is pushing ahead with the Sukuk measures in the Finance Bill 2009 indicates that the Brown government is committed to a Sukuk issuance, albeit this would depend on the pricing and timing. "The Treasury only finished its consultation in January 2009. The Finance Bill will be published sometime in May 2009. By the time the bill gets royal assent and the structure of the Sukuk is finalized it would be almost the end of 2009. So even if the UK government wanted to issue a Sukuk, realistically it would not have happened before the end of 2009 or early 2010. In any case, with the current UK government pricing for a debut sovereign Sukuk, no investors would buy it. The Islamic finance sector is return-driven. Therefore it would not be efficient or offer value for money to issue a Sukuk currently," he explained. But Thomas wants to see a UK sovereign Sukuk issuance also for another reason. "We need a risk-free bond for our balance sheet purposes. Until we get a benchmark yield such as the UK government issuance, you will not see the establishment of a Sukuk fund of funds," he explains. Article Details Publication: Arab News (Jeddah, Saudi Arabia) Geographic Code: 4EUUK Date: Apr 27, 2009 Words: 943	https://www.thefreelibrary.com/UK+promotes+City+as+center+for+global+Islamic+finance-a0198518948
MiLB Top 10 Prospects Flashback: 2011 South Atlantic League The SAL class of 2011 is notable for its depth, including future MVPs Bryce Harper and Christian Yelich as well as three other high quality regulars. MiLB Top 10 Prospects Flashback: 2011 South Atlantic League As a large league with agreeable springtime weather, the low Class A South Atlantic League is where many future Hall of Famers see their first taste of full-season ball. The list includesTom Glavine(1985),Craig Biggio(1987),Ivan Rodriguez(1989),Chipper Jones(1991),Derek Jeter(1993) andVladimir Guerrero(1995). Potential future Hall of FamersScott Rolen(1994),Andruw Jones(1995) andAdrian Beltre(1996) also played in the SAL. The South Atlantic League class of 2011 is notable for its depth, including future MVPsBryce Harper(No. 1) andChristian Yelich(No. 5) as well as quality regularsManny Machado(No. 2),Xander Bogaerts(No. 10) andMarcell Ozuna(No. 7). The depth continues. Harper,Jameson Taillon(No. 4) and Machado were the first three picks in the 2010 draft, whileJurickson Profar(No. 3) would become the No. 1 prospect in baseball in 2013. 2011 South Atlantic League Top 10 Prospects No Player Pos Team Org PA/IP WAR 1 Bryce Harper OF Hagerstown Nationals 4,871 36.6 2 Manny Machado SS Delmarva Orioles 4,977 35.9 3 Jurickson Profar SS Hickory Rangers 2,019 5.3 4 Jameson Taillon RHP West Virginia Pirates 466 9.1 5 Christian Yelich OF Greensboro Marlins 4,269 34.4 6 Jesse Biddle LHP Lakewood Phillies 92 -0.6 7 Marcell Ozuna OF Greensboro Marlins 4,109 22.4 8 Brandon Jacobs OF Greenville Red Sox — — 9 Jonathan Schoop SS Delmarva Orioles 3,281 10.8 10 Xander Bogaerts SS Greenville Red Sox 4,143 26.2 Harper displayed “exceptional hitting and power prowess” as perhaps the “most heralded minor leaguer ever.” The 18-year-old hit .318 with 14 homers and 19 steals in 72 games, earning a late promotion to Double-A. Machado showed “impressive bat speed and the ability to consistently barrel up the ball,” looking like a “plus hitter with at least average power.” A dislocated kneecap cut into his production, but he still moved to high Class A in the second half. The athletic Yelich rode a late surge to 15 homers and 32 steals while hitting .312. Yelich’s manager accurately summed him up this way: “He has good instincts and is going to be a very productive offensive player because he sees the ball very well and really knows the strike zone.” “Maturity” marked Bogaerts’ play in the South Atlantic League, where he hit .260 with 16 homers as an 18-year-old. He’s got some pop and life in that bat,” his manager said. “He’s an aggressive hitter and he hits the ball as hard and far as anyone you’ll see. You can envision him playing for a long time.” South Atlantic League All-Time BA No. 1 Prospects Players listed with career major league plate appearances/innings and FanGraphs WAR. Stats for active players current through mid August. Year Player Pos Team Org PA/IP WAR 1981 Jeff Reynolds 3B Greensboro Yankees — — 1982 Matt Winters OF Greensboro Yankees 122 -0.4 1983 Van Snider OF Charleston Royals 36 0.0 1984 Kevin Sliwinski 1B Florence Blue Jays — — 1985 Sil Campusano OF Florence Blue Jays 288 0.0 1986 Cameron Drew OF Asheville Astros 16 0.0 1987 Mark Whiten OF Myrtle Beach Blue Jays 3,523 13.1 1988 Derek Bell OF Myrtle Beach Blue Jays 5,068 13.0 1989 Willie Ansley OF Asheville Astros — — Year Player Pos Team Org PA/IP WAR 1990 Tito Navarro SS Columbia Mets 18 -0.4 1991 Rondell White OF Sumter Expos 5,852 23.8 1992 Cliff Floyd OF Albany Expos 6,063 24.7 1993 Terrell Wade LHP Macon Braves 126 1.0 1994 Ruben Rivera OF Greensboro Yankees 1,818 4.9 1995 Andruw Jones OF Macon Braves 8,664 67.0 1996 Adrian Beltre 3B Savannah Dodgers 12,130 84.1 1997 Ryan Minor 3B Delmarva Orioles 342 -2.8 1998 Alex Escobar OF Capital City Mets 439 1.4 1999 Rafael Furcal SS Macon Braves 7,237 33.1 Year Player Pos Team Org PA/IP WAR 2000 Josh Hamilton OF Charleston Rays 4,350 27.9 2001 Boof Bonser RHP Hagerstown Giants 417 0.9 2002 Gavin Floyd RHP Lakewood Phillies 1,250 14.9 2003 B.J. Upton SS Charleston Rays 5,858 24.4 2004 Delmon Young OF Charleston Rays 4,371 -1.3 2005 Scott Elbert LHP Columbus Dodgers 97 1.2 2006 Andrew McCutchen OF Hickory Pirates 6,849 49.5 2007 Desmond Jennings OF Columbus Rays 2,351 11.7 2008 Madison Bumgarner LHP Augusta Giants 1,863 34.2 2009 Martin Perez LHP Hickory Rangers 951 8.8 Year Player Pos Team Org PA/IP WAR 2010 Jon Singleton 1B Lakewood Phillies 420 -0.9 2011 Bryce Harper OF Hagerstown Nationals 4,725 36.4 2012 Jose Fernandez RHP Greensboro Marlins 471 13.6 2013 Eddie Butler RHP Asheville Rockies 264 -0.8 2014 Lucas Giolito RHP Hagerstown Nationals 451 5.6 2015 Yoan Moncada 2B Greenville Red Sox 1,568 10.1 2016 Victor Robles OF Hagerstown Nationals 780 3.1 2017 Sixto Sanchez RHP Lakewood Phillies 39 1.1 2018 D.L. Hall LHP Delmarva Orioles — — 2019 Jarred Kelenic OF West Virginia Mariners — —	https://www.baseballamerica.com/stories/milb-top-10-prospects-flashback-2011-south-atlantic-league/
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.” 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. 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. 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. 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. Wednesday 17 May 2023 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. 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. Saturday 6 May 2023 God save the King! Photo from our Coronation watch party today. 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 © 2023 Oxford Oratory. All rights reserved. The Oxford Oratory of St Philip Neri is a Registered Charity number 1018455	https://www.oxfordoratory.org.uk/publications/blog/post/9898-9898/blog/post/9864-now-we-see-as-in-a-mirror-dimly/blog/post/9861-9861/mass-intentions.php
Microorganisms \| Free Full-Text \| Current Applications of Absolute Bacterial Quantification in Microbiome Studies and Decision-Making Regarding Different Biological Questions High throughput sequencing has emerged as one of the most important techniques for characterizing microbial dynamics and revealing bacteria and host interactions. However, data interpretation using this technique is mainly based on relative abundance and ignores total bacteria load. In certain cases, absolute abundance is more important than compositional relative data, and interpretation of microbiota data based solely on relative abundance can be misleading. The available approaches for absolute quantification are highly diverse and challenging, especially for quantification in differing biological situations, such as distinguishing between live and dead cells, quantification of specific taxa, enumeration of low biomass samples, large sample size feasibility, and the detection of various other cellular features. In this review, we first illustrate the importance of integrating absolute abundance into microbiome data interpretation. Second, we briefly discuss the most widely used cell-based and molecular-based bacterial load quantification methods, including fluorescence spectroscopy, flow cytometry, 16S qPCR, 16S qRT-PCR, ddPCR, and reference spike-in. Last, we present a specific decision-making scheme for absolute quantification methods based on different biological questions and some of the latest quantitative methods and procedure modifications. Current Applications of Absolute Bacterial Quantification in Microbiome Studies and Decision-Making Regarding Different Biological Questions by Xiaofan Wang 1,† , Samantha Howe 1,† , Feilong Deng 1,2 and Jiangchao Zhao 1,* 1 Department of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR 72701, USA 2 Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, College of Life Science and Engineering, Foshan University, Foshan 528225, China Author to whom correspondence should be addressed. These authors have contributed equally to this work. Microorganisms 2021 , 9 (9), 1797; https://doi.org/10.3390/microorganisms9091797 Received: 30 July 2021 / Revised: 16 August 2021 / Accepted: 21 August 2021 / Published: 24 August 2021 (This article belongs to the Section Systems Microbiology ) Abstract High throughput sequencing has emerged as one of the most important techniques for characterizing microbial dynamics and revealing bacteria and host interactions. However, data interpretation using this technique is mainly based on relative abundance and ignores total bacteria load. In certain cases, absolute abundance is more important than compositional relative data, and interpretation of microbiota data based solely on relative abundance can be misleading. The available approaches for absolute quantification are highly diverse and challenging, especially for quantification in differing biological situations, such as distinguishing between live and dead cells, quantification of specific taxa, enumeration of low biomass samples, large sample size feasibility, and the detection of various other cellular features. In this review, we first illustrate the importance of integrating absolute abundance into microbiome data interpretation. Second, we briefly discuss the most widely used cell-based and molecular-based bacterial load quantification methods, including fluorescence spectroscopy, flow cytometry, 16S qPCR, 16S qRT-PCR, ddPCR, and reference spike-in. Last, we present a specific decision-making scheme for absolute quantification methods based on different biological questions and some of the latest quantitative methods and procedure modifications. Keywords: absolute count ; high throughput sequencing ; flow cytometer ; 16S rRNA ; qPCR 1. Introduction Subtle alterations in the host environment may induce significant shifts in microbial communities and the corresponding interplays between the host and microbiota [ 1 , 2 , 3 , 4 ]. The changes in abundances of certain taxa inhabiting the gut, skin, respiratory system, blood vessels, and other organs can play beneficial roles in human health or cause serious disease [ 5 , 6 ]. Hence, assessing community changes can provide an understanding of the underlying metabolic mechanisms and help direct the development of disease preventatives and therapies. High throughput sequencing is a robust tool used for large-scale profiling of microbial communities to reveal community structural differences. However, most data analyses resulting from the use of this technique are based on relative quantification, with the absolute bacterial abundance being discounted. Inappropriate interpretation from relative quantification may completely change the results of some studies [ 7 ]. For example, when two types of bacteria start with the same initial cell number, a treatment that doubles the cell number of bacteria A (while bacteria B remains unaffected) results in the same relative abundance between bacteria A and B (67% and 33%) as a treatment that halves bacteria B (while bacteria A remains unaffected). However, the two treatment effects are completely different [ 8 ]. In addition, compositional data using relative abundance is not appropriate for addressing certain biological problems, such as community interactions. Thus, precise quantification of bacterial loads is necessary. Currently available approaches for the absolute count of different specimen types are highly diverse and possess different strengths and weaknesses ( Table 1 ). In this review, we first discuss the concerns and limitations of using relative abundances under different biological conditions. Second, we briefly describe several recent cell- and molecular-based absolute bacterial quantification techniques. Lastly, we provide decision-making directions for method selection regarding different biological questions and challenges for future microbial studies. Table 1. Absolute quantification methods in microbiome studies. 2. Importance of Absolute Quantification for Biological Questions Although relative abundance measurement has been widely applied to study community shifts for many biological questions, the absolute bacterial load is crucial for many investigations [ 9 , 10 ]. For instance, bacteria load variations have been frequently reported in both cross-sectional and longitudinal human microbiome studies. Healthy adult human fecal samples have up to tenfold variation (10 10–11 cells/g) with a 3.8 × 10 10 cells/g daily fluctuation [ 11 ]. In addition, the overall mucosal bacterial loads in patients with gut dysbiosis-related diseases such as Crohn’s disease and inflammatory bowel disease are higher than those in healthy controls [ 12 ]. Changes in bacterial density, rather than compositional changes, have been discussed regarding hatching failure in birds. Eggshell-colonized pathogenic bacteria can multiply rapidly on eggshells in a mild environment and subsequently may have the opportunity to infect the embryo through eggshell pores [ 13 ]. In some cases, this eggshell infection is bacterial dose-dependent, and low bacterial amounts on eggshells (location-related), even comprising infertility-causing Neisseria species, may not cause embryo mortality [ 14 ]. However, other similar studies indicated a negative correlation between bacterial densities and hatching success but only in limited locations and avian species [ 9 , 15 ]. Furthermore, eggshell bacterial loads are influenced by various physiological and environmental factors, such as the size of uropygial glands and nest conditions, respectively. Hence, the hatching success rate can also be improved by the modification of these environmental factors, which is indicated by the eggshell total bacterial load. Merely focusing on community structures based on relative abundances will result in overlooking these important biological findings [ 16 ]. Microbial community changes in between soil location and development are better revealed using absolute count. Microbial abundances in 110 different soil types collected in the United States showed a greater variation: 30 fold when using phospholipid fatty acid (PLFA) metric and 210 fold when using 16S rRNA gene abundances [ 2 ]. In addition, Yang and his colleagues (2018) evaluated the microbial population dynamics in two soil types, a horizontal surface layer soil (Soil) and its parent material (PM) soil. The total bacteria count in the developed surface layer soil was 4.78 times less than the PM soil (3.55 × 10 8 and 1.7 × 10 9 cells/g, respectively). When evaluating the individual phyla abundances in these two soils, 20 out of 25 total phyla, including Acidobacteria and Chloroflexi phyla, showed significant changes from absolute quantification. While only 12 phyla, excluding the two phyla mentioned above, were detected using the relative quantification method. Moreover, at the genus level, 33.87% of the total genera showed opposite changes, described as decreased relative abundance but increased absolute abundance. This was due to the failure to detect the increase in total bacteria count. A similar scenario was observed in the decreased total count. In the same study, sodium azide-treated soil decreased the total indigenous bacteria from 3.85 × 10 8 to 9.56 × 10 7 cells/g. Among the 17 classified phyla in the soil sample, 15 phyla dropped significantly based on absolute quantification, while only nine phyla were detected using relative quantification. At the genus level, 40.58% of the total genera exhibited an upregulation trend using the relative quantification method, but downregulation was observed via the absolute quantification method. Hence, data interpretation initiated from relative abundance usually leads to false-positive results, and it is more likely that the change in absolute count of individual members drives the proportion changes within the group [ 17 ]. Absolute quantification is more suitable for analyzing complex bacterial interactions in a community. Parasitism, coexistence, predation, mutualism, competition, symbiosis, and antagonism are important inherent interactions that are encountered when exploring inner-microbial correlations [ 18 ]. Using traditional correlation methods like Pearson and Spearman when analyzing compositional data is inappropriate [ 19 , 20 ] because most microbiome data starts with a between-group normalization on the observed reads, which forces the data to fall into a compositional fashion and no longer reflects real biological features [ 21 , 22 ]. Microbial loads are not necessarily related to sequencing depth, and a zero in the relative abundance does not necessarily indicate an absence but could also be due to insufficient sampling depth [ 11 , 23 ]. Specific pairwise correlations on bacterial interactions between quantitative microbial profiling (QMP) and relative microbial profiling (RMP) have been studied in Vandeputte et al., 2017. Among 66 fecal samples from healthy volunteers, bacteria loads ranged from 5 × 10 10 to 3 × 10 11 cells/g. This 10-fold variation in bacterial density generated significant differences in microbiota interactions using QMP and RMP methods. The QMP network detected 76 significant co-varying genus pairs, including one negative correlation pair ( Phascolarctobacterium-Dialister , Spearman’s ρ = −0.57), while the RMP network only disclosed ten pairwise correlations, and half of them were negative relationships. Another five positive-correlated genus pairs, Methanobrevibacter-Akkermansia , Bacteroides-Bilophila , Alistipes-Barnesiella, Ruminococcus 2-Dorea , and Alistipes-Odoribacter, were detected by both QMP and RMP networks. In the RMP correlation analysis, Prevotella had antagonistic effects on Bilophila , Barnesiella , Alistipes , and Bacteroides , but these were not validated when the total bacterial count was included in the analysis. Hence, interactive correlations evaluated based on relative and absolute abundance partially coincide, and quantitative taxon profiling has greater biological meaning than compositional taxon profiling [ 11 ]. Another challenge posed by relative abundance quantification is microbiome analysis on low-biomass specimens such as the gut microbiota in newborn piglets [ 24 ], environmental air microbiotas [ 25 ], and medical facilities cleaning [ 26 ]. The high sensitivity of high throughput sequencing does not readily distinguish processing contaminants from actual samples. In a single-strain titration study, using Mo Bio PowerMag with a ClearMag bead cleanup step, the target strain was detected as low as five cells per sample. With an initial 50-cell input, only 28.8% of final sequences were aligned to the target strain, while other reads were identified as contamination. When testing samples containing a 500-cell input, the contaminant reads dropped to 10%. Overall, using the specific extraction protocol mentioned above, all samples constantly had 96.9 extraneous contaminant cells [ 24 , 27 ]. The handling of contaminants contributes differently to samples with different absolute cell numbers. Failure to determine absolute cell counts in specimens will reduce the importance of problems caused by contaminants and possibly give rise to false-positive signals. Hence, the precise and highly sensitive quantification of total bacterial counts or individual taxa show promise for unbiased interpretation of microbial dynamics and interactions. In the next section, we briefly discuss several quantification methods and strategies currently applied in absolute quantification and then provide a specific decision-making scheme based on different biological questions. Also, we describe some of the contemporary optimization techniques used to minimize certain biological obstacles. 3. Brief Description of Advanced Absolute Quantification Methods 3.1. Fluorescence Spectroscopy Dating back to the mid-1700s, bacterial cells were enumerated under a microscope via morphology discernment. Later, there was increasing interest focused on cellular function and metabolic features. As a result, a wide range of fluorescent dyes that bind to different cellular components (nucleic acids, membranes, and proteins) emerged as advanced tools enabling physiological and structural characterizations. Specifically, stains such as 4′,6-diamidino-2-phenylindole (DAPI), acridine orange, and SYBR Green I can penetrate cells and stain double-stranded DNA, thus enhancing the fluorescence of the molecule [ 28 ]. The fluorescence strength is related to DNA density and bacterial cell number, which allows the quantification of total bacteria in materials of interest without biological status acquisition. Sytox Green is a high DNA-affinity green dye that cannot penetrate membranes and is thereby used to detect dead cells that have lost membrane integrity [ 29 , 30 , 31 ]. Other dyes, including 7-aminoactinomycin D and propidium iodide (PI), are also cell impermeable and can only stain dead cells. The application of double nucleic acid stains, such as DAPI (blue fluorescence), allows for simultaneous targeting of both live and dead cells ( Figure 1 and Table 1 ). It is noteworthy that staining nucleic acids for enumerating dead or live cells sometimes has limitations due to complete DNA degradation in dead cells [ 29 ]. Certain stains (SYBR, PI, etc.) can bind to both single and double-stranded DNA, as well as RNA but with a lower performance. Other dyes (diazonium salt and tetrazolium salt) that can differentiate active cells by detecting different cellular metabolic activities will be described in a later section. Figure 1. Stains 4′,6-diamidino-2-phenylindole (DAPI; blue color), acridine orange (orange color), SYBR Green I (green color), and Vybrant (red) can penetrate cells and stain the double-stranded DNA. Sytox Green (green color), 7-aminoactinomycin D, and propidium iodide (PI; red color) are cell impermeable and can only stain dead cells or cells that have lost membrane integrity. Active bacteria quantification can be accomplished using certain dyes targeting metabolic functions, such as esterase (diazonium salt) and dehydrogenase activity (5-cyano-2,3-ditolyl tetrazolium chloride). 3.2. Flow Cytometry Flow cytometry, which was referred to as a fluorescence-activated cell sorter in the 1960s, was designed by Bonner, Sweet, Hulett, and Herzenberg. In 1978, the instrument became commercially available and was officially called ‘flow cytometry’. It allowed for the detection of white blood cells through the use of monoclonal antibodies. Within the next couple of decades, the number of applied fluorescent dyes and processing parameters greatly increased [ 32 ]. Flow cytometry is a multi-purpose detection device. Developed from fluorescence spectroscopy, it drives cells through a small orifice individually to initiate complex detection of each cell [ 33 ]. The narrow flow channel is equipped with a multi-color laser beam that can detect each passing cell. Electronic signals such as emitted fluorescence and forward and side scatter light are collected by a computer and translated into specific cellular information. Forward and side scatter light detect cellular size and surface evenness, whereas fluorescence provides positive signals that differentiate cells from non-relevant particles [ 34 ]. This sophisticated setting promises comprehensive detection of multiple physiological characteristics simultaneously with high speed and high resolution, thus qualifying as a widely used bacterial quantification method for heterogeneous microbiota specimens. The most commonly used stain for bacteria is SYBR green (1 or 10 μL/mL; 1:100 diluted in DMSO; 15 min at 37 °C) with the emission detector set at FL1 533/30 nm and FL3 > 670 nm [ 35 ]. Forward and side scattered signals are recorded simultaneously to assist in signal identification. Flow speeds from 17 to 200 μL/min were used in different studies [ 35 , 36 , 37 ]. Background disturbance is a problem because minerals, plant particles, and bacterial debris emit weak fluorescence signals without staining [ 38 ]. SYBR green is a strong stain that can greatly increase the fluorescence signal, which helps distinguish bacterial cells from the ‘background’ ( Figure 2 a–d). Vandeputte et al., 2017 set a threshold of 2000 on the FL1 channel to exclude non-significant background signals, also known as the negative signal. Under some circumstances (e.g., bovine respiratory microbiome quantification), a threshold on the FL1 channel is not enough to rule out all irrelevant compounds contained in the buffer. Hence, running a negative control of only buffer is necessary to guide the gating strategies ( Figure 2 e,f). Furthermore, the flow cytometer-based bacteria enumeration method has a low detection limit between 10 3 –10 4 CFU/mL, which allows the detection of a wide range of sample types, such as fecal, soil, and aquatic organisms [ 11 , 39 ] ( Table 1 ). Figure 2. Flow cytometer plots of the same specimens (culture-enriched feces consortium with more background noise: ( a , b ); pure culture of E. coli : ( c , d )) with or without SYBR green staining (blue: non-stained; red stained). Flow cytometer plotting of buffer was used as gating guidance to exclude noises (negative control, ( e )). Gating strategy used for bovine respiratory microbial quantification ( f ). 3.3. Spike-In with Reference Markers Another fast and advanced method often combined with high throughput sequencing is spiking the specimens with internal microorganism markers ( Table 1 ). The cell numbers and target nucleotide sequence of the internal markers are known, which allows for the calculation of the absolute bacterial number. This strategy simulates the capture-mark-recapture method used to evaluate wild animal populations, in which each processed sample spiked with a known amount of a microbial marker. The original bacterial load is calculated by dividing the absolute internal markers count by the relative abundance of internal markers [ 40 ]. There are different types of spiking markers that were used previously, including indigenous microorganism, synthetic, and heterogeneous markers. The marker selection and spiking strategy can be challenging since only validated markers can be used to achieve reliable results. More details of marker use will be discussed in later sections. 3.4. 16S qPCR and qRT-PCR Quantification Polymerase chain reaction (PCR), invented in the 1980s, was a major breakthrough and is used across a wide range of fields in biological science. The technique amplifies specific nucleic acid sequences in the template by millions-fold, which can be detected by incorporating certain fluorescent labels [ 41 ]. The target template can be genomic DNA or complementary DNA (reverse transcription product of mRNA, cDNA). The PCR technique subsequently evolved to possess more robust capabilities such as the enumeration of nucleic acid sequence copies such as quantitative polymerase chain reaction (qPCR). The 16S rRNA qPCR, a frequently used tool for gene expression detection and quantification in real-time, is commonly used for both absolute and relative quantification [ 42 , 43 ]. Absolute quantification is accomplished using a standard curve produced by amplifying a series of diluted DNA standards of known concentrations and copy numbers to convert threshold cycles to the absolute quantity of the target gene (16S rRNA gene). Circular plasmid DNA containing the gene of interest [ 42 , 44 ] and reference organism DNA [ 45 ] at different serial dilutions have been widely used as DNA templates to generate standard curves. 16S qPCR has been widely used as a complementary absolute quantification method that can be integrated into next-generation sequencing but provides only relative quantification. In parallel with normal library construction targeting the 16S rRNA hypervariable regions, the same universal bacterial primer set for next-generation sequencing was used in qPCR for total bacterial load quantification in each sample. Of note, when reference organism DNA is used as the standard, the total abundance for each taxon should be corrected for differences in the 16S rRNA copy number, which can be found in the rrnDB database [ 45 ]. Reverse transcription qPCR (qRT-PCR), which targets mRNA in actively metabolizing cells, can also be used for absolute quantification with a higher sensitivity compared to regular qPCR. Here, mRNA is converted to cDNA via reverse transcription and subsequently quantified using qPCR [ 46 ]. qRT-PCR has been used for bacterial detection and quantification when it is necessary to determine the number of active bacteria, such as in clinical settings, food industry, and activated sludge (wastewater remediation) [ 47 , 48 , 49 , 50 ]. Using 16S rRNA qPCR and qRT-PCR for absolute quantification is simple, economical, and highly sensitive [ 51 ]. 3.5. Droplet Digital PCR (ddPCR) Another PCR method used for absolute quantification is droplet digital PCR (ddPCR; Table 1 ), which was created in 2011. In this method, each 20 µL PCR reaction is distributed into approximately 20,000 ‘water-in-oil droplets’, which allows for the amplification of a single template. After amplification, flow cytometry is used to read the droplets. Each droplet is then scored as either 0 or 1, signifying a negative or positive digital facet of this method. These values are used for absolute quantification, which is calculated using Poisson statistics, and therefore, no standard curve is required [ 52 , 53 , 54 , 55 ] ( Figure 3 ). ddPCR can amplify as little as one copy per droplet [ 56 ]. Multiple studies have used ddPCR to enumerate total bacteria (using 16S primers) or specific classes of bacteria (using species- or taxon-specific primers). Ziegler et al., 2019 used ddPCR to quantify the bacterial DNA in the blood from patients with bloodstream infections. The results suggested that ddPCR could be used to quantify both the broad range of bacterial load and species-specific ddPCRs ( Staphylococcus aureus , Streptococcus pneumoniae , and Escherchia coli ) with similar sensitivities [ 57 ]. Studies have found that overall qPCR and ddPCR results are comparable, but that ddPCR was able to enumerate samples with lower target concentrations than qPCR when using Lactobacillus specific primers [ 53 ]. Also, the detection limit was lower and the detection range was wider for 16S ddPCR when compared to 16S qPCR [ 54 ]. Furthermore, compared to 16S qRT-PCR, 16S ddPCR was 10x more sensitive [ 55 ]. In addition, ddPCR can accurately quantify samples with a low abundance of the target gene and reduce background noise in negative control samples. This is demonstrated by ddPCRs significantly lower coefficients of variation and its ability to detect lower numbers of 16S rRNA gene copies compared to qPCR, while the sample 16S rRNA gene copies were the same [ 54 ]. Figure 3. General workflow of droplet digital PCR. DNA template was individually partitioned into approximately 20,000 ‘water-in-oil droplets’. After PCR amplification, flow cytometry is used to read the droplets. Each droplet is then scored as either 1 or 0, which signifies positive or negative and represents this method’s digital facet. These values are then used for absolute quantification using Poisson statistics. 4. Decision-Making Regarding Different Biological Questions 4.1. Differentiation between Active and Dead Cells Among these quantification methods, fluorescence spectroscopy, flow cytometry, and 16S qRT-PCR possess the ability to distinguish dead or enzymatically active cells from total cells in a sample ( Figure 4 ). Fluorescence spectroscopy and flow cytometry mainly exclude the dead cells with incomplete membranes through the utilization of membrane-impermeable dyes such as Sytox [ 58 ]. Roth et al., 1997 enumerated the beta-lactam antibiotic-resistant E. coli , contingent on cell membrane integrity, using flow cytometry and Sytox [ 31 ]. In addition, active bacterial quantification can be accomplished using certain dyes targeting metabolic activities, such as esterase and dehydrogenase activity [ 59 , 60 ]. Esterase activity is an indirect bacterial quantification method detecting fluorescence produced from cleaved esterase substrates by a local enzyme. Dehydrogenase activity can be measured using histochemical indicators, such as tetrazolium salt (5-cyano-2,3-ditolyl tetrazolium chloride), a typical indicator for respiratory activity that is used for active bacterial quantification [ 61 , 62 ]. However, metabolic activities do not indicate the viability of bacteria, especially when energy-independent enzymatic indicators are used. Certain enzyme activities can continue for more than a week after bacterial deactivation [ 59 ]. These differences can lead to discrepancies in data gathered using different metabolism-based quantification methods. Figure 4. Decision-making process of absolute quantification methods. Since transcription only occurs in live cells, qRT-PCR targeting mRNA can be used to quantify viable bacteria. Ma et al., 2018 used qRT-PCR and a standard curve to detect and quantify viable bacteria that have a high tolerance to antibiotic chemotherapy on spacers used in “two-stage revision total knee arthroplasty” [ 47 ]. Dolan et al., 2009 used qRT-PCR to quantify total viable bacteria present on beef carcasses to develop an alternative to the total viable count culture technique used to predict shelf life, and no significant differences were found when comparing the two quantification methods. However, they targeted the ribonuclease-P transcript rather than 16S rRNA [ 48 ]. Additionally, Bui et al., 2012 targeted 16S rRNA, as well as dnaJ and ciaB mRNA, utilizing qRT-PCR to detect and quantify Campylobacter jejuni in ‘naturally contaminated’ and spiked chicken fecal samples to determine if qRT-PCR could be used as an alternative to Campylobacter culture-based quantification. They concluded that qRT-PCR performed on the spiked fecal samples to measure C. jejuni survival was similar to results obtained via the culture method [ 49 ]. Furthermore, Johnston and Behrens., 2020 used 16S qRT-PCR, 16S qPCR, and next-generation sequencing to analyze the activated sludge microbiome from material used in wastewater remediation that were processed throughout the year [ 50 ]. Therefore, qRT-PCR serves as a sound approach to quantify live bacteria cells. 4.2. Absolute Quantification of Specific Taxa of Interest Absolute quantification of specific taxa can be achieved with a simple calculation: multiplying the relative abundance of the taxa generated by 16S rRNA amplicon sequencing with total cell counts. However, various technical biases could potentially be introduced into the results when using different absolute and relative quantification mechanisms, such as 16S rRNA copy number discrepancy and PCR primer coverage and specificity [ 63 ]. Alternatively, 16S qPCR, 16S RT-qPCR, and ddPCR could all directly detect taxa of interest using specifically designed primers without the need for total bacterial quantification ( Figure 4 ). Gobert et al., 2018 used both ddPCR and qPCR to quantify lactic acid-producing bacteria in piglet feces using Lactobacillus -specific primers [ 53 ]. Jian et al., 2020 applied an additional qPCR technique on four 10-log-fold diluted reference bacteria (i.e., Bacteroidetes , Clostridium cluster XIVa , Bifidobacterium, and Escherichia coli ) to quantify their absolute cell counts in feces, which were highly correlated with their absolute quantifications achieved by next-generation sequencing and total cell numbers. The total abundance for each taxon was corrected based on the 16S rRNA copy number, which could be found in the rrnDB database [ 45 ]. In addition, Matsuda et al., 2009 analyzed the predominant and subdominant members of the fecal microbiota from 40 healthy individuals using both 16S and 23S qRT-PCR and found that qRT-PCR was more sensitive than qPCR [ 64 ]. However, it is important to note that 16S rRNA transcript copy number is more indicative of protein synthesis potential, while 16S rRNA gene copy number is more indicative of the overall sample cell count [ 50 ]. Another concern associated with qRT-PCR is the risk of RNA degradation [ 65 ]. Another method that can directly enumerate specific taxa is fluorescence in situ hybridization (FISH), which recruits a fluorescently labeled probe that can hybridize the complementary sequences in the targeted cells. Because of its high sensitivity, it has been used to detect and/or quantify low abundance microbes and those with “low ribosome content” [ 66 , 67 ]. Although FISH provides only a relative abundance measurement, it can be combined with flow cytometry and microscopy to determine the absolute abundance of each taxon of interest independently of all bacterial members [ 63 , 68 , 69 ]. Furthermore, applying FISH with multiple dye-probe combinations allows for the detection of different types of bacteria simultaneously. Kuo et al., 2021 designed four different probes using dyes Cy3, FAM, Texas red, and Cy5, respectively, and successfully detected four coliform bacteria ( E. coli , K. pneumoniae , E. aerogenes , and C. freundii ) in water samples [ 70 ]. Detecting rare taxa in a community using FISH requires a great number (500–1000) of counted cells to maximize the precision of the targeted count [ 67 ]. 4.3. Absolute Quantification of Low Biomass Bacterial Samples Enumeration of low bacterial counts on sterile and non-sterile pharmaceutical equipment and products requires techniques with high sensitivity and precision, as well as the ability to exclude background noise. Quantitative methods that have been widely used in such areas include cell culture, qPCR, ddPCR, and flow cytometry [ 51 , 71 , 72 , 73 , 74 , 75 ] ( Figure 4 ). Culture-based quantification is impractical due to its low sensitivity, inaccuracy, intense labor, and immense time consumption. PCR-based approaches possess high sensitivity and short turnaround time, while flow cytometry, besides the benefits previously mentioned, can distinguish cell populations based on physiological features. Ahn et al., 2020 further compared these four absolute quantification approaches using twenty serial-diluted (1, 10, 100, and 1000 CFU/mL) strains of Burkholderia cepacia . Both qPCR and ddPCR successfully measured low genomic DNA ( B. cepacia PC783 and B. cenocepacia J2315) concentrations at 14.4 target copies/μL. ddPCR had a 10-fold greater sensitivity and was able to detect as low as 1.4 copies of B. cenocepacia J2315 DNA [ 51 ]. The high sensitivity of ddPCR was also demonstrated by Zeng et al., 2020 who used it to accurately quantify Streptococcus agalactiae levels as low as 5 pg/μL [ 76 ]. However, Ahn et al., 2020 found that ddPCR had a high detection limit, requiring DNA at 1.4 × 10 5 target copies/μL [ 51 ]. In another study, Sze and colleagues also found that samples with estimated DNA copy numbers greater than 10 5 must be diluted before quantification [ 54 ], which greatly increases sample processing time. Therefore, ddPCR requires a primary concentration estimation prior to dilution factor determination and 16S rRNA copy number conversion after dilution [ 77 ]. Overall, flow cytometry, qPCR, and ddPCR had greater detection capabilities (70.3%, 43.5%, and 66.8%, respectively) than culture-based methods (18.3% to 25.5%) when using nuclease-free water as the common suspension medium. Culture-enriched molecular profiling serves another important biological role. It can reveal low biomass and rare taxa in a bio-environment that failed to be detected by next-generation sequencing because of shallow sampling depth [ 78 ]. Although such methods provide less value in terms of absolute versus relative quantification, they can identify otherwise undetected bacterial types, which may play important roles in diversity and community dynamics. Enumeration of environmental air microbiotas still depends on culture and microscopy-related approaches in most cases due to the ultra-low biomass of these types of samples [ 75 , 79 ]. Extra steps are needed for microbiota amassment prior to quantification and sequencing to obtain enough DNA for processing, and these steps can influence DNA yields for a variety of reasons. Luhung et al. 2021 evaluated the effects of air flow rate, time interval, sonication wash, detergent, and other adjustments on bacterial recovery and DNA yield during the amassment. Specifically, the filter paper used for collecting air microbiota can be washed with PBS buffer to achieve a better microorganism recovery rate compared to direct DNA extraction from the filter paper. Additional sonication during washing had no impact on quantitative and metagenomic outcomes; however, washing with detergent increased the total DNA yield for both bacterial and fungal counts and their compositional profiling. Furthermore, overnight pre-incubation of samples at 55 °C greatly improved cellular lysis, especially for fungal analysis [ 25 ]. 4.4. Rapid Quantification for a Large Number of Samples Although ddPCR, flow cytometry, CARD-FISH, and cell culture can fulfill most quantification requirements for various kinds of biological studies (high sensitivity, specific taxa targeting, and low biomass detectability), the sample preparations and quantification procedures are very time consuming and laborious, especially for large sample sizes ( Figure 4 ). In contrast, qPCR, qRT-PCR, and spike-in require fewer steps and shorter operation times. qPCR and qRT-PCR, combined with a standard curve, can be used as complementary quantification methods for total bacterial counts that can be integrated with the downstream compositional analysis generated by sequencing. The spike-in method can be integrated into next-generation sequencing. It can provide absolute and relative quantifications simultaneously with simple operational steps, enabling rapid processing of many samples. However, spiking marker selection and spiking concentration are critical to the sequencing quality and the accuracy and sensitivity of the quantification. The spiked internal reference(s) should either not be or be rarely present in real specimens. Implementing this will avoid the addition of irrelevant reads to the samples and prevent further changing of the community structure. Background calibration of internal reference-like microbes for all samples largely increases the workload and complexity. Yang and his colleagues applied a spiked marker Escherichia coli O157:H7 into specimens for Miseq sequencing, which later was designated as “ Escherichia genus”. This genus was also present in the soil samples; thus, additional steps were needed to distinguish the indigenous Escherichia genus from the total detected amount [ 40 ]. In another study by Lou, who used the commercial strain Escherichia coli O157:H7 (EDL933) as an internal reference, a single-copy gene, fliC, was used for absolute quantification of EDL933 in a soil specimen using a standard curve of serially diluted fliC gene-inserted plasmids [ 80 ]. Although the indigenous reference-like bacteria in both the above-mentioned studies turned out to be negligible, extra caution was necessary when using strains that were already present in a specimen. Besides, adding those strains contributed to dose-dependent variations in the overall bacterial community structure, making the situation more complex [ 40 ]. Spiking non-relevant bacteria into specimens does not require indigenous calibration once the absolute bacterial load of the internal reference can be specifically and accurately quantified. In previous spike-in studies, Salinibacter ruber (hypersaline environments), Rhizobium radiobacter (soil), and Alicyclobacillus (thermo-acidophilic) were chosen as internal references for quantifying gut microbial specimens [ 7 ], while Aliivibrio fischeri or Thermus thermophiles , mostly found in marine animals, were used in soil specimens [ 2 ]. Titration in both studies was achieved by spiking the same number of internal references into serially diluted specimens or spiking serially diluted internal references into the same amount of sample to validate the accuracy of the spike-in quantification method. Overall, there was a linear relationship (0.6 < \|r\| < 0.96) between estimated total bacteria load (by internal references) and the total sample amount used for DNA extractions. This relationship indicated the internal reference spike-in method was a success, although variations were discovered when using different reference strains. In order to avoid altering the microbial community structure by incorporating internal references, 16S rRNA with artificially replaced variable regions was used as an internal reference [ 10 ]. This synthetic internal reference can be detected by high throughput sequencing techniques with real samples because it maintains the 16S rRNA conserved region. The aligned sequence cannot be classified to any database in NCBI, est, and est_human. Also, microbial structures were not affected by the insertion of synthetic internal references indicated by OTU richness and Bray–Curtis dissimilarity analysis. The amount of internal reference used determines the calibration accuracy and sequencing quality. Overloading internal references will reduce the total reads generated from real microbial samples and decreases the sequencing depth, whereas spiking a low amount of internal references may not serve as a functional internal control. In the 10-fold titration model, adding 1% internal reference increased the coefficient of determination of the linear regression model from 0.79 to 0.91 compared to what was achieved by inserting 0.1% internal reference [ 2 ]. Moreover, spiking a serially diluted internal reference (except synthetic references) into soil specimens contributes to various community structure alterations, leading to bias in the original sample [ 40 ]. Hence, preliminary testing for a qualified range of internal reference content is important, especially in specimens with a large amount of community variation. Adding internal references to a sample before (whole cells) or after (extracted DNA) processing can result in a slightly different calibration mechanism. Adding such a reference before DNA extraction can normalize the variations generated from DNA extraction [ 10 ]. Moreover, commercial extraction kits and protocols have different efficiencies regarding the recovery of total genomic DNA [ 27 ]. Overall, high throughput sequencing with an accompanying universal internal reference is a functional method for determining the absolute bacterial counts in samples. 4.5. Absolute Quantification of Bacteria Based on Other Features Under certain circumstances, a subgroup of bacteria with specific molecular features such as morphology, function, and interactive activity may need to be distinguished ( Figure 4 ). For instance, in aquatic environments, bacteria potentially carry either low or high nucleic acid content (LNA and HNA), representing two main groups with different metabolic and ecological properties [ 81 , 82 ]. LNA bacteria have stronger resistance to the stresses encountered in severe marine environments than HNA, while HNA have a greater metabolic rate than LNA, except in barren environments [ 83 ]. Studying the distribution of these two bacterial groups could provide more insights into interpreting the relationships between microorganisms and the marine environment. Hence, for such purposes, a single-cell enumeration method using flow cytometry that records physical and chemical characteristics is frequently used for most aquatic microbiome studies such as sea, sewage, lake, and drinking water [ 37 , 84 , 85 , 86 ]. Specifically, green fluorescence intensity from HNA is 3–5 times greater than LNA and serves as the main separation criteria for these two cell populations [ 37 , 84 , 87 ]. The LNA and HNA can be gated by a duo-parameter scatter-plot of green fluorescence (520 nm) against side scatter [ 37 ]. Using this gating and staining strategy, the distribution of LNA and HNA was revealed to be significantly associated with the season, salinity, and chlorophyll-α [ 88 , 89 ]. Another technique that can be used prior to compositional analysis to separate the substances based on size (rate-zonal centrifugation) and density (isopycnic centrifugation) is density gradient centrifugation. This allows direct downstream analysis of each subpopulation. This method has been used to separate aquatic microbes that differ in cell size and metabolic properties, including isolating viruses of interest from background noises [ 90 , 91 , 92 , 93 , 94 ]. It can be combined with other absolute quantification approaches such as flow cytometry and qPCR to enumerate bacterial groups with similar morphology. By targeting functional or phylogenetic marker genes, qPCR can enumerate groups of bacteria with certain biological functions. Blaud et al., 2021 quantified ammonia-oxidizing bacteria abundances that play an important role in nitrification by targeting the amoA gene via qPCR [ 95 ]. In another published study, absolute copy numbers of nitrogen-related functional genes ( amoA , narG , napA , nirS , nirK, and nosZ ) were quantified by qPCR to evaluate the effects of phosphogypsum and medical stone on nitrogen gas emissions during aerobic composting [ 96 ]. Catalyzed reporter deposition (CARD)-FISH is an improved version of FISH that has a 200-fold greater sensitivity than FISH and can be used to analyze physiology, metabolic activity, and ecological interactions [ 67 , 68 , 97 , 98 ]. Besides the benefits of specific taxa detection, double CARD-FISH using multiple fluorescent tracers allows the exhibition of the processes of interactive activities directly among communities, such as predator-prey interactions [ 99 ]. Using CARD-FISH together with Taq-sequencing allowed the morphological visualization of certain rare or uncultured taxon-specific cells ( Rozellomycota s./.) [ 100 ]. Furthermore, this approach can be combined with flow cytometry and next-generation sequencing to explore compositional dynamics and shed light on ecological interactions between different microbes [ 68 , 101 ]. 5. Conclusions In conclusion, compositional profiling based solely on relative abundance that is generated by 16S rRNA sequencing can lead to an incorrect interpretation of microbiota dynamics. Recently, methodologies regarding rapid and precise absolute counts have gained a renewed prominent focus. Fluorescence spectroscopy, flow cytometry, and 16S qRT-PCR possess the capabilities to enumerate only viable bacterial cells. Additionally, a bacterial community can be quantified into subgroups based on morphology, size, density, cellular functions, and interactive relationships. These specific features can be recognized using flow cytometry, qPCR, and CARD-FISH with or without extra sample processing, such as density gradient centrifugation. Depending on different sample types, cell culture, qPCR, ddPCR, and flow cytometry have been utilized for absolute quantification of samples with low biomass. Among these methods, ddPCR had the lowest detection limit. When direct quantification of specific taxa is needed, 16S qPCR, 16S RT-qPCR, and ddPCR can be applied using specifically designed primers. FISH combined with flow cytometry also offers an advanced approach for targeting specific taxa. However, some of these quantification approaches are laborious and increase the required workload, especially when targeting specific taxa. When absolute abundance is preferred, spiking internal references into raw specimens offers a practical and time-saving method for quantification in studies requiring a large number of samples. However, choosing the appropriate spiking reference selection and concentration is crucial to maximizing the sequencing quality, accuracy, and sensitivity of the quantification. We have discussed the most widely used bacterial load quantification methods, including fluorescence spectroscopy, flow cytometry, 16S qPCR, 16S qRT-PCR, ddPCR, and reference spike-in from various biological angles and provided a systematic decision-making scheme for future microbial investigations. Author Contributions X.W., S.H., and J.Z. wrote and edited the manuscript; X.W. and F.D. graphed the charts; X.W. and S.H. generated the table. All authors have read and agreed to the published version of the manuscript. Funding This manuscript was partially funded by USDA NIFA, grant number (2018-67015-27479). Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. References Zhang, Z.; Qu, Y.; Li, S.; Feng, K.; Wang, S.; Cai, W.; Liang, Y.; Li, H.; Xu, M.; Yin, H. 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Active bacteria quantification can be accomplished using certain dyes targeting metabolic functions, such as esterase (diazonium salt) and dehydrogenase activity (5-cyano-2,3-ditolyl tetrazolium chloride). Figure 2. Flow cytometer plots of the same specimens (culture-enriched feces consortium with more background noise: ( a , b ); pure culture of E. coli : ( c , d )) with or without SYBR green staining (blue: non-stained; red stained). Flow cytometer plotting of buffer was used as gating guidance to exclude noises (negative control, ( e )). Gating strategy used for bovine respiratory microbial quantification ( f ). Figure 3. General workflow of droplet digital PCR. DNA template was individually partitioned into approximately 20,000 ‘water-in-oil droplets’. After PCR amplification, flow cytometry is used to read the droplets. Each droplet is then scored as either 1 or 0, which signifies positive or negative and represents this method’s digital facet. These values are then used for absolute quantification using Poisson statistics. Figure 4. Decision-making process of absolute quantification methods. Table 1. Absolute quantification methods in microbiome studies. Absolute Quantification Method Major Applications (Published) Advantages Limitations/Concerns References Fluorescence spectroscopy Aquatic, soil, food and beverage, and air High affinity; multiple dye selection to distinguish both live and dead cells Fail to stain dead cells with complete DNA degradation; some dyes bind both DNA and RNA Gordon et al., 2017, Guzaev et al., 2017, Saint-Ruf et al., 2010, Sieracki et al., 1999, Auty et al., 2001, CARD-FISH + flow cytometry/qPCR Aquatic Direct quantification of specific taxa; detects both live and dead cells; provides insights for function, morphology, and ecology among taxa Large population of cells are required for rare taxa detection; possibility of unspecific probe binding; Sample fixation may cause operation and efficiency biases; background noise Hinzke et al., 2021, Kuo et al., 2021, Piwosz et al., 2021, Priest et al., 2021, Neuenschwander et al., 2015, Kubota et al., 2013 Flow cytometry Feces, aquatic, and soil Rapid; single cell enumeration; flexible parameters based on physiological characteristics; capability to differentiate live and dead cells Background noise exclusion may be required; gating strategy; dilution may be required; not ideal for complex systems/heterogeneous samples Luhung et al., 2021, Heinrichs et al., 2021, Xu et al., 2021, Zhu et al., 2019, Deng et a., 2019, Vandeputte et al., 2017, Prest et al., 2013, Berney et al., 2007, Longnecker et al., 2005, Salcher et al., 2011 Spike-in with internal reference Soil, sludge, and feces Rapid; easy incorporation into high throughput sequencing; high sensitivity; easy handling Internal reference, spiking amount, and spiking time point can greatly affect the accuracy; 16S rRNA copy number calibration possibly needed. Yang et al., 2018, Tourlousse et al., 2017, Smets et al., 2016, Lou et al., 2018, Stämmler et al., 2016 16S qPCR Feces, clinical (lung), soil, plant, air, and aquatic Directly quantifies specific taxa; cost-effective and easy handling; high sensitivity; compatible with low biomass samples 16S rRNA copy number calibration may be needed; PCR-related biases exist; standard curves are required Luhung et al., 2021, Callegari et al., 2021, Blaud et al., 2021, Lei et al., 2021, Jian et al., 2020, Vandeputte et al., 2017, Stoddard et al., 2015, Sze et al., 2014, Brankatschk et al., 2012 16S qRT-PCR Clinical (joint infection), food safety, feces, sludge, water remediation, and soil High resolution and sensitivity; directly quantifies specific taxa; detects active cells; compatible with low biomass samples More of an approximation for protein synthesis than overall cell count; unstable RNA/RNA degradation; 16S rRNA copy number calibration may be needed Ma et al., 2018, Johnston and Behrens, 2020, Bui et al., 2012, Boyer and Combrisson, 2013, Kim et al., 2014, Stoddard et al., 2015, Matsuda et al., 2009 ddPCR Clinical (lung, bloodstream infection), air, feces, and soil Applicable to low concentrations of DNA; directly quantify specific taxa; high throughput capabilities, and no standard curve needed; compatible with low biomass samples Dilutions are required for high concentrated template; may require a large number of replicates Luhung et al., 2021, Ahn et al., 2020, Zeng et al., 2020, Sze et al., 2014, Kim et al., 2014, Ziegler et al., 2019, Gobert et al., 2018 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. AMA Style Wang X, Howe S, Deng F, Zhao J. Current Applications of Absolute Bacterial Quantification in Microbiome Studies and Decision-Making Regarding Different Biological Questions. Microorganisms. 2021; 9(9):1797. https://doi.org/10.3390/microorganisms9091797 Chicago/Turabian Style Wang, Xiaofan, Samantha Howe, Feilong Deng, and Jiangchao Zhao. 2021. "Current Applications of Absolute Bacterial Quantification in Microbiome Studies and Decision-Making Regarding Different Biological Questions" Microorganisms9, no. 9: 1797. https://doi.org/10.3390/microorganisms9091797 Wang, X.; Howe, S.; Deng, F.; Zhao, J. Current Applications of Absolute Bacterial Quantification in Microbiome Studies and Decision-Making Regarding Different Biological Questions. Microorganisms 2021, 9, 1797. https://doi.org/10.3390/microorganisms9091797 AMA Style Wang X, Howe S, Deng F, Zhao J. Current Applications of Absolute Bacterial Quantification in Microbiome Studies and Decision-Making Regarding Different Biological Questions. Microorganisms. 2021; 9(9):1797. https://doi.org/10.3390/microorganisms9091797 Wang, Xiaofan, Samantha Howe, Feilong Deng, and Jiangchao Zhao. 2021. "Current Applications of Absolute Bacterial Quantification in Microbiome Studies and Decision-Making Regarding Different Biological Questions" Microorganisms9, no. 9: 1797. https://doi.org/10.3390/microorganisms9091797	https://www.mdpi.com/2076-2607/9/9/1797
Publications - Global Disability Innovation Hub The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good. Type Journal Paper Themes Assistive & Accessible Technology Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems Jamie Danemayer,Cathy Holloway,Youngjun Cho, Nadia Berthouze, Aneesha Singh, William Bhot, Ollie Dixon, Marko Grobelnik, John Shawe-Taylor Paper highlights: Assistive technology (AT) information networks are insular among stakeholder groups, causing unequal access to information. Participants often cited fragmented international marketplaces as a barrier and valued info-sharing across industries. Current searches produce biased results in marketplaces influenced by commercial interests and high-income contexts. Smart features could facilitate searching, update centralised data sources, and disseminate information more inclusively. International Journal of Human-Computer Studies; 2023 Abstract Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems Ninety percent of the 1.2 billion people who need assistive technology (AT) do not have access. Information seeking practices directly impact the ability of AT producers, procurers, and providers (AT professionals) to match a user's needs with appropriate AT, yet the AT marketplace is interdisciplinary and fragmented, complicating information seeking. We explored common limitations experienced by AT professionals when searching information to develop solutions for a diversity of users with multi-faceted needs. Through Template Analysis of 22 expert interviews, we find current search engines do not yield the necessary information, or appropriately tailor search results, impacting individuals’ awareness of products and subsequently their availability and the overall effectiveness of AT provision. We present value-based design implications to improve functionality of future AT-information seeking platforms, through incorporating smarter systems to support decision-making and need-matching whilst ensuring ethical standards for disability fairness remain. Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems Type Journal Paper Themes Assistive & Accessible Technology Evaluating the use of a thermoplastic socket in Kenya: A pilot study Giulia Barbareschi, Wesley Teerlink, Josepg Gakunga Njuguna, Purity Musungu, Mary Dama Kirino, andCatherine Holloway According to estimates from the World Health Organization, in 2010, there were more than 30 million people in need of prosthetic and orthotic devices across Africa, Asia, and Latin America. 1This number is likely to have grown significantly in the past decade, in line with trends recorded for the general need of assistive technology. 2For many people who undergo a lower limb amputation, access to an appropriate prosthesis is essential to restore functional mobility and ensure good quality of life. 3Ultimately, an appropriate lower-limb prosthesis (LLP) can enable people with amputation to fulfill their desired role in their family, work, and community life. 4 Prosthetic and Orthotics International; 2022 Abstract Evaluating the use of a thermoplastic socket in Kenya: A pilot study Background: Many people with amputations who live in low-resourced settings struggle to access the workshops where qualified prosthetists provide appropriate care. Novel technologies such as the thermoplastic Confidence Socket are emerging, which could help facilitate easier access to prosthetic services. Objectives: The objective of this study was to evaluate the satisfaction and the performance of transtibial prosthesis featuring the Confidence Socket. Study design: This is a longitudinal repeated-measures design study. Methods: A convenience sample of 26 participants who underwent transtibial amputation were fitted with the Confidence Socket. The performance of the socket was evaluated after a follow-up period between 1 month and 6 months using the L test of functional mobility and the amputee mobility predictor. Satisfaction with the prosthesis was measured using the Trinity Amputation and Prosthetic Experience Scales and purposefully designed 7-point Likert scales. Results: Ten of the 26 participants returned for follow-up. Perceived activity restriction and L test times improved significantly at follow-up, but the self-reported satisfaction with the Confidence Socket was lower at follow-up compared with that after fitting. Conclusions: The Amparo Confidence Socket represents a potentially viable alternative to improve access to appropriate prosthesis in Kenya, but some aspects of users’ self-reported satisfaction should be further investigated. Cite Evaluating the use of a thermoplastic socket in Kenya: A pilot study Barbareschi G, Teerlink W, Njuguna JG, Musungu P, Kirino MD, Holloway C. Evaluating the use of a thermoplastic socket in Kenya: A pilot study. Prosthet Orthot Int. 2022 Oct 1;46(5):532-537. doi: 10.1097/PXR.0000000000000130. Epub 2022 Mar 25. PMID: 35333813; PMCID: PMC9554758. Evaluating the use of a thermoplastic socket in Kenya: A pilot study Type Journal Paper Themes Assistive & Accessible Technology Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges Jamie Danemayer, Andrew Young, Siobhan Green, Lydia Ezenwa, Michael Klein This study synthesizes learnings from three distinct datasets: innovator applications to the COVIDaction data challenges, surveys from organizers from similarly-aimed data challenges, and a focus group discussion with professionals who work with COVID-19 data. Thematic and topic analyses were used to analyze these datasets with the aim to identify gaps and barriers to effective data use in responding to the pandemic. Data & Policy; 2023 Abstract Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges Innovative, responsible data use is a critical need in the global response to the coronavirus disease-2019 (COVID-19) pandemic. Yet potentially impactful data are often unavailable to those who could utilize it, particularly in data-poor settings, posing a serious barrier to effective pandemic mitigation. Data challenges, a public call-to-action for innovative data use projects, can identify and address these specific barriers. To understand gaps and progress relevant to effective data use in this context, this study thematically analyses three sets of qualitative data focused on/based in low/middle-income countries: (a) a survey of innovators responding to a data challenge, (b) a survey of organizers of data challenges, and (c) a focus group discussion with professionals using COVID-19 data for evidence-based decision-making. Data quality and accessibility and human resources/institutional capacity were frequently reported limitations to effective data use among innovators. New fit-for-purpose tools and the expansion of partnerships were the most frequently noted areas of progress. Discussion participants identified building capacity for external/national actors to understand the needs of local communities can address a lack of partnerships while de-siloing information. A synthesis of themes demonstrated that gaps, progress, and needs commonly identified by these groups are relevant beyond COVID-19, highlighting the importance of a healthy data ecosystem to address emerging threats. This is supported by data holders prioritizing the availability and accessibility of their data without causing harm; funders and policymakers committed to integrating innovations with existing physical, data, and policy infrastructure; and innovators designing sustainable, multi-use solutions based on principles of good data governance. Cite Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges Danemayer, J., Young, A., Green, S., Ezenwa, L., & Klein, M. (2023). Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges. Data & Policy, 5, E11. doi:10.1017/dap.2023.6 Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges Type Editorial Themes Culture and Participation COVID-19 as social disability: the opportunity of social empathy for empowerment Ikenna D Ebueny, Emma M Smith,Catherine Holloway, Rune Jensen, Lucía D'Arino, Malcolm MacLachlan Social empathy is ‘the ability to more deeply understand people by perceiving or experiencing their life situations and as a result gain insight into structural inequalities and disparities’. Social empathy comprises three elements: individual empathy, contextual understanding and social responsibility. COVID-19 has created a population-wide experience of exclusion that is only usually experienced by subgroups of the general population. Notably, persons with disability, in their everyday lives, commonly experience many of the phenomena that have only recently been experienced by members of the general population. COVID-19 has conferred new experiential knowledgeon all of us. We have a rare opportunity to understand and better the lives of persons with disabilities for whom some aspects of the COVID- 19 experience are enduring. This allows us greater understanding of the importance of implementing in full a social and human rights model of disability, as outlined in the UNCRPD. BMJ Global Health; 2020 Abstract COVID-19 as social disability: the opportunity of social empathy for empowerment COVID-19 has conferred new experiential knowledge on society and a rare opportunity to better understand the social model of disability and to improve the lives of persons with disabilities. The COVID-19 experience may offer contextual knowledge of the prepandemic lives of persons with disabilities and foster greater social awareness, responsibility and opportunities for change towards a more inclusive society. Information, family and social relationships, health protection and healthcare, education, transport and employment should be accessible for all groups of the population. The means must be developed and deployed to ensure equity – the deployment of resources so that people with different types of needs have the same opportunities for living good lives in inclusive communities. We have learnt from COVID-19 that inclusive healthcare and universal access should be the new normal, that its provision as a social good is both unifying and empowering for society as a whole. COVID-19 as social disability: the opportunity of social empathy for empowerment Ebuenyi ID, Smith EM, Holloway C , et alCOVID-19 as social disability: the opportunity of social empathy for empowerment BMJ Global Health2020;5:e003039. COVID-19 as social disability: the opportunity of social empathy for empowerment Type Editorial Themes Assistive & Accessible Technology Research Group Social Justice Developing inclusive and resilient systems: COVID-19 and assistive technology Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi,Catherine Holloway&Victoria Austin While the inadequacies of our existing assistive technology systems, policies, and services have been highlighted by the acute and rapidly changing nature of the COVID-19 pandemic, these failures are also present and important during non-crisis times. Each of these actions, taken together, will not only address needs for more robust and resilient systems for future crises, but also the day-to-day needs of all assistive technology users. We have a responsibility as a global community, and within our respective countries, to address these inadequacies now to ensure an inclusive future. Disability & Society; 2020 Abstract Developing inclusive and resilient systems: COVID-19 and assistive technology Assistive technology is a critical component of maintaining health, wellbeing, and the realization of rights for persons with disabilities. Assistive technologies, and their associated services, are also paramount to ensuring individuals with functional limitations have access to important health and social service information, particularly during a pandemic where they may be at higher risk than the general population. Social isolation and physical distancing have further marginalized many within this population. We have an opportunity to learn from the COVID-19response to develop more inclusive and resilient systems that will serve people with disabilities more effectively in the future. In this Current Issues piece, we present a starting point for discussion, based on our experiences working to promote access to assistive technologies through inclusive and sustainable systems and policies. Developing inclusive and resilient systems: COVID-19 and assistive technology Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi, Catherine Holloway & Victoria Austin (2021) Developing inclusive and resilient systems: COVID-19 and assistive technology, Disability & Society, 36:1, 151-154, DOI:10.1080/09687599.2020.1829558 Developing inclusive and resilient systems: COVID-19 and assistive technology Type Journal Paper Themes Assistive & Accessible Technology Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey Emma M Smith, Maria Luisa Toro Hernandez, Ikenna D Ebuenyi, Elena V Syurina,Giulia Barbareschi, Krista L Best,Jamie Danemayer,Ben Oldfrey, Nuha Ibrahim,Catherine Holloway, Malcolm MacLachlan The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19.Objective:The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis. International Journal of Health Policy and Management; 2020 Abstract Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey Abstract Background:The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19.Objective:The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis. Methods:This study was a rapid, international online qualitative survey in the 6 United Nations (UN) languages (English, French, Spanish, Russian, Arabic, Mandarin Chinese) facilitated by extant World Health Organization (WHO) and International Disability Alliance networks. Themes and subthemes of the qualitative responses were identified using Braun and Clarke's 6-phase analysis. Results:Four primary themes were identified in in the data: Disruption of Services, Insufficient Emergency Preparedness, Limitations in Existing Technology, and Inadequate Policies and Systems. Subthemes were identified within each theme, including subthemes related to developing resilience in AT systems, based on learning from the pandemic. Conclusion:COVID-19 has disrupted the delivery of AT services, primarily due to infection control measures resulting in lack of provider availability and diminished one-to-one services. This study identified a need for stronger user-centred development of funding policies and infrastructures that are more sustainable and resilient, best practices for remote service delivery, robust and accessible tools and systems, and increased capacity of clients, caregivers, and clinicians to respond to pandemic and other crisis situations. Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey Smith EM, Toro Hernandez ML, Ebuenyi ID, Syurina EV, Barbareschi G, Best KL, Danemayer J, Oldfrey B, Ibrahim N, Holloway C, MacLachlan M. Assistive Technology Use and Provision During COVID-19: Results From a Rapid Global Survey. Int J Health Policy Manag. 2022 Jun 1;11(6):747-756. doi: 10.34172/ijhpm.2020.210. PMID: 33201656; Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey Type Editorial Research Group Social Justice Assistive Technology (AT), for What? Vicki Austin, Catherine Holloway This year (2022) has seen the publication of the World’s first Global Report on Assistive Technology (GReAT) [1]. This completes almost a decade of work to ensure assistive technology (AT) access is a core development issue. The lack of access to assistive products (APs), such as wheelchairs, hearing aids, and eyeglasses, as well as less well-referenced products such as incontinence pads, mobile phone applications, or walking sticks, affects as many as 2.5 billion people globally. Furthermore, the provision of APs would reap a 1:9 return on investment [2]. This could result in a family in need netting (or living without) over GBP 100,000 in their lifetime [2] or more, if we count dynamic overspills in the economy such as employment of assistive technology services and manufacturing of devices [3]. Societies; 2021 Abstract Assistive Technology (AT), for What? Amartya Sen’s seminal Tanner lecture: Equality of What?began a contestation on social justice and human wellbeing that saw a new human development paradigm emerge—the capability approach (CA)—which has been influential ever since. Following interviews with leading global assistive technology (AT) stakeholders, and users, this paper takes inspiration from Sen’s core question and posits, AT for what?arguing that AT should be understood as a mechanism to achieve the things that AT users’ value. Significantly, our research found no commonly agreed operational global framework for (disability) justice within which leading AT stakeholders were operating. Instead, actors were loosely aligned through funding priorities and the CRPD. We suggest that this raises the possibility for (welcome and needed) incoming actors to diverge from efficiently designed collective action, due to perverse incentives enabled by unanchored interventions. The Global Report on Assistive Technology (GReAT) helps, greatly! However, we find there are still vital gaps in coordination; as technology advances, and AT proliferates, no longer can the device-plus-service approach suffice. Rather, those of us interested in human flourishing might explore locating AT access within an operational global framework for disability justice, which recognizes AT as a mechanism to achieve broader aims, linked to people’s capabilities to choose what they can do and be. Assistive Technology (AT), for What? Austin, V.; Holloway, C. Assistive Technology (AT), for What? Societies2022, 12, 169.https://doi.org/10.3390/soc120... Assistive Technology (AT), for What? Type Journal Paper Themes Assistive & Accessible Technology Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries Margaret Savage, Sarah Albala, Frederic Seghers, Rainer Katte, Cynthia Liao, Mathilde Chaudron, Novia Afdhila Development outcomes are inextricably linked to the health of the marketplace that delivers products and services to people in low- and middle- income countries (LMIC). Shortcomings in the market for assistive technology (AT) contribute to low access in LMIC. Market shaping is aimed at improving a market’s specific outcomes, such as access to high quality, affordable AT, by targeting the root causes of these shortcomings. The paper summarizes the findings of a market and sector analysis that was conducted under the UK aid funded AT2030 programme and aims to discuss how market shaping can help more people gain access to the AT that they need and what are the best mechanisms to unlock markets and commercial opportunity in LMICs. Assistive Technology The Official Journal of RESNA; 2021 Abstract Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries Development outcomes are inextricably linked to the health of the marketplace that delivers products and services to people in low- and middle-income countries (LMIC). Shortcomings in the market for assistive technology (AT) contribute to low access in LMIC. Market shaping is aimed at improving a market’s specific outcomes, such as access to high quality, affordable AT, by targeting the root causes of these shortcomings. The paper summarizes the findings of market analyses conducted under the UK aid funded AT2030 programme in support of ATscale and aims to discuss how market shaping can help more people gain access to the AT that they need and what are the best mechanisms to unlock markets and commercial opportunity in LMICs. The paper also explores how market shaping for AT markets could be part of a mission-oriented approach AT policy. A mission-oriented approach can help accelerate progress toward a common objective among stakeholders, at country or global level. While market-shaping activities direct the outcomes of the market toward a specific end goal, such as access to quality, affordable products and services, missions are more comprehensive and include other policy interventions and stakeholder collaborations in order to create a robust and sustainable structure. Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries Margaret Savage, Sarah Albala, Frederic Seghers, Rainer Kattel, Cynthia Liao, Mathilde Chaudron & Novia Afdhila (2021) Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries, Assistive Technology, 33:sup1, 124-135, DOI: 10.1080/10400435.2021.1991050 Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries Type Journal Paper Themes Assistive & Accessible Technology Assistive technology access in longitudinal datasets: a global review Jamie Danemayer, Sophie Mitra,Cathy Holloway, Shereen Hussein A person’s access to assistive products such as hearing aids, wheelchairs, and glasses, is an essential part of their ability to age in a healthy way. But, according to the World Health Organization, a staggering 90% of people who need assistive products worldwide, do not have access to them. In many instances access is limited or simply non-existent. This is often due to assistive products being too expensive, demand outweighing supply, not always being suitable to use in different environments, or even the lack of availability of trained providers. In such circumstances, people are more likely to age ‘unhealthily’ if they do not have access to assistive products that are designed to support their day to day functioning and independence. International Journal of Population Data Science; 2023 Abstract Assistive technology access in longitudinal datasets: a global review Functional limitations become more prevalent as populations age, emphasising an increasingly urgent need for assistive technology (AT). Critical to meeting this need trajectory is understanding AT access in older ages. Yet few publications examine this from a longitudinal perspective. This review aims to identify and collate what data exist globally, seeking all population-based cohorts and repeated cross-sectional surveys through the Maelstrom Research Catalogue (searched May 10, 2022) and the Disability Data Report (published 2022), respectively. Datasets incorporating functional limitations modules and question(s) dedicated to AT, with a wave of data collection since 2009, were included. Of 81 cohorts and 202 surveys identified, 47 and 62 meet inclusion criteria, respectively. Over 40% of cohorts were drawn from high-income countries which have already experienced significant population ageing. Cohorts often exclude participants based on pre-existing support needs. For surveys, Africa is the most represented region (40%). Globally, 73% of waves were conducted since 2016. 'Use' is the most collected AT access indicator (69% of cohorts and 85% of surveys). Glasses (78%) and hearing aids (77%) are the most represented AT. While gaps in data coverage and representation are significant, collating existing datasets highlights current opportunities for analyses and methods for improving data collection across the sector. Assistive technology access in longitudinal datasets: a global review Danemayer, J., Mitra, S., Holloway, C. and Hussein, S. (2023) “Assistive technology access in longitudinal datasets: a global review”, International Journal of Population Data Science, 8(1). doi: 10.23889/ijpds.v8i1.1901. Assistive technology access in longitudinal datasets: a global review Type Journal Paper Themes Assistive & Accessible Technology Estimating need and coverage for five priority assistive products: A systematic review of global population based research Jamie Danemayer, Dorothy Boggs, Vinicius Delgado Ramos, Emma M. Smith, Ariana Kular, William Bhot, Felipe Ramos Barajas, Sarah Polack,Catherine Holloway Assistive technology (AT) includes assistive products (APs) and related services that can improve health and well-being, enable increased independence and foster participation for people with functional difficulties, including older adults and people with impairments or chronic health conditions. 1This paper uses the umbrella term ‘functional difficulty’ (FD) to refer to all of these groups. This systematic review was undertaken to identify studies presenting population-based estimates of need and coverage for five APs (hearing aids, limb prostheses, wheelchairs, glasses and personal digital assistants) grouped by four functional domains (hearing, mobility, vision and cognition). BMJ Global Health; 2021 Abstract Estimating need and coverage for five priority assistive products: A systematic review of global population based research Introduction:To improve access to assistive products (APs) globally, data must be available to inform evidence based decision-making, policy development and evaluation, and market-shaping interventions. Methods:This systematic review was undertaken to identify studies presenting population-based estimates of need and coverage for five APs (hearing aids, limb prostheses, wheelchairs, glasses and personal digital assistants) grouped by four functional domains (hearing, mobility, vision and cognition). Results:Data including 656 AP access indicators were extracted from 207 studies, most of which (n=199, 96%) were cross-sectional, either collecting primary (n=167) or using secondary (n=32) data. There was considerable heterogeneity in assessment approaches used and how AP indicators were reported; over half (n=110) used a combination of clinical and self-reported assessment data. Of 35 studies reporting AP use out of all people with functional difficulty in the corresponding functional domains, the proportions ranged from 4.5% to 47.0% for hearing aids, from 0.9% to 17.6% for mobility devices, and from 0.1% to 86.6% for near and distance glasses. Studies reporting AP need indicators demonstrated >60% unmet need for each of the five APs in most settings. Conclusion:Variation in definitions of indicators of AP access have likely led to overestimates/underestimates of need and coverage, particularly, where the relationship between functioning difficulty and the need for an AP is complex. This review demonstrates high unmet need for APs globally, due in part to disparate data across this sector, and emphasises the need to standardise AP data collection and reporting strategies to provide a comparable evidence base to improve access to APs. Cite Estimating need and coverage for five priority assistive products: A systematic review of global population based research Danemayer J, Boggs D, Delgado Ramos V, et al. Estimating need and coverage for five priority assistive products: a systematic review of global population-based research. BMJ Global Health 2022;7:e007662. doi:10.1136/bmjgh-2021-007662 Estimating need and coverage for five priority assistive products: A systematic review of global population based research Type Workshop Themes Assistive & Accessible Technology Research Group Disability Interactions Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Sahan Bulathwela, María Pérez-Ortiz,Catherine Holloway, John Shawe-Taylor This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Workshop on Machine Learning for the Developing World (ML4D) at the Conference on Neural Information Processing Systems 2021; 2021 Abstract Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Artificial Intelligence (AI) in Education has been said to have the potential for building more personalised curricula, as well as democratising education worldwide and creating a Renaissance of new ways of teaching and learning. Millions of students are already starting to benefit from the use of these technologies, but millions more around the world are not. If this trend continues, the first delivery of AI in Education could be greater educational inequality, along with a global misallocation of educational resources motivated by the current technological determinism narrative. In this paper, we focus on speculating and posing questions around the future of AI in Education, with the aim of starting the pressing conversation that would set the right foundations for the new generation of education that is permeated by technology. This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Finally, we ask what would it take for this educational revolution to provide egalitarian and empowering access to education, beyond any political, cultural, language, geographical and learning ability barriers. Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Type Workshop Themes Assistive & Accessible Technology Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Tabish Ahmed, Sahan Bulathwela The informational needs of people are highly contextual and can depend on many different factors such as their current knowledge state, interests and goals [1, 2, 3]. However, an effective information retrieval companion should minimise the human effort required in i) expressing a human information need and ii) navigating a lengthy result set. Using topical representations of the user history (e.g. [4]) can immensely help formulating zero shot queries and refining short user queries that enable proactive information retrieval (IR). While the world has digital textual information in abundance, it can often be noisy (e.g. extracted through Automatic Speech Recognition (ASR), PDF text extraction etc.), leading to state-of-the-art neural models being highly sensitive to the noise producing sub-optimal results [5]. This demands denoising steps to refine both query and document representation. In this paper, we argue that Wikipedia, an openly available encyclopedia, can be a humanly intuitive knowledge base [6] that has the potential to provide the world view many noisy information Retrieval systems need. Published at the First Workshop on Proactive and Agent-Supported Information Retrieval at CIKM 2022; 2022 Abstract Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Extracting useful information from the user history to clearly understand informational needs is a crucial feature of a proactive information retrieval system. Regarding understanding information and relevance, Wikipedia can provide the background knowledge that an intelligent system needs. This work explores how exploiting the context of a query using Wikipedia concepts can improve proactive information retrieval on noisy text. We formulate two models that use entity linking to associate Wikipedia topics with the relevance model. Our experiments around a podcast segment retrieval task demonstrate that there is a clear signal of relevance in Wikipedia concepts while a ranking model can improve precision by incorporating them. We also find Wikifying the background context of a query can help disambiguate the meaning of the query, further helping proactive information retrieval. Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Type Journal Paper Themes Assistive & Accessible Technology Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes Kate Mattick,Ben Oldfrey, Maggie Donovan-Hall, Grace Magomere, Joseph Gakunga,Catherine Holloway An estimated 1.5 million people undergo limb amputation each year [1]. Low- and middle-income countries (LMICs) are projected to have a rapid increase in people living with an amputation in the coming years due to prevalence of non-communicable dis-ease, trauma and conflict [1–3]. This paper explores the personal and system factors that motivate and enhance outcomes for patients accessing a prosthetic service and using a lower-limb prosthesis within a low resource setting. Disability and Rehabilitation; 2022 Abstract Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes PurposeTo explore the personal and system factors that motivate and enhance outcomes for patients accessing a prosthetic service and using a lower-limb prosthesis within a low resource setting. Materials and methodsThis study employed a qualitative approach to explore the motivations and satisfaction of individuals with lower limb loss engaging with a prosthetic service in Mombasa, Kenya. In-depth interviews were conducted over Microsoft Teams with 10 lower limb prosthesis users and thematic analysis was applied. ResultsFive key themes emerged: acceptance, self-determination, hope, clinician relationship and perception. These findings demonstrate the importance of hopeful thinking and a supportive community in overcoming physical and stigmatising challenges. The findings further highlight the value of the service provider relationship beyond just prescribing an assistive device. ConclusionThese results have relevance in developing patient-centred services, assistive devices and personnel training that are responsive, motivating, and cognisant of the service user. This is of particular interest as assistive technology services are newly developed in low resource settings. Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes Kate Mattick, Ben Oldfrey, Maggie Donovan-Hall, Grace Magomere, Joseph Gakunga & Catherine Holloway (2022) Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes, Disability and Rehabilitation, DOI:10.1080/09638288.2022.2152875 Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes Type Journal Paper Themes Culture and Participation Research Group Social Justice “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone Victoria Austin,Catherine Holloway, Ignacia Ossul Vermehren, Abs Dumbuya,Giulia Barbareschiand Julian Walker The World Health Organisation (WHO) estimates that there are currently one billion people in the world who need access to assistive technology (AT). Yet over 90% currently do not have access to assistive products (AP)—such as wheelchairs, hearing aids, walking sticks and eyeglasses—they need, nor and the systems and services necessary to support their appropriate provision [1]. This shocking deficit is set to double by 2050, with about two billion of us likely to require AT but no anticipated reduction in lack of access. The World Health Organisation defines AT as the “the umbrella term covering the systems and services related to the delivery of assistive products and services”, which are products that “maintain or improve an individual’s functioning and independence, thereby promoting their well-being” [2], and the importance of AT provision is strongly highlighted in the Convention on the Rights of Persons with Disabilities (CRPD) [3]. AT has also been shown to be essential to achieving many of the United Nation’s Sustainable Development Goals (SDG) [4]. Without access to AT, many persons with disabilities are unable to go to school, be active in their communities, earn an income, or play a full role in their families [5]. As a recent study found, “AT can make the impossible possible for people living with a wide range of impairments, but a lack of access to basic AT …excludes individuals and reduces their ability to live full, enjoyable, and independent lives” [6]. International Journal of Environmental Research and Public Health; 2021 Abstract “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone The importance of assistive technology (AT) is gaining recognition, with the World Health Organisation (WHO) set to publish a Global Report in 2022. Yet little is understood about access for the poorest, or the potential of AT to enable this group to participate in the activities of citizenship; both formal and informal. The aim of this qualitative study was to explore AT as mediator of participation in citizenship for persons with disabilities who live in two informal settlements in Freetown, Sierra Leone (SL). The paper presents evidence from 16 participant and 5 stakeholder interviews; 5 focus groups and 4 events; combining this with the findings of a house-to-house AT survey; and two national studies—a country capacity assessment and an informal markets deep-dive. Despite citizenship activities being valued, a lack of AT was consistently reported and hindered participation. Stigma was also found to be a major barrier. AT access for the poorest must be addressed if citizenship participation for persons with disabilities is a genuine global intention and disability justice is to become a reality. “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone Austin, V.; Holloway, C.; Ossul Vermehren, I.; Dumbuya, A.; Barbareschi, G.; Walker, J. “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone. Int. J. Environ. Res. Public Health2021, 18, 5547.https://doi.org/10.3390/ijerph... “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone Type Editorial Themes Assistive & Accessible Technology Research Group Disability Interactions The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative Chapal Khasnabis,Catherine Holloway, Malcolm MacLachlan We are now in an era of assistive care and assistive living—whereby many people, of all ages, in good health, and those who are more frail, or with cognitive or functional impairments, are using a broad range of technologies to assist and enhance their daily living. Assistive living 1is becoming an important part of population health and rehabilitation, which can help to maximise an individual's abilities, regardless of age or functional capacity. This encouraging shift in ethos has been strengthened by the response to the COVID-19 pandemic, in which a plethora of digital and remote technologies have been used. The Lancet; 2020 The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative Type Journal Paper Themes Assistive & Accessible Technology Research Group Local Productions Additive manufacturing techniques for smart prosthetic liners B Oldfrey, A Tchorzewska, R Jackson, M Croysdale, R Loureiro,C Holloway, M Miodownik Elastomeric liners are commonly worn between socket and limb by prosthetic wearers. This is due to their superior skin adhesion, load distribution and their ability to form a seal. Laboratory tests suggest that elastomeric liners allow reduced shear stress on the skin and give a higher cushioning effect on bony prominences, since they are soft in compression, and similar to biological tissues [1]. However, they also increase perspiration reducing hygiene and increasing skin irritations. Prosthetic users in general face a myriad of dermatological problems associated with lower limb prosthesis such as ulcers, cysts, and contact dermatitis, which are exacerbated by the closed environment of a fitted socket where perspiration is trapped and bacteria can proliferate [2]. Medical Engineering & Physics; 2021 Abstract Additive manufacturing techniques for smart prosthetic liners Elastomeric liners are commonly worn between the prosthetic socket and the limb. A number of improvements to the state of the art of liner technology are required to address outstanding problems. A liner that conforms to the residuum more accurately, may improve the skin health at the stump-socket interface. Previous work has shown that for effective thermal management of the socket environment, an active heat removal system is required, yet this is not available. Volume tracking of the stump could be used as a diagnostic tool for looking at the changes that occur across the day for all users, which depend on activity level, position, and the interaction forces of the prosthetic socket with the limb. We believe that it would be advantageous to embed these devices into a smart liner, which could be replaced and repaired more easily than the highly costly and labour-intensive custom-made socket. This paper presents the work to develop these capabilities in soft material technology, with: the development of a printable nanocomposite stretch sensor system; a low-cost digital method for casting bespoke prosthetic liners; a liner with an embedded stretch sensor for growth / volume tracking; a model liner with an embedded active cooling system. Additive manufacturing techniques for smart prosthetic liners , Additive manufacturing techniques for smart prosthetic liners, Medical Engineering & Physics, Volume 87, 2021, Pages 45-55, ISSN 1350-4533,https://doi.org/10.1016/j.mede.... Type Journal Paper Themes Assistive & Accessible Technology Culture and Participation Research Group Disability Interactions “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya Giulia Barbareschi, Mark T. Carew, Elizabeth Aderonke Johnson, Norah Kopi,Catherine Holloway Stigmatizing attitudes and beliefs towards disability represent one of the most pervasive and complex barriers that limits access to health care, education, employment, civic rights and opportunities for socialization for people with disabilities [1,2,3]. The damaging impact of disability stigma is widely acknowledged and, according to article 8 of the UN Convention on the Rights of Persons with disabilities, developing strategies, campaigns, policies and other initiatives to combat disability stigma and ensure that all people with disabilities are treated with dignity and respect is also a duty of the 182 countries who ratified the treaty [4]. Although the majority of literature focused on understanding disability stigma has been carried out in high-income settings [5,6,7], in the last decade, an increasing number of scholars have conducted studies looking at the negative stereotypes, prejudices and inaccurate beliefs that shape disability stigma in the Global South [3,8,9,10]. Most of these studies have described how these stigmatizing beliefs are often driven by a combination of personal and societal factors, ranging from misconceptions concerning the causes of different impairments (e.g., disability to be seen as a form of curse or punishment); assumptions about the lack of capabilities of people with disabilities; or discriminatory practices that actively endorse separation between people with and without disabilities [3,9,11,12]. Yet, there is a dearth of comparative studies that examine the perspectives of both people with and without disabilities of disability stigma and discrimination, including how the use of assistive technology may shape stigmatizing interactions. International Journal of Environmental Research and Public Health; 2021 Abstract “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya Disability stigma in many low- and middle-income countries represents one of the most pervasive barriers preventing people with disabilities from accessing equal rights and opportunities, including the uptake of available assistive technology (AT). Previous studies have rarely examined how disability stigma may be shaped through factors endemic to social interactions, including how the use of assistive technology itself may precipitate or alleviate disability stigma. Through two strands of work, we address this gap. Via a series of focus groups with Kenyans without disabilities (Study 1) and secondary data analysis of consultations with Kenyans with disabilities and their allies (Study 2), we identify shared and divergent understandings of what shapes disability stigma and discrimination. Specifically, Kenyans with and without disabilities were cognizant of how religious/spiritual interpretations of disability, conceptions of impairments as “different” from the norm, and social stereotypes about (dis)ability shaped the experience of stigma and discrimination. Moreover, both groups highlighted assistive technology as an influential factor that served to identify or “mark” someone as having a disability. However, whereas participants without disabilities saw assistive technology purely as an enabler to overcome stigma, participants with disabilities also noted that, in some cases, use of assistive technologies would attract stigma from others. “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya Barbareschi G, Carew MT, Johnson EA, Kopi N, Holloway C. “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya. International Journal of Environmental Research and Public Health. 2021; 18(8):4272.https://doi.org/10.3390/ijerph... “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya Type Journal Paper Themes Inclusive Design Culture and Participation Research Group Disability Interactions Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement Giulia Barbareschi,Ben Oldfrey, Long Xin, Grace N. Magomere, Wyclife A. Wetende, Carol Wanjira, Joyce Olenja,Victoria Austin, andCatherine Holloway The World Health Organisation estimate that there are approximately a billion people with disabilities who require access to appropriate assistive technology and this number is set to double by 2050 [82]. Assistive technologies (ATs) play a crucial role in the lives of people with disabilities and are necessary to be able to access essential services and participate in family and community life according to one’s aspirations [40, 62, 68, 81]. Although this is not often specifcally mentioned, the large majority of people with disabilities will routinely use more than one assistive device in their everyday lives [25, 26]. For example a person with a visual impairment is likely to use a white cane to navigate from their house to the office where they work and have a screen-reader, or an equivalent accessibility software, on their computer to be able to do their work once in the office [17]. ASSETS '20: Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility; 2020 Abstract Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement Living in informality is challenging. It is even harder when you have a mobility impairment. Traditional assistive products such as wheelchairs are essential to enable people to travel. Wheelchairs are considered a Human Right. However, they are difficult to access. On the other hand, mobile phones are becoming ubiquitous and are increasingly seen as an assistive technology. Should therefore a mobile phone be considered a Human Right? To help understand the role of the mobile phone in contrast of a more traditional assistive technology – the wheelchair, we conducted contextual interviews with eight mobility impaired people who live in Kibera, a large informal settlement in Nairobi. Our findings show mobile phones act as an accessibility bridge when physical accessibility becomes too challenging. We explore our findings from two perspective – human infrastructure and interdependence, contributing an understanding of the role supported interactions play in enabling both the wheelchair and the mobile phone to be used. This further demonstrates the critical nature of designing for context and understanding the social fabric that characterizes informal settlements. It is this social fabric which enables the technology to be useable. Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement Giulia Barbareschi, Ben Oldfrey, Long Xin, Grace Nyachomba Magomere, Wycliffe Ambeyi Wetende, Carol Wanjira, Joyce Olenja, Victoria Austin, and Catherine Holloway. 2020. Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal settlement. In Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS '20). Association for Computing Machinery, New York, NY, USA, Article 50, 1–13.https://doi.org/10.1145/337362... Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement Type Editorial Themes Assistive & Accessible Technology Culture and Participation Research Group Social Justice Critical Junctures in Assistive Technology and Disability Inclusion Dr Maria Kett,Catherine Holloway,Vicki Austin,Dr Maria Kett It is clear from the events of the last 18 months that while technology has a huge potential for transforming the way we live and work, the entire ecosystem—from manufacturing to the supply chain—is vulnerable to the vagaries of that ecosystem, as well as having the potential to exacerbate new and existing inequalities [1]. Nowhere has this been more apparent than in the lives of people with disabilities, who make up around 15% of the world’s population and already face barriers to accessing education, employment, healthcare and other services [2]. Some of these barriers are a result of unequal access and opportunities. However, there is a growing movement to better understand how assistive technology systems and services can be designed to enable more robust and equitable access for all. As part of this growing movement, the Paralympic Games in Tokyo this autumn saw the launch of a new global campaign to transform the lives of the world’s 1.2 bn persons with disabilities: the ‘WeThe15’ campaign reached more than 4.5 billion people through its marketing and stands ready to be the biggest of its kind in history. Next year, the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF), AT scale and GDI Hub will publish the first World Report on Access to Assistive Technology, which will include research from the £20 million, UK Aid funded, GDI Hub-led, programme, AT2030. Ahead of that, in this Special Issue, we focus on how some events and situations—as diverse as the coronavirus pandemic and the Paralympics—can act as ‘critical junctures’ that can enable a rethink of the status quo to facilitate and promote change. Sustainability; 2021 Critical Junctures in Assistive Technology and Disability Inclusion Kett, M.; Holloway, C.; Austin, V. Critical Junctures in Assistive Technology and Disability Inclusion. Sustainability2021, 13, 12744.https://doi.org/10.3390/su1322... Type Book Research Group Disability Interactions Disability Interactions Creating Inclusive Innovations Catherine Holloway,Giulia Barbareschi Abstract Disability Interactions Creating Inclusive Innovations Disability interactions (DIX) is a new approach to combining cross-disciplinary methods and theories from Human Computer Interaction (HCI), disability studies, assistive technology, and social development to co-create new technologies, experiences, and ways of working with disabled people. DIX focuses on the interactions people have with their technologies and the interactions which result because of technology use. A central theme of the approach is to tackle complex issues where disability problems are part of a system that does not have a simple solution. Therefore, DIX pushes researchers and practitioners to take a challenge-based approach, which enables both applied and basic research to happen alongside one another. DIX complements other frameworks and approaches that have been developed within HCI research and beyond. Traditional accessibility approaches are likely to focus on specific aspects of technology design and use without considering how features of large-scale assistive technology systems might influence the experiences of people with disabilities. DIX aims to embrace complexity from the start, to better translate the work of accessibility and assistive technology research into the real world. DIX also has a stronger focus on user-centered and participatory approaches across the whole value chain of technology, ensuring we design with the full system of technology in mind (from conceptualization and development to large-scale distribution and access). DIX also helps to acknowledge that solutions and approaches are often non-binary and that technologies and interactions that deliver value to disabled people in one situation can become a hindrance in a different context. Therefore, it offers a more nuanced guide to designing within the disability space, which expands the more traditional problem-solving approaches to designing for accessibility. This book explores why such a novel approach is needed and gives case studies of applications highlighting how different areas of focus—from education to health to work to global development—can benefit from applying a DIX perspective. We conclude with some lessons learned and a look ahead to the next 60 years of DIX. Disability Interactions Creating Inclusive Innovations Type Editorial Themes Assistive & Accessible Technology Research Group Disability Interactions Introduction to the companion papers to the global report on assistive technology Johan Borg, Wei Zhang, Emma M. Smith,Cathy Holloway GReAT, but do we care? If accessible, assistive technology would be life changing for a billion people across the world today – and two billion people in 2050 (WHO,2018). It would make the difference between independence and dependence, inclusion and exclusion, life and death. It holds the potential to improve and transform health, education, livelihood and social participation; fundamental human rights everyone is entitled to. And if we are lucky to grow old, the chances are that we all would use assistive technology by then. But do we care? Assistive Technology, The Official Journal of RESNA; 2021 Johan Borg, Wei Zhang, Emma M. Smith & Cathy Holloway (2021) Introduction to the companion papers to the global report on assistive technology, Assistive Technology, 33:sup1, 1-2, DOI:10.1080/10400435.2021.2003658 Type Journal Paper Themes Assistive & Accessible Technology Climate & Crisis Resilience Research Group Disability Interactions Measuring assistive technology supply and demand: A scoping review Jamie Danemayer,Dorothy Boggs, Emma M. Smith, Vinicius Delgado Ramos, Linamara Rizzo Battistella,Cathy Holloway,and Sarah Polack An assistive product (AP) is defined as a product used exter-nally to the human body, whose primary purpose is to main-tain or improve an individual’s functioning and independence and thereby promote his or her well-being (WHO, 2016). Global population aging forecasts a rise in the need for solu-tions that support participation and independence, including APs. In this paper, we review current population-level AP supply and demand estimation methods for five priority APs and provide recommendations for improving national and global AP market evaluation. Assistive Technology The Official Journal of RESNA; 2021 Measuring assistive technology supply and demand: A scoping review The supply of and market demand for assistive products (APs) are complex and influenced by diverse stakeholders. The methods used to collect AP population-level market data are similarly varied. In this paper, we review current population-level AP supply and demand estimation methods for five priority APs and provide recommendations for improving national and global AP market evaluation. Abstracts resulting from a systematic search were double-screened. Extracted data include WHO world region, publication year, age-groups, AP domain(s), study method, and individual assessment approach.497 records were identified. Vision-related APs comprised 65% (n = 321 studies) of the body of literature; hearing (n = 59), mobility (n = 24), cognitive (n = 2), and studies measuring multiple domains (n = 92) were proportionately underrepresented. To assess individual AP need, 4 unique approaches were identified among 392 abstracts; 45% (n = 177) used self-report and 84% (n = 334) used clinical evaluation. Study methods were categorized among 431 abstracts; Cross-sectional studies (n = 312, 72%) and secondary analyses of cross-sectional data (n = 61, 14%) were most common. Case studies illustrating all methods are provided. Employing approaches and methods in the contexts where they are most well-suited to generate standardized AP indicators will be critical to further develop comparable population-level research informing supply and demand, ultimately expanding sustainable access to APs. Measuring assistive technology supply and demand: A scoping review Jamie Danemayer, Dorothy Boggs, Emma M. Smith, Vinicius Delgado Ramos, Linamara Rizzo Battistella, Cathy Holloway & Sarah Polack (2021) Measuring assistive technology supply and demand: A scoping review, Assistive Technology, 33:sup1, S35-S49, DOI: 10.1080/10400435.2021.1957039 Type Journal Paper Themes Assistive & Accessible Technology Research Group Humanitarian & Disasters Meeting AT needs in humanitarian crises: The current state of provision Golnaz Whittaker, Gavin Adam Wood, Giulia Oggero,Maria Kett, Kirstin Lange This paper discusses the evidence available in the literature for the scale and quality of AT provision interventions in crises, and what is known about the challenges and facilitators of provision. We conducted a search of the academic literature and retained literature that reported on any form of AT provision following crisis, where international humanitarian response was in place, published in English between January 2010 and June 2020. Assistive Technology The Official Journal of RESNA; 2021 Abstract Humanitarian coordination systems increasingly recognize and aim to respond to the needs of people with disabilities within populations affected by crises, spurred on by the UN Convention on the Rights of Persons with Disabilities (CRPD) which was adopted in 2006. Many agencies state their aim to meet the requirements of the CRPD using a “twin track” approach: ensuring the inclusion of people with disabilities in mainstream provision, alongside targeted support for their needs, which may include the need for Assistive Technology (AT). However, there is very little evidence of AT provision in humanitarian settings, which is a specific and urgent need for many people including the elderly and people with disabilities, and an implicit requirement of Article 11 of the CRPD and World Health Assembly resolution on improving access to assistive technology. There is also little evidence of effective mechanisms for AT provision in humanitarian settings. This is despite high and growing levels of unmet AT need in crises, and despite the legally binding requirement in the CRPD to provide AT for those who need it. AT provision faces unique challenges in humanitarian settings. This paper discusses the evidence available in the literature for the scale and quality of AT provision interventions in crises, and what is known about the challenges and facilitators of provision. We conducted a search of the academic literature and retained literature that reported on any form of AT provision following crisis, where international humanitarian response was in place, published in English between January 2010 and June 2020. We found very few examples in that academic literature of systematic and coordinated AT provision at the acute stage of crisis, and even less in the preparedness and post-acute stages. However, it is difficult to assess whether this is the result of insufficient academic attention or reflects a lack of provision. The small body of academic literature that describes AT provision in humanitarian settings paints a picture of small-scale provision, specialized to single types of impairments, and delivered by predominantly by NGOs. We also conducted a search of the gray literature, using the same inclusion criteria, in two countries: Afghanistan and South Sudan (case studies forthcoming). This gray literature provided supplementary evidence of the types of AT providers and AT provision available in those protracted crises. There are very few examples of how AT services can be scaled up (from a very low baseline) and maintained sustainably within a strengthened health system. The literature also describes more examples of provision of assistive products for mobility over assistive products for other impairments. If the paucity of literature on AT provision in humanitarian settings is a reflection of the scale of provision, this implies a deficiency in humanitarian response when it comes to providing people with AT needs with the essential products and services to which they have a right, and which will enable their access to basic, life-saving assistance. We conclude by providing recommendations for urgent actions that the AT and humanitarian community must take to fill this critical gap in the provision of essential products and services for a potentially marginalized and excluded group. Meeting AT needs in humanitarian crises: The current state of provision Golnaz Whittaker, Gavin Adam Wood, Giulia Oggero, Maria Kett & Kirstin Lange (2021) Meeting AT needs in humanitarian crises: The current state of provision, Assistive Technology, 33:sup1, S3-S16, DOI: 10.1080/10400435.2021.1934612 Type Journal Paper Themes Assistive & Accessible Technology Research Group Local Productions Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? Ben Oldfrey,Giulia Barbareschi, Priya Morjaria, Tamara Giltsoff, Jessica Massie, Mark Miodownik andCatherine Holloway From multiple studies conducted through the FCDO AT2030 Programme, as well as key literature, we examine whether Assistive Technology (AT) provision models could look towards more sustainable approaches, and by doing this benefit not only the environment, but also address the problems that the current provision systems have. Sustainability Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? From multiple studies conducted through the FCDO AT2030 Programme, as well as key literature, we examine whether Assistive Technology (AT) provision models could look towards more sustainable approaches, and by doing this benefit not only the environment, but also address the problems that the current provision systems have. We show the intrinsic links between disability inclusion and the climate crisis, and the particular vulnerability people with disabilities face in its wake. In particular, we discuss how localised circular models of production could be beneficial, facilitating context driven solutions and much needed service elements such as repair and maintenance. Key discussion areas include systems approaches, digital fabrication, repair and reuse, and material recovery. Finally, we look at what needs be done in order to enable these approaches to be implemented. In conclusion, we find that there are distinct parallels between what AT provision models require to improve equitable reliable access, and strategies that could reduce environmental impact and bring economic benefit to local communities. This could allow future AT ecosystems to be key demonstrators of circular models, however further exploration of these ideas is required to make sense of the correct next steps. What is key in all respects, moving forward, is aligning AT provision with sustainability interventions. Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? Oldfrey, B.; Barbareschi, G.; Morjaria, P.; Giltsoff, T.; Massie, J.; Miodownik, M.; Holloway, C. Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? Sustainability2021, 13, 10867.https://doi.org/10.3390/su1319... Type Journal Paper Themes Assistive & Accessible Technology Research Group Local Productions A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems Catherine Holloway, Dafne Zuleima Morgado Ramirez,Tigmanshu Bhatnagar,Ben Oldfrey, Priya Morjaria, Soikat Ghosh Moulic, Ikenna D. Ebuenyi,Giulia Barbareschi,Fiona Meeks, Jessica Massie, Felipe Ramos-Barajas, Joanne McVeigh, Kyle Keane, George Torrens, P. V.M. Rao, Malcolm MacLachlan,Victoria Austin, Rainer Kattel, Cheryl D Metcalf & Srinivasan Sujatha It is essential to understand the strategies and processes which are deployed currently across the Assistive Technology (AT) space toward measuring innovation. The main aim of this paper is to identify functional innovation strategies and processes which are being or can be deployed in the AT space to increase access to AT globally. Assistive Technology The Official Journal of RESNA A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems It is essential to understand the strategies and processes which are deployed currently across the Assistive Technology (AT) space toward measuring innovation. The main aim of this paper is to identify functional innovation strategies and processes which are being or can be deployed in the AT space to increase access to AT globally. We conducted a scoping review of innovation strategies and processes in peer-reviewed literature databases and complemented this by identifying case studies demonstrating innovation strategies. The review includes WHO world region, publication year, AT type and a sector analysis against the Systems-Market for Assistive and Related Technologies Framework. We analyzed the case studies and interviews using thematic analysis. We included 91 papers out of 3,127 after review along with 72 case studies. Our results showed that product innovations were more prevalent than provision or supply innovations across papers and case studies. Case studies yielded two themes: open innovation (OI); radical and disruptive innovation. Financial instruments which encourage OI are needed and we recommend pursuing OI for AT innovation. Embedding AT within larger societal missions will be key to success governments and investors need to understand what AT is and their translational socioeconomic value. A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems Catherine Holloway, Dafne Zuleima Morgado Ramirez, Tigmanshu Bhatnagar, Ben Oldfrey, Priya Morjaria, Soikat Ghosh Moulic, Ikenna D. Ebuenyi, Giulia Barbareschi, Fiona Meeks, Jessica Massie, Felipe Ramos-Barajas, Joanne McVeigh, Kyle Keane, George Torrens, P. V.M. Rao, Malcolm MacLachlan, Victoria Austin, Rainer Kattel, Cheryl D Metcalf & Srinivasan Sujatha (2021) A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems, Assistive Technology, 33:sup1, 68-86, DOI:10.1080/10400435.2021.1970653 A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems Type Journal Paper Themes Inclusive Design Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities Mikaela Patrick,Iain McKinnon Public spaces, including recreational and social spaces, are often not prioritised. Inclusive public spaces are fundamental to participation and inclusive in society. Including persons with disabilities in the design and planning of the built environment supports equal rights and helps identify people’s aspirations for inclusive environments. Four city case studies will be discussed in this paper: Ulaanbaatar, Mongolia; Varanasi, India; Surakarta, Indonesia; and Nairobi, Kenya. The Journal of Public Space Abstract Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities This paper presents some of the findings from a global research study on inclusive infrastructure and city design and will focus on inclusive public spaces. Persons with disabilities can experience multi-dimensional exclusion from urban life, including but not limited to physical, attitudinal and social barriers. Public spaces, including recreational and social spaces, are often not prioritised. Inclusive public spaces are fundamental to participation and inclusive in society. Including persons with disabilities in the design and planning of the built environment supports equal rights and helps identify people’s aspirations for inclusive environments.Four city case studies will be discussed in this paper: Ulaanbaatar, Mongolia; Varanasi, India; Surakarta, Indonesia; and Nairobi, Kenya. Research participants and objectives are organised by three stakeholder groups: People - first-hand experiences of persons with disabilities living in the city and their aspirations for a more inclusive city Policy - the awareness and understanding of inclusive design among policy-makers Practice - the awareness and understanding of inclusive design among practitioners including barriers to implementation, opportunities and the relationship with assistive technology Methods include document reviews, interviews, photo diaries and co-design workshops with participatory and inclusive engagement of persons with disabilities throughout. Findings on public spaces are discussed in three ways: The types of public spaces valued by participants in each of the four cities. The barriers and challenges experienced by persons with disabilities in the public realm. Aspirations for more inclusive public spaces and opportunities for inclusive design The paper concludes by discussing how the targeted stakeholder groups of people, policy and practice also help represent three essential dimensions of inclusive city design and forming a framework for successful implementation and delivery and supporting targets set out through the UNCRPD and Sustainable Development Goals (SDGs). Cite Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities Patrick, M. and McKinnon, I. (2022) “Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities”, The Journal of Public Space, 7(2), pp. 93–116. doi: 10.32891/jps.v7i2.1500. Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities Type Journal Paper Themes Culture and Participation Research Group Social Justice Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change Jessica Noske-Turner, Emma Pullen, Mufunanji Magalasi, Damian Haslett, Jo Tacchi Communication & Sport Abstract Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change The purpose of this commentary is to discuss how Paralympic coverage in sub-Saharan Africa can be effectively mobilised to stimulate discursive and structural change around disability. Paralympic coverage has demonstrated its pedagogical power to engage public(s) and challenge stigma toward disability. Yet, the Global picture of Paralympic broadcasting is deeply uneven, with audiences in parts of the Global South afforded limited opportunities to watch the Games. Considering this, the International Paralympic Committee has begun to broadcast Paralympic coverage across sub-Saharan Africa with an explicit aim to challenge stigma toward disability. In this article, we draw on examples from research to argue that ideas from the field of Communication for Social Change (CfSC) can add value towards this aim. We begin by providing a brief overview of CfSC before critically examining one of the field’s key concepts – Communicative (E)ecologies. Following this, we critically reflect on the potential of Paralympic broadcasting as a vehicle for social change and disability rights agendas in sub-Saharan Africa. We argue that thinking with CfSC concepts show the importance of a ‘decentred’ media approach that engages with disability community advocacy groups, localised communication activities and practices, and culturally specific disability narratives. Cite Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change Noske-Turner, J., Pullen, E., Magalasi, M., Haslett, D., & Tacchi, J. (2022). Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change. Communication & Sport, 10(5), 1001–1015.https://doi.org/10.1177/216747... Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Troy Bodkin Doctoral Thesis. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. Loughborough University Abstract Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design For many years, the biggest issue that causes discomfort and hygiene issues for patients with lower limb amputations have been the interface between body and prosthetic, the socket. Often made of an inflexible, solid polymer that does not allow the residual limb to breathe or perspire and with no consideration for the changes in size and shape of the human body caused by changes in temperature or environment, inflammation, irritation and discomfort often cause reduced usage or outright rejection of the prosthetic by the patient in their day to day lives. To address these issues and move towards a future of improved quality of life for patients who suffer amputations, Loughborough University formed the Next Generation Prosthetics research cluster. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. The research presented in this thesis is based on three primary studies. The first study involved the conception of a CAD criteria, deciding what features are needed to represent the various properties the future socket outlined by the research cluster needs. These criteria were then used for testing three CAD systems, one each from the Parametric, Non Uniform Rational Basis Spline (NURBS) and Polygon archetypes respectively. The result of these tests led to the creation of a hybrid control workflow, used as the basis for finding improvements. The second study explored emerging CAD solutions, various new systems or plug-ins that had opportunities to improve the control model. These solutions were tested individually in areas where they could improve the workflow, and the successful solutions were added to the hybrid workflow to improve and reduce the workflow further. The final study involved taking the knowledge gained from the literature and the first two studies in order to theorise how an ideal CAD system for producing future prosthetic sockets would work, with considerations for user interface issues as well as background CAD applications. The third study was then used to inform the final deliverable of this research, a software design specification that defines how the system would work. This specification was written as a challenge to the CAD community, hoping to inform and aid future advancements in CAD software. As a final stage of research validation, a number of members of the CAD community were contacted and interviewed about their feelings of the work produced and their feedback was taken in order to inform future research in this area. Cite Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Bodkin, Troy L. (2017): Specifying a hybrid, multiple material CAD system for next-generation prosthetic design. Loughborough University. Thesis.https://hdl.handle.net/2134/25...; Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Giulia Barbareschi Doctoral Thesis. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. UCL (University College London) Abstract YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Transferring independently to and from their wheelchair is an essential routine task for many wheelchair users but it can be physically demanding and can lead to falls and upper limb injuries that reduce the person’s independence. New assistive technologies (ATs) that facilitate the performance of wheelchair transfers have the potential to allow wheelchair users to gain further independence. To ensure that users’ needs are addressed by ATs, the active involvement of wheelchair users in the process of design and development is critical. However, participation can be burdensome for many wheelchair users as design processes where users are directly involved often require prolonged engagement. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. A related outcome based on these contributions is a framing document to share knowledge between wheelchair users and designers to provide focus and promote an equal collaboration among participants. Cite YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Barbareschi, Giulia. “YouTransfer, YouDesign : a Participatory Approach to Design Assistive Technology for Wheelchair Transfers / Giulia Barbareschi.” Thesis (Ph.D.)--University College London, 2018., 2018. Print. YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Understanding wrist splint user needs and personalisation through codesign Charlotte Pyatt A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy at Loughborough University. Loughborough University Abstract Understanding wrist splint user needs and personalisation through codesign Wrist splints are a common treatment for rheumatoid arthritis, however their effectiveness is compromised by patients not wearing splints as often as prescribed. Previous research has identified a number of reasons for non-compliance, but typically lacks insights that could lead to improved splint design. This thesis investigates the motivators for patients to wear and not wear their wrist splints and, the impact of personalisation of splint appearance on patient wear. The work is based on the premise that digital design and manufacturing processes, such as Computer-Aided Design (CAD) and 3D Printing, can produce bespoke splints on demand. The research begins with a literature review across the core areas of: splinting, additive manufacture, product appearance and personalisation. This literature review identifies gaps in knowledge from which research questions are established for the work. The research employs a qualitative, generative design research approach and, follows a codesign framework employing telling, making and enacting tools. The thesis is made up of three studies. The first study is a sensitisation study and uses design probes to prepare the participants for the research and begin exploring the problem space. The second is a comprehensive study into participants splint wear behaviour and uses context mapping and scenario picture card tools to investigate the motivators for participants to wear and not wear wrist splints, along with positive and negative outcomes or wearing/not wearing splints. The final study uses a personalisation toolkit to elicit patient needs for a future wrist splint design and investigate self-reported expectations regarding compliance of patients who used the toolkit. The research finds that patient compliance is affected by practical and aesthetic limitations of current splints. It identifies 4 motivating factors to wear a splint and 10 motivating factors to not wear a splint. Additionally, it identifies 6 positive outcomes of wearing splints, 6 negative outcomes of wearing splints, 3 positive outcomes of not wearing splints and 3 negative outcomes of not wearing splints. Requirements for an improved splint design are established and form the basis of the design for a prototype personalisation toolkit. Testing of this toolkit reveals that patients are keen to own more than one splint and personalise splints to match the scenario in which it is to be worn. Patients reported that they expected to be more compliant with a personalised splint when compared to their current splint. Cite Understanding wrist splint user needs and personalisation through codesign Pyatt, Charlotte (2018): Understanding wrist splint user needs and personalisation through codesign. Loughborough University. Thesis.https://doi.org/10.26174/thesi...; Share Understanding wrist splint user needs and personalisation through codesign Type PhD Themes Assistive & Accessible Technology Shared Control for Wheelchair Interfaces Dr Chinemelu Ejiamatu Muoma Ezeh Doctoral Thesis. Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch. UCL (University College London) Abstract Shared Control for Wheelchair Interfaces Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch. Control is shared between a powered wheelchair user, using an alternative interface and a pow- ered wheelchair fitted with sensors. This shared control then produces a resulting motion that is close to what the user desires to do but a motion that is also safe. A path planning algorithm on the wheelchair is implemented using techniques in mo- bile robotics. Afterwards, the output of the path planning algorithm and the user’s com- mand are both modelled as random variables. These random variables are then blended in a joint probability distribution where the final velocity to the wheelchair is the one that maximises the joint probability distribution. The performance of the probabilistic approach to blending the user’s inputs with the output of a path planner, is benchmarked against the most common form of shared control called linear blending. The benchmarking consists of several experiments with end users both in a simulated world and in the real-world. The thesis concludes that probabilistic shared control provides safer motion compared with the traditional shared control for difficult tasks and hard-to-use interfaces. Cite Shared Control for Wheelchair Interfaces Ezeh, Chinemelu Ejiamatu Muoma. Shared Control for Wheelchair Interfaces. UCL (University College London), 2018. Print. Share Shared Control for Wheelchair Interfaces Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Materials For Facial Prostheses In Resource Limited Countries Sophia Esther Liiba Tetteh A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University Loughborough University Abstract Materials For Facial Prostheses In Resource Limited Countries Facial prostheses are artificial devices that replace a missing body part in the facial and neck regions of the body. Defects or deformities in these regions can lead to functional deficiencies; social and psychological effects in addition to cosmetic defects. Restoration or rehabilitation in resource limited countries is usually provided by charities and organisations volunteering assistance overseas, with some training of local staff in the fabrication of these prostheses. Furthermore, these countries typically lack technical knowhow and trained personnel. In industrialised nations maxillofacial prosthetics has developed into a sophisticated medical speciality requiring highly skilled staff and expensive facilities. In resource limited countries surgical procedures may be an option for rehabilitation of these deformities/defects however, they tend to be unavailable or unaffordable and donated prostheses are not suitable. Hence, this research explores, from first principles, the appropriate and affordable local provision of maxillofacial prostheses in resource constrained regions. The investigation provides knowledge on identifying requirements for resource limited areas, resulting in the creation of a guideline constituting priorities, requirements and specifications. It further explores the viability of potentially cheaper, locally available candidate materials via weathering and antimicrobial methods in ascertaining material longevity. Cite Materials For Facial Prostheses In Resource Limited Countries Tetteh, Sophia (2019): Materials for facial prostheses in resource-limited countries. Loughborough University. Thesis.https://doi.org/10.26174/thesi...; Materials For Facial Prostheses In Resource Limited Countries Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Rhys James Williams Thesis: Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past. UCL, ProQuest Dissertations Publishing Abstract Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Amongst lower-limb prosthesis wearers, thermal discomfort is a common problem with an estimated prevalence of more than 50%. Overheating does not just create discomfort to the user, but it has been linked to excessive sweating, skin damage caused by a moist environment and friction. Due to impermeable prosthetic components and a warm moist environment, minor skin damage can result in skin infections that can lead to prosthesis cessation, increased social anxiety, isolation and depression. Despite the seriousness of thermal discomfort, few studies explore the issue, with research predominantly constrained to controlled laboratory scenarios, with only one out of laboratory study. In this thesis, studies investigate how thermal discomfort arises and what are the consequences of thermal discomfort for lower-limb prosthesis wearers. Research studies are designed around the principles of presenting lived experiences of the phenomenon and conducting research in the context of participants' real-life activities. A design exploration chapter investigates modifying liner materials and design to create a passive solution to thermal discomfort. However, this approach was found to be ineffective and unfeasible. Study 1 presents a qualitative study which investigates the user experience of a prosthesis, thermal discomfort and related consequences. Study 2 explores limb temperature of male amputees inside and outside the laboratory, with the latter also collecting perceived thermal comfort (PTC) data. Finally, Study 3 investigates thermal discomfort in the real-world and tracks limb temperature, ambient conditions, activities, and experience sampling of PTC. While there were no apparent relationships presented in sensor data, qualitative data revealed that in situations where prosthesis wearers perceived a lack of control, thermal discomfort seemed to be worse. When combined, the studies create two knowledge contributions. Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past. Cite Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Williams, Rhys James. “Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers.” ProQuest Dissertations Publishing, 2020. Print. Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Design rules for additively-manufactured wrist splints Sarah Kelly A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University. Loughborough University Abstract Design rules for additively-manufactured wrist splints Additive Manufacturing (AM) often known by the term three-dimensional printing (3DP) has been acknowledged as a potential manufacturing revolution. AM has many advantages over conventional manufacturing techniques; AM techniques manufacture through the addition of material - rather than traditional machining or moulding methods. AM negates the need for tooling, enabling cost-effective low-volume production in high-wage economies and the design & production of geometries that cannot be made by other means. In addition, the removal of tooling and the potential to grow components and products layer-by-layer means that we can produce more from less in terms of more efficient use of raw materials and energy or by making multifunctional components and products. The proposed Centre for Doctoral Training (CDT) in Additive Manufacturing and 3D Printing has the vision of training the next generation of leaders, scientists and engineers in this diverse and multi-disciplinary field. As AM is so new current training programmes are not aligned with the potential for manufacturing and generally concentrate on the teaching of Rapid Prototyping principles, and whilst this can be useful background knowledge, the skills and requirements of using this concept for manufacturing are very different. This CDT will be training cohorts of students in all of the basic aspects of AM, from design and materials through to processes and the implementation of these systems for manufacturing high value goods and services. The CDT will also offer specialist training on aspects at the forefront of AM research, for example metallic, medical and multi-functional AM considerations. This means that the cohorts graduating from the CDT will have the background knowledge to proliferate throughout industry and the specialist knowledge to become leaders in their fields, broadening out the reach and appeal of AM as a manufacturing technology and embedding this disruptive technology in company thinking. In order to give the cohorts the best view of AM, these students will be taken on study tours in Europe and the USA, the two main research powerhouses of AM, to learn from their international colleagues and see businesses that use AM on a daily basis. One of the aims of the CDT in AM is to educate and attract students from complementary basic science, whether this be chemistry, physics or biology. This is because AM is a fast moving area. The benefits of having a CDT in AM and coupling with students who have a more fundamental science base are essential to ensure innovation & timeliness to maintain the UK's leading position. AM is a disruptive technology to a number of industrial sectors, yet the CDTs industrial supporters, who represent a breadth of industrial end-users, welcome this disruption as the potential business benefits are significant. Growing on this industry foresight, the CDT will work in key markets with our supporters to ensure that AM is positioned to provide a real and lasting contribution & impact to UK manufacturing and provide economic stability and growth. This contribution will provide societal benefits to UK citizens through the generation of wealth and employment from high value manufacturing activities in the UK. Cite	https://www.disabilityinnovation.com/publications?page=8&type=workshop+phd+journal-paper+editorial+book

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